Coffee Intake Linked to Lower Diabetes Risk

June 26, 2006 (Eurekalert) - Drinking coffee, especially when it is decaffeinated, may be associated with a reduced risk of type 2 diabetes, according to a report in the June 26 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.

Previous studies in the United States and Europe have linked coffee to a reduced risk of type 2 diabetes, according to background information in the article. The link between coffee and diabetes risk appears to be consistent across different ages and body weights; in addition, most research has found that the more coffee an individual generally drinks, the lower his or her risk for diabetes. However, it remains unclear whether it is the caffeine or another ingredient in coffee that may confer a protective effect.

Mark A. Pereira, Ph.D., and colleagues at the University of Minnesota, Minneapolis, studied coffee intake and diabetes risk in 28,812 postmenopausal women in Iowa over an 11-year period. At the beginning of the study, in 1986, the women answered questions about their risk factors for diabetes, including age, body mass index, physical activity, alcohol consumption and smoking history. They also reported how often they consumed a variety of foods and beverages over the previous year, including regular and decaffeinated coffee.

Based on information reported in the initial questionnaire, about half of the women (14,224) drank one to three cups of coffee per day; 2,875 drank more than six cups; 5,554 four to five cups; 3,231 less than one cup; and 2,928 none. Over the following 11 years, 1,418 of the women reported on surveys that they had been newly diagnosed with type 2 diabetes. After adjusting the data for some of the other diabetes risk factors, women who drank more than six cups of any type of coffee per day were 22 percent less likely than those who drank no coffee to be diagnosed with diabetes; those who drank more than six cups of decaffeinated coffee per day had a 33 percent reduction in risk compared with those who drank none.

Overall caffeine intake did not appear to be related to diabetes risk, further suggesting that some other ingredient in coffee was responsible. "Magnesium, for which coffee is a good source, could explain some of the inverse association between coffee intake and risk of type 2 diabetes mellitus through known beneficial effects on carbohydrate metabolism," the authors write. However, the study found no association between this mineral and diabetes risk. Other minerals and nutrients found in the coffee bean--including compounds known as polyphenols that have also been shown to help the body process carbohydrates and antioxidants that may protect cells in the insulin-producing pancreas--may contribute to its beneficial effects and should be examined in future studies.

"In summary, we observed an inverse association between coffee consumption, especially decaffeinated coffee consumption, and the risk of type 2 diabetes mellitus over an 11-year period in postmenopausal women residing in the state of Iowa," the authors conclude. "Although the first line of prevention for diabetes is exercise and diet, in light of the popularity of coffee consumption and high rates of type 2 diabetes mellitus in older adults, these findings may carry high public health significance."

Posted by dlife at 02:40 PM | Comments (0)

One-Third of Adults with Diabetes Still Don’t Know They Have It

May 25, 2006 - The prevalence of diagnosed diabetes in U.S. adults age 20 and older has risen from about 5.1 percent to 6.5 percent, according to researchers at the National Institutes of Health (NIH) and the Centers for Disease Control and Prevention (CDC), who analyzed national survey data from two periods — 1988 to 1994 and 1999 to 2002. However, the percentage of adults with undiagnosed diabetes did not change significantly over the years studied. About 2.8 percent of U.S. adults — one-third of those with diabetes — still don’t know they have it.

The study, published in the June 2006 issue of Diabetes Care, notes that type 2 diabetes accounts for up to 95 percent of all diabetes cases and virtually all undiagnosed diabetes cases. Diabetes is a group of diseases marked by high levels of blood glucose resulting from defects in insulin production, insulin action, or both. It is the most common cause of blindness, kidney failure, and amputations in adults and a major cause of heart disease and stroke.

Over the years studied, about 26 percent of adults age 20 and older continued to have impaired fasting glucose (IFG), a form of pre-diabetes. IFG, in which blood glucose measured after an overnight fast is high but not yet diagnostic of diabetes, increases the risk of heart disease as well as the risk of developing type 2 diabetes.

“It’s important to know if you have pre-diabetes or undiagnosed type 2 diabetes,” said Dr. Larry Blonde, chair of the National Diabetes Education Program (NDEP), jointly sponsored by the NIH, CDC, and 200 partner organizations. “You should talk to your health care professional about your risk. If your blood glucose is high but not high enough to be diagnosed as diabetes, losing weight and increasing physical activity will greatly lower your risk of getting type 2 diabetes. If you have diabetes, controlling your blood glucose, blood pressure, and cholesterol will prevent or delay the complications of diabetes.”

The researchers also found that:

nearly 22 percent of people age 65 and older had diabetes.
about 13 percent of non-Hispanic blacks age 20 and older had diabetes. Diabetes was twice as common in non-Hispanic blacks compared to non-Hispanic whites.
about 13 percent of non-Hispanic blacks age 20 and older had diabetes. Diabetes was twice as common in non-Hispanic blacks compared to non-Hispanic whites.
about 8 percent of Mexican Americans age 20 and older had diabetes. Because the average age of Mexican Americans is younger than for other groups, the age-and sex-adjusted prevalence of diabetes in Mexican Americans is twice that of non-Hispanic whites and about equal to that of non-Hispanic blacks.
IFG and undiagnosed diabetes were about 70 percent more common in men than in women, especially in non-Hispanic white men.
nearly 40 percent of people age 65 and older had IFG, which becomes more common with age.

In the study, the researchers compared two slices of data, one from 1988 to 1994 and the other from 1999 to 2002. The data were derived from a national sample of U.S. adults age 20 years and older who took part in the National Health and Nutrition Examination Survey (NHANES) conducted by the CDC’s National Center for Health Statistics. Survey participants were interviewed in their homes and received a physical exam with a blood test, which included a glucose reading taken after an overnight fast. The NHANES is unique because it includes a blood test that detects undiagnosed diabetes and IFG.

“This study updates and generally corroborates earlier analyses that were based on 2 years of NHANES data,” said lead author Catherine Cowie, Ph.D., of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). “We’re seeing a rising prevalence of diagnosed diabetes that is not substantially offset by a drop in the rate of undiagnosed — about one-third of adults with diabetes still don’t know they have it. Another 26 percent of adults have a form of pre-diabetes.”

Pre-diabetes, which usually causes no symptoms, is serious because many people with the condition develop type 2 diabetes in the next 10 years. Also, pre-diabetes substantially raises the risk of a heart attack or stroke even if type 2 diabetes does not develop.

People with pre-diabetes may have IFG or impaired glucose tolerance (IGT) or both.

In IFG, blood glucose is high (100 to 125 milligrams per deciliter or mg/dL) after an overnight fast but not high enough to be diagnostic of diabetes.
In IGT, blood glucose is high (140 to 199 mg/dL) 2 hours after drinking a sugary drink in an oral glucose tolerance test but not high enough to be diagnostic of diabetes.
In the current study, researchers did not assess the prevalence of IGT because an oral glucose tolerance test was not a part of the survey.

People with pre-diabetes can often prevent or delay diabetes if they lose a modest amount of weight by cutting calories in their diet and increasing physical activity (for example, walking 30 minutes a day 5 days a week). A major study of people with IGT has shown that lifestyle changes leading to a 5 to 7 percent weight loss lowered diabetes onset by 58 percent.

If you are over age 45, you should consult your health care provider about testing for pre-diabetes or diabetes. If you are younger than 45, overweight, and have another risk factor, you should ask about testing. You are at greater risk of developing pre-diabetes and type 2 diabetes if you:

are age 45 or older
have a family history of diabetes
are overweight
have an inactive lifestyle (exercise less than three times a week)
are members of a high-risk ethnic population (e.g., African American, Hispanic/Latino American, American Indian and Alaska Native, Asian American, Pacific Islander)
have high blood pressure: 140/90 mm/Hg or higher
have an HDL cholesterol less than 35 mg/dL or a triglyceride level 250 mg/dL or higher
have had diabetes that developed during pregnancy (gestational diabetes) or have given birth to a baby weighing more than 9 pounds
have polycystic ovary syndrome, a metabolic disorder that affects the female reproductive system
have acanthosis nigricans (dark, thickened skin around neck or armpits)
have a history of disease of the blood vessels to the heart, brain, or legs
have had IFG or IGT on previous testing.

In its “Small Steps. Big Rewards. Prevent Type 2 Diabetes” campaign, the NDEP (www.ndep.nih.gov/) is reaching out to people at risk for type 2 diabetes with the message that they have the power to turn the tide against this disease. The NDEP campaign, “Control Your Diabetes for Life,” encourages people with diabetes to control their blood glucose as well as their blood pressure and cholesterol. By keeping all three as close to normal as possible, people with diabetes can prevent or delay the development and progression of diabetes complications, which affect the heart, eyes, nerves, kidneys, and blood vessels.

For more diabetes statistics, http://diabetes.niddk.nih.gov/dm/pubs/statistics/index.htm

Posted by dlife at 02:43 PM | Comments (1)

Studies Reveal Generational Cycle of Mother's Early Puberty Driving Child's Obesity Risk and Early Puberty

Other Pediatric Studies at ENDO 2006 Address Short Stature and Insulin Pumps

BOSTON, June 25 /PRNewswire/ -- A new study not only confirms the link between childhood obesity and early onset of puberty but also demonstrate that a mother's age at her first period is linked to her children's risk for obesity. Taken together, the results suggest a spiraling generational link between obesity and early puberty.

This study, as well as two others on treatment of diabetes in children, will be discussed at a media roundtable on Sunday, June 25th at 2:00 P.M. EDT during ENDO 2006, the 88th Annual Meeting of The Endocrine Society at the Boston Convention & Exhibition Center.

Early Puberty for Mother Predicts Rapid Infant Growth and Childhood Obesity

A related study by Dr. Ken Ong of the UK Medical Research Council and University of Cambridge set out to find possible inherited reasons for such findings, that larger girls are more likely to mature earlier. Ong found that mothers who had completed their own puberty early were shorter and fatter than other mother. They gave birth to offspring who grew rapidly during infancy, became more overweight during childhood, and themselves had earlier puberty.

In the ALSPAC birth cohort study from Bristol UK, Ong looked at the body mass index (BMI) for more than 6,000 children at age 9. The children of mothers who had periods before the age of 11 were far more likely to have larger BMI measurements and body fat than children whose mother's did not go through puberty until 15 or later. In addition, a more detailed review of childhood growth for more than 900 of the children revealed that offspring of mothers with early puberty grew more rapidly than the others only during the first two years of life and they then remained taller and fatter as children.

"We have identified a remarkable but common inherited growth pattern, starting with rapid infancy growth and weight gain, taller childhood stature, but earlier maturation and completion of growth resulting in slightly shorter adult stature" said Ong. "We knew that age when girls have their first period is an inherited trait, transmitted from mother to child. Now it appears that this trans-generational trait also has important influences on infancy and childhood growth rates and on obesity risks throughout life."

Insulin Pump Therapy in Very Young Children with Diabetes

While the use of insulin infusion pumps in young diabetic children is increasing, there is little information about the long-term effectiveness of this treatment. A study by Dr. Linda DiMeglio of Indiana University compared two groups of preschool children, one that used intensive insulin injection therapy for the first six months before switching to the pump and one that used the pump throughout the study time.

The study measured the level of hemoglobin A1c as well as the body mass index (BMI) at the time of enrollment, time of pump start and at six, 12, 18 and 24 months after pump start. Despite the potential to have a more liberalized diet once the pump was in place, there were no significant increases in BMI for age and hemoglobin A1c levels remained improved.

"The persistent reduction of hemoglobin A1c, during a time when children are transitioning into school and receiving some care outside of the home, is encouraging for the continued use of this technology in very young children," said DiMeglio.

Evaluation and Treatment Patterns for Pediatric type 2 Diabetes

With the prevalence of Type 2 diabetes increasing in children, it is important to understand the impact of current patterns of treatment and their relationship to controlling symptoms before complications occur. Doctors at the University of Florida in Gainesville, the University of Texas in Houston, the University of Colorado Medical School, the University of South Carolina Medical School, Children's Hospital of Philadelphia, Driscoll Children's Hospital in Corpus Christi, TX and Akron Children's Hospital in Akron, OH joined together to review data on nearly 600 young patients with type 2 diabetes.

The results were sobering: Most children had either worsening or no change in their blood glucose levels over time; this could be attributed to either poor compliance with treatment or simply worsening of the disease following its natural course. In addition, elevations in blood cholesterol or triglycerides were seen in almost one third of patients, and a few of these young patients were already showing signs of nerve and eye damage related to diabetes.

"Despite early onset of complications in patients with type 2 diabetes, a significant number of young patients are not evaluated for complications and cardiovascular risk factors by pediatric endocrinologists," said Dr. Vanessa Davis, one of the researchers for the study. "Such screening will be particularly important to prevent heart disease, diabetes-related complications and to improve long term quality of life for these children".

Posted by dlife at 02:38 PM | Comments (0)

New Perspective Emerges on Metabolic Syndrome

Leaders of the American Diabetes Association and the American Heart Association Announce Joint Letter at ENDO 2006, Annual Meeting of The Endocrine Society

BOSTON, June 25 (PRNewswire) - Though they have markedly different opinions on the controversial Metabolic Syndrome, leaders of the American Heart Association and the American Diabetes Association announced at the annual meeting of The Endocrine Society that they will co-publish a statement on Monday expressing a desire for the organizations to work together on the topic of "cardio-metabolic risk."

Despite their differences of opinion, both organizations are working together to prevent heart disease, stroke and diabetes, said Robert H. Eckel, president of the American Heart Association, a physician and professor at the University of Colorado.

Eckel presented alongside John Buse, vice president of the American Diabetes Association in a debate at The Endocrine Society annual meeting entitled "Controversies in Endocrinology: Impact and Management of the Metabolic Syndrome."

The two organizations represented by Buse and Eckel clearly still have differing viewpoints on the Metabolic Syndrome, as articulated last year in a paper published by the American Diabetes Association, "The Metabolic Syndrome: Time for a Critical Appraisal."

The Metabolic Syndrome is loosely defined as a cluster of medical conditions -- including obesity, high blood pressure, high LDL cholesterol (and low HDL) -- that increase the risks of diabetes and cardio-vascular disease.

The American Heart Association, according to Eckel, supports identifying and treating the syndrome through lifestyle modifications and other treatments.

But the American Diabetes Association, Buse said, believes that the definition of the syndrome is poor, and that risk prediction of cardiovascular disease is also poor. Further, he said there is little benefit to treating the syndrome as a whole rather than identifying and treating the various components.

The letter, to be released Monday, uses the term "cardio-metabolic risk," new terminology which Buse said may signify a new way of describing and therefore treating the condition known as Metabolic Syndrome.

The debate also included representatives of the FDA and the pharmaceutical industry.

Founded in 1916, The Endocrine Society is the world's oldest, largest, and most active organization devoted to research on hormones, and the clinical practice of endocrinology. Today, The Endocrine Society's membership consists of over 12,000 scientists, physicians, educators, nurses and students in more than 80 countries. Together, these members represent all basic, applied, and clinical interests in endocrinology. The Endocrine Society is based in Chevy Chase, Maryland. To learn more about the Society, and the field of endocrinology, visit our web site at http://www.endo-society.org/.

Posted by dlife at 02:36 PM | Comments (0)

Diabetes, heart disease can herald early GI cancers

LOS ANGELES (May 23, 2006) – Heart disease and diabetes are among the most common conditions plaguing Americans today, and they are related to a host of other diseases. Research presented today at Digestive Disease Week® 2006 (DDW) now also demonstrates that these conditions can be warning signs for some types of digestive cancers, and may lead to early screening and interventions that may help prevent the onset of cancer or lead to earlier detection and treatment. Furthermore, certain treatments for these diseases may actually reduce digestive cancer risk. DDW is the largest international gathering of physicians and researchers in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery.

"The presence of diabetes or heart disease can be a signal for clinicians to evaluate patients' risk for digestive cancers," said Randall W. Burt, M.D., professor of medicine, University of Utah School of Medicine and Interim Executive Director, Huntsman Cancer Institute at the University of Utah. "The associations between these two diseases and cancer, as shown in these studies, provide a critical tool to diagnose cancer early when patients might benefit most from treatment. These studies also suggest that certain treatments for heart disease, in particular ACE inhibitors, may reduce the risk of colon, pancreatic and esophageal cancers."

Resectability of Pre-Symptomatic Pancreatic Cancer and its Relationship to Onset of Diabetes: A Retrospective Review of CT Scans and Fasting Glucose Values Prior to Diagnosis [Abstract 952]

Pancreatic cancer is one of the deadliest forms of cancer, claiming the lives of nearly 32,000 people in the United States each year. With few visible symptoms, pancreatic cancer is often difficult to catch early and many patients are not diagnosed until the cancer is too advanced for surgery.

Up to 80 percent of pancreatic cancer patients are diabetic and research now suggests that a recent diagnosis of diabetes may be a marker of early pancreatic cancer. This study looked at CT scans of pancreatic cancer patients who were also diabetic to determine if a new diabetes diagnosis indeed signals early pancreatic cancer, hoping that it would help with asymptomatic detection and a better chance of successful treatment with surgery.

Mario Pelaez-Luna, M.D., and study partners at the Mayo Clinic in Rochester, Minn. examined the CT scans of 20 patients who had at least one abdominal scan prior to being diagnosed with pancreatic cancer. These initial scans were reviewed to determine the condition of the patient's pancreas – no changes, some pancreatic duct narrowing or blockage, early, small tumors, or advanced tumors.

The 20 patients had undergone a total of 23 CT scans six or more months prior to their diagnosis of pancreatic cancer. All scans done more than six months prior to diagnosis showed no definite evidence of cancer. At the time of cancer diagnosis, 80 percent of the cancers were too advanced to be treated with surgery. With regard to the relationship to diabetes, all scans prior to the onset of diabetes were found normal. When patients first showed high blood sugar levels suggestive of diabetes, 85 percent still had a normal-appearing pancreas or showed early cancer; only 15 percent of cancers were advanced. The cancer was diagnosed, on average, five months after the diabetes first developed.

The research suggests that the number of pancreatic cancers amenable to surgical treatment can be greatly increased if the diagnosis is made even six months earlier. Diabetes associated with pancreatic cancer occurs at a time when the tumor is still treatable by surgery. Thus, a new diabetes diagnosis can be a warning sign that pancreatic cancer may be present, leading to an early cancer diagnosis with potentially better outcomes.

"Pancreatic cancer is difficult to treat. By the time patients develop symptoms, the cancer is already at an advanced stage" said Mario Pelaez-Luna, M.D., lead author of the study. "However, discovering new links between pancreatic cancer and other conditions such as diabetes is helping us identify clues to early diagnosis. The only hope of offering surgical treatment to more patients with pancreatic cancer is diagnosing the disease before symptoms develop."

Type 2 Diabetes Mellitus: The Impact on Colorectal Adenoma Risk in Women [Abstract S1245]

Having Type 2 Diabetes Mellitus raises a person's risk for developing colorectal cancer, and while there have been several studies linking insulin resistance to colorectal cancer risk, there is little data on whether women with diabetes are more at risk for colorectal adenomas, or polyps, which can become cancerous.

In this study, researchers from Washington University in St. Louis, MO., selected 600 women undergoing screening colonoscopies – 100 had Type 2 (adult onset) diabetes and 500 were non-diabetic. Both groups were similar in terms of age, race, having a first-degree relative with colorectal cancer and body mass index.

Results showed that diabetics had increased rates of adenoma than non-diabetics (37 percent versus 24 percent) and advanced adenoma, larger adenomas and/or with more abnormal cells (14 percent versus 6 percent). Researchers compared 245 obese women with 321 non-obese women and found that the obese women had a higher rate of adenoma (32 percent versus 22 percent). Obese diabetics compared with non-obese, non-diabetics had increased rates of any adenoma (42 percent versus 23 percent) and advanced adenoma (19 percent versus 7 percent). A multivariate analysis that took into account age, race, diabetes, hypertension, cholesterol levels, body mass index, and NSAID use showed that diabetes was a risk factor for both adenomas and advanced adenomas and increased age was a risk factor for adenomas.

"This study took a careful look at women with diabetes to determine how gender might impact the diabetes-colorectal cancer connection, and results show colon cancer is indeed a concern for diabetic women," said Jill E. Elwing, M.D., of Washington University and lead study author. "Colorectal cancer screening is critical for this population, as their diabetic condition raises their risk of colorectal cancer."

Patients With Coronary Artery Disease Are At High Risk For Developing Colorectal Cancer and Adenoma: An Interim Analysis of a Prospective Study [Abstract 208]

Colorectal cancer is one of the most common but curable cancers, when caught early. This underscores the importance of identifying high risk patients and screening them to ensure early detection and treatment. Investigators from the University of Hong Kong conducted a prospective study to evaluate potential risk factors for colorectal cancer and found that patients with coronary artery disease (CAD) were also prone to colorectal cancer and adenoma, most likely as a result of common risk factors for both diseases. Both conditions share risk factors including male sex, old age, diabetes, smoking, high fat diet, sedentary life style and high body mass index (BMI).

Researchers administered coronary exams in 307 patients, diagnosing coronary artery disease (CAD) in those who had at least 50 percent blockage in one of the main heart arteries. The group of patients with CAD (46.3 percent) showed a higher incidence of adenomas and cancer than the patients who did not have CAD (30.3 percent versus 19.4 percent), including having larger adenomas with abnormal cells (16.9 percent versus 6.7 percent). Five cases of colorectal cancers were detected in the CAD group (3.5 percent) and none were detected in the group that did not have CAD. Analysis of the data showed a strong association between colorectal cancer and adenomas and CAD, with male smokers most at risk to have both diseases.

"Patients with CAD are at high risk of developing colorectal adenomas," said Annie On On Chan, M.D., University of Hong Kong and lead study author. "The two diseases share risk factors, and screening by colonoscopy of these patients should be mandatory to help prevent the disease and, if necessary, encourage early treatment."

Posted by dlife at 03:02 PM | Comments (1)

Less Sleep Linked to Weight Gain

Newswise — Women who sleep 5 hours or less per night weigh more on average than those who sleep 7 hours, according to a study to be presented at the American Thoracic Society International Conference on May 23rd.

The study found that women who slept for 5 hours per night were 32% more likely to experience major weight gain (defined as an increase of 33 pounds or more) and 15% more likely to become obese over the course of the 16-year study compared with women who slept 7 hours. Women who slept for 6 hours were 12% more likely to have major weight gain and 6% more likely to become obese compared with women who slept 7 hours a night.

The study included 68,183 middle-aged women who were enrolled in the Nurses Health Study. They were asked in 1986 about their typical night’s sleep, and were then asked to report their weight every 2 years for 16 years.

On average, women who slept 5 hours or less per night weighed 5.4 pounds more at the beginning of the study than those sleeping 7 hours and gained an additional 1.6 pounds more over the next 10 years.

“That may not sound like much, but it is an average amount—some women gained much more than that, and even a small difference in weight can increase a person’s risk of health problems such as diabetes and hypertension,” said lead researcher Sanjay Patel, M.D., Assistant Professor of Medicine at Case Western Reserve University in Cleveland, OH.

Dr. Patel noted that this is by far the largest study to track the effect of sleep habits on weight gain over time. “There have been a number of studies that have shown that at one point in time, people who sleep less weigh more, but this is one of the first studies to show reduced sleep increases the risk of gaining weight over time.”

The researchers looked at the women’s diets and exercise habits to see if they could account for part of the findings. “Prior studies have shown that after just a few days of sleep restriction, the hormones that control appetite cause people to become hungrier, so we thought that women who slept less might eat more. But in fact they ate less,” Dr. Patel said. “That suggests that appetite and diet are not accounting for the weight gain in women who sleep less.”

The researchers also asked women about how much they participated in exercise activities such as running, jogging or playing tennis. But they didn’t find any differences in physical activity that could explain why women who slept less weighed more.

“We don’t have an answer from this study about why reduced sleep causes weight gain, but there are some possibilities that deserve further study,” Dr. Patel said. “Sleeping less may affect changes in a person’s basal metabolic rate (the number of calories you burn when you rest). Another contributor to weight regulation that has recently been discovered is called non-exercise associated thermogenesis, or NEAT, which refers to involuntary activity, such as fidgeting or standing instead of sitting. It may be that if you sleep less, you move around less, too, and therefore burn up fewer calories.”

Posted by dlife at 02:55 PM | Comments (0)

Joslin Researcher Available to Comment on New Study Showing Adults With Two Parents with Type 2 Diabetes Show Early Signs of Cardiovascular Disease

BOSTON, June 23, 2006 (Joslin) - Joslin Diabetes Center's Allison M. Goldfine, M.D., has just published an interesting study in the Journal for the American College of Cardiology that found adults with two parents who have type 2 diabetes show early signs of atherosclerosis (plaque building up in the arteries) even when the adult children themselves do not have diabetes.

The study examined 38 adults without diabetes in their mid-to-late 30s. Nineteen of the adults had two parents with type 2 diabetes and were found to have impaired blood vessel responsiveness. Please refer to the American College of Cardiology's press release below for more details.

Dr. Goldfine is an Investigator in Joslin's Section on Cellular and Molecular Physiology, Assistant Director of Clinical Research at Joslin, Associate Physician at Brigham and Women's Hospital and Assistant Professor of Medicine at Harvard Medical School.

If you would like to interview Dr. Goldfine about this study, please contact Marge Dwyer or Jenny Eriksen from Joslin's Communications Office at 617-732-2415 or via email at marjorie.dwyer@joslin.harvard.edu or jenny.eriksen@joslin.harvard.edu.

Posted by dlife at 02:34 PM | Comments (0)

Children of Diabetics Show Signs of Atherosclerosis

Impaired blood vessel responses seen even though study participants did not have diabetes

BETHESDA, MD, June 23, 2006 (Joslin) - The blood vessels of people whose parents both have type 2 diabetes do not respond as well to changes in blood flow as those of people without a family history of diabetes, even if they do not have diabetes themselves, according to a new study in the June 20, 2006, issue of the Journal of the American College of Cardiology.

"We find that offspring of type 2 diabetic parents have endothelial dysfunction, even when they do not have diabetes. If early treatment can prevent progression of atherosclerosis, then identifying groups of persons at risk for diabetes in whom early atherosclerosis may be present is clinically important," said Allison B. Goldfine, M.D. from the Joslin Diabetes Center and Brigham and Women's Hospital in Boston, Massachusetts.

None of the 38 adults (mid- to late-30s) in this study had diabetes, but half of them were the offspring of two diabetic parents. The researchers restricted blood flow in the arms of the participants using a blood pressure cuff. Then, using ultrasound, they compared how blood vessels in the arms of participants responded to the surge in blood flow when the cuff was released. Blood vessel responsiveness was impaired in all 19 participants (9 men and 10 women) whose parents had diabetes.

Diabetes is a leading cause of heart disease. Other studies have linked higher blood sugar levels to impaired responsiveness of the lining of blood vessels (endothelial dysfunction); but this is the first study to demonstrate that even when blood sugar is below the diabetic range, modest increases in blood sugar can contribute to endothelial dysfunction. Endothelial dysfunction in this population shows a predisposition to atherosclerosis.

Type 2 diabetes, also known as adult-onset diabetes, is linked to overweight and obesity. However, obesity and other common risk factors, including age, gender, ethnicity, cholesterol, blood pressure and insulin resistance did not explain the differences observed between participants who had a family history of diabetes and those who did not.

"Persons whose parents both have type 2 diabetes have endothelial dysfunction. This predisposition to atherosclerosis is present even when the offspring do not have diabetes themselves. Insulin resistance has been suggested to be important to both the development of diabetes and cardiovascular disease in large populations. However, in this high-risk group, even the most insulin sensitive offspring had diminished endothelial function," Dr. Goldfine said.

The problem seems to be related to the availability of nitric oxide, a key signaling chemical that triggers blood vessel dilation. The researchers reported that there was no difference between the two groups of participants in how much their blood vessels dilated after treatment with nitroglycerin, which boosts nitric oxide levels in the blood.

While physicians already are told to aggressively combat heart disease risk factors in patients with diabetes, the results of this study suggest even apparently healthy people may have blood vessel problems, if they have a strong family history of diabetes. The researchers did not perform genetic analyses of the participants. In this case, family history includes both genetic inheritance and environmental factors.

"Persons with a strong family history of diabetes are at increased risk of atherosclerosis in addition to risk of diabetes. They may benefit from aggressive cardiovascular risk factor modification, including blood pressure and lipid control, weight management and smoking cessation to reduce their risk of heart attack and stroke," Dr. Goldfine said. "Blood sugar levels, even in the non-diabetic range contribute importantly to endothelial dysfunction and thus the atherosclerotic process. This raises the question of when doctors should recommend interventions to lower glucose levels and what should be the appropriate level of glucose recommended to patients with diabetes."

Dr. Goldfine noted that this study included only a small number of participants. However, she said it did a better job than earlier studies of matching the offspring of diabetics to control subjects; so that the effects of family history could be distinguished from the effects of risk factors such as insulin resistance, obesity, cholesterol and blood pressure.

Ann Marie Schmidt, M.D. from Columbia University Medical Center in New York, NY, who was not connected with this study, said the study was "quite informative," particularly the finding that the participants with a family history of diabetes showed signs of impaired endothelial function in their blood vessels even when they were not only free of diabetes itself, but even when they lacked any insulin resistance, which is one key early sign of a type of diabetes.

"These studies point out that genetic, and perhaps environmental, influences, as the groups were all first-degree relatives, critically impact on endothelial function. Although it is tempting to strictly predict genetic differences underlie this finding, the influence of dietary habits, exercise patterns and perhaps environmental exposures cannot be discounted," Dr. Schmidt said. "Taken together, this fascinating study suggests that irrespective of family history, efforts to limit factors leading to insulin resistance may have frank benefits in enhancing endothelial health and integrity."

Dr. Schmidt noted that the study had only a small number of participants. She also pointed out that the participants with a family history of diabetes had higher fasting glucose levels than the participants without a family history of diabetes.

Posted by dlife at 02:32 PM | Comments (0)

New Gene Therapy Technique for Potential Treatment of Type I Diabetes

Newswise (May 22, 2006) — Researchers at Baylor University Medical Center at Dallas and the Baylor Research Institute have developed a novel technique to deliver insulin genes to the pancreas, the organ that produces the body’s insulin. This approach is a major step in the potential treatment of Type I diabetes since patients with the disease do not produce enough insulin on their own. The research results were published in the May 2006 issue of the Proceedings of the National Academy of Sciences.

Insulin is a hormone that allows blood glucose (blood sugar) to enter the cells of the body to be used for energy. The technique, known as ultrasound-targeted microbubble destruction (UTMD), delivers these insulin genes to the organ via microscopic “bubbles.” Once the bubbles reach their target, they are burst with ultrasound releasing the insulin genes into the pancreas.

Using UTMD, researchers delivered the bubbles containing human insulin genes into the pancreas of rats and later found that the rat’s blood sugar had been subsequently lowered. Another gene that regulates insulin production, known as hexokinase I, was successfully delivered using UTMD as well, and resulted in increased blood insulin and decreased blood sugar in the rats.

“Not only was their blood sugar lowered, but there was no evidence of any damage to the pancreas,” says Paul Grayburn, M.D., principal investigator of the study. “Other forms of gene therapy are usually invasive and unlike the UTMD technique, do not target the tissues and organs specifically.”

Currently, patients with Type I (juvenile onset) diabetes must inject themselves with insulin daily to keep their blood sugar levels balanced in addition to following strict nutritional guidelines. Dr. Grayburn says that the UTMD technique is one of the most important steps in the development of a successful treatment of diabetes without the need for daily insulin injections.

“Now that we have successfully delivered insulin genes to the pancreas, our ultimate goal is to research the regeneration of insulin-producing cells in patients with Type I diabetes,” says Dr. Grayburn.

In the future, Dr. Grayburn says that the UTMD technique for gene delivery can be used to deliver therapeutic agents to other organs as well.

Nationwide, more than one million people have Type 1 (juvenile onset) diabetes. Diabetes – the fifth deadliest disease in the United States – affects the body’s ability to produce or respond to insulin. People with Type 1 diabetes are at increased risk for many serious complications, including heart disease, blindness, nerve damage and kidney damage.

Dr. Grayburn’s research was supported by a grant from the National Institutes of Health and by the Mary Alice M. and Mark Shepherd, Jr. Endowment Fund in Cardiology and Cardiovascular Surgery and Research. The study was also held in conjunction with researchers from Duke University and UT Southwestern Medical Center.

Baylor University Medical Center at Dallas, a 997-bed not-for-profit academic hospital, is a major patient care and research center in the southwest. In 2005, U.S. News & World Report recognized Baylor Dallas for the 13th consecutive year in its “America’s Best Hospitals” guide in several medical specialties. Baylor Dallas serves as the flagship hospital of Baylor Health Care System.

The Baylor Research Institute, an affiliate of Baylor Health Care System, promotes and supports clinically relevant research, bringing innovative treatments from the laboratory workbench to the patient bedside. Investigators at Baylor are conducting more than 500 active research protocols spanning more than 20 medical specialties.

Posted by dlife at 03:06 PM | Comments (0)

Metabolic Syndrome Significantly Boosts Risk of Heart Failure in Middle Age

May 22, 2006 (British Medical Journal) — Metabolic syndrome significantly boosts the chances of heart failure in middle age, suggests research published ahead of print in Heart.

Metabolic syndrome refers to a cluster of conditions, including obesity, high blood pressure, unfavourable blood fat levels, and diabetes.

The researchers base their findings on regular monitoring of more than 2,300 men who were aged 50 between 1970 and 1974 and who were tracked until the age of 70.

The presence of metabolic syndrome at the start of the study was strongly associated with the subsequent development of heart failure. Men with the syndrome were almost twice as likely to develop heart failure as those without.

This was independent of any other established risk factors for heart failure, such as coronary artery disease, a heart attack, smoking, and poorly working heart valves.

The authors suggest that metabolic syndrome may directly affect the heart itself as well as boosting the build up of fatty deposits in the arteries.

The likely mechanism is insulin resistance and the subsequent excess insulin circulating in the blood, say the authors. Insulin may excessively enlarge the heart muscle (myocardium), so impairing its capacity.

High circulating levels of insulin also stimulate the sympathetic nervous system, thought to be a risk factor in heart failure, and cause heart muscle cells to wither and/or stiffen.

Click here to view the paper in full: http://press.psprings.co.uk/heart/june/ht89011.pdf.

Posted by dlife at 03:04 PM | Comments (0)

RBP4 Predicts Type 2 Diabetes

BOSTON, June 14, 2006 (Newswise) – A study in the June 15 issue of The New England Journal of Medicine (NEJM) reveals that elevated levels of a molecule called RBP4 (retinol binding protein 4) can foretell early stages in the development of insulin resistance, a major cause of type 2 diabetes as well as cardiovascular disease.

The new findings, led by researchers at Beth Israel Deaconess Medical Center (BIDMC), offer a potential new target for the development of anti-diabetic therapies to lower serum RBP4 levels as well as an early means of identifying individuals who are at risk of developing diabetes – before the onset of overt disease.

“Type 2 diabetes is a rapidly increasing epidemic in the Western world,” explains senior author Barbara Kahn, MD, Chief of the Division of Diabetes, Endocrinology and Metabolism at BIDMC and Professor of Medicine at Harvard Medical School. “Since it is now occurring even in childhood, predictions indicate that it could shorten lifespan in the U.S. for the first time in more than a century.”

Insulin resistance develops when the body’s muscles, fat and liver cells lose the ability to respond to the hormone insulin. Because insulin is necessary to enable the body to take up sugar from blood and convert it into energy, this impairment results in a buildup of glucose in the bloodstream.

“Insulin resistance not only predisposes individuals to type 2 diabetes, it is also a major risk factor for cardiovascular disease,” adds co-lead author Timothy Graham, MD, an investigator in the Kahn laboratory. “Unfortunately, in the clinical setting, it is often difficult to distinguish individuals with and without insulin resistance.”

Last year, in a study conducted in animals, Kahn’s laboratory made the discovery that RBP4, a protein secreted from fat, can cause insulin resistance. Prior to this, the molecule was recognized only for its role in the transport of vitamin A.

In this new research, Graham, together with co-lead author Qin Yang, MD, PhD, set out to determine whether levels of RBP4, as measured in blood, correlate with the presence or absence of insulin resistance. (Study subjects represented three separate cohorts from San Diego, California; Goteberg, Sweden; and Leipzig, Germany.)

They first studied individuals with either obesity, impaired glucose tolerance (a “pre-diabetic” state), or with type 2 diabetes, comparing the blood levels of RBP4 in these insulin-resistant subjects with levels found in non-obese healthy subjects. Their results showed that not only were RBP4 levels higher in all cases in which insulin resistance was high, but that elevated serum RBP4 was also closely associated with components of the metabolic syndrome, including increased body mass index, waist-to-hip ratio, serum triglyceride levels, and systolic blood pressure, as well as decreased levels of high-density lipoprotein (HDL), or good, cholesterol.

The study was then extended to subjects with normal body weight and normal blood glucose, but with a strong family history of type 2 diabetes. “These are people who appear healthy, but have a high risk of developing diabetes due to their genetic background,” explains Ulf Smith, MD, PhD, of Sahlgrenska Hospital, Goteberg, Sweden, where this group of subjects was based. As predicted, the investigators found elevated RBP4 levels among this group as well.

Finally, the authors tested whether a therapeutic intervention – in this case, exercise – could lower RBP4 levels and increase insulin sensitivity. They found that all of the people who improved their insulin sensitivity with exercise also lowered their serum RBP4 levels. Among the one-third of the subjects who did not improve their insulin sensitivity, neither did RBP4 levels go down.

“Collectively, these findings tell us that RBP4 is a useful marker for therapeutic improvement and that this protein could play a causal role in insulin resistance in humans, just as our lab previously showed in mice,” says Kahn. Furthermore, she adds, because RBP4 levels consistently corresponded with insulin resistance -- even among lean subjects whose genetic risk for the development of diabetes might otherwise be overlooked -- this protein could be an important marker for type 2 diabetes among the general population.

“Being able to determine diabetes risk well before the onset of symptoms could provide an important opportunity for patients to take preventive measures,” she adds. “For those who are overweight or sedentary, this could mean making changes to their diet and fitness routines. For those who are lean and fit, but have a family history of type 2 diabetes, this could mean taking antidiabetic medication. Either way, these findings could help clinicians to better manage this growing epidemic.”

In addition to Kahn, Graham and Yang, study coauthors include Christopher Watson of BIDMC; Matthias Bluher, MD and Andreas Oberbach, MD, of the University of Leipzig Medical Center, Germany; Ann Hammarstedt, PhD, Per-Anders Jansson, MD, PhD, and Ulf Smith, MD, of Sahlgrenska University Hospital, Goteborg, Sweden; and Theodore Ciaraldi, PhD and Robert Henry, MD, of the Veterans Affairs San Diego Healthcare System.

This study was funded, in part, by grants from the National Institutes of Health, the American Diabetes Association, the Swedish Diabetes Association, and the Takeda Pharmaceutical Company, LTD.

Beth Israel Deaconess Medical Center is a patient care, research and teaching affiliate of Harvard Medical School and ranks fourth in National Institutes of Health funding among independent hospitals nationwide. BIDMC is clinically affiliated with the Joslin Diabetes Center and is a research partner of the Dana-Farber/Harvard Cancer Center. BIDMC is the official hospital of the Boston Red Sox. For more information, visit http://www.bidmc.harvard.edu.

Posted by dlife at 02:30 PM | Comments (0)

New Data On Renin Inhibitor SPP100 (Rasilez) Demonstrates Its Potential Use In Diabetic Patients

Robust efficacy and safety data presented at European Society of Hypertension meeting

BASEL, Switzerland and BRIDGEWATER, N.J., June 13, 2006 (PRNewswire-FirstCall) - Speedel (SWX: SPPN) is very pleased with the Phase III clinical data on SPP100 (Rasilez(1) in the treatment of hypertension in diabetic patients presented today by Novartis in Madrid at the 16th Meeting of the European Society of Hypertension (ESH). The data demonstrated the robust efficacy and good safety profile of SPP100 as a monotherapy and in co-administration with ramipril, an ACE(2) inhibitor. SPP100 is the first-in-class once daily oral renin inhibitor that Speedel successfully developed through Phase I and II clinical trials before Novartis exercised its license-back option in 2002. The U.S. Food and Drug Administration (FDA) in April 2006 accepted for review Novartis' new drug application (NDA) for SPP100 as a treatment for hypertension both as monotherapy and in co-administration with other anti-hypertensives.

Dr. Jessica Mann, Speedel Medical Director, said: "This new data underlines the potential of SPP100 in diabetic hypertensives, a segment of the hypertension population which is at a higher risk of having cardiovascular events than those hypertensive patients without diabetes. SPP100 offers additional blood pressure control and is well tolerated when co-administered with ramipril -- this is critical given that so many patients, especially those with hypertension and diabetes, are taking combination treatments in order to reach blood pressure targets."

The ESH meeting in Madrid is the first time that this data on SPP100 (Rasilez) has been presented in a scientific forum in Europe. The data presented today were from a clinical trial in 837 patients with diabetes and hypertension. Such patients are at an increased cardiovascular risk and the American Diabetes Association (ADA) recommends a lower blood pressure (BP) goal (< 130/80 mmHg) than patients with hypertension but without diabetes. In order to achieve such BP targets, most patients require therapy with multiple antihypertensive therapies. The use of SPP100 together with the ACE inhibitor ramipril (a first line therapy recommended by the ADA), not only decreases blood pressure further than ramipril alone through its additive effects, but also shows sustained 24-hour blood pressure control in these patients.

The number of adults with diabetes in the world is estimated to increase from 135 million in 1995 to 300 million in the year 2025(3).

The data from the Phase III clinical trial was presented today by investigators in the format of two posters:

SPP100 has greater BP lowering effect than ramipril and additional BP lowering effect when combined with ramipril in patients with diabetes and hypertension(4):

* After 8 weeks treatment, co-administration therapy with SPP100 and
ramipril provided superior reductions in MSDBP(5) from baseline compared
with either monotherapy

* By week 8, MSSBP(6) reductions from baseline were significantly greater
with both SPP100 monotherapy and SPP100/ramipril co-administration
therapy compared with ramipril monotherapy

* By the end of the study significantly more patients had responded to
SPP100 monotherapy and to SPP100/ramipril co-administration therapy than
ramipril monotherapy

* Co-administration therapy provided a clinically relevant additional BP
reduction of 4.6/2.1 mmHg over that achieved with standard ACE-I
treatment

* All treatments were well tolerated. As expected, the incidence of cough
was lower with SPP100 as a monotherapy than with ramipril. With
co-administration therapy the incidence of cough was lower than with
ramipril alone -- an unanticipated result that suggests an attenuation
of ACE-I induced cough

Adding SPP100 to ramipril improves 24-hour BP control compared to ramipril alone in patients with diabetes and hypertension(7):

* All treatments provided effective 24-hour BP lowering from baseline,
with SPP100/ramipril co-administration therapy providing significantly
greater ADBP(8) lowering than ramipril monotherapy

* Smoothness indices indicate that SPP100 monotherapy and SPP100/ramipril
co-administration therapy provide BP lowering from baseline with less
variability over the 24 hour period than ramipril alone

* Reductions from baseline in BP during the early morning BP surge were
greater with SPP100 monotherapy and SPP100/ramipril co-administration
therapy than with ramipril alone, suggesting that SPP100 based regimens
may provide greater protection for patients during the early morning
period of increased cardiovascular risk

Speedel believes that SPP100 has a five year lead over the next generation of renin inhibitors being developed in the industry. Speedel's own family of renin inhibitors includes SPP635 currently in Phase I with results due in the second half of 2006, followed by the SPP1100 series currently in toxicology testing with a compound due for entry into man before the end of 2006, and the SPP800 series currently in late-stage pre-clinical profiling.

About SPP100 (aliskiren, Rasilez(9)

SPP100 (aliskiren, Rasilez) is the first-in-class oral renin inhibitor. The development of SPP100 is the result of over 20 years of research on renin. Renin is the key enzyme at the top of the Renin Angiotensin System (RAS), one of the key regulators of blood pressure. The RAS is a cascade, starting with renin, leading to angiotensin I and finally to angiotensin II. Angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin II receptor antagonists (ARBs) have been developed to block this system "down stream" and have shown clinical efficacy in patients with hypertension and other cardiovascular diseases.

Inhibition of renin, articulated as Plasma Renin Activity (PRA) is believed to be very important in end-organ protection (e.g. heart and kidney). PRA is a surrogate marker for several cardio-renal diseases, such as myocardial infarction and chronic renal disease. A renin inhibitor can lower PRA efficiently whereas most current leading anti-hypertensive drug classes such as diuretics, ACE-Is and ARBs increase PRA levels.

Speedel in-licensed SPP100 from Novartis in 1999, and successfully completed 18 clinical trials through Phase I and II in about 500 patients and healthy volunteers. Based on the results generated during this programme, Novartis exercised a license-back option in 2002, and in March 2004 Novartis started trials with SPP100 in Phase III as monotherapy for hypertension and in Phase IIb as combination therapy. Phase III trials are ongoing in the US, EU, and Japan, with first regulatory submission in the US already filed in Q1 2006 and planned in the EU during 2006.

Speedel believes that it is the first company to establish successfully a clinical proof of concept in Phase II and to have developed and filed for patent protection a commercially viable manufacturing process for a renin inhibitor, an area of industry research for over 20 years. In a Phase II study of 200 patients conducted by Speedel, it was demonstrated that SPP100 achieves dose-dependent blood pressure reduction. The study also showed that 150mg and 300mg SPP100 once daily were comparable to Losartan 100mg, which is double the starting dose of this ARB (Stanton, Jensen, Nussberger, O'Brien, Hypertension.2003; 42: 1137-1143).

About Hypertension

Hypertension is a major risk factor for heart disease and the main risk factor for stroke and heart attack, and can also lead to heart and kidney failure, so-called "end-organ damage". This disease is estimated to affect approximately 190 million people in the seven key markets (United States, Japan, Germany, France, United Kingdom, Italy and Spain), representing the largest indication for prescription pharmaceuticals worldwide, with approximately USD 39 billion in global annual sales in 2004, according to Datamonitor, IMS Health and Business Insights.

Hypertension is a common disorder in which blood pressure is abnormally high, placing undue stress on the heart, blood vessels and other organs such as the kidney and the brain. Blood pressure is determined in two phases as the heart contracts and relaxes. Systolic blood pressure represents the force that blood exerts on the walls of arteries as the heart contracts to pump out blood. Diastolic blood pressure represents the force as the heart relaxes to allow the blood to flow into the heart.

Due to its wide prevalence and impact on cardiovascular health, hypertension is a major cause of disease and death in Europe and North America. More than one in three Europeans and North Americans over the age of 35 suffers from hypertension -- but for the vast majority of patients who undergo hypertension treatment, the causes of high blood pressure are unknown. More than 40 % of patients undergoing treatment with current therapies do not reach targeted blood pressure levels, and so there is a considerable unmet medical need.

The latest potential therapeutic agents for hypertension are renin inhibitors. Renin is an enzyme produced in the kidneys in response to reduced renal perfusion. Through a cascade of biological events, renin acts to bring about sodium retention, an increase in blood pressure, and restoration of renal perfusion, which shuts off the signal for renin release. For hypertensive individuals, renin inhibitors are currently being investigated as a therapy that may provide benefits over current therapies to reduce blood pressure, decrease salt retention and may protect end organs such as the kidney, heart and brain.

About Speedel

Speedel is a public biopharmaceutical company that seeks to create value for patients, partners and investors by developing innovative therapies for cardiovascular and metabolic diseases. Speedel is a world leader in renin inhibition, a promising new approach with significant potential for treating cardiovascular diseases. Our lead compound SPP100 (Rasilez), the first-in-class renin inhibitor, is partnered with Novartis for development and commercialisation in hypertension, and the NDA was filed with the FDA in the US in Q12006. Our pipeline covers three different modes of action, and in addition to SPP100, includes SPP301 in Phase III, SPP200 in Phase II, SPP635 in Phase I, and several pre-clinical projects.

Speedel develops novel product candidates through focused innovation and smart drug development from lead identification to the end of Phase II. We either partner with big pharma for Phase III and commercialisation in primary-care indications, or we may ourselves complete Phase III development in specialist indications. Candidate compounds for development and the company's intellectual property come from our late-stage research unit Speedel Experimenta and from in-licensing. Our team of approximately 70 employees, including over 30 experienced pharmaceutical scientists, is located at our headquarters and laboratories in Basel, Switzerland and at offices in New Jersey, USA and Tokyo, Japan.

In March 2006 the company raised gross proceeds of CHF 83.95 million (approximately EUR 53m or USD 64m) through the public offering of 500,000 treasury shares. As a private company, we have previously raised gross proceeds of CHF 239 million (approximately EUR 154 million or USD 183 million) from private placements of equity securities and two convertible loans and we have had total revenues, principally from milestone payments, of CHF 57.7 million (approximately EUR 37 million or USD 44 million). The company's shares were listed on the SWX Swiss Exchange under the symbol SPPN on 08 September 2005.

Posted by dlife at 02:27 PM | Comments (0)

Liraglutide Phase 2 Study Shows Increased Insulin Secretion and Improved Blood Glucose Control in People with Type 2 Diabetes

WASHINGTON, June 13, 2006 (PRNewswire) - Liraglutide, an investigational treatment for type 2 diabetes under development by Novo Nordisk, improved the ability of pancreatic beta cells to secrete insulin in people with type 2 diabetes, according to findings from a late-breaking presentation today at the 66th annual meeting of the American Diabetes Association (ADA).(1)

The findings from the study, part of a larger, double-blind, placebo-controlled, randomized trial conducted over 14 weeks,(2) specifically showed that liraglutide increased the maximum capacity of beta cells to secrete insulin. In addition, insulin secretion was increased in the so-called "first phase" insulin response, which is typically diminished in patients with type 2 diabetes.

The larger trial showed that liraglutide reduced levels of A1C, the primary endpoint and a measure of a person's average blood glucose level over the past two to three months. Additionally, participants on the highest dose of liraglutide lost significantly more weight than did those on placebo by the end of the 14-week study.

"The prevalence of type 2 diabetes continues to increase, and we need to research and develop new therapies for the condition," said study investigator Sten Madsbad, M.D., DMSc., Department of Endocrinology, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark. "We are excited by these results as they demonstrate that liraglutide monotherapy significantly improves blood glucose control without risk of major or minor hypoglycemia, is well tolerated, lowers body weight and may help improve the body's ability to produce insulin."

Pancreatic beta cells are responsible for producing insulin, a hormone that helps transport glucose from the bloodstream into body cells, providing them an important source of energy and preventing blood glucose from becoming dangerously high. People with type 2 diabetes, the most common form of the condition, do not produce enough insulin or their body cells are less sensitive to it. While diet, exercise and weight loss may initially maintain control of blood glucose levels (glycemic control), beta cell function declines over time, necessitating therapy with one or more oral antidiabetic (OAD) agents that boost insulin secretion or heighten insulin sensitivity. As beta cell function further declines and OAD therapy eventually fails, insulin therapy is required.

One problem with insulin and some OAD therapies is that they can reduce blood glucose levels too low (hypoglycemia), which can also be dangerous. Liraglutide acts to lower blood glucose only when levels become too high,(3,4) and studies show it is associated with a low risk of hypoglycemia.(5,6) Furthermore, in animal models, liraglutide has been shown to decrease beta-cell apoptosis (programmed cell death) and increase beta-cell mass.(7,8,9,10,11)

Studies and findings

The larger study was a double-blind, placebo-controlled, randomized trial conducted over 14 weeks and included 165 patients with type 2 diabetes who were previously treated with diet or a single oral antidiabetic agent. After an initial four-week washout period, patients were randomized to one of three once-daily doses of liraglutide (0.65 mg, 1.25 mg and 1.9 mg) or placebo.

Improved blood glucose control was achieved with liraglutide monotherapy. Levels of A1C, the primary endpoint, were significantly reduced compared to placebo in all liraglutide treatment groups (p<0.0001). At the highest dose, the average reduction of A1C vs. placebo was 1.74 percent. Between 43 and 50 percent of patients who received liraglutide and 8 percent on placebo reached an A1C level of less than or equal to 7 percent. The improved glycemic control was achieved with no major or minor hypoglycemic episodes. In addition, patients on liraglutide had a reduction in bodyweight, with those on the highest dose losing approximately three kg (6.6 pounds) vs baseline and 1.2 kg (2.5 pounds) vs placebo after 14 weeks.

Liraglutide was well tolerated by participants in all groups, with the main adverse events being related to the gastrointestinal (GI) system. Nausea, which was experienced by 10 percent of participants in the high-dose group, and diarrhea, were the most common adverse events; however, the frequency of all GI events declined over time.

The late-breaking findings were from a subgroup of 39 participants who were also part of the larger trial. At baseline and after 14 weeks, these participants underwent standard tests to assess first-phase insulin secretion and maximal beta cell insulin secretory capacity. Of 39 participants who began the study, 28 completed the 14 weeks of treatment. The two higher doses of liraglutide (1.25 mg and 1.9 mg) significantly increased maximal beta cell insulin secretory capacity compared to placebo by 114 percent and 97 percent, respectively (p<0.05 for both doses), and first-phase insulin secretion by 124 percent and 107 percent, respectively (p<0.05).

Posted by dlife at 12:00 PM | Comments (0)

New Study Assesses Accuracy of Abbott's Investigational FreeStyle Navigator(TM) Continuous Glucose Monitoring System

Clinical Results Presented at ADA Scientific Sessions Suggest Accuracy and Stability Over Five Days of Wear

WASHINGTON, June 13, 2006 (PRNewswire-FirstCall) - Abbott announced today the presentation of results from a new study designed to assess the accuracy of the FreeStyle Navigator(TM) Continuous Glucose Monitoring System for people with diabetes. The study met its primary endpoint of demonstrated accuracy and stability over five days of wear.

Study results were discussed by William L. Clarke, M.D., professor of pediatrics at the University of Virginia Health System, in a presentation today during the 66th annual Scientific Sessions of the American Diabetes Association.

FreeStyle Navigator Continuous Glucose Monitoring System is an investigational device under FDA review. The system includes a five-day sensor, a transmitter, and a wireless receiver with a built-in FreeStyle(R) blood glucose monitoring system. The system is designed to provide glucose readings once per minute, high / low glucose alarms and projected glucose alarms.

The accuracy of FreeStyle Navigator was assessed in 58 subjects ranging in age from 18 to 64. Comparison of the FreeStyle Navigator system measurements (n=20,362) with a laboratory reference method (YSI) gave a mean absolute relative difference of 12.8% and a median absolute relative difference of 9.3%. On the Clarke Error Grid (CEG), 81.7% (n=16627) of measurements were in zone A, and 16.7% (n=3398) were in zone B (as compared to YSI). The Clarke Error Grid compares readings from a lab reference to a reading from a glucose monitoring device at a specific point in time. The variance between the two readings is placed on a grid within clinical categories, also known as zones. Each zone is labeled A, B, C, D, or E. Points in the A zone are clinically accurate and most consistent with the lab reference value. B zone readings are clinically acceptable. Points in the C, D, and E zones are progressively less accurate.

"Frequent and accurate glucose monitoring is an essential element of achieving tight glycemic control. The accuracy, particularly in the A zone, of continuous glucose monitoring sensors is critical to assessing the benefits that patients can derive from the technology," said Dr. Clarke. "In clinical studies presented by Abbott earlier this week, the FreeStyle Navigator system, under development, has set a new threshold for point glucose accuracy in a continuous glucose monitoring system."

"We look forward to making FreeStyle Navigator available to people with diabetes and we're very pleased that the system continues to demonstrate excellent accuracy in clinical studies," said Ed Fiorentino, president, Abbott Diabetes Care.

Posted by dlife at 11:58 AM | Comments (0)

Testosterone Levels Correlate with Insulin Resistance and Insulin Sensitivity in Type 2 Diabetes Patients

Findings from this analysis of diabetic patients call for more research to evaluate benefits of testosterone replacement therapy in Type 2 diabetes patients

MALVERN, Pa., June 12, 2006 (PRNewswire-FirstCall) - Auxilium Pharmaceuticals, Inc. , a specialty pharmaceutical company, announced that new findings presented today at the American Diabetes Association's 66th Annual Scientific Sessions suggest that abnormally low testosterone levels may be linked to progression of type 2 diabetes. The data are obtained from patient screening for a prospective study and include 568 men with type 2 diabetes. Researchers found a general increase in insulin resistance in patients with type 2 diabetes who have low total testosterone levels, compared to Type 2 diabetes patients with normal total testosterone levels. Recent studies have highlighted the potential importance of androgen concentrations in relation to insulin sensitivity. This latest cohort analysis provides evidence of the need for additional investigation into the effects that testosterone replacement therapy has on insulin resistance, glucose regulation and progression of type 2 diabetes. Data were presented today in a poster titled, "Comparison of Indices of Insulin Resistance and Insulin Secretion between Hypogonadal and Non-Hypogonadal type 2 Diabetic Patients" (Abstract #606-P), at the American Diabetes Association's 66th Annual Scientific Sessions in Washington, DC. The study was sponsored by Auxilium Pharmaceuticals, Inc.

The objective of the analysis was to characterize possible differences in insulin resistance (IR) and insulin secretion (IS) between hypogonadal (total testosterone < 300 ng/dL) and non-hypogonadal type 2 diabetic participants. Of the subjects in the analysis, 252 (44.4%) were classified as hypogonadal and 316 subjects (55.6%) were classified non-hypogonadal. The homeostatic model assessment (HOMA) method was used in this study to assess beta cell function and insulin resistance from basal (fasting) glucose and insulin or C-peptide concentrations. The HOMA IR for hypogonadal subjects was 7.6 and 5.1 for the non-hypogonadal subjects (P < 0.0001). The HOMA IS was 113.3 and 93.3 for hypogonadal and non-hypogonadal subjects, respectively (P = 0.018). The comparison of these index values suggests a generalized increase in insulin resistance in Type 2 diabetes patients with low total testosterone levels.

"Given that insulin resistance is an important indicator for diabetes progression and a common cause of mortality in diabetic patients, these findings naturally raise the question of the effect that testosterone supplementation has on insulin resistance and whether it may help counter the progression of type 2 diabetes," said Marc S. Rendell, M.D., Creighton Diabetes Center, an Investigator in this study. "Our data suggest that it is important to assess testosterone levels in male patients with diabetes and to treat low levels as part of the overall plan of therapy"

Testosterone is an androgen hormone that is primarily responsible for normal growth and development of male sex organs. The normal range for total testosterone in men is generally 300 to 1,000 nanograms per deciliter (ng/dL), depending on the lab performing the test and the methodology used.

A decrease in testosterone production, when testosterone levels drop below the normal range, is known medically as hypogonadism. A simple blood test conducted by a physician can determine if a man has low testosterone.

Researchers are accumulating clinical evidence that links low testosterone levels to long-term medical conditions such as metabolic syndrome, Type 2 diabetes, coronary heart disease, osteoporosis and depression. Additionally, studies have shown that men who suffer from obesity, diabetes or hypertension may be twice as likely to have low testosterone levels. Several published studies have shown the beneficial effects on men's health by normalizing testosterone levels with testosterone replacement therapy.

Posted by dlife at 12:22 PM | Comments (0)

Novocell Presents Phase I/II Data on Safety and Response to Encapsulated Islets at the American Diabetes Association's 66th Annual Scientific Session

Novocell's Chief Scientific Officer Speaks in a Symposium on Engineering Stem Cells to Endoderm the First Step to Producing Unlimited Numbers of Insulin-Producing Islet Cells

WASHINGTON, June 12 (PRNewswire) - Novocell, Inc., a stem cell engineering company, presented preliminary data from its phase I/II proof-of-principle clinical trial for encapsulated primary human islet allografts in a late-breaking poster presentation today at the American Diabetes Association's 66th Scientific Session.

The poster entitled "Encapsulated Human Islet Allografts -- Phase I/II Clinical Trial" described safety and efficacy results following subcutaneous implants of encapsulated human islet allografts into patients with type I diabetes of long standing duration. The first two partially implanted patients are showing early evidence of encapsulated islet function. The recipients are not showing evidence of encapsulated islet destruction by autoimmune reactions or allograft rejection to date. The patients only received transient low dose cyclosporine (50-100 ng/ml 12hr trough) and do not receive cyclosporine long term or any other form of immunosuppression.

"Patients are free of any safety concerns or adverse events to date," commented David Scharp, M.D., Chief Medical Officer. "We hope to see additional efficacy as these recipients receive increasing doses of encapsulated islets."

The single site study is being conducted in San Antonio, Texas, with Co-Principal Investigators, Sherwyn Schwartz, MD, Director of the Diabetes and Glandular Disease Center and Paraic Mulgrew, MD, of the Transplant Institute at the Christus Santa Rosa Hospital. The study is partially funded by the Juvenile Diabetes Research Foundation.

Novocell believes its proof of principle study is important to demonstrate the safety and efficacy of the encapsulation technology that can be used with the unlimited source of insulin-producing cells developed from stem cells to treat patients with diabetes.

Toward this goal, Chief Scientific Officer Emmanuel Baetge, Ph.D. will discuss engineering stem cells into definitive endoderm, the gatekeeper cells that are required to produce unlimited quantities of human islet cells, in a symposium entitled "First Steps in Making Beta-Cells from Stem Cells" on Tuesday, June 13th from 8 a.m. to 10 a.m. at this same meeting. Dr. Baetge's work in this area was published in Nature Biotechnology in December of 2005 and reviewed in the New England Journal of Medicine in February 2006. He will also address the importance of the endoderm in the creation of insulin-producing islet cells.

The combination of stem cell engineering and cell encapsulation addresses the two primary issues currently limiting islet implant therapy for the treatment of diabetes: chronic immunosuppression and islet cell supply. Novocell is currently engineering stem cell derived endoderm for the production of insulin-producing islet cells as a solution to the limited islet supply for implantation in people with diabetes.

Posted by dlife at 12:13 PM | Comments (0)

Joslin Scientists Discover Surprising Signs of Residual Islet Cell Functioning in People with Type 1 Diabetes in the 50-Year Medalist Study

Study to be presented June 12 at the American Diabetes Association's 66th Scientific Sessions in Washington, D.C.

BOSTON, June 12, 2006 - Scientists at Joslin Diabetes Center have discovered that a surprisingly high percentage of people with type 1 diabetes (insulin-dependent) who have had the disease for 50 years or longer (The Joslin Medalists) may still have residual functioning, insulin-producing islet cells and/or islet cell antibodies. The findings will be presented June 12 at the American Diabetes Association (ADA) 66th Annual Scientific Sessions in Washington, D.C.

"It is surprising that some Medalists still have c-peptide secretion, a sign of insulin production, and some are positive for antibodies to the islets, another sign that some islet function or mass still is present. The significance of these findings is that even after such a prolonged period of diabetes, some patients still have residual islet function," said George L. King, M.D., the study's lead author. Dr. King is Joslin's Research Director, Head of the Section on Vascular Cell Biology, head of Joslin's 50-Year Medalist Study and a Professor of Medicine at Harvard Medical School.

In addition, the researchers found 48 percent of the total participants reported no or very little microvascular complications, such as kidney and eye problems, which demonstrates that long duration of diabetes does not always progress to complications. There also was no significant difference in age, duration, age of onset or long-term glucose control measured by A1C (glycated hemoglobin) levels between those with or without complications.

This talk is one of nearly 80 presentations to be delivered by Joslin scientists at the ADA's Scientific Sessions, Friday, June 9, through Tuesday, June 13. Some 15,000 scientists, physicians and health professionals will attend the conference, to be held at the Washington Convention Center. The talk, "Immune Tolerance and Other Treatment Approaches for Type 1 Diabetes," is scheduled for June 12 at an 8-10 a.m. EST session on Immunology/Transplantation. [Abstract Number 278-OR: "Positivity of C-peptide, GADA and IA2 antibodies in Type 1 Diabetic Patients with Extreme Duration"]

Since 1970, Joslin Diabetes Center in Boston has awarded medals or certificates to people with type 1 diabetes who have been insulin-dependent continuously for at least 25 years. To date there have been approximately 2,400 50-Year Medals awarded and 17 distinctive 75-Year Medals. The Medalist Study began in April 2005 to identify physiological, clinical, genetic and other factors shared by the Medalists.

The study being presented at the ADA meeting is part of the second phase of the Joslin 50-Year Medalist Study that is assessing these factors in 326 patients with more than 50 years of insulin-dependent diabetes. It evaluated a subset of 125 people with type 1 diabetes for biomarkers of insulin function. Of this group, 12.7 percent had a c-peptide level greater than 0.3 ng/mL, which indicates active islet cells and some residual insulin production. Most of the Medalists have the characteristics associated with type 1 diabetes with or without the presence of c-peptide.

In addition, 23.2 percent of the c-peptide positive participants produced either of two antibodies, GADA and IA2, which attack islet cells. The study also found that 17 percent of participants who were not c-peptide positive produced GADA or IA2 antibodies to the islet cells, another indication that a small amount of islet cells may still be present and/or functioning.

"The findings are phenomenal," said Hillary Keenan, Ph.D., research associate at Joslin and co-investigator on the 50-Year Medalist Study, who will present the findings. "This is the first study to look at the specific biomarkers for islet cell presence in people with a 50-year duration of insulin-dependent diabetes." Other Joslin investigators in the study included Alessandro Doria, M.D., Ph.D., Lloyd Paul Aiello, M.D., Ph.D., Korey Hood, Ph.D., and Jennifer Sun, M.D.

The group also was tested for other clinical parameters, such as cholesterol, triglycerides, body mass index and daily insulin dose. The data shows no significant difference in clinical parameters for participants with or without c-peptide. For example, the average total cholesterol of the c-peptide positive participants was 146 compared to 162 for the participants who did not produce c-peptide.

"If we could find out the reason for their lack of complications, we could perhaps prevent kidney or eye disease," said Dr. King. The study has been investigating whether other factors, such as lifestyle or longevity genes, play a role in the development of complications, reported Dr. Keenan.

Overall, the study opens new avenues for research and treatment of type 1 diabetes. "The findings suggest that many patients, even after many years of diabetes, may still have some residual islet function. If a way can be found to stimulate islet growth, we could improve their diabetes and reduce insulin usage or better control blood glucose levels. If islets were returned to normal levels, they wouldn't need to take insulin," said Dr. King.

Of the 326 Joslin 50-Year Medalist Study respondents who have completed an extensive health questionnaire, 175 were female and 151 were male, with an average age of 70 years. The average age of diabetes onset was 13 years and average duration of type 1 diabetes 57 years. The data collected so far show that individuals who have survived 50 years or more have a greatly reduced risk of nephropathy and retinopathy.

Funding for the study was provided by the Juvenile Diabetes Research Foundation.

About Joslin Diabetes Center
Joslin Diabetes Center, dedicated to conquering diabetes in all of its forms, is the global leader in diabetes research, care and education. Founded in 1898, Joslin is an independent nonprofit institution affiliated with Harvard Medical School. Joslin research is a team of more than 300 people at the forefront of discovery aimed at preventing and curing diabetes. Joslin Clinic, affiliated with Beth Israel Deaconess Medical Center in Boston, the nationwide network of Joslin Affiliated Programs, and the hundreds of Joslin educational programs offered each year for clinicians, researchers and patients, enable Joslin to develop, implement and share innovations that immeasurably improve the lives of people with diabetes. As a nonprofit, Joslin benefits from the generosity of donors in advancing its mission. For more information on Joslin, call 1-800-JOSLIN-1 or visit www.joslin.org.

Posted by dlife at 12:08 PM | Comments (0)

Study Shows New Non-Invasive Device Screens Diabetes Better Than Fasting Plasma Diabetes Biomarkers Found in Skin Shown to Correlate Well With Diabetes Risk

WASHINGTON, June 12, 2006 (PRNewswire) - Researchers reported a new non-invasive technology that uses fluorescent light to detect the presence of abnormal concentrations of diabetes-related biological markers found in skin was able to significantly outperform fasting plasma glucose (FPG) as a screening test for pre-diabetes and type 2 diabetes. Results from a clinical study presented at the 66th annual Scientific Sessions of the American Diabetes Association, held here, showed a prototype medical device using the technology was able to identify 20 percent more patients with type 2 diabetes or its precursor. The study was conducted by researchers from the University of New Mexico School of Medicine, TriCore Reference Labs, InLight Solutions and VeraLight -- the developer of the non-invasive diabetes screening device it calls, "Scout."

Skin AGEs Predict Diabetes and Its Complications

Previous studies have shown that the presence of so-called "advanced glycation endproducts," or AGEs, found in skin correlate well with diabetes and are a predictor of the disease's serious complications. Analogous to a "diabetes odometer," AGEs are a sensitive metric for the cumulative damage the body has endured due to the effects of abnormally high blood sugar. They affect the proteins that make up blood vessels, connective tissue and skin, and are thought to be major factors in aging and age-related chronic diseases. According to medical experts, non-invasive skin detection of AGEs could replace the fasting plasma glucose test as the medical workhorse for screening people suspected of having diabetes.

"AGEs have been well-recognized as a diabetes biomarker and as a predictor of complications that may lead to blindness and kidney disease," said Robert E. Ratner, M.D., vice president of scientific affairs at Medstar Research Institute, Baltimore-Washington area's largest healthcare delivery system. "Until the advent of VeraLight's technology and the Scout system, a skin biopsy was the only way to detect AGEs which made them impractical for clinical use. With a simple, non-invasive technology, skin AGEs will be a valuable tool for identifying people with sub-clinical disease. Lack of a fasting requirement, overall convenience and superior accuracy may make this the technology of choice for diabetes and pre-diabetes screening."

Scout Technology More Sensitive Than Fasting Glucose Test

The study was undertaken in 328 subjects at risk for diabetes or pre-diabetes to evaluate VeraLight's non-invasive Scout technology against the FPG test, which measures a patient's blood sugar after a 12-hour fast. The oral glucose tolerance test, which measures blood glucose two hours after oral administration of a 75-gram glucose load, was used as a confirmatory test. The subjects in the study ranged in age from 21 to 88 years old. The results were analyzed to compare each test's "receiver-operator characteristics" -- a statistical measure that graphically illustrates a test's false-positive relationship to sensitivity (a measure of true positives). At the lower, impaired fasting glucose threshold of 100 milligrams per deciliter (mg/dl), the FPG sensitivity was 57.5 percent with a specificity (a measure of true normals) of 78 percent. At that specificity, the Scout sensitivity was 68.9 percent, showing the ability to detect 20 percent more individuals with diabetes or its precursor.

VeraLight Scout

Weighting about 10 pounds, the VeraLight Scout utilizes proprietary fluorescence spectroscopic technology that does not require patient fasting. The subject inserts the palm-side of the forearm into the system, which resembles a drug-store blood-pressure monitor. In about a minute the Scout shines various wavelengths of light on the skin to stimulate fluorescence that is measured by the machine to provide an indication of diabetes risk based on the presence of AGEs. The instrument optically calibrates for skin pigmentation so that performance is not diminished by skin coloration. A specially designed fiber-optic probe couples the excitation light to the subject and relays resulting skin fluorescence to a detection module. The system's software utilizes multivariate statistical techniques that are applied to the spectra to obtain a diabetes risk score.

Need for Early and More Accurate Diabetes Screening

More than 73 million Americans -- one third of the adult population -- now have diabetes or may be on their way to getting it, according to a NIDDK study published in the June issue of Diabetes Care. The study showed 9.3 percent of adults age 20 and older (19.3 million people) had diabetes in 1999-2002. While the prevalence of undiagnosed diabetes has remained essentially stable since 1988-1994 at 2.8 percent, the prevalence of diagnosed diabetes rose sharply during the same period -- from 5.1 percent to 6.5 percent of the population.

Another 26 percent of Americans had impaired fasting glucose, a form of pre-diabetes. In pre-diabetes, glucose levels are higher than normal, even though they are not yet high enough for a diagnosis of diabetes. Pre-diabetes often leads to diabetes if steps are not taken to prevent it.

Due to their inaccuracy and inconvenience, current screening methods for diabetes are grossly inadequate. The result is that 50% of diabetics are not identified until they present 5-to-9 years into the disease with one or more (often irreversible) complications. A more accurate and convenient screening method could dramatically reduce the costs and morbidity associated with such complications, allowing patients to halt or reverse disease progression.

In 2002 the United States spent $132 billion on diabetes treatment and complications, or approximately 10 percent of all national healthcare expenditures. Most of this was for complications -- yet numerous clinical studies have demonstrated the effectiveness of early therapeutic intervention in preventing the disease or mitigating these complications.

About VeraLight

VeraLight, based in Albuquerque, N. M., is a privately held medical instrumentation company that was established in 2004 as an independent spinout of InLight Solutions to focus on a comprehensive approach to non-invasive diabetes screening. The company's mission is to help stem the tide of the world wide diabetes epidemic through early diabetes detection, thus enabling initiation of therapies that can prevent diabetes or reduce its complications. VeraLight develops and acquires intellectual property, products, and services that contribute to this mission. For more information see http://www.veralight.com.

Posted by dlife at 12:06 PM | Comments (0)

Levemir(R) Helps Patients Significantly and Safely Improve Control in a Real World Study

Study supports evidence of improved control while maintaining weight neutrality in actual clinical practice - in one of the largest worldwide observational diabetes studies to date - with data from more than 10,000 patients

WASHINGTON, June 12, 2006 (PRNewswire-FirstCall) - Novo Nordisk today announced results from the German cohort of 10,276 patients enrolled in the observational PREDICTIVE(TM) trial, which found Levemir(R) (insulin detemir [rDNA origin] injection) improved blood sugar control (A1C) and reduced episodes of major hypoglycemia (low blood sugar) with no weight gain in actual clinical practice. The primary endpoint was safety. These results and the findings of a separate sub-group analysis were presented at the 66th Scientific Sessions of the American Diabetes Association in Washington, D.C.

In PREDICTIVE, Levemir demonstrated significant improvement in blood sugar control - A1C levels were reduced significantly in both type 1 and type 2 diabetes patients. In addition, patients with type 2 diabetes lost weight, while type 1 patients maintained their weight while using Levemir. Weight gain is a common side effect of insulin therapy(1) and Levemir is the first insulin to show less weight gain versus other basal insulins in 12 of 12 controlled clinical trials. Among people with diabetes, 90 to 95 percent have type 2 diabetes(2) and 80 percent of people with diabetes are overweight or obese(3).

Additionally, an analysis of a sub-group of this study of type 2 diabetes patients (n=511) focused on patients who switched from NPH or glargine to Levemir. These patients experienced significant improvement in A1C, and reduced episodes of major hypoglycemia. Both patient groups also experienced weight reduction.

"Novo Nordisk continues to make a difference by bringing innovative treatments to meet the individual needs of the growing number of people living with diabetes," said Alan Moses, Associate Vice President of Clinical Research and Medical Affairs at Novo Nordisk. "The recent addition of Levemir to our robust diabetes portfolio should not only help patients reach recommended A1C levels, but may also help physicians break down barriers to initiating insulin therapy."

PREDICTIVE Study Key Findings (Poster# 511-P)

PREDICTIVE (Predictable Results and Experience in Diabetes through Intensification and Control to Target: An International Variability Evaluation), a multi-center observational study, is assessing the safety and efficacy of Levemir and providing insights into different treatment patterns and blood sugar control. The primary endpoint of the study was safety, including the incidence of major hypoglycemic events. The findings are from the German cohort of 10,276 patients (26 percent type 1, 73
percent type 2, 1 percent other classification), with a mean follow-up period of 14.5 weeks after initiation of Levemir:

-- Levemir reduced mean A1C levels by 0.54 percent for type 1 and 0.89
percent for type 2 diabetes patients (P<0.001 for both)

-- Episodes of major hypoglycemia were significantly reduced in type 1
patients and as well as type 2 patients. In type 1 patients, major
hypoglycemic episodes dropped from 1.08 per patient year in the four
weeks prior to study start to 0.12 per patient year in the four weeks
before follow-up (P<0.001). In type 2 patients, major episodes dropped
from 0.3 to 0.06 per patient year (P<0.001)

-- Twenty eight serious adverse drug reactions were reported during the
follow up period of 14.5 weeks, the majority of which were hypoglycemic
episodes

-- Type 1 patients gained no weight and type 2 patients experienced a
slight reduction in body weight during the study (-0.6kg, P<0.001)

-- 73 percent of type 2 patients used Levemir once daily

"With the prevalence of diabetes expected to exceed 333 million by 2025(4), this study not only provides us with an opportunity to validate the benefits of Levemir in clinical practice but it will also provide valuable information about diabetes treatment patterns and glycemic control," said Dr. Hans-Joachim Luddeke, an investigator in the PREDICTIVE study in Munich, Germany. "This will help to inform further improvements in the management of this potential pandemic."

In the sub-group analysis of patients with type 2 diabetes who switched from NPH (n=251) or glargine (n=260) to Levemir (Poster# 614-P), A1C was reduced by 0.57 percent and 0.58 percent, respectively. In these patients, no major hypoglycemia was observed for Levemir (NPH insulin switches decreased from 0.4 to 0/patient years, insulin glargine switches decreased from 0.3 to 0/patients years). Furthermore, patients in both groups switching from NPH and glargine experienced slight weight reduction (-0.9 kg and -0.8 kg, respectively).

Novo Nordisk recently initiated the PREDICTIVE 303 study in the U.S. to investigate a simple self-titration algorithm to help patients achieve their A1C targets with Levemir.

Posted by dlife at 12:03 PM | Comments (0)

Glucon Announces New Clinical Study Results of Aprise(TM) in a Poster Presentation at the American Diabetes Association's 66th Scientific Sessions, in Washington, D.C.

BOULDER, Colo, June 12, 2006 (BUSINESS WIRE) - Aprise is a Non-Invasive, Continuous Blood Glucose Monitoring Device Glucon Inc., developer of innovative continual blood glucose monitoring devices, announced the complete results of its recent clinical study of Aprise at the American Diabetes Association's 66th Scientific Sessions, in Washington, D.C., June 9-13, 06 The data are also published in the Scientific Sessions Abstract Book, the June supplement to the journal Diabetes.

Dr. Ram Weiss presented Glucon's poster, titled Non Invasive Continuous Glucose Monitoring - Results from the First 62 Subjects. The presentation is part of the Clinical Therapeutics/New Technology Glucose Monitoring and Sensing category, number 408-P in the Poster Session in the Exhibit Hall. Dr. Weiss is a senior pediatric endocrinologist at Hadassah - Hebrew University School of Medicine in Jerusalem.

"Of the personal, non-invasive, continual blood glucose technologies currently in development, Glucon's Aprise is the most advanced in the clinical investigation process," noted Glucon's CEO Dan Goldberger.

The analysis of the data generated by the 62 subjects included 979 pairs of reference values and prospective, sensor derived glucose determinations. The mean absolute relative difference (RAD) of the sample was 19.9% with a median RAD of 13.2%. The mean and median differences were both around -5 -6 mg/dl (0.28 - 0.33 mmol/l)indicating a slight over estimation of the sensor. When all of the results were plotted using the Clarke error grid (figure 1), 66.5%, 28.1%, 1%,4.4% and 0% were within the A, B, C, D and E ranges respectively.

"When the three study protocols were analyzed separately, the mean RAD for the oral glucose tolerance tests and the meal tolerance tests was superior to the mean RAD of the glucose infusion studies (17% vs. 19% vs. 22% respectively). Similarly, the prevalence of range D errors in the Clark error grid was smaller in OGTTs vs. meal tolerance tests and glucose infusion studies (2.1% vs. 5% vs. 8.6% respectively)," said Dr. Weiss.

Aprise(TM) is intended for self monitoring diabetic patients. It is the only device able to read blood glucose levels directly from a blood vessel, without puncturing the skin, through the use of a novel Photoacoustic (optical and sound-based) technology, proven to be superior to optics alone. The reading can be updated every five minutes or faster, allowing patients to respond to real time information. Aprise also signals when glucose levels rise or fall beyond acceptable levels.

"The study data further supports earlier findings that Aprise performs favorably in comparison to conventional finger stick glucose monitoring devices. We are currently developing the next generation of Aprise, which will be even smaller, lighter weight and comfortable to wear," said Glucon President Ron Nagar.

About Glucon

Glucon (www.glucon.com) is developing a pipeline of automated, continual, blood glucose (sugar) monitoring devices for home and clinical use. Glucon was founded in 2000 by Israeli scientists including Company President Ron Nagar. The company's flagship product, Aprise, is currently undergoing extensive clinical trials. Seed financing was provided by InnoMed Ventures. Additional investors include Giza Venture Capital, Infinity Venture Capital Fund, Ascend Technology Ventures, and several others.

Posted by dlife at 12:00 PM | Comments (2)

Meditation May Improve Cardiac Risk Factors in Patients With Coronary Heart Disease

June 12, 2006 (Eurekalert) - A relaxation technique known as transcendental meditation may decrease blood pressure and reduce insulin resistance among patients with coronary heart disease, according to a report in the June 12 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.

Transcendental meditation, derived from the ancient Vedic tradition in India, is taught through a standard protocol involving lectures, personal instruction and group meetings, according to background information in the article. It has previously been shown to lower blood pressure but its effect on other risk factors associated with coronary heart disease, including those linked to the metabolic syndrome, has not been thoroughly examined. The metabolic syndrome refers to a cluster of symptoms that increase cardiac risk, including high blood pressure (hypertension), abdominal obesity, high cholesterol and insulin resistance, which occurs when the body is unable to use the insulin produced by the pancreas to process sugar into energy.

Maura Paul-Labrador, M.P.H., Cedars-Sinai Medical Center, Los Angeles, and colleagues conducted a 16-week trial of transcendental meditation in patients with coronary heart disease. Fifty-two participants (average age 67.7 years) were instructed in transcendental meditation and 51 control patients (average age 67.1 years) received health education. At the beginning and end of the trial, the patients fasted overnight and then gave a blood sample, participated in a medical history review and underwent tests of blood vessel function and heart rate variability. Heart rate variability testing assesses the functioning of the autonomic nervous system, which controls the heart and other involuntary muscles.

Overall, of the 103 participants who were enrolled, 84 (82 percent) completed the study. At the end of the trial, patients in the transcendental meditation group had significantly lower blood pressure; improved fasting blood glucose and insulin levels, which signify reduced insulin resistance; and more stable functioning of the autonomic nervous system. "These physiological effects were accomplished without changes in body weight, medication or psychosocial variables and despite a marginally statistically significant increase in physical activity in the health education group," the authors write.

"These current results also expand our causal understanding of the role of stress in the rising epidemic of the metabolic syndrome," they continue. "Although current low levels of physical activity, unhealthy eating habits and resultant obesity are triggers for this epidemic, the demands of modern society may also be responsible for higher levels of chronic stress." Such stress causes the release of cortisol and other hormones and neurotransmitters, which over time damage the cardiovascular system.

"Our results, demonstrating beneficial physiological effects of transcendental meditation in the absence of effects on psychosocial variables, suggest that transcendental meditation may modulate response to stress rather than alter the stress itself, similar to the physiological impact of exercise conditioning," the authors write. This method of controlling the body's response to stress may provide a new target for the treatment and prevention of coronary heart disease, warranting further study, they conclude.

Posted by dlife at 11:58 AM | Comments (0)

Nationwide Long-term Study Shows Brain Function Not Impaired By Tight Diabetes Control and Severe Hypoglycemia

Joslin Diabetes Center Psychiatrist To Present DCCT Follow-up Cognitive Study June 12 at the American Diabetes Association's 66th Scientific Sessions in Washington, D.C.

BOSTON, June 12, 2006 (Joslin) - The landmark Diabetes Control and Complications Trial (DCCT) funded by the National Institutes of Health, which followed 1,441 people with type 1 diabetes for a decade until 1993, showed conclusively that tight blood glucose control significantly reduces the risk of developing complications of diabetes such as eye, kidney and nerve disease. But the DCCT also showed that tight control -- achieved by taking three or more insulin injections daily -- can come at a cost: Patients in the trial who kept their blood glucose levels as close to the normal range as possible were three times as likely to suffer episodes of severe hypoglycemia -- abnormally low blood glucose levels that can cause confusion, irrational behavior, convulsions and unconsciousness. This finding raised the fear that, although tight control may lower the risk of developing other diabetes complications, it might also lead to a long-term loss of cognitive ability.

Now there is good news from Joslin Diabetes Center researchers in collaboration with investigators at the University of Pittsburgh Medical Center, George Washington University and the DCCT/EDIC Research Group. After following three-quarters of the original DCCT participants for an additional 6.5 years, the researchers found no link between multiple severe hypoglycemic reactions and impaired cognitive function in people with type 1 diabetes in the study. "This study provides further support for the safety of intensive diabetes therapy and the benefits of maintaining good glycemic control," says the study's principal investigator, Alan M. Jacobson, M.D., head of Joslin's Behavioral and Mental Health Research Section and Professor of Psychiatry at Harvard Medical School. "While acute episodes of hypoglycemia can impair thinking and can even be life-threatening, patients with type 1 diabetes do not have to worry that such episodes will impair their long-term abilities to perceive, reason and remember."

The study is among approximately 80 presentations that Joslin scientists will deliver at the American Diabetes Association's 66th Annual Scientific Sessions being held at the Washington Convention Center in Washington, D.C, from Friday, June 9, through Tuesday, June 13. More than 15,000 scientists, physicians and other healthcare professionals from around the world will attend the conference. The study will be presented during a presentation of Late Breaking Clinical Studies on Monday, June 12, 4:30-6:30 p.m. in the Washington Convention Center, Hall D. [Abstract Number 750232: "Effects of Intensive and Conventional Treatment on Cognitive Function Twelve Years after the Completion of the Diabetes Control and Complications Trial (DCCT)"]

To determine whether tight control has long-term adverse effects on cognitive function, the researchers examined 1,059 participants in the original DCCT trial: 537 patients receiving intensive therapy with either an insulin pump or three or more daily insulin injections; and 522 patients receiving conventional therapy of one or two injections daily. For the period of this study, 652 patients reported no hypoglycemic (low blood glucose) events resulting in coma or seizure; 348 reported from one to five events; and 59 patients reported more than five.

All of the patients were evaluated using the same neuropsychological tests that researchers administered during the DCCT trial, tools that analyzed abilities in eight cognitive domains: problem solving, learning, immediate memory, delayed recall, spatial information, attention, psychomotor efficiency and motor speed. Adjusting for age, sex, years of education, length of follow-up, and the number of cognitive tests taken, the researchers found no change in any of the eight areas. Higher A1C readings among patients -- which indicate less, not tighter, control -- were associated with a modest decline in motor speed and psychomotor efficiency, but no other cognitive domain was affected.

"This is very good news for patients with type 1 diabetes," says Dr. Jacobson. "Severe hypoglycemia can still be a very dangerous condition. But with proper education, self-care and close medical follow-up, the risk of severe hypoglycemia can be lessened. Now we know that patients don't have to worry about damaging their mental abilities as they work to significantly decrease their risks of developing diabetic retinopathy, neuropathy, nephropathy and cardiovascular disease."

Type 1 (insulin-dependent) diabetes accounts for between 5 and 10 percent (between 700 thousand and 1.4 million people) of all cases of diabetes diagnosed in the United States. In this form of diabetes, an autoimmune process has destroyed the insulin-producing islet cells in the pancreas, so patients must inject insulin daily to survive. Type 1 can strike people at any age. In type 2 diabetes, the far more common form of the disease, patients can generally produce some of their own insulin. However, many need insulin or oral medications that can put them at risk of hypoglycemia.

The Epidemiology of Diabetes Interventions and Complications Study (EDIC), a follow-up study of DCCT participants, is examining the long-term effects of conventional vs. intensive diabetes treatment on the development and progression of diabetic complications. "The DCCT was the world's first major clinical trial in type 1 diabetes. Today, more than 20 years after it was launched, it continues to provide invaluable insights regarding the importance of intensive glucose control in type 1 diabetes," said Catherine Cowie, Ph.D., of the National Institute of Diabetes and Digestive and Kidney Diseases, the part of the NIH that sponsored the study. Joslin is one of 28 clinical centers around the country participating in EDIC.

Collaborating with Dr. Jacobson in this study were Christopher M. Ryan, Ph.D., of the University of Pittsburgh School of Medicine; Patricia A. Cleary, M.S., and Barbara Waberski, M.S., of George Washington University's Biostatistics Center; Amanda Burwood and Katie Weinger, Ed.D., R.N., of Joslin; Meg Bayless, R.N., of the University of Iowa; William Dahms, M.D., of Case Western Reserve University; Nancy Silvers, R.N., of the University of Pittsburgh Medical Center; and Judy Harth, R.N., of The University of Western Ontario.

The study was supported by grants from the National Institutes of Health and Joslin Diabetes Center.

Posted by dlife at 11:55 AM | Comments (0)

New Results from the Landmark PROactive Trial Found That ACTOS® (pioglitazone HCl) Reduced the Occurrence of Major Adverse Cardiovascular Events

Additional results showed ACTOS delayed the need for insulin use in high-risk patients with type 2 diabetes

Washington, DC, June 12, 2006 – New analyses from the landmark PROactive Study found that ACTOS® (pioglitazone HCl), an oral antidiabetic medication, significantly reduced the occurrence of major adverse cardiovascular events (MACE) such as heart attacks (excluding silent heart attacks), nonfatal stroke, acute coronary syndrome (ACS) and cardiovascular death in high-risk patients with type 2 diabetes. Additionally, results showed that ACTOS significantly decreased the progression to permanent insulin use. These results were presented as three separate abstracts at the American Diabetes Association (ADA) 66th Annual Scientific Sessions.

“What is unique about these new data is that while earlier PROactive results found a combined risk reduction of heart attack stroke and death by 16 percent in high-risk patients treated with ACTOS, we saw a greater risk reduction when we looked at the wider scope of major adverse cardiovascular events, in this high-risk population,” said Erland Erdmann, M.D., chairman of the PROactive Executive Committee, and director of the Clinic III for Internal Medicine, University of Cologne, Germany.

“Separate analyses suggest a significant decrease in the amount of insulin needed, as well as a delay in the need for permanent insulin use among patients taking ACTOS,” said Robert Spanheimer, M.D., medical director for diabetes and metabolism at Takeda Pharmaceuticals North America, Inc. “As type 2 diabetes is a progressive disease requiring multiple therapies, many patients eventually need supplementary insulin to manage their condition. For patients with type 2 diabetes and established cardiovascular disease, these results could lead to the potential for less dependence on daily insulin use.”

Major Adverse Cardiac Events
Composite endpoints of cardiovascular events are standard measures for comparing treatments in large outcome studies and are referred to as major adverse cardiovascular events (MACE). Patients with type 2 diabetes are at particularly high risk for these events. In this analysis of the PROactive study, there were pre-specified and post-hoc MACE endpoints, which looked at a combination of fatal and nonfatal heart attacks, nonfatal strokes, and death.

This analysis demonstrated statistically significant risk reductions with ACTOS compared with placebo for the heart attack endpoint (23 percent, P=0.046), major adverse cardiovascular events (MACE1) endpoints of cardiovascular death, nonfatal heart attack or nonfatal stroke (18 percent, P=0.020), and MACE2 endpoints of all-cause mortality, nonfatal heart attack, nonfatal stroke or acute coronary syndrome (17 percent, P=0.010).

At the end of the study, 339 patients (13 percent) in the ACTOS group had a first event that contributed to the MACE2 endpoint, compared with 409 (15.5 percent) in the placebo group. Additionally, 108 (4.1 percent) ACTOS patients had a myocardial infarction, compared to 140 (5.3 percent) in the placebo group, excluding a silent myocardial infarction.

Insulin Sparing and Insulin Delay
Type 2 diabetes is a progressive disease requiring multiple therapies to achieve blood glucose control; many patients will eventually require insulin. Two additional analyses from the PROactive study examined the effects of ACTOS therapy on insulin use. The results demonstrated that ACTOS reduced the number of patients on insulin and mean daily insulin dose, and delayed need for permanent insulin use.

In one analysis, the one third of patients who were treated with insulin at baseline in the PROactive study (ACTOS = 864, placebo = 896) were evaluated:

A1C values, a test that measures a person's average blood glucose level over the past two to three months, and mean insulin doses were similar between treatment groups at baseline.

A rapid and sustained decrease in insulin doses was observed with patients taking ACTOS, as compared to a progressive increase with placebo.

By study end, the mean insulin dose was lower with ACTOS (42 U/d) than with placebo (55 U/d; P<0.0001) and insulin had been discontinued in 9 percent of patients in the ACTOS group vs 2 percent in the placebo group (P<0.0001).
In the second analysis, the two thirds of PROactive patients (ACTOS = 1741 and placebo = 1737) who were not on insulin at baseline were evaluated. The study demonstrated that ACTOS delayed the need for permanent insulin use – defined as daily use for greater than or equal to ninety days, or ongoing use at death/final visit. In fact, twice as many placebo patients progressed to permanent insulin use, as compared to ACTOS patients (N=362 and N=183, respectively) with projected rates for time to permanent insulin use 11 percent and 21 percent for the ACTOS and placebo groups, respectively (P<0.0001).

In addition, ACTOS patients not on insulin at baseline showed improved A1C values compared with placebo patients at final visit (6.97 percent vs 7.49 percent, P<0.0001). Overall, progression to permanent insulin use was reduced by 50 percent at three years with ACTOS vs placebo, and better glycemic control was seen with ACTOS. The incidence of hypoglycemia was higher in the ACTOS-treated group than in the placebo group.

About the PROactive Study
PROactive (PROspective PioglitAzone Clinical Trial In MacroVascular Events) was the first study to prospectively look at the reduction in total mortality and macrovascular morbidity using a glucose-lowering agent. It was a randomized, double-blind, placebo-controlled outcome study of 5,238 patients with type 2 diabetes and macrovascular disease. Patients were randomized to receive either ACTOS or placebo in addition to other blood glucose medications and on top of standard of care treatment (including the routine use of anti-hypertensives such as ACE inhibitors and beta blockers; glucose-lowering agents such as metformin, sulfonylureas and insulin; antiplatelet drugs such as aspirin, and lipid-modifying medicines such as statins and fibrates).

This study focused on two key endpoints: a primary combination endpoint of seven different macrovascular events including both disease and procedural endpoints; and a principal secondary combination of disease endpoints including death, heart attack and stroke.

As reported at the European Association for the Study of Diabetes (EASD) Annual Meeting in September 2005, the primary endpoint was reduced by 10 percent but had not reached statistical significance by study end (P=0.095). The principal secondary endpoint showed that ACTOS significantly reduced the combined risk of heart attacks, strokes and death by 16 percent (P=0.027) in high-risk patients with type 2 diabetes.

For more information, visit www.proactive-results.com. (This independent website is supported by an unrestricted educational grant by Takeda Pharmaceutical Company Limited and Eli Lilly and Company.)

About ACTOS
ACTOS works by directly targeting insulin resistance, a condition in which the body does not efficiently use the insulin it produces to control blood glucose levels. ACTOS is taken once daily as an adjunct to diet and exercise, and is approved for use for type 2 diabetes as monotherapy to lower blood glucose and in combination therapy with insulin, sulfonylureas or metformin.

Additional Information
ACTOS is not for everyone. ACTOS can cause fluid retention that may lead to or worsen heart failure, so tell your doctor if you have a history of these conditions. Talk to your doctor immediately if you experience rapid weight gain, fluid retention, or shortness of breath while taking ACTOS. If you have moderate to severe heart failure, ACTOS is not recommended. Your doctor should perform a blood test to check for liver problems before you start ACTOS and periodically thereafter.

Do not take ACTOS if you have active liver disease. Talk to your doctor immediately if you experience nausea, vomiting, stomach pain, tiredness, loss of appetite, dark urine, or yellowing of the skin. If you are of childbearing age, talk to your doctor before taking ACTOS as it could increase your chance of becoming pregnant. Some people taking ACTOS may experience flu-like symptoms, mild to moderate swelling of legs and ankles, and anemia. When taking ACTOS with insulin or sulfonylureas, you may be at risk for low blood glucose.

Takeda Pharmaceuticals North America, Inc.
Based in Lincolnshire, Ill., Takeda Pharmaceuticals North America, Inc., is a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, the largest pharmaceutical company in Japan. In the United States, Takeda currently markets oral diabetes, insomnia, cholesterol-lowering and gastroenterology treatments, and through the Takeda Global Research & Development Center, Inc., the company has a robust pipeline with compounds in development for diabetes, cardiovascular disease and other conditions. Takeda is committed to striving toward better health for individuals and progress in medicine by developing superior pharmaceutical products. To learn more about the company and its products, visit www.tpna.com.

Posted by dlife at 11:53 AM | Comments (0)

Abnormal Glucose Metabolism May Contribute to Chronic Nerve Disorder

CHICAGO, June 12, 2006 (JAMA/Archives) - Abnormal glucose metabolism, which occurs when the body has difficulty processing sugar (glucose) into energy, is twice as common among patients with chronic nerve dysfunction of unknown cause than among the general population and may be a risk factor for the condition, according to a study posted online today that will appear in the August 2006 print issue of Archives of Neurology, one of the JAMA/Archives journals.

Many older adults experience nerve disorders known as neuropathy, some of which are characterized by symptoms of "burning feet" and other unpleasant sensations in the lower leg, according to background information in the article. Diabetes, genetic disorders, exposure to toxic substances and a condition called amyloidosis in which extra protein-based substances accumulate in the body tissues can all cause neuropathy, but many cases do not have an easily identifiable underlying cause. When laboratory tests cannot determine the cause, the condition is known as chronic idiopathic axonal polyneuropathy; a cause is eventually found in only 7 to 30 percent of these cases.

Charlene Hoffman-Snyder, M.S.N., N.P.-B.C., Mayo Clinic, Arizona, and colleagues identified 100 consecutive patients (60 women and 40 men) with chronic idiopathic axonal polyneuropathy who were evaluated between January 2003 and January 2005. Patients underwent a complete neurological evaluation and had a fasting plasma glucose test, which measures the levels of glucose in the blood after eight hours of not eating, and a two-hour oral glucose tolerance test, which determines how well the body processes glucose by drawing blood two hours after fasting patients ingest a dose of glucose. "The fasting plasma glucose level alone does not always identify patients with impaired glucose tolerance and neither does the two-hour oral glucose tolerance test always detect patients with impaired glucose metabolism," the authors write. "Both tests are, however, useful to detect hyperglycemia [high blood sugar] and the consequences of disordered glucose metabolism."

According to the two-hour oral glucose tolerance test, 62 patients (62 percent) with neuropathy had abnormal fasting glucose metabolism, including 24 with undiagnosed diabetes. (This compares with 33 percent of patients of similar ages in the general population with abnormal glucose metabolism as previously estimated by the Centers for Disease Control and Prevention in other published reports.) The results of the current study suggest that abnormal glucose metabolism may be a risk factor for neuropathy.

"Conventional thinking among diabetologists is that diabetic polyneuropathies are the result of prolonged hyperglycemia," the authors write. "Like previous studies, this investigation supports the hypothesis that distal axonal polyneuropathies may occur in much earlier stages of abnormal glucose metabolism than previously thought. Recent studies suggest that the neuropathy associated with impaired glucose tolerance may be milder than neuropathies traditionally associated with diabetes mellitus and may be the earliest detectable sign of abnormal glucose metabolism."

Posted by dlife at 11:50 AM | Comments (0)

Novel Method Revealed for Predicting and Preventing Treatment-Associated Weight Gain

WASHINGTON DC, June 11, 2006 (MARKET WIRE) -- Entelos, Inc. (LSE: ENTL) announced today that it presented data in a poster session at the 66th Annual American Diabetes Association Meeting. This presentation revealed the first-ever mathematical means for predicting not only the amount of weight gain expected for patients receiving type 2 diabetes treatments -- a common side effect -- but also the decrease in food intake necessary to prevent it (poster #564P). Such information can help doctors counsel type 2 diabetes patients on ways to minimize weight gain during treatment, which should enhance drug efficacy and improve their control of blood sugar levels.

"Many drugs have unexpected effects that either interfere with their efficacy or the patient's ability to function normally," said Mikhail Gishizky, Ph.D., chief scientific officer of Entelos. "Taking an in silico approach allows researchers to tease apart complex biological networks and clearly understand underlying mechanisms in the human body. This information can be used to develop novel methods for better managing patient care, as well as to help develop new drugs and diagnostics, and to identify biomarkers."

Scientific Findings

Increases in body weight can accompany treatment with many type 2 diabetes drugs, preventing them from achieving full efficacy. This increase reflects a shift in energy balance, with urinary glucose excretion (glycosuria) playing an important and underappreciated role in the energy balance shift. To investigate the impact of common type 2 diabetes drugs on glycosuria and weight gain, 117 clinically representative virtual patients with normal glomerular filtration rates and renal function were treated with nateglinide (N), pioglitazone (P), or insulin (I) for six to twelve months, and body weight, A1C, and urinary glucose loss were measured. Food intake and energy expenditure were maintained at pre-treatment levels. Results show a strong correlation between the calories gained from decreased renal glucose loss and the increase in body weight, with r2 = 0.93, 0.94, 0.92 for N, P, and I treatment, respectively. This weight gain was also consistent with published reports. Additional correlations were found between pre-treatment A1C and increased body weight, with r2 = 0.63, 0.65, 0.61 for N, P, and I, respectively. Based on these relationships, a mathematical formula was developed that accurately predicts not only the amount of weight patients can expect to gain, but also the quantitative modifications in energy balance necessary to prevent it. Clinicians can use these findings to adopt a strategy to counsel type 2 diabetes patients on optimal methods for minimizing weight gain during treatment, which will enhance efficacy and improve glycemic management.

About Metabolism PhysioLab Platform

Entelos® Metabolism PhysioLab® platform is a large-scale mathematical model of human physiology that supports research in the areas of obesity and type 2 diabetes. The platform includes the physiology and pathophysiology of metabolic disease, as well as the underlying cellular mechanisms. Processes that the model can simulate include the digestion, absorption, storage, mobilization, and oxidation of carbohydrate, fat, and protein, as well as the hormonal regulation of these processes. In vivo responses to typical tests (e.g., glucose-insulin clamps, glucose tolerance tests, and mixed meal ingestion) are also included, as are physical activity and available therapies. Due to the heterogeneity of these diseases, over 150 virtual patients have been created that span the disease spectrum, from lean, insulin-resistant to severely obese, severely diabetic subtypes. The platform is capable of simulating human in vivo plasma levels for more than 20 metabolites and hormones.

About Entelos

Entelos, Inc. (www.entelos.com) is a US-based life sciences company that applies engineering principles and mathematical modeling approaches to simulate human biology. The company helps its pharmaceutical and biotechnology partners increase the efficiency of the drug discovery, development, and commercialization process by accurately predicting human response to therapeutic intervention. Entelos' teams of life scientists and engineers use its proprietary computer platforms, called PhysioLab systems, and create "virtual patients" to test novel therapies, translate animal data to predict human response, and optimize clinical trial designs in diseases such as asthma, obesity, type I and type II diabetes, and rheumatoid arthritis. In addition to co-development and internal research programs, Entelos partners with pharmaceutical and biotechnology companies worldwide.

Posted by dlife at 11:48 AM | Comments (0)

Investigational Treatment Ruboxistaurin Demonstrated Promise in Reducing the Occurrence of Vision Loss Caused by Diabetic Retinopathy

Phase 3 data presented at 66th Annual ADA Scientific Sessions

WASHINGTON, DC – June 11, 2006 – Eli Lilly and Company (NYSE: LLY) today announced encouraging results from an analysis of pooled data from two, three-year phase 3 trials that showed ruboxistaurin mesylate reduced the risk of sustained moderate vision loss by 41 percent when compared to placebo in patients with moderate to severe, nonproliferative diabetic retinopathy (DR). Vision loss occurred in only 6.1 percent of patients treated with ruboxistaurin compared to 10.2 percent of patients treated with placebo. Ruboxistaurin (proposed brand name ArxxantTM) is an investigational drug for the treatment of DR, a diabetic eye disease.

The findings were presented in an oral session at the American Diabetes Association’s (ADA) 66th Annual Scientific Sessions in Washington, DC, and are included in Lilly’s new drug application (NDA) submitted to the FDA in February 2006.

“These data are exciting because they show that ruboxistaurin has the potential to be the first oral therapy to specifically reduce the risk of vision loss caused by diabetic retinopathy,” said Lloyd Paul Aiello, MD, PhD, lead investigator of the study, director, Beetham Eye Institute & Section on Eye Research, Joslin Diabetes Center, and associate professor of ophthalmology, Harvard Medical School in Boston, MA. “This could be an important clinical development for the millions of people around the world who are at risk for vision loss caused by this serious disease.”

Study Details
Vision loss (measured in the study as sustained moderate vision loss or SMVL) occurred in only 6.1 percent of patients treated with ruboxistaurin compared to 10.2 percent of patients treated with placebo, equaling a 41 percent relative risk reduction (P=0.011) over three years.1 Vision loss (SMVL) was defined as a three-line loss on the eye chart that was sustained for at least 6 months.1

Comprised of data from the PKC-DRS and PKC-DRS2 studies, the combined analysis examined a total of 813 patients treated with 32mg per day of ruboxistaurin (n=412) or placebo (n=401) derived from two multi-center, randomized, placebo-controlled, double-masked, phase 3 trials that were similar in design and implementation.1 The analysis examined whether ruboxistaurin could reduce the risk of long-term, or sustained moderate vision loss caused by diabetic retinopathy.1 Patients had moderate to severe nonproliferative diabetic retinopathy at the start of the study.1 The beneficial effect of ruboxistaurin was not accompanied by a reduction in the progression of study patients from nonproliferative to proliferative diabetic retinopathy.

Clinical Safety Evaluation
A separate analysis of data from 11 studies, of the safety of 32 mg per day of ruboxistaurin in patients with at least one diabetic microvascular complication (including diabetic retinopathy), also presented at the ADA Scientific Sessions, found ruboxistaurin was generally well tolerated and had an overall adverse event profile, as well as a serious adverse event profile similar to placebo. Serious adverse events occurred in 23.2 percent of patients taking placebo compared to 20.8 percent of patients taking ruboxistaurin.3 In addition, ruboxistaurin had no effect on glucose or blood pressure control. This data presentation reported on a clinical safety data base which includes a total of 2,804 patients with type 1 or type 2 diabetes combined from 11 phase 2 and 3 placebo-controlled, double-masked trials, for up to four years.3 The only treatment-emergent adverse event that occurred with a frequency of greater than or equal to two percent and occurred significantly more often in the ruboxistaurin group was indigestion.3

About Diabetic Retinopathy
Diabetic retinopathy is a relatively common microvascular complication in individuals with dia-betes that can lead to a sudden and debilitating impact on vision. In the United States, an esti-mated 4.1 million adults aged 40 and older have diabetic retinopathy (40.3% of persons with dia-betes mellitus) with 899,000 having vision-threatening retinopathy (8.2%). For persons with type 1 diabetes, the crude prevalence of diabetic retinopathy is about 80%.

Diabetic retinopathy is recognized as the leading cause of blindness in the working aged population, which exacts huge human and financial costs. , Yet blindness is only a part of the story. Even mild vision loss can lead to difficulties in reading, driving, employment, and mobility as well as an increased risk of accidental injuries. , , For the diabetes patient, vision loss can lead to additional issues as functional difficulties further exacerbate patients’ ability in disease self-management that leads to a worsening of metabolic control.

Nonproliferative diabetic retinopathy (NPDR) occurs when the smallest blood vessels in the retina are damaged.6 Patients with NPDR can develop diabetic macular edema (DME), which is the most common cause of vision loss in patients with NPDR.8 DME occurs when the macula (the area of the retina that allows sharp vision) swells with fluid.

In the most advanced or proliferative stage of diabetic retinopathy (PDR), new blood vessels grow abnormally from the back of the eye6 and they may subsequently cause severe vision loss.6

About Ruboxistaurin
Ruboxistaurin limits protein kinase C beta (PKC ) overactivation, and it is the first of a new class of compounds being investigated for the treatment of diabetic retinopathy.

The laboratory of George L. King, MD, research director at Joslin Diabetes Center and professor of medicine at Harvard Medical School first proposed that PKC  activation is responsible for the development of diabetic retinopathy and other microvascular damages induced by diabetes.

Lilly submitted a new drug application (or NDA) to seek approval from the U.S. Food and Drug Administration for ruboxistaurin for the treatment of diabetic retinopathy in February 2006. The FDA has informed Lilly that it will conduct a priority review of Lilly's NDA submission for ruboxistaurin.

Lilly’s Leadership in Diabetes
Through a long-standing commitment to diabetes care, Lilly provides patients with breakthrough treatments that enable them to live longer, healthier and fuller lives. Since 1923, Lilly has been the industry leader in pioneering therapies to help health care professionals improve the lives of people with diabetes, and research continues on innovative medicines to address the unmet needs of patients.

About Lilly
Lilly, a leading innovation-driven corporation, is developing a growing portfolio of first-in-class and best-in-class pharmaceutical products by applying the latest research from its own worldwide laboratories and from collaborations with eminent scientific organizations. Headquartered in Indianapolis, Ind., Lilly provides answers – through medicines and information – for some of the world's most urgent medical needs. Additional information about Lilly is available at www.lilly.com.

About Joslin Diabetes Center
Joslin Diabetes Center, dedicated to conquering diabetes in all of its forms, is the global leader in diabetes research, care and education. Founded in 1898, Joslin is an independent nonprofit institution affiliated with Harvard Medical School. Joslin research is a team of more than 300 people at the forefront of discovery aimed at preventing and curing diabetes. Joslin Clinic, affiliated with Beth Israel Deaconess Medical Center in Boston, the nationwide network of Joslin Affiliated Programs, and the hundreds of Joslin educational programs offered each year for clinicians, researchers and patients, enable Joslin to develop, implement and share innovations that immeasurably improve the lives of people with diabetes. For more information on Joslin, call 1-800-JOSLIN-1 or visit www.joslin.org.

This press release contains forward-looking statements about the potential of the investigational compound ruboxistaurin for the treatment of diabetic retinopathy and reflects Lilly’s current beliefs. However, as with any pharmaceutical product under development, there are substantial risks and uncertainties in the process of development and regulatory review. There is no guarantee that the product will receive regulatory approvals, or that the regulatory approval will be for the indication(s) anticipated by the company. There is also no guarantee that the product will prove to be commercially successful. For further discussion of these and other risks and uncertainties, see Lilly’s filings with the United States Securities and Exchange Commission. Lilly undertakes no duty to update forward-looking statements.

Posted by dlife at 11:45 AM | Comments (0)

OREXIGEN(TM) Therapeutics Reports Positive Phase II Results for Contrave(TM) Combination-Therapy to Treat Obesity

Top-Line Positive Data Presented at American Diabetes Association Scientific Sessions - Data Include First Public Disclosure of the Contrave Ingredients-

SAN DIEGO and WASHINGTON, June 10, 2006 (PRNewswire) - OREXIGEN(TM) Therapeutics, Inc., a privately held clinical-stage neuroscience company developing a novel strategic approach to the treatment of obesity, today announced that the company's lead program, Contrave(TM), a combination of two centrally-acting medications, demonstrated greater sustained weight loss in a six month Phase II clinical study than either monotherapies or placebo. The findings showed that in the subjects using Contrave more than half of those who completed the trial demonstrated 5% weight loss over 24 weeks, 18% demonstrated 10% weight loss, and the trajectory of these weight loss curves showed no evidence of a plateau. These top line Phase II data for Contrave were presented at the 66th annual Scientific Sessions of the American Diabetes Association (ADA) in Washington, DC.

"These results show the greater potential for weight loss that can be achieved by combining therapies," said Louis Aronne, M.D., Clinical Professor of Medicine at Weill Cornell University Medical College and director of the Comprehensive Weight Control Program at New York Presbyterian Hospital-Weill Cornell Medical Center, who addressed the findings as part of a plenary session, at the ADA meeting." Dr. Aronne continued: "Thirty percent of American adults are obese and at significant health risk and it is clear that properly-designed medical interventions can help treat this epidemic."

Contrave is a rationally formulated combination of CNS products designed to achieve weight loss and then to off-set the body's natural compensatory mechanisms to avoid the typical weight loss plateau. The company disclosed for the first time that Contrave is a proprietary formulation of naltrexone, used to treat narcotic and alcohol dependency,and bupropion, a dopamine and norepinephrine reuptake inhibitor. Though neither of these individual products has been approved for weight loss by the FDA, several million patients have received these medications for other uses over the last twenty years. The company is further refining the formulation and optimal dose ratio of the two agents as part of its ongoing Phase III clinical program.

"This naltrexone/bupropion combination derives from our identification of specific neuronal systems in the brain that balance energy expenditure and appetite to regulate body weight," said Gary Tollefson, M.D., Ph.D., OREXIGEN president and CEO. "We believe that the positive findings we report today offer proof of concept for our Contrave clinical program."

The Contrave combination is based on in vitro studies that show naltrexone acts synergistically with bupropion to stimulate the proopiomelancortin (POMC) system in the brain to release alpha-MSH, a hormone that increases energy expenditure and reduces hunger. Naltrexone also blocks autoinhibition of POMC by the body's natural opiate beta-endorphin. Orexigen scientists believe that blocking this autoinhibition is an important element in preventing the typical plateau and weight regain observed with most obesity interventions.

The multi-center study was conducted at 8 US academic centers and evaluated 206 obese subjects with a body mass index of 30 to 40 with each of the monotherapies, the combination and placebo along with a minimal diet and exercise program. The Phase II findings were presented at the ADA by the study's principal investigator, Frank Greenway, M.D., chief of the Clinical Obesity Laboratory and Outpatient Research Clinic at the Pennington Biomedical Research Center.

A companion product now in Phase II testing, Excalia(TM), is believed to be working via a distinctly different approach within appetite and energy pathways with a goal of providing a more substantial weight loss profile. More information about the company and its programs is available at http://www.orexigen.com.

Posted by dlife at 04:03 PM | Comments (0)

Study Demonstrated Once-Weekly Exenatide LAR Improved Glucose Control in Patients with Type 2 Diabetes

WASHINGTON, D.C., June 10, 2006 – Amylin Pharmaceuticals, Inc. (Nasdaq: AMLN), Eli Lilly and Company (NYSE: LLY) and Alkermes, Inc. (Nasdaq: ALKS) today announced detailed results from a safety and efficacy study of the long-acting release (LAR) formulation of BYETTA® (exenatide) injection. Data from the study demonstrated that 86 percent of patients using the higher of two doses of the once-weekly formulation of exenatide were able to achieve recommended levels of glucose control, as measured by hemoglobin A1C (A1C) with an average improvement of approximately 2 percent compared to placebo. These study findings were presented today at the 66th Annual Scientific Sessions of the American Diabetes Association (ADA) in Washington, D.C.

The study was conducted in 45 patients with type 2 diabetes unable to achieve adequate glucose control with metformin or a diet and exercise regimen. The patients received a once-weekly subcutaneous injection of exenatide LAR (either 0.8 mg or 2.0 mg) or placebo. After 15 weeks of treatment there was a 12-week safety monitoring period during which no study medication was administered.

Dose-dependent improvements in A1C and weight loss were observed at 15 weeks. At the beginning of the study, the average A1C of study participants was approximately 8.5 percent. In subjects receiving the 2.0 mg dose of exenatide LAR, the average reduction in A1C was 1.7 percent compared to an increase of 0.4 percent in the placebo group. Those receiving the 0.8 mg dose improved with an average decrease in A1C of 1.4 percent.

In patients administered 0.8 mg or 2.0 mg of exenatide LAR, 33 percent and 86 percent achieved A1C levels of 7 percent or less, respectively. None of the patients given placebo achieved this target level of glucose control. A1C is a reflection of a person’s average glucose level over approximately three months and often used by doctors as a measure of glucose management.

Fasting blood glucose levels were reduced by an average of 39 mg/dL in the 2.0 mg arm and 43 mg/dL in the 0.8 mg arm compared to an average increase of 18 mg/dL in the placebo group at week 15. Average fasting blood glucose level at the beginning of the study was 179 mg/dL. Patients who received 2.0 mg of exenatide LAR also experienced average reductions in body weight of 8.4 pounds at week 15 with no evidence of plateau at this point in time; body weight remained essentially unchanged for the 0.8 mg and placebo groups. The most frequent adverse event was mild nausea, experienced by 27 percent of subjects in the 2.0 mg dose group and 19 percent of subjects in the 0.8 mg dose group compared to 15 percent in the placebo group. No severe hypoglycemia was observed, and no subjects receiving either dose of exenatide LAR withdrew because of adverse events. These detailed findings supplement the preliminary results released in 2005.

"In this study, the long-acting formulation of exenatide improved glycemic and weight control and was well tolerated as a combination therapy with metformin or as stand alone therapy with diet and exercise," said Dennis Kim, MD, Senior Director, Medical Affairs, Amylin Pharmaceuticals and an author of the study. "These early results suggest exenatide LAR can be clinically beneficial to patients with type 2 diabetes."

Exenatide LAR uses the proprietary Medisorb® drug-delivery technology developed by Alkermes. The technology encapsulates active medication into polymer-based microspheres that are injected into the body, where they degrade slowly – gradually releasing the drug at a carefully controlled rate.

On April 28, 2005, the Food and Drug Administration (FDA) approved twice daily exenatide under the trade name BYETTA for use by people with type 2 diabetes who are unsuccessful at controlling their blood sugar levels despite using commonly prescribed oral medications metformin, a sulfonylurea or both. Amylin, Lilly and Alkermes are working together to develop a sustained release, subcutaneous injection of exenatide for the treatment of type 2 diabetes based on Alkermes’ proprietary Medisorb® injectable long-acting release drug delivery technology. Exenatide LAR has not been approved by the FDA for marketing in the United States.

About BYETTA
BYETTA is the first incretin mimetic, a class of drugs for the treatment of type 2 diabetes. BYETTA exhibits many of the same effects as the human incretin hormone glucagon-like peptide-1 (GLP-1). GLP-1, secreted in response to food intake, has multiple effects on the intestine, liver, pancreas and brain that work in concert to regulate blood sugar.1

Safety and Tolerability of BYETTA
Adverse events associated with BYETTA are generally mild to moderate in intensity. In clinical trials, the most frequently reported adverse event was mild-to-moderate, dose-dependent nausea. With continued therapy, the frequency and severity of nausea decreased over time in most patients.

Patients receiving BYETTA in combination with a sulfonylurea may be at a higher risk of hypoglycemia or low blood sugar. To reduce this risk, decreasing the dose of sulfonylurea may be considered. When patients begin taking BYETTA, the symptoms, treatment and conditions that predispose development of hypoglycemia should be explained to them, and the patient’s usual instructions for hypoglycemia management should be reviewed and reinforced.

Patients should also be advised that treatment with BYETTA may lead to a reduction in appetite, food intake and/or body weight, and that there is no need to modify the dosing regimen due to such effects.

BYETTA is not a substitute for insulin in insulin-requiring patients. BYETTA should not be used in patients with type 1 diabetes. Use of BYETTA is not recommended in patients with end-stage renal disease or severe renal impairment, or in patients with severe gastrointestinal disease. BYETTA should be used with caution in patients receiving oral medications that require rapid gastrointestinal absorption.

For complete safety profile and other important prescribing considerations, visit www.BYETTA.com.

About Incretin Mimetics
Incretin mimetics is a distinct class of treatment in the fight against diabetes. An incretin mimetic works to mimic the anti-diabetic or glucose-lowering actions of naturally occurring human hormones called incretins. These actions include stimulating the body’s ability to produce insulin in response to elevated levels of blood sugar, inhibiting the release of a hormone called glucagon following meals, slowing the rate at which nutrients are absorbed into the bloodstream and reducing food intake. BYETTA is the first FDA-approved incretin mimetic.

About Diabetes
Diabetes affects an estimated 194 million adults worldwide2 and more than 20 million in the United States.3 Approximately 90 to 95 percent of those affected have type 2 diabetes, a condition characterized by failure of the pancreatic beta cells to adequately respond to the increased demands for insulin that occur as a result of obesity-related insulin resistance.4 Diabetes is the sixth leading cause of death by disease in the United States3 and costs approximately $132 billion per year in direct and indirect medical expenses. Type 2 diabetes usually occurs in adults over the age of 40, but is increasingly common in younger people.3

According to the Centers for Disease Control and Prevention’s National Health and Nutrition Examination Survey, approximately 60 percent of diabetes patients do not achieve target hemoglobin A1C levels (less than 7 percent according to ADA guidelines5) with their current treatment regimen.6

About Amylin, Lilly, and Alkermes
Amylin Pharmaceuticals is a biopharmaceutical company committed to improving lives through the discovery, development and commercialization of innovative medicines. Amylin has developed and gained approval for two first-in-class medicines for diabetes, SYMLIN® (pramlintide acetate) injection and BYETTA® (exenatide) injection. Amylin is located in San Diego, California with over 1200 employees nationwide. Further information on Amylin Pharmaceuticals, its marketed products, and its pipeline in metabolism is available at www.amylin.com.

Through a long-standing commitment to diabetes care, Lilly provides patients with breakthrough treatments that enable them to live longer, healthier and fuller lives. Since 1923, Lilly has been the industry leader in pioneering therapies to help health care professionals improve the lives of people with diabetes, and research continues on innovative medicines to address the unmet needs of patients. For more information about Lilly's current diabetes products visit http://www.lillydiabetes.com.

Lilly, a leading innovation-driven corporation, is developing a growing portfolio of first-in-class and best-in-class pharmaceutical products by applying the latest research from its own worldwide laboratories and from collaborations with eminent scientific organizations. Headquartered in Indianapolis, Ind., Lilly provides answers – through medicines and information – for some of the world's most urgent medical needs. Additional information about Lilly is available at http://www.lilly.com.

Alkermes, Inc. is a pharmaceutical company that develops products based on sophisticated drug delivery technologies to enhance therapeutic outcomes in major diseases. The Company’s products include: the first and only long-acting atypical antipsychotic medication approved for use in schizophrenia, marketed worldwide by Janssen-Cilag (Janssen), a wholly owned subsidiary of Johnson & Johnson; and VIVITROLTM (naltrexone for extended-release injectable suspension), the first and only once-monthly injectable medication approved for the treatment of alcohol dependence. The Company has a pipeline of extended-release injectable products and pulmonary drug products based on its proprietary technology and expertise. Alkermes’ product development strategy is twofold: the Company partners its proprietary technology systems and drug delivery expertise with several of the world’s finest pharmaceutical companies and it also develops novel, proprietary drug candidates for its own account. The Company’s headquarters are in Cambridge, Massachusetts, and it operates research and manufacturing facilities in Massachusetts and Ohio.

Posted by dlife at 04:01 PM | Comments (1)

New Study Illustrates Economic Benefit of Weight Loss in People with Type 2 Diabetes

WASHINGTON, DC June 10, 2006 – A new study demonstrated that even a small percentage of weight loss could lower health care costs among people with type 2 diabetes. Data from the study, titled “Short Term Economic Impact of Weight Change Among Patients with Type 2 Diabetes,” were presented today at the 66th Annual Scientific Sessions of the American Diabetes Association (ADA) in Washington, DC. The study was funded by an unrestricted research grant from Amylin Pharmaceuticals, Inc. and Eli Lilly and Company.

The study, which included data gathered from an HMO claims database between 1997-2005, showed that study participants with diabetes who experienced 1 percent weight loss decreased their average health care costs by 3.6 percent over the 12 months following the weight loss, or approximately $256. Results were even more significant among patients considered obese (BMI ≥ 30). For this group, a 1 percent weight loss was associated with a 5.6 percent decrease in health care costs, or approximately $408.

“The results of this short-term study suggest the benefits weight loss can have beyond disease management and overall health among people with type 2 diabetes. There’s a dollars and cents incentive for patients and the entire health care system to devote resources to weight loss and disease management,” said E.Q. Wu, PhD, senior associate, Health Economics and Outcomes Practice for Analysis Group, Inc. and study author. “The study also reinforces the need for patients with diabetes to have alternatives that do not cause weight gain, which can be one of the most challenging side effects associated with many treatment options for people with type 2 diabetes.”

According to the Centers for Disease Control and Prevention, chronic diseases, including diabetes and obesity, account for more than 75 percent of the nation’s health care spending. Total annual health care spending in the U.S. rose to 1.9 trillion dollars in 2004, according to the Centers for Medicaid and Medicare Services. While advances have been made in the diagnosis and treatment of diabetes, the ADA lists diabetes as the fifth leading cause of death by disease in the United States, resulting in 2002 costs of approximately $132 billion in direct and indirect medical expenses.

An estimated 30 percent of U.S. adults aged 20 years and older – over 60 million people – are obese and an estimated 194 million adults worldwide and almost 21 million in the United States have diabetes. Approximately 90 to 95 percent of those affected have type 2 diabetes, a condition characterized by progressive failure of beta cells to produce appropriate levels of insulin, coupled with the body's inability to respond normally to insulin. Ninety percent of people with type 2 diabetes are considered overweight, and type 2 diabetes occurs at an earlier age in overweight people. ,

About the Study
In the study, 458 patients with type 2 diabetes who were on antidiabetic therapy were identified through a third-party payer. Data were gathered on the patients’ baseline weight and a second weight measurement taken approximately six months later. The study assessed the impact of weight change on the total health care costs over one year following the second weight measure. Weight change was measured as the percent difference from the baseline weight measurement.

Researchers evaluated administrative claims and medical chart information for continuously enrolled adults (average age 58 years, average baseline BMI of 33.7 kg/m2) with type 2 diabetes from the HMO’s claims database (1997 – 2005). The study controlled for patient baseline demographics, co-morbidities, body mass index, hemoglobin A1C and prior resource utilization.

About Amylin and Lilly
Amylin Pharmaceuticals, Inc. is a biopharmaceutical company committed to improving lives through the discovery, development and commercialization of innovative medicines. Further information on Amylin Pharmaceuticals, Inc. and its pipeline to treat metabolic diseases is available at www.amylin.com.

Through a long-standing commitment to diabetes care, Lilly provides patients with breakthrough treatments that enable them to live longer, healthier and fuller lives. Since 1923, Lilly has been the industry leader in pioneering therapies to help health care professionals improve the lives of people with diabetes, and research continues on innovative medicines to address the unmet needs of patients. For more information about Lilly’s current diabetes products visit www.lillydiabetes.com.

Lilly, a leading innovation-driven corporation, is developing a growing portfolio of first-in-class and best-in-class pharmaceutical products by applying the latest research from its own worldwide laboratories and from collaborations with eminent scientific organizations. Headquartered in Indianapolis, Ind., Lilly provides answers - through medicines and information - for some of the world's most urgent medical needs. Additional information about Lilly is available at www.lilly.com.

Posted by dlife at 02:42 PM | Comments (0)

Doctors Failing to Intensify Needed Therapy in People With Diabetes

Clinical Inertia Means Hypertension and High Glucose Levels Inadequately Treated

WASHINGTON, June 10, 2006 (PRNewswire) - Four independent studies showing that doctors are failing to intensify therapy in people with type 2 diabetes and high blood glucose levels or high blood pressure were reported here today at the American Diabetes Association's 66th Annual Scientific Sessions. Their findings suggest that clinical inertia -- lack of physician action in the face of abnormal findings -- may be an important barrier to effective diabetes management.

"Physicians do not appear to be aware of the American Diabetes Association guidelines or choose not to follow them because, in the population we studied, the antihypertensive regimen was intensified in only 26 percent of visits in which the individuals had elevated blood pressure," said Alexander Turchin, MD, MS, Associate Physician, Division of Endocrinology, Brigham and Women's Hospital, and Instructor in Medicine, Harvard Medical School, in a recent interview.

"Our study showed that failure to appropriately intensify antihypertensive treatment is a very common problem in diabetes care, because physicians intensified antihypertensive treatment in only 12 percent of visits in which we found sub-optimally controlled blood pressure," said Shari Bolen, MD, Senior Clinical Fellow in Internal Medicine, The Johns Hopkins University School of Medicine, in a recent interview.

Other studies identified failure to intensify treatment to maintain blood glucose levels at the recommended A1C goal of less than 7%. A1C is a blood test that measures blood glucose levels over a period of two to three months. A U.S. study found that physicians delayed therapy intensification for those on oral anti-diabetic drugs on average until A1C was 8.5%. Another study indicated that up to 75 percent of people with type 2 who were using insulin alone in the UK and Germany may have levels exceeding 7%.

Some 20.8 million adults and children in the United States have diabetes, a group of serious diseases characterized by high blood glucose levels that result from defects in the body's ability to produce and/or use insulin. Diabetes can lead to severely debilitating or fatal complications, such as heart disease, blindness, kidney disease, and amputations. It is the fifth leading cause of death by disease in the U.S. Type 2 diabetes involves insulin resistance -- the body's inability to properly use its own insulin. It usually occurs in those who are over 45 and overweight, but it has increasingly been seen in obese children and teens in recent years.

Clinical Inertia in Hypertension -- Brigham and Women's

The Brigham and Women's Hospital study reviewed nearly 11,000 outpatient records of 1,244 hypertensive people with diabetes followed by 166 physicians from 2000 to 2004. They analyzed the blood pressure results and evidence of antihypertensive therapy intensification and found that the regimens were intensified in only 26 percent of visits where elevated blood pressure was documented.

"The level of increase in the blood pressure significantly affected the likelihood that the treatment would be intensified," explained Dr. Turchin, who was the lead author on the study. For every 10 mm of mercury of systolic pressure, the probability of an intensification of the antihypertensive regimen increased 40 percent; for every 10 mm of mercury of diastolic pressure, the probability increased 20 percent.

"It is not surprising that physicians would react more to systolic than diastolic pressure because elevated systolic pressure has a very strong correlation with cardiovascular complications," he explained.

A physician's age also affected the likelihood of treatment of intensification. The younger the physician, the greater the probability that medication would be intensified. "It could be that the younger physician, having just completed a residency, is more aware of the current American Diabetes Association guidelines," said Dr. Turchin.

If the individual belonged to a minority group, the physician was about 10 percent more likely to intensify the antihypertensive regimen, likely due to the fact that non-Caucasians have a higher rate of complications arising from hypertension.

"While some reasons for not intensifying therapy at a given visit are valid -- such as that the provider was not the individual's regular physician or that the person has a history of stabilizing pressure by the next visit -- the majority of people with diabetes with elevated blood pressure do not have treatment intensified appropriately at a given visit," said Dr. Turchin. "Our analysis enables us to identify which doctors are not intensifying therapy so that we can provide professional education and feedback to them, which has been shown in other studies to decrease clinical inertia and improve outcomes."

Clinical Inertia in Hypertension -- Johns Hopkins

The Johns Hopkins study looked at 254 people with type 2 diabetes and hypertension in a managed care program of government employees and their dependents who were generally adherent and whose physicians were part of an academically affiliated outpatient center.

"Through a review of medical records and pharmacy and claims data from 1999 to 2001, we identified 1,374 visits with sub-optimally controlled blood pressure, during which physicians intensified antihypertensive treatment in only 12 percent of visits," said Dr Bolen, who was lead author on the study.

In this study, elevations in diastolic and systolic blood pressure were about equally as likely to trigger intensification. For every 10 mm of mercury increase, the provider was 40 percent more likely to intensify. Also the reason for the visit was another factor. Physicians were twice as likely to intensify if it was a routine visit as compared to an urgent visit. Intensification was almost twice as likely if the person was seen by their regular doctor as opposed to a covering provider.

"Several factors were associated with a 40 to 50 percent lesser likelihood of intensification including a higher glucose level or a history of coronary heart disease, suggesting in both instances that the physician focused on other clinical concerns to the detriment of attention to the hypertension problem," said Dr. Bolen. Co-management of the individual with a cardiologist yielded a similar lesser likelihood of intensification, suggesting that the physician was perhaps erroneously relying on the cardiologist to manage the blood pressure.

"Improvements in continuity of care and care coordination are possible targets to help improve outcomes in hypertension management for people with diabetes," said Dr. Bolen.

Clinical Inertia in Oral Anti-Diabetes Agents

A study of clinical inertia in the prescribing of oral anti-diabetic drugs was based on a retrospective analysis of the pharmacy and lab claims of a commercial, preferred-provider organization model of a national managed care organization. Individuals covered by this plan are geographically diverse across the U.S. The health plan provides fully insured coverage for physician, pharmacy and hospital services, with 23 million participants dating back to 1994. To "create" a study group, they identified 9,416 people who had received a first prescription of an oral anti-diabetic drug -- either metformin, a sulfonylurea, or a thiazolidinedione -- between January 2001 and April 2004.

"At the time they started on these anti-diabetic drugs, the average A1C was 8.4% which included the 33 percent who were at or below the ADA goal of less than 7%," reported Craig A. Plauschinat, PharmD, MPH, Outcomes Research Manager, Novartis Pharmaceuticals Corp., who was senior author of the study. "Unfortunately, this included 67 percent who were well above the goal at A1C levels of 9.5%."

The average time to therapy intensification -- when the physician added another oral anti-diabetic drug -- was 240 days. By that time, the average A1C was 8.5%, but 67 percent of these individuals had A1C levels approaching 10%.

"Disturbingly, 50 percent of those who were intensified did not have an A1C in their charts prior to the addition of a second drug," said Dr. Plauschinat. "It is unknown how the physician made the decision to add a second drug in the absence of A1C testing, although it is possible the decision was based on a finger stick glucose test in the office or patient reports of home blood glucose testing." The study only looked at claims, not physician notes.

He observed that infrequent A1C monitoring may have contributed to delayed therapy intensification. On average, these patients only had one A1C test annually, in contrast to the twice a year testing recommend by the ADA when individuals are at the A1C goal and the four times a year recommended for those not at goal.

"Interventions assisting patients and physicians to recognize and overcome clinical inertia represent a specific opportunity to improve glycemic control in type 2 diabetes," said Dr. Plauschinat.

Failure of Insulin Therapy in Type 2 Diabetes

More complex problems were at work in a study of insulin therapy, which involves one or more insulin injections daily. Those on insulin therapy are typically expected to self-monitor their blood glucose levels daily with finger-stick blood testing, enabling them to modify their insulin, diet, and exercise levels, under their physician's guidance, to achieve recommended glycemic targets.

To assess the extent to which such targets are actually achieved, researchers obtained the last recorded A1C levels of adults with type 2 in Germany and the UK who were prescribed insulin. The data was obtained from Intercontinental Medical Statistics, a company that collects data for pharmaceutical firms. The data was sampled from 6 million records from 1,045 physicians in 983 practices in Germany, and from 3.6 million records from 630 physicians in 200 practices in the UK.

"Overall, the average A1C for 3,658 individuals was 8.4%," said Stephen Gough, MD, Professor of Medicine at the Institute of Biomedical Research, the Medical School, University of Birmingham, and consultant physician at the University Hospital Birmingham, NHS Foundation Trust, UK. Dr. Gough was the lead author on the study. However, about one third had A1C levels greater than or equal to 9% and 18.2% had A1Cs greater than or equal to 10%.

Similar proportions of patients were poorly controlled in both countries. The International Diabetes Federation, which establishes guidelines for physicians in Europe, like the American Diabetes Association, also recommends that treatment be instituted to keep blood glucose levels below 7%.

"If this sample is representative, which we believe it is, glycemic control may be suboptimal for up to three-quarters of the people using insulin alone to control type 2 diabetes," said Dr. Gough. "Identifying and overcoming obstacles that prevent optimal insulin therapy, including adequate intensification when needed, is essential if the gap between recommended glycemic targets and control is to be closed."

However, Dr. Gough was reluctant to blame the results entirely on clinical inertia because he believes the problem is more complex in patients on insulin. He noted that some physicians are fearful of causing hypoglycemia, especially in the elderly or in those with co-morbidities, where tight control can be a problem. Further, some patients simply refuse to take multiple injections every day.

Nonetheless, he acknowledges that further physician education is needed with regard to achieving optimal glycemic control, such as how to mix different types of insulin properly and/or how to teach patients to use such insulins and new devices.

"Many physicians are still locked into once a day insulin injections, and you often cannot get good diabetes control with that approach," said Dr. Gough. "Many patients need additional injections -- so the physician has to deal with complexity and patient education -- to help those with diabetes achieve appropriate control."

The American Diabetes Association is the nation's leading voluntary health organization supporting diabetes research, information and advocacy. Founded in 1940, the Association has offices in every region of the country, providing services to hundreds of communities. For more information, please call the American Diabetes Association at 1-800-DIABETES (1-800-342-2383) or visit http://www.diabetes.org. Information from both these sources is available in English and Spanish.

Posted by dlife at 02:36 PM | Comments (0)

Abbott's Investigational FreeStyle Navigator(TM) Continuous Glucose Monitoring System Shows Promise in Two New Studies

In Pediatric and Adult Trials Presented at ADA Scientific Sessions, FreeStyle Navigator System Demonstrated Clinical Accuracy, Safety

WASHINGTON, June 10, 2006 (PRNewswire-FirstCall) - Abbott announced today the presentation of results from two new studies that met the predefined endpoints designed to assess the accuracy, safety and efficacy of the FreeStyle Navigator(TM) Continuous Glucose Monitoring System for children and adults. Both studies will be presented during poster sessions beginning Saturday, June 10th, at the 66th annual Scientific Sessions of the American Diabetes Association.

The FreeStyle Navigator Continuous Glucose Monitoring System is an investigational device under FDA review. The system includes a five-day sensor, a transmitter, and a wireless receiver with a built-in FreeStyle(R) blood glucose monitoring system. The system is designed to provide glucose readings once per minute, high/low glucose alarms and projected glucose alarms.

Pediatric Accuracy Study - NIH DirecNet

In a National Institutes of Health (NIH) funded DirecNet trial of 30 children (ages 4 to 17) in both inpatient and outpatient settings, FreeStyle Navigator system accuracy and precision were sustained for five days of wear and were similar in different insertion locations (arm, abdomen or hip). In addition, accuracy of the FreeStyle Navigator system was similar during inpatient use and when used at home; and it was accurate during exercise and after meals. DirecNet will present the trial results in a poster (number 391-P) entitled, "Accuracy of the FreeStyle Navigator Continuous Glucose Monitoring System in Children with Type 1 Diabetes Mellitus."

"The need for frequent blood glucose monitoring remains a barrier to achieving excellent diabetes control -- an accurate, real-time continuous glucose system such as FreeStyle Navigator would provide valuable information for improved diabetes management," said Peter Chase, M.D., professor of pediatrics and clinical director emeritus of the Barbara Davis Center for Childhood Diabetes at the University of Colorado Health Sciences Center. "These data are promising and suggest the potential value of FreeStyle Navigator in the management of type 1 diabetes in both children and adults."

"FreeStyle Navigator has proven to be highly accurate in clinical studies to date," said Ed Fiorentino, president, Abbott Diabetes Care. "Based on the promising results obtained from the NIH DirecNet study, and via other clinical studies we hope to initiate, Abbott intends to file a supplemental PMA with the FDA for a pediatric indication in the post-approval period."

Performance During Home Use Study

In a second study, the safety and efficacy of the FreeStyle Navigator system was evaluated in the home use environment in 123 type 1 and type 2 diabetes subjects who completed the study. The data obtained from this trial were submitted to the U.S. Food and Drug Administration as part of Abbott's PMA for the FreeStyle Navigator system. The study was designed for a total of 40 days of sensor wear (arm or abdomen). Performance was evaluated through a comparison between over 11,000 values obtained from the FreeStyle Navigator system and simultaneous pairs of blood glucose values. The overall mean absolute relative difference in these values was 14.4 +/- 13.4 percent, and in a Clarke Error Grid (CEG) analysis, 96.8 percent of the values fell in zone A or zone B. The Clarke Error Grid compares readings from a lab reference to a reading from a glucose monitoring device at a specific point in time. The variance between the two readings is placed on a grid within clinical categories, also known as zones. Each zone is labeled A, B, C, D, or E. Points in the A zone are clinically accurate and most consistent with the lab reference value. B zone readings are clinically acceptable. Points in the C, D, and E zones are progressively less accurate.

"While not a primary endpoint, patients in this study spent significantly less time in hypoglycemic and hyperglycemic states during the unblinded phase of the trial," said Bruce Bode, M.D., medical director of Atlanta Diabetes Associates. For a person with diabetes, less time spent in either a hypo- or hyperglycemic state has been correlated with reduced risk for a number of serious, sometimes life-threatening complications. Study results will be presented in a poster (number 2-LB) entitled, "Performance of the FreeStyle Navigator Continuous Glucose Monitoring System During Home Use."

Posted by dlife at 02:33 PM | Comments (1)

New Study Shows an Innovative Mealtime Insulin Dosing Algorithm May Provide a Safe and Effective Alternative to Carbohydrate Counting for Patients With Type 2 Diabetes

Type 2 Diabetes Patients Using a New Insulin Dosing Strategy Achieved a Mean A1C of 6.6% after 24 Weeks of Combination Therapy with Rapid-Acting Apidra(R) (insulin glulisine [rDNA origin] injection) and 24-hour Lantus(R) (insulin glargine [rDNA origin] injection)

WASHINGTON, June 10 /PRNewswire-FirstCall/ -- Results from a new study presented at the American Diabetes Association's (ADA) 66th Annual Scientific Sessions found that a simple algorithm to adjust mealtime insulin based on pre-meal glucose patterns is just as effective as the more complex carbohydrate counting method -- a standard technique that many diabetes patients find difficult to use. The new algorithm may provide patients with an easier method to dose their mealtime insulin therapy.

After 24 weeks of combination therapy with rapid-acting Apidra(R) and 24- hour Lantus(R), patients using both the new mealtime dosing algorithm and the traditional carbohydrate counting method were able to achieve mean A1C levels of 6.6% (p<0.0001), helping the majority of patients achieve the ADA's recommended blood sugar control target of A1C<7%. Additionally, the rate of symptomatic hypoglycemia (blood glucose<50 mg/dl) was lower in the group that used the new algorithm (4.9 vs 8.0 events/patient year, p=0.02).

"This new dosing approach relies on a simple algorithm that allows patients to start with a fixed dose of mealtime glulisine and then adjust to target based on premeal glucose patterns. This is an easy way to dose and adjust mealtime insulin that should meet the needs of many patients who are not prepared to undertake the equally effective but more complex carbohydrate counting method," explained study author Richard M. Bergenstal, MD, executive director, International Diabetes Center, Park Nicollet Health Services, Minneapolis, MN. "Also, the A1C reductions seen in this study help further demonstrate that good glycemic control is possible and often associated with basal:bolus regimens. Basal:bolus regimens like the glulisine/glargine combination used in this trial simulate the normal physiologic insulin response that occurs in people without diabetes and there are many people with type 2 diabetes who would benefit from such a regimen."

About the Study

Two hundred and seventy-three subjects participated in this open-label, multicenter, randomized, 24-week study. The study compared the change in glycemic control, as measured by Hemoglobin A1c (HbA1c) from baseline to study week 24; in subjects receiving glulisine as mealtime insulin following a variable bolus insulin regimen (based on carbohydrate counting) vs a fixed bolus insulin regimen; with glargine as basal insulin in both arms of the study. All participants had a confirmed type 2 diabetes diagnosis with the disease uncontrolled on two or more insulin injections per day.

All participants were switched to basal/bolus therapy with once-daily glargine titrated to fasting blood glucose<95mg/dL and premeal glulisine to targets of <100 mg/dL pre- lunch/dinner and 130 mg/dL at bedtime +/- metformin. Premeal glulisine was adjusted weekly. One group used a simple algorithm to add 1, 2 or 3U based on premeal glucose patterns. The other group, which used carbohydrate counting, adjusted dose based on the I:C ratio.

Study Results

At the end of the 24-week period, A1C was significantly reduced in both arms (p<0.0001) from an initial 8.2% to a final 6.6% with no difference (-1.46% vs -1.59%, p=0.24) between the algorithm and carbohydrate counting groups, respectively. The algorithm group received significantly higher doses of glulisine (110.2 vs 94.3U, p=0.04) and glargine (103.4 vs 87.0U, p=0.0001) and had significantly less symptomatic hypoglycemia <50 mg/dL (4.9 vs 8.0 events/patient year, p=0.02) than the carbohydrate counting group.

No differences were observed for the proportion of participants achieving A1C<7% (73.0% vs 69.2%, p=0.7) or weight gain (3.7 vs 2.4 kg, p=0.06), for the algorithm and carbohydrate counting groups, respectively. Both groups concluded the study with a basal:bolus ratio of 50:50 and used 1.8-2 U/kg of insulin/day. Adverse events in each group were similar and included infection, gastrointestinal disorders and nervous system-related events.

About Diabetes

Diabetes is a chronic, widespread condition in which the body does not produce or properly use insulin, the hormone needed to convert glucose (sugar) into energy. It is estimated that more than 20 million Americans have diabetes, including 6.2 million who remain undiagnosed. At the same time, approximately half of those diagnosed are not achieving the general blood sugar control standard of A1C <7% recommended by the American Diabetes Association (ADA). The A1C test measures blood glucose levels over a two- to three-month period.

Important Safety Information for Apidra(R)

Apidra is indicated for the treatment of adult patients with diabetes mellitus for the control of hyperglycemia. Apidra has a more rapid onset of action and a shorter duration of action than regular human insulin. Apidra should normally be used in regimens that include a longer-acting insulin or basal insulin analog. Apidra is contraindicated during episodes of hypoglycemia and in patients hypersensitive to Apidra or one of its excipients.

Apidra differs from regular human insulin by its rapid onset of action and shorter duration of action. When used as a mealtime insulin, the dose of Apidra should be given within 15 minutes before or within 20 minutes after starting a meal. Because of the short duration of action of Apidra, patients with diabetes also require a longer-acting insulin or insulin infusion pump therapy to maintain adequate glucose control. Any change of insulin should be made cautiously and only under medical supervision. Changes in insulin strength may result in the need for a change in dose. Concomitant oral antidiabetic treatment may need to be adjusted. As with all insulin preparations, the time course of Apidra action may vary in different individuals or at different times in the same individual and is dependent on site of injection, blood supply, temperature, and physical activity. Glucose monitoring is recommended for all patients with diabetes. Hypoglycemia is the most common adverse effect of insulin therapy, including Apidra. The timing of hypoglycemia may differ among various insulin formulations. Adverse events commonly associated with human insulin therapy include hypoglycemia, allergic reactions, injection site reaction, lipodystrophy, pruritus, and rash.

Posted by dlife at 02:14 PM | Comments (0)

BYETTA® Extension Study Shows Sustained Improvements in Blood Glucose Control and Progressive Weight Loss after Two Years

WASHINGTON, D.C., June 10, 2006 – Amylin Pharmaceuticals, Inc. (NASDAQ: AMLN) and Eli Lilly and Company (NYSE: LLY) today announced two-year study results showing that BYETTA® (exenatide) injection sustained improvements in blood sugar control and reduced body weight in people with type 2 diabetes who previously did not achieve adequate control of their blood sugar on common oral medications. These findings were presented at the 66th Annual Scientific Sessions of the American Diabetes Association (ADA) in Washington, D.C.

BYETTA (pronounced bye-A-tuh), was approved in April 2005 as an adjunctive therapy for patients who are not achieving blood sugar control on metformin and/or a sulfonylurea.

After two years of treatment, patients sustained an average hemoglobin A1C (A1C) reduction of 1.1 percent from baseline. This A1C reduction compares to an A1C reduction of 1.1 percent at the end of the initial 30-week clinical trial, demonstrating sustained efficacy over the two-year period. A1C measures a person’s average glucose level over a three-month period and is often used by doctors to assess blood glucose management. The ADA recommends a target A1C of less than 7 percent; fifty percent of patients in this study reached an A1C of 7 percent or less, and 31 percent achieved an A1C of 6.5 percent or less after two years of treatment.

Average weight loss improved to 10 pounds from the average of five pounds seen after 30 weeks. Fasting blood glucose was reduced 25 mg/dL.

Additionally, HOMA-B, a clinical measurement of beta-cell function, was assessed in a subset of study participants. Beta cells are the insulin producing cells in the pancreas. Participants treated with BYETTA showed significant improvement in HOMA-B from study start to end after two years.

"The benefit of controlling blood sugar levels and the associated weight reduction demonstrated by patients taking BYETTA is significant since these are important clinical goals that many patients have difficulty achieving long term," said Dr. Robert Henry, lead investigator and Chair of the Veterans Medical Research Foundation Advisory Research Committee. "Results from these long-term data support BYETTA’s continuing ability to help people with type 2 diabetes better manage their disease."

There were 283 patients from the original 30-week exenatide pivotal trials that completed 2 years of BYETTA treatment in open-label extension trials. All patients in this “completer cohort” received BYETTA twice daily in addition to their current diabetes treatment. Data collected and assessed over two years demonstrated that long-term administration of BYETTA in combination with metformin, a sulfonylurea or both, resulted in sustained reductions in blood sugar and progressive reductions in weight.

About BYETTA
BYETTA is the first incretin mimetic, a class of drugs for the treatment of type 2 diabetes. BYETTA exhibits many of the same effects as the human incretin hormone glucagon-like peptide-1 (GLP-1). GLP-1, secreted in response to food intake, has multiple effects on the intestine, liver, pancreas and brain that work in concert to regulate blood sugar.1

Safety and Tolerability
Adverse events associated with BYETTA are generally mild to moderate in intensity. In clinical trials, the most frequently reported adverse event was mild-to-moderate, dose-dependent nausea. With continued therapy, the frequency and severity of nausea decreased over time in most patients.

Patients receiving BYETTA in combination with a sulfonylurea may be at a higher risk of hypoglycemia or low blood sugar. To reduce this risk, decreasing the dose of sulfonylurea may be considered. When patients begin taking BYETTA, the symptoms, treatment and conditions that predispose development of hypoglycemia should be explained to them, and the patient’s usual instructions for hypoglycemia management should be reviewed and reinforced.

Patients should also be advised that treatment with BYETTA may lead to a reduction in appetite, food intake and/or body weight, and that there is no need to modify the dosing regimen due to such effects.

BYETTA is not a substitute for insulin in insulin-requiring patients. BYETTA should not be used in patients with type 1 diabetes. Use of BYETTA is not recommended in patients with end-stage renal disease or severe renal impairment, or in patients with severe gastrointestinal disease. BYETTA should be used with caution in patients receiving oral medications that require rapid gastrointestinal absorption.

For complete safety profile and other important prescribing considerations, visit www.BYETTA.com.

About Incretin Mimetics
Incretin mimetics is a distinct class of treatment in the fight against diabetes. An incretin mimetic works to mimic the anti-diabetic or glucose-lowering actions of naturally occurring human hormones called incretins. These actions include stimulating the body’s ability to produce insulin in response to elevated levels of blood sugar, inhibiting the release of a hormone called glucagon following meals, slowing the rate at which nutrients are absorbed into the bloodstream and reducing food intake. BYETTA is the first FDA-approved incretin mimetic.

About Diabetes
Diabetes affects an estimated 194 million adults worldwide2 and more than 20 million in the United States.3 Approximately 90 to 95 percent of those affected have type 2 diabetes, a condition characterized by failure of the pancreatic beta cells to adequately respond to the increased demands for insulin that occur as a result of obesity-related insulin resistance.4 Diabetes is the sixth leading cause of death by disease in the United States3 and costs approximately $132 billion per year in direct and indirect medical expenses. Type 2 diabetes usually occurs in adults over the age of 40, but is increasingly common in younger people.3

According to the Centers for Disease Control and Prevention’s National Health and Nutrition Examination Survey, approximately 60 percent of diabetes patients do not achieve target hemoglobin A1C levels (less than 7 percent according to ADA guidelines5) with their current treatment regimen.6

About Amylin and Lilly
Amylin Pharmaceuticals is a biopharmaceutical company committed to improving lives through the discovery, development and commercialization of innovative medicines. Amylin has developed and gained approval for two first-in-class medicines for diabetes, SYMLIN® (pramlintide acetate) injection and BYETTA® (exenatide) injection. Amylin is located in San Diego, California with over 1200 employees nationwide. Further information on Amylin Pharmaceuticals, its marketed products, and its pipeline in metabolism is available at www.amylin.com.

Lilly, a leading innovation-driven corporation, is developing a growing portfolio of first-in-class and best-in-class pharmaceutical products by applying the latest research from its own worldwide laboratories and from collaborations with eminent scientific organizations. Headquartered in Indianapolis, IN, Lilly provides answers - through medicines and information - for some of the world's most urgent medical needs. Additional information about Lilly is available at www.lilly.com.

Posted by dlife at 02:12 PM | Comments (0)

BYETTA® Shown to Reduce Blood Glucose Levels When Added to Patients Using a TZD

Most patients saw improvements in three critical measures of blood glucose control

WASHINGTON, DC, June 10, 2006 – Amylin Pharmaceuticals, Inc. (NASDAQ: AMLN) and Eli Lilly and Company (NYSE: LLY) today announced detailed findings from a study that showed BYETTA® (exenatide) injection lowered blood glucose levels for people with type 2 diabetes who had not achieved target blood glucose levels despite the use of a thiazolidinedione (TZD) with or without metformin. Patients using BYETTA showed improvements in three important measures of blood glucose control: fasting blood glucose, postprandial blood glucose and hemoglobin A1C (A1C), which improved by approximately 0.9 percent compared to the control group. Sixty-two percent of study participants using BYETTA who completed the full study reached target A1C of 7 percent or less. Less than 7 percent is the target for good glucose control as recommended by American Diabetes Association (ADA).

BYETTA treatment also resulted in a reduction in average body weight. BYETTA-treated patients lost an average of approximately three pounds of body weight, while those treated with placebo lost on average approximately one-half pound.

These findings were presented at the 66th Annual Scientific Sessions of the ADA in Washington, DC. BYETTA (pronounced bye-A-tuh), was approved in April 2005 as an adjunctive therapy for patients with type 2 diabetes who are not achieving blood sugar control on metformin and/or a sulfonylurea.

“In the context of treating the underlying defects in people with type 2 diabetes – beta-cell dysfunction and insulin resistance – using combination therapies is a sensible approach for patients,” said Bernard Zinman, MD, Director of the Leadership Sinai Centre for Diabetes, Mount Sinai Hospital in Toronto, Ontario and a lead author of the study. “These data indicate that the addition of BYETTA to TZDs can be a clinically meaningful treatment for patients.”

In the first quarter of 2006, Amylin and Lilly submitted a supplemental New Drug Application to the Food and Drug Administration seeking approval of BYETTA as an add-on therapy to treatment with a TZD with or without metformin in patients with type 2 diabetes.

Key Findings

A1C reduction:

• At the end of the study, patients on BYETTA experienced an average reduction in A1C of 0.8 percent from baseline compared to an increase of 0.1 percent in the control group.

• Of patients completing the full study, 62 percent treated with BYETTA as a combination therapy achieved an A1C of 7 percent or less, compared to approximately 16 percent in the control group.

Glucose measurements:

• Patients treated with BYETTA had average fasting glucose, measured before breakfast, that was 27 mg/dL (1.50 mmol/l) lower than the control group.

• As measured by 7-point glucose monitoring, BYETTA significantly reduced average 2-hour post-meal glucose surges following breakfast and dinner by 34 mg/dL (1.89 mmol/l) from baseline.

• 7-point glucose monitoring throughout the day demonstrated a significant reduction in average glucose concentrations in patients receiving BYETTA.
Weight change:

• Patients in the BYETTA arm showed an average weight reduction of 3.3 pounds compared with an average weight reduction of 0.4 pounds during treatment in the control arm.

Hypoglycemia:

• Rates of mild and moderate hypoglycemia (low blood sugar) were similar between the BYETTA and placebo treatments. No severe hypoglycemia was reported.
Other adverse events:

• The most common adverse event was mild to moderate nausea reported by approximately 40 percent of the patients in the BYETTA group, compared to 15 percent of patients receiving placebo.

Study Design/Protocol
233 patients with elevated A1C in spite of oral diabetes therapy were involved in the randomized, placebo-controlled, parallel, double-blind trial for 16 weeks. The trial was designed to determine if BYETTA can be used safely and effectively as adjunctive therapy to a TZD alone (~20 percent) or with a TZD and metformin (~80 percent), for people with type 2 diabetes. Study participants were randomized into either of two treatments: the first group received a fixed dose of BYETTA (5µg twice-a-day for first four weeks, then 10µg twice-a-day for remainder of study) in conjunction with a TZD, with or without metformin, and the second group received placebo with a TZD, again with or without metformin. The average A1C at baseline was 7.9 percent.

These detailed findings supplement the primary results released in 2005.

About BYETTA
BYETTA is the first incretin mimetic, a class of drugs for the treatment of type 2 diabetes. BYETTA exhibits many of the same effects as the human incretin hormone glucagon-like peptide-1 (GLP-1). GLP-1, secreted in response to food intake, has multiple effects on the intestine, liver, pancreas and brain that work in concert to regulate blood sugar.1

Safety and Tolerability
Adverse events associated with BYETTA are generally mild to moderate in intensity. In clinical trials, the most frequently reported adverse event was mild-to-moderate, dose-dependent nausea. With continued therapy, the frequency and severity of nausea decreased over time in most patients.

Patients receiving BYETTA in combination with a sulfonylurea may be at a higher risk of hypoglycemia or low blood sugar. To reduce this risk, decreasing the dose of sulfonylurea may be considered. When patients begin taking BYETTA, the symptoms, treatment and conditions that predispose development of hypoglycemia should be explained to them, and the patient’s usual instructions for hypoglycemia management should be reviewed and reinforced.

Patients should also be advised that treatment with BYETTA may lead to a reduction in appetite, food intake and/or body weight, and that there is no need to modify the dosing regimen due to such effects.

BYETTA is not a substitute for insulin in insulin-requiring patients. BYETTA should not be used in patients with type 1 diabetes. Use of BYETTA is not recommended in patients with end-stage renal disease or severe renal impairment, or in patients with severe gastrointestinal disease. BYETTA should be used with caution in patients receiving oral medications that require rapid gastrointestinal absorption.

For complete safety profile and other important prescribing considerations, visit www.BYETTA.com.

About Incretin Mimetics
Incretin mimetics is a distinct class of treatment in the fight against diabetes. An incretin mimetic works to mimic the anti-diabetic or glucose-lowering actions of naturally occurring human hormones called incretins. These actions include stimulating the body’s ability to produce insulin in response to elevated levels of blood sugar, inhibiting the release of a hormone called glucagon following meals, slowing the rate at which nutrients are absorbed into the bloodstream and reducing food intake. BYETTA is the first FDA-approved incretin mimetic.

About Diabetes
Diabetes affects an estimated 194 million adults worldwide2 and more than 20 million in the United States.3 Approximately 90 to 95 percent of those affected have type 2 diabetes, a condition characterized by failure of the pancreatic beta cells to adequately respond to the increased demands for insulin that occur as a result of obesity-related insulin resistance.4 Diabetes is the sixth leading cause of death by disease in the United States3 and costs approximately $132 billion per year in direct and indirect medical expenses. Type 2 diabetes usually occurs in adults over the age of 40, but is increasingly common in younger people.3

According to the Centers for Disease Control and Prevention’s National Health and Nutrition Examination Survey, approximately 60 percent of diabetes patients do not achieve target hemoglobin A1C levels (less than 7 percent according to ADA guidelines5) with their current treatment regimen.6

About Amylin and Lilly
Amylin Pharmaceuticals is a biopharmaceutical company committed to improving lives through the discovery, development and commercialization of innovative medicines. Amylin has developed and gained approval for two first-in-class medicines for diabetes, SYMLIN® (pramlintide acetate) injection and BYETTA® (exenatide) injection. Amylin is located in San Diego, California with over 1200 employees nationwide. Further information on Amylin Pharmaceuticals, its marketed products, and its pipeline in metabolism is available at www.amylin.com.

Lilly, a leading innovation-driven corporation is developing a growing portfolio of first-in-class and best-in-class pharmaceutical products by applying the latest research from its own worldwide laboratories and from collaborations with eminent scientific organizations. Headquartered in Indianapolis, IN, Lilly provides answers - through medicines and information - for some of the world's most urgent medical needs. Additional information about Lilly is available at www.lilly.com.

Through a long-standing commitment to diabetes care, Lilly provides patients with breakthrough treatments that enable them to live longer, healthier and fuller lives. Since 1923, Lilly has been the industry leader in pioneering therapies to help health care professionals improve the lives of people with diabetes, and research continues on innovative medicines to address the unmet needs of patients. For more information about Lilly’s current diabetes products visit www.lillydiabetes.com.

Posted by dlife at 02:08 PM | Comments (0)

Late Breaking Data at ADA 2006 Shows Amylin-Leptin Co-Administration Reduces Body Weight and Body Fat in Animal Studies

WASHINGTON, June 10, 2006 (PRNewswire-FirstCall) - Amylin Pharmaceuticals, Inc. (Nasdaq: AMLN - News) today announced study results showing that co-administration of two neurohormones known to have a role in body weight control, amylin (produced by beta cells in the pancreas) and leptin (produced by fat cells), resulted in sustained, fat-specific weight loss in a leptin-resistant animal model of obesity.

These findings were presented at the 66th Annual Scientific Sessions of the American Diabetes Association (ADA) in Washington, D.C in a poster titled "Leptin Responsivity Restored in Leptin-Resistant Diet-Induced Obese Rats: Synergistic Actions of Amylin and Leptin for Reduction in Body Weight and Fat."

"These findings provide preclinical proof of concept that amylin can restore leptin responsiveness in obese leptin-resistant animals. The study further demonstrates the potential to treat obesity with a combination therapy that employs multiple weight-regulating neurohormones," said Alain Baron, Senior Vice President, Research, at Amylin Pharmaceuticals. "A clinical study to further substantiate these results is planned to start later this year."

In leptin-resistant, diet-induced obese rats, co-administration of amylin and leptin resulted in a decrease in food intake and body weight greater than that seen with either hormone. The amylin plus leptin combination also increased fat oxidation (fat stores used up) and prevented the fall in energy expenditure (calories used up) that is usually expected with weight loss. Weight loss occurred due to decreased fat mass, while lean tissue was preserved.

he full abstract is available online at http://scientificsessions.diabetes.org by searching for abstract number 52-LB.

"We will pursue the development of novel obesity therapies with the same scientific rigor we brought to the development of our first-in-class diabetes drugs BYETTA® and SYMLIN®," said Ginger L. Graham, Amylin's Chief Executive Officer. "We see great potential in examining how integrated neurohormonal pathways can be used to treat obesity and other metabolic disorders. This approach is in line with our research philosophy that hormones with multiple actions may have tremendous potential, whether used alone or as part of a combination therapy."

Amylin acquired exclusive rights to the leptin molecular franchise and on- going clinical program earlier this year.

About Amylin

Amylin Pharmaceuticals is a biopharmaceutical company committed to improving lives through the discovery, development and commercialization of innovative medicines. Amylin has developed and gained approval for two first-in-class medicines for diabetes, SYMLIN® (pramlintide acetate) injection and BYETTA® (exenatide) injection. Amylin's research and development activities leverage the company's expertise in metabolism to develop promising therapies to treat diabetes, obesity and cardiovascular disease. Amylin is located in San Diego, California with over 1200 employees nationwide. Further information on Amylin Pharmaceuticals is available at www.amylin.com.

This press release contains forward-looking statements about Amylin. The company's actual results could differ materially from those discussed in this press release due to a number of risks and uncertainties, including that clinical trials will replicate previous preclinical study or clinical trial results; that clinical trials will commence or conclude when planned; risks that Amylin's compounds will not receive regulatory approval and in the FDA's approval process generally; risks that Amylin's research approach will be able to develop product candidates or result in approved products; and risks and uncertainties inherent in the drug discovery and development process. These and additional risks and uncertainties are described more fully in the Company's recently filed Form 10-Q. Amylin disclaims any obligation update these forward-looking statements.

Posted by dlife at 01:57 PM | Comments (0)

Data on AIR® Inhaled Insulin System Presented at American Diabetes Association Meeting

Results Include First-Ever Data on Inhaled Insulin in Patients with COPD and Studies on Patient Training and Dosing Flexibility

WASHINGTON, DC – June 10, 2006 – Eli Lilly and Company (NYSE: LLY) and Alkermes, Inc. (Nasdaq: ALKS) today reported new study results of the companies’ investigational AIR® Inhaled Insulin System (AIR insulin system), including the first published analysis of the effect of chronic obstructive pulmonary disease (COPD) on inhaled insulin absorption and action; the importance to patients of simple, patient-directed training of an inhaled insulin system; and dosing flexibility with the AIR insulin system. These study findings were presented at the American Diabetes Association’s (ADA) 66th Annual Scientific Sessions. The AIR insulin system is currently in Phase 3 clinical development by Lilly and Alkermes, and is being studied as an innovative treatment for type 1 and type 2 diabetes.

Oral presentation (Abstract 111-OR): "Pharmacokinetics (PK) and Glucodynamics (GD) of Human Insulin Inhalation Powder (HIIP) in Subjects with Chronic Obstructive Pulmonary Disease (COPD)," Klaus Rave, MD, Profil Institute for Metabolic Research, Neuss, Germany.

This Phase 1 study is the first published analysis of the effect of COPD on inhaled insulin absorption and action and was designed to evaluate the impact compromised lung function has on inhaled insulin dose delivery. As expected in a patient population with compromised lung function, the absorption and action of AIR® Inhaled Insulin (AIR insulin) was reduced by a consistent amount in the presence of COPD. The results also demonstrate that AIR insulin was able to deliver similar results on different days in patients with or without COPD and was generally well-tolerated.

According to the National Heart, Lung, and Blood Institute, more than 12 million people in the United States have been diagnosed with COPD – a progressive condition made up of emphysema and chronic bronchitis, both inflammatory diseases of the lungs. It is speculated that COPD may also be a risk factor, particularly among women, for developing type 2 diabetes.

"Having a non-invasive insulin option that is safe and effective in multiple patient populations is potentially an important advance in the treatment of diabetes and could help patients move earlier and more easily to insulin use," said Klaus Rave, MD, Profil Institute for Metabolic Research, Neuss, Germany. "Because of COPD’s prevalence and its potential correlation with type 2 diabetes, particularly in women, it’s important to study the safety, efficacy and predictability of AIR insulin in many patient populations, including in people with compromised lung function."

Study Design
In this open-label, randomized, three-period crossover trial, pharmacokinetic and glucodynamic responses to AIR insulin were compared with subcutaneous insulin lispro in 15 nonsmoking healthy subjects (mean age 38y) and 30 nonsmoking subjects with moderate COPD – 15 each with chronic bronchitis (mean age 53y) and emphysema (mean age 58y) – using standard glucose clamp methodology, a process for measuring the absorption of and an individual's response to insulin. Subjects received two single doses of AIR insulin (5.2 mg) and one dose of subcutaneous insulin lispro (12 units). Pharmacokinetic and glucodynamic measures were assessed using blood tests, and safety was assessed using pulmonary function tests (PFTs) before and after each clamp and by spirometry – bedside breathing tests – performed four times during clamps. Key results included:

• Total insulin exposure and metabolic effect after subcutaneous insulin lispro were comparable in all three groups. Compared with healthy subjects, AIR insulin absorption was reduced by 22 percent (p=0.13) in subjects with emphysema and by 44 percent (p<.001) in those with chronic bronchitis. The metabolic effect of the AIR insulin dose was reduced in emphysema subjects (33%, p<.01) and chronic bronchitis subjects (40%, p<.01).

• AIR insulin was well-tolerated by patients with COPD. PFTs and spirometry safety measures showed no difference between AIR insulin and subcutaneous insulin lispro treatments, with modest decreases in FEV1 (forced expiratory volume) and FVC (forced vital capacity) in both COPD groups. No statistically significant differences between the pre-and post-clamp PFTs were observed.

• The reproducibility of action and absorption responses to repeat administration of the same dose of AIR insulin was similar in healthy subjects and in patients with COPD.

Training Study Data
Poster presentation (Abstract 424-P): "A Comparison of Standard vs Intensive Training on Usage of the Human Insulin Inhalation Powder (HIIP) Delivery System in Type 2 Diabetes (T2D) Patients," Julio Rosenstock, MD, Dallas Diabetes and Endocrine Center at Medical City.

Study Design
This Phase 2 trial in people with type 2 diabetes was designed to compare two levels of training intensity, either standard/patient-directed training, or intensive/provider-coached training for the AIR insulin system on overall blood glucose levels. In this Phase 2, four-week, multi-center, single-blind noninferiority trial, 102 patients with type 2 diabetes were randomized to receive preprandial AIR insulin plus metformin and one of two different levels of training intensity, either standard/patient-directed training or intensive/provider-coached training. Standard training consisted of written directions and a call-in number for assistance. Intensive training included standard training in addition to observation and coaching feedback from a clinician as well as inhalation spirometry training.

The impact of the level of training on blood sugar control was evaluated based on measures of 2-hour postprandial blood glucose (PPBG) and HbA1c (A1C) and the impact the level of training has on safety and blood sugar control. Safety assessments included PFTs, chest x-rays, insulin antibody binding, hypoglycemia, adverse events and body weight. System suitability, compliance with directions, inhalation flow rate and pharmacokinetics were also investigated. Key results included:

• Results demonstrated that the AIR insulin system is easy to use and can be supported by simple, patient-driven training while helping patients manage blood sugar levels.

• Both PPBG and A1C improved similarly and significantly (p<0.001) from baseline in the standard and intensive patient groups.

• Both training methods had similar rates of compliance with training directions (>90%), and similar safety profiles. As noted in previous studies, cough was the most commonly reported adverse event and was reported by eight percent of all subjects in the study.

• AIR insulin exposure was also similar between groups.

• No discontinuations occurred due to difficulty of use or dislike of the system.

Posted by dlife at 01:55 PM | Comments (0)

OREXIGEN(TM) Therapeutics Reports Positive Phase II Results for Contrave(TM) Combination-Therapy to Treat Obesity

Top-Line Positive Data Presented at American Diabetes Association Scientific Sessions - Data Include First Public Disclosure of the Contrave Ingredients-

SAN DIEGO and WASHINGTON, June 10, 2006 (PRNewswire) - OREXIGEN(TM) Therapeutics, Inc., a privately held clinical-stage neuroscience company developing a novel strategic approach to the treatment of obesity, today announced that the company's lead program, Contrave(TM), a combination of two centrally-acting medications, demonstrated greater sustained weight loss in a six month Phase II clinical study than either monotherapies or placebo. The findings showed that in the subjects using Contrave more than half of those who completed the trial demonstrated 5% weight loss over 24 weeks, 18% demonstrated 10% weight loss, and the trajectory of these weight loss curves showed no evidence of a plateau. These top line Phase II data for Contrave were presented at the 66th annual Scientific Sessions of the American Diabetes Association (ADA) in Washington, DC.

"These results show the greater potential for weight loss that can be achieved by combining therapies," said Louis Aronne, M.D., Clinical Professor of Medicine at Weill Cornell University Medical College and director of the Comprehensive Weight Control Program at New York Presbyterian Hospital-Weill Cornell Medical Center, who addressed the findings as part of a plenary session, at the ADA meeting." Dr. Aronne continued: "Thirty percent of American adults are obese and at significant health risk and it is clear that properly-designed medical interventions can help treat this epidemic."

Contrave is a rationally formulated combination of CNS products designed to achieve weight loss and then to off-set the body's natural compensatory mechanisms to avoid the typical weight loss plateau. The company disclosed for the first time that Contrave is a proprietary formulation of naltrexone, used to treat narcotic and alcohol dependency,and bupropion, a dopamine and norepinephrine reuptake inhibitor. Though neither of these individual products has been approved for weight loss by the FDA, several million patients have received these medications for other uses over the last twenty years. The company is further refining the formulation and optimal dose ratio of the two agents as part of its ongoing Phase III clinical program.

"This naltrexone/bupropion combination derives from our identification of specific neuronal systems in the brain that balance energy expenditure and appetite to regulate body weight," said Gary Tollefson, M.D., Ph.D., OREXIGEN president and CEO. "We believe that the positive findings we report today offer proof of concept for our Contrave clinical program."

The Contrave combination is based on in vitro studies that show naltrexone acts synergistically with bupropion to stimulate the proopiomelancortin (POMC) system in the brain to release alpha-MSH, a hormone that increases energy expenditure and reduces hunger. Naltrexone also blocks autoinhibition of POMC by the body's natural opiate beta-endorphin. Orexigen scientists believe that blocking this autoinhibition is an important element in preventing the typical plateau and weight regain observed with most obesity interventions.

The multi-center study was conducted at 8 US academic centers and evaluated 206 obese subjects with a body mass index of 30 to 40 with each of the monotherapies, the combination and placebo along with a minimal diet and exercise program. The Phase II findings were presented at the ADA by the study's principal investigator, Frank Greenway, M.D., chief of the Clinical Obesity Laboratory and Outpatient Research Clinic at the Pennington Biomedical Research Center.

A companion product now in Phase II testing, Excalia(TM), is believed to be working via a distinctly different approach within appetite and energy pathways with a goal of providing a more substantial weight loss profile. More information about the company and its programs is available at http://www.orexigen.com.

Posted by dlife at 11:43 AM | Comments (0)

Studies Aim to Preserve Insulin Production in Type 1 Diabetes

Type 1 Diabetes TrialNet Centers Begin New Trials

June 9, 2006 (NIH News) - Eighteen medical centers in the United States, Canada, Europe, and Australia have begun new clinical studies in type 1 diabetes, the National Institutes of Health (NIH) announced today at the annual scientific meeting of the American Diabetes Association (ADA). The NIH-funded studies seek to slow or stop the immune system's attack on insulin-producing cells in two groups of people: those newly diagnosed with type 1 diabetes and those at risk for developing it.

"It would be a tremendous step forward if insulin-producing cells can be shielded from further destruction by immune cells," said Elias A. Zerhouni, M.D., NIH Director. "We stand to learn a great deal from these promising studies, which are exploiting the knowledge gained from earlier research in immunology, endocrinology, and the biology of type 1 diabetes."

Type 1 diabetes is an autoimmune disease that accounts for 5 to 10 percent of diagnosed diabetes cases in the United States -- up to a million people. It arises when a person's own immune system destroys beta cells in the pancreas. Beta cells sense blood glucose and produce the hormone insulin, which regulates glucose and converts it to energy.

Formerly called juvenile onset diabetes, type 1 diabetes usually develops in children and young adults. People with this form of diabetes typically need three or more insulin injections a day or treatment with an insulin pump, as well as careful monitoring of blood glucose and attention to diet and exercise, to properly control their blood glucose.

The immune destruction of beta cells begins well before a person develops the symptoms of diabetes and continues long after the disease is diagnosed. During the "honeymoon phase," the months after diabetes is diagnosed, most patients still have a reservoir of functioning beta cells that, with the help of insulin injections, makes it easier to control blood glucose. If the honeymoon period can be extended, researchers hope that more patients would be able to tightly control their blood glucose. Well controlled glucose is critical to preventing or delaying serious damage to the eyes, nerves, kidneys, heart, and blood vessels.

STUDIES FOR NEWLY DIAGNOSED PATIENTS
Researchers participating in Type 1 Diabetes TrialNet are now conducting two studies that seek to safely preserve insulin production in people diagnosed with type 1 diabetes in the previous 3 months. "The more beta cells a person has, the easier it is to control diabetes and prevent complications," said TrialNet chair Jay Skyler, M.D., of the University of Miami. "With these studies, we hope to stop the immune system's attack on these cells and keep the disease from getting worse."

A number of studies have already shed light on how a subgroup of T cells, the "warrior" cells of the immune system, seek out and attack insulin-producing cells. B cells, another group of immune cells that were initially seen as idle bystanders, are now thought to raise the alarm by presenting antigens to T cells, urging them to take action.

This new insight is now being tested in a clinical study that seeks to "turn off" the alert by reducing the number of circulating B cells. In this study, researchers are testing the use of Rituximab, a monoclonal antibody that binds to a receptor on the surface of B cells and destroys them. Rituximab, approved by the Food and Drug Administration to treat B cell non-Hodgkin's lymphomas, has also been used with minimal toxicity to treat autoimmune diseases, such as chronic idiopathic thrombocytopenia, myasthenia gravis, and rheumatoid arthritis.

In another TrialNet study, patients are randomly assigned to one of three groups receiving mycophenolate mofetil (MMF) alone; MMF plus daclizumab (DZB); or placebo. Both MMF and DZB, which slow immune cell activity, have been approved by the Food and Drug Administration to prevent organ rejection after an organ transplant.

Both the new Rituximab trial and the ongoing MMF/DZB trial are recruiting patients with type 1 diabetes diagnosed within the previous three months. In each study, patients are randomly assigned to receive the experimental treatment or placebo. Participants will be closely monitored for any possible side effects of the drugs.

STUDY FOR NEWBORNS AT RISK FOR TYPE 1 DIABETES Some studies show that the immune destruction of beta cells is linked to an inflammatory process triggered by specific cytokines, molecules that regulate communication among immune cells. TrialNet researchers hope to quell this inflammation and prevent the development of autoantibodies with docosahexaenoic acid (DHA), an omega-3 fatty acid that may have anti-inflammatory benefits. "Nutritional Intervention to Prevent Type 1 Diabetes (NIP)" is a pilot study of DHA being conducted in babies less than 5 months old who have immediate family members with type 1 diabetes. The "NIP" study is also screening pregnant mothers in their third trimester whose babies are at risk for type 1 diabetes, either because the mother has type 1 diabetes herself or other immediate relatives have the disease.

NATURAL HISTORY STUDY
TrialNet researchers are also probing the causes of type 1 diabetes by examining the immune and metabolic events that precede the onset of diabetes symptoms. They are screening two groups of relatives of those with type 1 diabetes: first-degree relatives ages 1 to 45 and second-degree relatives ages 1 to 20. Screening involves a simple blood test for the autoantibodies that appear in at-risk people years before diabetes develops. The presence of autoantibodies to GAD, IA-2, and insulin point to a greater risk for developing type 1 diabetes. For a person with high-risk genes who has all three antibodies, the risk of developing diabetes in the next 5 years is greater than 50 percent.

After enrolling in the study, participants will be closely monitored for diabetes development and may be eligible to participate in studies that try to arrest the disease.

Type 1 diabetes is caused by a combination of genetic and environmental factors. About 18 regions of the genome have been linked to type 1 diabetes risk. The most well studied region is IDDM1, which contains the human leukocyte antigen (HLA) genes that encode immune response proteins. Specific variations in these genes predispose a person to the disease, but having them does not guarantee that someone will develop the disease. One or more external co-factors, such as a viral infection or component of the diet, appear to trigger immune cells' misguided attack on beta cells in genetically susceptible people. Researchers are working to identify all the genes and environmental triggers that contribute to the risk of developing type 1 diabetes, and they have already learned a great deal about assessing an individual's level of risk.

The studies are funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the National Institute of Child Health and Human Development, and the National Institute of Allergy and Infectious Diseases within the NIH. The ADA and the Juvenile Diabetes Research Foundation International (JDRF) also support the initiative.

For more information about the studies, see www.DiabetesTrialnet.org or call 1-800-HALT-DM1 (1-800-425-8361).

The National Institutes of Health (NIH) -- "The Nation's Medical Research Agency" -- includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

Posted by dlife at 01:48 PM | Comments (0)

Diabetes Research Takes Wing Thanks to Long-Lived Fruit Fly

June 7, 2006 (Eurekalert) - The creation of an extraordinarily long-lived fruit fly by genetics researchers at the University of Rochester has led scientists down an unexpected new path in the fight against diabetes. The mutant fly is serving as a portal for understanding the factors that determine how nutrition and stress set the foundation for metabolic syndrome and diabetes, why diabetes occurs more frequently as people age, and indeed why people live as long as they do.

Dirk Bohmann, Ph.D., and Henri Jasper, Ph.D., are focusing on a cell signaling system that responds to stress and works in tandem with the insulin receptor that is central to diabetes. They recently received $2.5 million from the National Institutes of Health to conduct the next phase of their studies.

Why spend such funds on a fly that lives 40 percent longer than the average fly? Because of its promise for human health. New findings on aging, diabetes, and stress converge on the fly the team created. Later this month Bohmann will discuss the fly's implications for aging and health at a symposium in Sweden sponsored by the Wenner-Gren Foundations and also at the exclusive International Workshop on the Molecular and Developmental Biology of Drosophila, sponsored by the European Molecular Biology Organization, in Crete.

Bohmann and Jasper showed in 2003 that boosting the amount of a molecular signal known as JNK in a fruit fly allows the fly to live 85 days instead of 60, by spurring the fly to defend itself more aggressively against the oxidative stress that accelerates with aging. Such stress comes from the same chemical process that makes cars rust in the Rochester winter: Free-wheeling molecules known as free radicals zing through materials and run roughshod over anything in their way, including vital proteins and DNA. It's a major reason why generally our bodies falter as we age – we're literally dinged to death by free radicals.

While scientists knew that JNK in a fly cranks up the anti-oxidants, helping to keep the integrity of genes and proteins intact in the same way people hope substances like vitamins C and E might, few had considered that simply boosting the amount of JNK could have such a broad impact on life span.

Then, in another surprise, Jasper and Bohmann showed that JNK targets the same protein as the widely studied insulin receptor, central to human health and to the disease process that underlies diabetes. The finding has opened up an untapped route for possibly interfering with the disease process that underlies diabetes.

"Obesity is on the rise dramatically, and after decades of increasing life span among people in the United States, there is talk that life expectancy is actually expected to fall soon, largely due to the epidemic of obesity and diabetes," said Bohmann. "It's a huge health issue. Many people have this problem – it's not going away anytime soon.

"This research isn't so much about making people to live to 120 as it is about preventing diseases like diabetes, heart disease, or Alzheimer's. We're trying to identify the mechanisms that cause damage to our body as we age, and prevent them. This has opened a new playing field for people in aging research."

The work was initially supported by the Nathan Shock Center, funded by the National Institute on Aging, and the Upstate Coalition of Aging Research. Now, Bohmann will use $1.4 million in a new five-year study exploring the relationship between JNK and the insulin receptor, while Jasper will use $1.1 million in a four-year study investigating just how much control JNK seems to wield over insulin production.

It's likely, for instance, that JNK counters the effects of the insulin receptor and inhibits the production of insulin, a crucial hormone that converts the food we eat into forms that the body can utilize. JNK detects stress in the environment and not only prepares the body to deal with insults from the environment, but also limits the amount of insulin, preparing the body for stress by slowing its metabolism and limiting its energy output. It might also offer a new way to control insulin production.

Like JNK, the insulin receptor is also involved in determining life span. Caloric restriction – limiting the calories an organism ingests – generally increases lifespan in organisms ranging from worms to flies, and maybe humans. Somehow, JNK and the insulin receptor together seem to work in tandem to affect life span.

"We're learning that an organism's life span may not be limited by design," said Bohmann. "It was once thought that people and other organisms could simply live only a certain number of years and that's it. Instead, our genes play a crucial role in determining and adjusting how long we live. Can we control this process more fully? Perhaps it's possible to re-set the body's aging clock and maybe make someone live longer."

It was Bohmann's questions about cancer-causing genes 20 years ago that led him to focus on JNK, a signaling system that plays a role not only in cancer but in many normal body processes. For several years he has worked with Jasper, using fruit flies to try to unravel the molecular signals that enable cancer cells to grow. Jasper earned his doctoral degree under Bohmann's guidance in 2002 and is now an assistant professor of Biology.

Bohmann initially studied cancer in human cells, then switched to studying fruit flies because he felt that making findings important to human health would happen more rapidly using flies, then transferring the findings to people. He notes that the same molecular signals that control how cells divide in fruit flies control how cells divide in people.

"We continue to be amazed at how similar a fruit fly is to a person," says Bohmann. "We can accomplish the same thing in fruit flies that we would only be able to do with a lot more money, taking a lot longer, in other ways. And many of these experiments could never be done in people or even mice. Working first in fruit flies speeds up the process toward finding potential treatments or cures for diseases like cancer."

See All June 2006 Articles

Posted by dlife at 01:45 PM | Comments (0)

Hopkins Researchers Discover Potential New Approach to Treating Diabetes

June 7, 2006 (Eurekalert) - Scientists at Johns Hopkins have uncovered a surprising and novel way of lowering blood sugar levels in mice by manipulating the release of sugar by liver cells. The results, published in the June issue of Cell Metabolism, have implications for treating conditions like diabetes.

The discovery by researchers in Hopkins' Institute of Basic Biomedical Sciences and McKusick-Nathans Institute for Genetic Medicine reveals that a protein called GCN5 is critical for controlling a domino-like cascade of molecular events that lead to the release of sugar from liver cells into the bloodstream. Understanding the role of GCN5 in maintaining blood sugar levels is leading to a clearer picture of how the body uses sugar and other nutrients to make, store and spend energy.

"Understanding the ways that energy production and use are controlled is crucial to developing new drugs and therapies," says the report's senior author, Pere Puigserver, Ph.D., an assistant professor of cell biology at Hopkins.

The inability to properly regulate blood sugar levels leads to conditions like obesity and diabetes. Both type 1 and type 2 diabetes cause blood sugar levels to stay too high, which can lead to complications like blindness, kidney failure and nerve damage.

"Diabetes is a really big problem, even when patients are given insulin and stay on strict diets," says Carles Lerin, Ph.D., a postdoctoral fellow in cell biology at Hopkins and an author of the report. "In the absence of a cure for the disease, we are really trying to focus on finding better treatment because currently available methods just don't work that efficiently," he says.

The body keeps blood sugar – known as glucose – within a narrow range. Extra glucose floating through the bloodstream, which is common after eating a meal, is captured and kept in the liver. When blood glucose runs low, the liver releases its stores back into the bloodstream. When those reserves are tapped out, liver cells turn on genes to make more glucose to fuel the body.

The research team found that GCN5 chemically alters another protein called PGC-1alpha that normally turns on a set of genes to manufacture enzymes required for glucose release. When GCN5 is fully functional in liver cells, this cascade is turned off and glucose is not released from those cells. Removal of functional GCN5 from liver cells restores the cells' ability to release glucose.

The researchers showed that GCN5 alters its target, sabotaging it by adding a chemical tag called an acetyl group. By using molecules that glow fluorescently, the researchers saw under high-power microscopes that GCN5 carries its tagged target to a different location in the cell's nucleus – sequestering it away from the genes it's normally meant to turn on.

"GCN5 has been generally shown to turn on genes. No one knew that GCN5 could be used to turn off pathways" says Lerin. "It was a bit of a surprise."

When the researchers put GCN5 into live mice, they found that it can in fact decrease blood glucose levels. Liver cells in mice that were given no food for 16 hours actively release glucose into the bloodstream. Introducing GCN5 into their livers, however, causes blood glucose levels in these mice to be reduced.

"These results show that changing GCN5 is sufficient to control the sugar balance in mice," says Puigserver. "Therefore, GCN5 has the potential to be a target for therapeutic drug design in the future."

Posted by dlife at 01:39 PM | Comments (0)

Approval Granted for Harvard Stem Cell Institute Researchers to Attempt Creation of Disease-Specific Embryonic Stem Cell Lines

June 6, 2006 (Harvard University Gazette) - After more than two years of intensive ethical and scientific review, Harvard Stem Cell Institute (HSCI) researchers at Harvard and Children's Hospital Boston have been cleared to begin experiments using Somatic Cell Nuclear Transfer (SCNT) to create disease-specific stem cell lines in an effort to develop treatments for a wide range of now-incurable conditions afflicting tens of millions of people.

As far as is known, this decision marks the beginning of the first noncommercial effort in the United States to use human embryonic stem cells in a series of experiments whose principle has already been proven in animals. The work is being entirely supported with private funds because of the federal restrictions on human embryonic stem cell work. If successful, it will mark a major step forward in the effort to use stem cells to treat chronic diseases.

The work will be conducted by two groups headed by HSCI senior investigators: Douglas Melton, co-director of the Harvard Stem Cell Institute and Thomas Dudley Cabot Professor of Natural Science in Harvard's Faculty of Arts and Sciences (FAS), and HSCI principal faculty member Assistant Professor Kevin Eggan, of the FAS Department of Molecular and Cellular Biology; and Harvard Medical School Associate Professor George Daley of Children's Hospital Boston, who has already begun some of his experiments.

Melton's work will focus on diabetes; Eggan will initially work with Melton on diabetes, and then plans to focus on neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS) - better known as Lou Gehrig's disease. Daley's group will focus on blood disorders. Daley was one of the principal scientists who in 2002 demonstrated in a mouse model the feasibility of using SCNT to treat immune deficiency.

Harvard University Provost Steven E. Hyman said during a June 6 telephone press conference that the work has been the subject of "more than two years of thoughtful, intensive review by as many as eight different Institutional Review Boards and Stem Cell oversight committees at five different institutions," including Harvard, Children's Hospital, Partners Health Care, Brigham and Women's Hospital, Boston IVF, and Columbia University.

Harvard University President Lawrence H. Summers called the approvals "a seminal event in the University's effort to advance this tremendously promising area of science and fulfill that promise as quickly as possible for the countless patients suffering from diabetes, Parkinson's disease, heart disease, cancers, and a host of other illnesses.

"While we understand and respect the sincerely held beliefs of those who oppose this research, we are equally sincere in our belief that the life-and-death medical needs of countless suffering children and adults justifies moving forward with this research," Summers said, referring to the controversy over embryonic stem cell work.

The Harvard Stem Cell Institute, co-directed by Melton, a Howard Hughes Medical Institute investigator, and David Scadden, a professor of medicine at Harvard Medical School and director of the Center of Regenerative Medicine at Massachusetts General Hospital, is a unique collaborative effort that includes 99 principal investigators and hundreds of additional scientists in laboratories at Harvard University and at many of Harvard's affiliated hospitals. The institute is dedicated to advancing all forms of stem cell science from laboratory bench to patient bedside as quickly as possible.

Somatic Cell Nuclear Transfer involves removing nuclei, which contain the cellular DNA (genes) from egg cells, and replacing them with the nuclei of donor cells. The resulting cell is subject to a chemical, or electrical, charge that triggers cell division and the creation of an embryo genetically identical to the donor of the nuclei. In the HSCI experiments, aimed at understanding diseases, the nuclei will be taken from skin cells donated by patients suffering from diabetes, blood diseases, and neurodegenerative diseases.

The controversy

Research involving human embryonic stem cells is controversial because extracting the cells - which can differentiate into any cell or tissue type in the body - requires the destruction of a human embryo, albeit a blastocyst of only a few hundred cells, literally half the size of the period at the end of this sentence. Opponents of the work contend that no potential medical benefit can justify the destruction of what they view as a human life, or even as a person.

But Melton responds that "all human cells, even individual sperm and eggs, are 'living.' The relevant question is 'when does personhood begin?' That's a valid theological or philosophical question, but from the scientific perspective, this work holds enormous potential to save lives, cure diseases, and improve the health of millions of people. The reality of the suffering of those individuals far outweighs the potential of blastocysts that would never be implanted and allowed to come to term even if we did not do this research," he said.

Melton, in collaboration with Kevin Eggan and Douglas Powers of Boston IVF , has already created 31 stem cell lines using left-over frozen embryos donated by couples who went through in vitro fertilization (IVF), and has distributed those stem cell lines to scientists around the world.

The work

Embryonic stem cells are the master cells of the body, capable of developing into any tissue type. The researchers will seek to learn how to control that differentiation, with a goal of eventually creating lines of cells that can, for instance, produce insulin-making islet cells in the pancreas, which are depleted or absent in diabetics. Melton and Eggan's first nuclear transfer experiments will attempt to create diabetes specific stem cells by removing the nuclei from skin cells taken from diabetic volunteers at the Naomi Berrie Diabetes Center at Columbia University Medical Center and inserting them into donor eggs from which the nuclei have been removed.

In addition to collaborating with Melton on this project, Eggan, whose work is supported by the Stowers Medical Institute, is seeking approvals to study diseases of the nervous system.

Children's Hospital researcher and HSCI Executive Committee member George Daley explains that the ultimate goal of all three HSCI researchers, once they understand how embryonic stem cells are programmed to differentiate into specific cell types, is to literally move a patient's disease into a petri [laboratory] dish. "We plan to take skin cells from a patient with a genetic disease, like sickle cell anemia or any one of more than 40 bone marrow disorders, and reprogram that skin cell back to its embryonic state. We can then study the disease using these cells, correct their genetic defects and coax the repaired cells to become normal blood cells. Our ultimate goal is to return the repaired cells to the patients." Such cells, genetically identical to the patients receiving them, would be accepted by the patient's immune system and wouldn't require the use of immunosuppressive drugs.

Egg donation and reimbursement

Research using human embryonic stem cells is ineligible for federal funding, including grants from the National Institute of Health; only private money may be used to support SCNT research. Harvard University and Children's Hospital have business processes and financial controls in place to ensure that no federal money is used in support of this research.

Under the protocol approved by the Institutional Review Board (IRB) of Harvard's Faculty of Arts and Science, and the IRB of Boston IVF, where the ova will be collected for Melton and Eggan's work, donors will not be paid. They will, however, be reimbursed for travel and other expenses, such as child care, directly related to the research, and they will be provided with a special insurance policy in case medical care is necessitated by any possible complications associated with the donation procedure.

Couples looking for ova donors in order to become pregnant pay - and often pay large sums - for ova; the HSCI researchers and IRBs decided against compensating donors to avoid even the suggestion of inducement that payment might raise.

While that was one important area of focus for the FAS and Boston IVF IRBs and Harvard's stem cell oversight committee, an even more important issue was making sure that donor consent was truly informed. The committees struggled to ensure not only that potential donors would understand all potential risks associated with ova donation, but would also understand that they will be contributing to basic science experiments, and that it will be many years - at best - before patients benefit directly from the work.

Speaking of the IRB decisions at Harvard, Children's Hospital, Boston IVF, Brigham and Women's Hospital - where Daley is obtaining ova for his experiments - and Columbia University allowing the Harvard Stem Cell Institute SCNT work to proceed, Melton says, "I think Harvard University has done the right thing by giving this research very careful review by multiple boards, and allowing plenty of time for reconsideration and reflection. If this new technology is to realize its promise, scientists should have the support of the community and proceed deliberately and carefully."

Posted by dlife at 01:34 PM | Comments (0)

Old Technology Helps Find New Test for Leg Artery Disease

Who says the 70's are over. Doctors at the University of Virginia Health System are using technology developed in the disco era to invent a new diagnostic test for clogged leg arteries.

June 6, 2006 (Newswise) — Between 8 and 12 million Americans are affected by peripheral arterial disease, or PAD, where the arteries that bring blood to the legs are blocked by atherosclerotic plaque. The incidence of PAD is expected to rise in coming decades as the population ages, one reason it’s vital to develop new methods to diagnose the severity of PAD and develop new drugs to treat it.

By examining the physiology of patients who exercised under a magnetic resonance imaging scanner (MRI), doctors at the University of Virginia Health System have devised a new test to diagnose and follow peripheral arterial disease. This test shows promise in helping drug companies test new PAD medications and, perhaps in the near future, may give doctors the ability to tell which patients are at risk for developing PAD-related complications and require stenting, bypass surgery or even amputation of a leg.

A UVa cardiologist, Dr. Christopher Kramer, and his colleagues, measured how fast the leg muscles of patients with PAD, and people without PAD, recovered a phosphorus substance called phosphocreatine (PCr), the major energy “store” in muscle cells. Tests at UVa on 20 patients with mild to moderate PAD and 14 people without PAD, showed that the median time to recover phosphocreatine at the end of exercise in PAD patients was three times slower, 91 seconds in the PAD group versus 35 seconds in the normal group.

“Not only is this a good test that can discriminate patients with PAD from those without the disease,” Kramer said, “but a longer exercise time was a marker of worse outcomes in PAD patients. Those patients with events, including amputations and surgery, had a longer recovery time.” Kramer’s findings are published in the June 6 issue of the Journal of the American College of Cardiology found on the web at: http://www.cardiosource.com/jacc/index.asp

What was unusual is that the UVa doctors stepped back in time and used a measurement technique developed in the 1970’s called MR spectroscopy, the forerunner to modern MR imaging. “We were somewhat surprised that of all new tests for PAD that we have been developing, the one that seemed to work the best is spectroscopy. It’s relatively simple and not particularly sexy, but very accurate physiologically,” Kramer said.

All of the patients tested exercised to exhaustion on a special push-pedal machine in an MRI scanner. A spectroscopy coil in the MRI then took readings of the phosphocreatine level in the legs every 15 seconds for several minutes afterward. “If the blood flow is poor,” Kramer explained, ”PCr recovery is slow, because the muscle is not getting the energy sources it needs to restore PCr. It is an energy-dependant process.”

Right now, doctors use several tests to measure PAD severity, including measuring blood pressure in the ankles and comparing it to blood pressure in the arms. Doctors can also do an angiogram of the artery, using dye to show where blockages exist. But, Kramer said, “if you are following a patient over weeks and months, you don’t want to do multiple angiograms if you don’t have to, and certainly not x-rays or CT scans because of the radiation and contrast dye involved.” Yet another reason this new test may be so valuable.

Kramer said people with peripheral arterial disease often have coronary and cerebrovascular disease as well. The risk factors for PAD include smoking, high blood pressure, high lipids and diabetes. People with PAD generally have pain in the calves when they exercise. Those with severe disease can have pain at rest and tissue loss, including ulcers.

The study: David C. Isbell, Stuart S. Berr, Alicia Y. Toledano, Frederick H. Epstein, Craig H. Meyer, Walter J. Rogers, Nancy L. Harthun, Klaus D. Hagspiel, Arthur Weltman, and Christopher M. Kramer. Delayed Calf Muscle Phosphocreatine Recovery After Exercise Identifies Peripheral Arterial Disease. J Am Coll Cardiol 2006 47: 2289-2295.

Posted by dlife at 01:26 PM | Comments (0)

Increased Sensitivity to Nerve Signals Keeps Diabetes at Bay

June 6, 2006 (Eurekalert) - Nerve signals relayed directly to the pancreas after eating a meal play a critical role in normal blood sugar control, according to a report in the June 7, 2006, Cell Metabolism. Therefore, drugs that increase the sensitivity to such signals might offer a new approach to diabetes treatment, the researchers said.

Mice in which the pancreas cells that produce insulin, or beta cells, lack so-called M3 muscarinic acetylcholine receptors develop some symptoms of diabetes, including impaired glucose tolerance and reduced insulin release, the authors report. M3 receptors are normally on the receiving end of messages relayed by involuntary nerves that indicate the presence of food.

In contrast, mice genetically altered to harbor an excess number of beta cell M3 receptors show the opposite: a profound increase in glucose tolerance and insulin release, the researchers found. Moreover, such animals become resistant to developing symptoms of diabetes or prediabetes when fed a high-fat diet.

The findings suggest that drugs that boost the activity of the M3 receptors on pancreatic beta cells might have therapeutic potential, said Jurgen Wess of the National Institute of Diabetes and Digestive and Kidney Diseases.

"There may be ways to specifically drive up the number of M3 receptors expressed in pancreatic beta cells," Wess said. "It might also be possible to enhance M3 receptor signaling in beta cells by targeting proteins that modulate M3 receptor function in a specific fashion."

Receptors of the same type are also found in other parts of the body, he explained. Therefore, drugs that directly stimulate M3 receptors in general would likely come with problematic side effects--for example, causing smooth muscles to contract.

One of three branches of the involuntary nervous system, the parasympathetic, or "rest and digest" system fulfills many roles--slowing the heart rate, dilating blood vessels, and stimulating digestive secretions.

Food intake is known to trigger an increase in parasympathetic nerve impulses involving signals of different origins that are integrated in the brain, the researchers said. In the pancreas, parasympathetic nerve endings release the messenger acetylcholine before and most likely after food is absorbed.

"However, the importance of parasympathetic innervation of pancreatic beta cells in maintaining normal glucose balance had remained controversial," Wess said. "Much of this controversy has arisen because peripheral parasympathetic nerves release at least five different neurotransmitters, and increased parasympathetic outflow affects the function of many organs and tissues that have important metabolic functions."

The researchers overcame those difficulties in the current study by examining the glucose tolerance and insulin release of otherwise normal mice that were deficient for M3 receptors only in pancreatic beta cells, and in mice that contained an increased number of M3 receptors specifically in beta cells.

"We've established an important role for the native M3 receptor in beta cells in maintaining normal insulin release and blood glucose levels," Wess said. "It's also clear from our findings that the parasympathetic nervous system's modulation of blood sugar is not a transient event--its effects on the pancreas are sustained for a long time after a meal."

Posted by dlife at 01:24 PM | Comments (0)

Gardenia Fruit Compound Starting Point for Diabetes Therapy

June 6, 2006 (Eurekalert) - A Gardenia fruit extract traditionally used in Chinese medicine to treat the symptoms of type 2 diabetes does indeed contain a chemical that reverses some of the pancreatic dysfunctions that underlie the disease, researchers report in the June 7, 2006, Cell Metabolism. The chemical therefore represents a useful starting point for new diabetes therapies, they said.

Such a drug could offer a big advance, the group added, as no currently available therapy for diabetes actually targets the underlying causes of disease in insulin-producing pancreatic beta cells. Insulin controls blood levels of glucose, the body's main energy source. In those with diabetes, insulin deficiency or insulin resistance causes blood sugar concentrations to rise.

The team discovered that Gardenia extract contains the chemical "genipin." Previously known for its ability to cross-link proteins, they now find that the chemical also blocks the function of the enzyme called uncoupling protein 2 (UCP2) through another mechanism. In both animals and humans, high concentrations of UCP2 appear to inhibit insulin secretion from the pancreas and increase the risk of type 2 diabetes.

"We think the increase in UCP2 activity is an important component of the pathogenesis of diabetes," said Bradford Lowell of Beth Israel Deaconess Medical Center and Harvard Medical School. "Our goal therefore was to discover a UCP2 inhibitor capable of working in intact cells, as such an inhibitor could theoretically represent a lead compound for agents aimed at improving beta cell function in type 2 diabetes."

Study coauthor Chen-Yu Zhang's familiarity with traditional Chinese medicine led the team to consider the extract of Gardenia jasminoides Ellis fruits. Pancreas cells taken from normal mice secreted insulin when treated with the extract, they found, whereas the cells of mice lacking UCP2 did not. The results suggested that the extract worked through its effects on the UCP2 enzyme.

"When I first saw the results, I was in disbelief," Lowell said. "I didn't think we could ever be that lucky." However, blinded repetition of the initial experiments confirmed the results every time, he said.

Through a series of chemical analyses, the researchers then zeroed in on genipin as the active compound. Genipin, like the extract, stimulated insulin secretion in control but not UCP2-deficient pancreas cells.

They further found that acute addition of genipin to isolated pancreatic tissue reversed high glucose- and obesity-induced dysfunction of insulin-producing beta cells. A derivative of genipin that lacked the chemical's cross-linking activity continued to inhibit UCP2, they reported.

That's a good sign for the therapeutic potential of genipin-related compounds, according to Lowell, as such indiscriminate cross-linking would likely have adverse effects. However, further work will need to examine whether inhibition of UCP2 itself might also have some negative consequences.

In addition to the possibility of new drugs, the findings might also prove a boon to the use of Gardenia extract itself for the treatment of disease, particularly in eastern Asia, Zhang said.

Irrespective of genipin's potential for clinical applications, its benefits within the scientific community are already clear, Lowell added.

"Genipin represents an extremely useful investigational tool for studying a number of aspects of UCP2 biology," Lowell added. UCP2 plays a role in the process by which food is converted into energy storage molecules by cellular powerhouses called mitochondria in cells throughout the body.

Posted by dlife at 01:21 PM | Comments (0)