For High Blood Pressure Patients, Preventing or Reducing Enlarged Heart May Decrease Risk for Diabetes

October 31, 2007 (Newswise) — High-blood-pressure patients treated for enlarged heart (left ventricular hypertrophy, LVH) who have regression or prevention of LVH may also have a better chance of preventing diabetes. Led by physician-scientists at NewYork-Presbyterian Hospital/Weill Cornell Medical Center, the research is published in the November Hypertension, a journal of the American Heart Association (AHA).

An estimated 20 percent of all high-blood-pressure patients, or 12 million Americans, have LVH and are at increased risk of developing diabetes.

The study reports a 38-percent reduced risk of developing diabetes for high-blood-pressure patients who demonstrated regression of LVH during treatment for high blood pressure, with a 26-percent reduced risk after adjusting for other risk factors for diabetes. The reduction in risk of diabetes was independent of treatment type and of the degree of blood pressure change in this population.

"A healthy heart is a prerequisite for the health of the body as a whole. Our previous research has shown that treating enlarged heart in high-blood-pressure patients reduces the risk for a variety of cardiovascular conditions. This new study finds an important new benefit -- namely a better chance of avoiding diabetes among patients who exhibit a reduction of their hypertrophy during treatment," says the study's principal investigator, Dr. Peter Okin, director of clinical affairs and professor of medicine in the Greenberg Division of Cardiology at Weill Cornell Medical College and attending physician at NewYork-Presbyterian/Weill Cornell.

An editorial about the study in the journal notes that "the study by Okin et al extends our knowledge and understanding of the importance of LVH reversal by showing the beneficial metabolic effects of treatment-induced regression of LVH in a large series of patients with hypertensive heart disease."

Unfortunately, for high-blood-pressure patients who already have diabetes, high blood pressure treatment is less effective at reducing their LVH compared to patients without diabetes. In addition, regression of LVH in hypertensive patients with diabetes does not appear to be associated with a reduction in cardiovascular events, according to a 2006 study by Dr. Okin and colleagues, making prevention of diabetes in patients with hypertension an important goal.

The study used data from the Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) study conducted between 1995 and 2001. In the blinded study, patients received daily 50 mg doses of either losartan or atenolol.

Co-authors of the current study included Drs. Richard B. Devereux of NewYork-Presbyterian/Weill Cornell and Weill Cornell Medical College, and physician-scientists from Merck Research Laboratories (Upper Gwynedd, Pa.), Sahlgrenska University Hospital/Östra (Sweden), Ullevål University Hospital (Norway) and Umeå University (Sweden).

The study was supported in part by a grant from Merck & Co. Inc., West Point, Pa.

Posted by dlifenews at 11:05 AM | Comments (0)

National Diabetes Month, 2007

A Proclamation By the President of the United States of America

October 31, 2007 (The White House) - Diabetes is a debilitating disease that affects millions of Americans of all ages and all walks of life. National Diabetes Month is an opportunity to raise awareness about risk factors, prevention, and treatment of this serious disease.

Diabetes is a chronic illness that leaves the body unable to produce or properly use insulin to maintain healthy blood glucose levels. The two most common forms of the disease that affect our citizens are Type 1 and Type 2 diabetes. Type 1 diabetes, once known as juvenile diabetes, is usually diagnosed in children and young adults who are unable to produce insulin and require daily medication. Type 2 diabetes, the most common form of the disease, is often attributed to lifestyle risk factors and can be controlled by a modified diet, regular physical activity, and medication. Americans can take steps to control the disease and lower the risk of complications such as heart disease, stroke, and kidney disease by maintaining healthy eating and exercise habits, and consulting with a doctor about diabetes testing.

My Administration is committed to providing better care for people living with diabetes and furthering efforts to find a cure. We have supported research initiatives and education programs that encourage healthy living, and we have also modified Medicare coverage to include diabetes screenings. This year, the National Institutes of Health estimates that more than $1 billion will be spent on diabetes research. By working together, we can help identify problems early, manage them before they grow worse, and help ensure more Americans live longer, healthier lives.

Throughout National Diabetes Month, we recognize the medical professionals, scientists, researchers, and all those whose efforts have made a positive difference in the fight against diabetes. By raising public awareness, we can help combat the effects of diabetes in our society and bring hope to children and families living with this disease.

NOW, THEREFORE, I, GEORGE W. BUSH, President of the United States of America, by virtue of the authority vested in me by the Constitution and laws of the United States, do hereby proclaim November 2007 as National Diabetes Month. I call upon all Americans to learn more about the risk factors and symptoms associated with diabetes and to observe this month with appropriate programs and activities.

IN WITNESS WHEREOF, I have hereunto set my hand this thirty-first day of October, in the year of our Lord two thousand seven, and of the Independence of the United States of America the two hundred and thirty-second.

GEORGE W. BUSH

Posted by dlifenews at 11:01 AM | Comments (0)

Preventing or Reducing Enlarged Heart May Decrease Risk for Diabetes

October 31, 2007 (EurekAlert) - High-blood-pressure patients treated for enlarged heart (left ventricular hypertrophy, LVH) who have regression or prevention of LVH may also have a better chance of preventing diabetes. Led by physician-scientists at NewYork-Presbyterian Hospital/Weill Cornell Medical Center, the research is published in the November Hypertension, a journal of the American Heart Association (AHA).

An estimated 20 percent of all high-blood-pressure patients, or 12 million Americans, have LVH and are at increased risk of developing diabetes.

The study reports a 38-percent reduced risk of developing diabetes for high-blood-pressure patients who demonstrated regression of LVH during treatment for high blood pressure, with a 26-percent reduced risk after adjusting for other risk factors for diabetes. The reduction in risk of diabetes was independent of treatment type and of the degree of blood pressure change in this population.

"A healthy heart is a prerequisite for the health of the body as a whole. Our previous research has shown that treating enlarged heart in high-blood-pressure patients reduces the risk for a variety of cardiovascular conditions. This new study finds an important new benefit -- namely a better chance of avoiding diabetes among patients who exhibit a reduction of their hypertrophy during treatment," says the study's principal investigator, Dr. Peter Okin, director of clinical affairs and professor of medicine in the Greenberg Division of Cardiology at Weill Cornell Medical College and attending physician at NewYork-Presbyterian/Weill Cornell.

An editorial about the study in the journal notes that "the study by Okin et al extends our knowledge and understanding of the importance of LVH reversal by showing the beneficial metabolic effects of treatment-induced regression of LVH in a large series of patients with hypertensive heart disease."

Unfortunately, for high-blood-pressure patients who already have diabetes, high blood pressure treatment is less effective at reducing their LVH compared to patients without diabetes. In addition, regression of LVH in hypertensive patients with diabetes does not appear to be associated with a reduction in cardiovascular events, according to a 2006 study by Dr. Okin and colleagues, making prevention of diabetes in patients with hypertension an important goal.

Posted by dlifenews at 10:31 AM | Comments (0)

Obese Children Show Early Signs of Heart Disease

October 30, 2007 (EurekAlert) - Children who are obese or who are at risk for obesity show early signs of heart disease similar to obese adults with heart disease, a study by researchers at Washington University School of Medicine in St. Louis has found.

“Based on this study, these subtle markers can help us predict who could be at risk for heart disease and heart attacks,” said Angela Sharkey, M.D., associate professor of pediatrics at Washington University School of Medicine and a pediatric cardiologist at St. Louis Children’s Hospital.

The study was published in the Winter 2007 issue of the Journal of Cardiometabolic Syndrome.

Childhood obesity in the United States is an epidemic -- nationwide, 19 percent of children ages 6 to 11 and 17 percent of those 12 to 19 are overweight, according to the Centers for Disease Control and Prevention (CDC). Those who are overweight during childhood also have an increased risk of obesity in adulthood and are at greater risk for complications such as diabetes, high blood pressure and heart disease, because obesity increases total blood volume, which leads to extra stress on the heart.

Sharkey and Steven M. Lorch, M.D., a former fellow at the School of Medicine now at University of Texas Health Science Center at Houston, analyzed data from 168 children ages 10 to 18 who had been referred to them for cardiac ultrasound with symptoms including heart murmur, chest pain, acid reflux or high blood cholesterol. Based on CDC guidelines for body mass index for age (BMIA), 33 patients were found to have a BMIA as obese, or the 95th percentile or above for their age; 20 had a BMIA that classified them as at risk for obesity, or between the 85th and 94th percentile; and 115 were considered normal, or below the 85th percentile.

To analyze the hearts of the obese children and those at risk, Sharkey and Lorch used a new tissue Doppler imaging technique called vector velocity imaging which tracks the movement of the heart’s muscular wall. Any changes in the rate of motion of heart muscle were averaged within each group and compared to the normal rate of motion.

“In the patients who are obese, the rate of motion of heart muscle changed,” Sharkey said. “As a child’s BMIA increases, we see alterations in both the relaxation and contraction phase of the heartbeat. Many of these changes that have been seen in adults were assumed to be from long-standing obesity, but it may be that these changes start much earlier in life than we thought.”

As vector velocity imaging becomes more broadly available, Sharkey said, it could potentially help pediatric cardiologists follow these children more closely over time to see if changes in the heart progress.

“We may be able to determine whether we could intervene in the process, such as focusing the families on understanding the importance of regular exercise and dietary modifications for weight loss and prescribing statin drugs for high-blood cholesterol,” she said.

Sharkey said the results of the study give more ammunition to physicians to use in counseling pediatric patients and their parents about the risks of obesity and the need to attain a healthy weight.
“Even in teenagers, obesity leads to decreased myocardial performance and abnormal diastolic function,” she said.

Further study is needed to determine how soon the changes in the heart set in after a child becomes obese and whether those changes are reversible with weight loss.

Posted by dlifenews at 10:20 AM | Comments (0)

Rare Diabetes Foot Complication Becoming More Common

October 25, 2007 (Newswise) — At first, Kim Schraeder didn’t worry about the swelling in her left foot.

After all, it was pulling double-duty while her other foot recovered from surgery.

“I have a high threshold for pain,” she says. “It hurt to walk on it, but I didn’t think it was serious.”

Just a year earlier, doctors diagnosed the 48-year-old mother of four with diabetes. The recent surgery on her right foot corrected a bunion to prevent reoccurring diabetic ulcers. As Schraeder’s bunion
recovery moved forward, her left foot moved outwards. Her ankle bent inwards. The foot grew so swollen none of her shoes fit. The skin was warm and red. Schraeder started to worry.

During a follow-up visit with her foot and ankle surgeon, she spoke up. Her doctor took one look and said, “We have a problem.”

Schraeder was diagnosed with a rare diabetic complication called Charcot foot. It is estimated to affect less than one percent of people with diabetes. Now doctors with the American College of Foot and Ankle Surgeons (ACFAS) say Charcot foot’s prevalence appears to be growing as more Americans get diabetes.
Some worry that few patients – or their diabetes care providers – seem to know about this complication or its warning signs.

Charcot foot is a sudden softening of the foot’s bones caused by severe neuropathy, or nerve damage, a common diabetic foot complication. It can trigger an avalanche of problems, including joint loss, fractures, collapse of the arch, massive deformity, ulcers, amputation, and even death. As the disorder progresses, the bottom of the foot can become convex, bulging like the hull of a ship. Since most people with Charcot cannot feel pain in their lower extremities, they continue walking on the foot, causing further injury.

Charcot cannot be reversed, but its destructive effects can be stopped if the complication is detected early.

The symptoms of Charcot foot appear suddenly. They include warm and red skin, swelling and pain. A person with diabetes who has a red, hot, swollen foot or ankle requires emergency medical care because these can also be symptoms of deep vein thrombosis or an infection.

Doctors say Charcot’s ambiguous symptoms can lead to misdiagnosis. Since patients don’t feel pain, doctors may presume the swelling is due to infection and prescribe antibiotics. Meanwhile the patient continues walking on a foot that is collapsing.

“More people with diabetes, their families and their care providers need to know about Charcot foot,” says J. T. Marcoux. DPM, FACFAS, one of only a handful of Massachusetts foot and ankle surgeons who performs Charcot foot reconstructions. “When I diagnose a patient with this complication, I telephone their primary care doctor and educate them about it as well.”

Schraeder says no one told her about Charcot. “It was not even in my vocabulary,” she says. “If someone had educated me, I think I would have been more aware that I had a major problem.”

But educating patients and their care providers is only half the battle. Keith Jacobson, DPM, FACFAS is the Houston foot and ankle surgeon who diagnosed and reconstructed Schraeder’s Charcot foot. He and Marcoux say there’s little they can do when patients are apathetic or in “diabetic denial.”

“I’ve had patients who are literally blind, on dialysis and neuropathic who refuse to admit they have diabetes,” says Jacobson. “I have seen horrific deformities with this condition.”

Marcoux tells of a middle-aged woman he diagnosed with Charcot. Typically the first order of business is to immobilize the foot by putting the patient in a boot or cast, and to keep the patient off the foot by using crutches or a wheelchair. Marcoux says his patient was “in massive denial” about her Charcot diagnosis.

“I tried to get her off the foot, but she wouldn’t do it” he says, “Six months later she came in with a bone infection and a gaping hole in her foot.”

Foot and ankle surgeons expect to see more patients like that as diabetes rates soar.

Today, Schraeder is back to walking on both feet. Three months after her Charcot diagnosis, she underwent reconstructive surgery. Her recovery included spending three months in a “halo” external fixator where a series of pins and screws are placed into the bones and connected to clamps and rods outside the skin. She then wore a custom shoe boot for nearly a year.

The experience taught her four children to appreciate their mother a lot more, since all the cooking, cleaning, and laundry fell on their shoulders.

“They’re all like hawks now,” she says. “If I’m sitting here with bare feet, they’ll look to make sure they’re not red, hot and swollen.”

Posted by dlifenews at 11:08 AM | Comments (1)

Smoked Cannabis Proven Effective in Treating Neuropathic Pain

October 24, 2007 (EurekAlert) - Smoked cannabis eased pain induced in healthy volunteers, according to a study by researchers at the University of California, San Diego (UCSD) Center for Medical Cannabis Research (CMCR.) However, the researchers found that less may be more.

In the placebo controlled study of 15 subjects, a low dose of cannabis showed no effect, a medium dose provided moderate pain relief, and a high dose increased the pain response. The results suggest a "therapeutic window" for cannabis analgesia, according to lead researcher Mark Wallace, M.D., professor of anesthesiology at UCSD School of Medicine and Program Director for the UCSD Center for Pain Medicine.

The paper, to be published in the November issue of the journal Anesthesiology, is the second published study out of the CMCR. Headquartered at UCSD, the CMCR is collaboration between UCSD and UC San Francisco that was funded by a state-funded initiative in 1999 to rigorously study the safety and efficacy of medicinal cannabis in treating diseases.

The study used capsaicin, an alkaloid derived from hot chili peppers that is an irritant to the skin, to mimic the type of neuropathic pain experienced by patients with HIV/AIDS, diabetes or shingles – brief, intense pain following by a longer-lasting secondary pain. The subjects were healthy volunteers who inhaled either medical cannabis or a placebo after pain was induced. The marijuana cigarettes were formulated under NIH supervision to contain either zero, two, four or eight percent delta-9-tetrahydrocannabinol (THC.)

“Subjects reported a decrease in pain at the medium dose, and there was also a significant correlation between plasma levels of THC, the active ingredient in cannabis, and decreased pain,” said Igor Grant, M.D., F.R.C.P.(C), professor and Executive Vice-Chair of the Department of Psychiatry, the director of the CMCR. “Interestingly, the analgesic effect wasn’t immediate; it took about 45 minutes for the cannabis to have an impact on the pain,” he said.

The results, showing a medium-dose (4% THC by weight) of cannabis to be an effective analgesic, converged with results from the CMCR’s first published study, a paper by UCSF researcher Donald Abrams, M.D. published in the journal Neurology in February 2007. In that randomized placebo-controlled trial, patients smoking the same dose of cannabis experienced a 34% reduction in HIV-associated sensory neuropathy pain—twice the rate experienced by patients receiving a placebo.

“This study helps to build a case that cannabis does have therapeutic value at a medium-dose level,” said Grant. “It also suggests that higher doses aren’t necessarily better in certain situations – something also observed with other medications, such as antidepressants.”

The researchers stated that more and larger studies need to be conducted to measure the efficacy of cannabis, noting that medical marijuana could play an important role in treating patients who don’t respond well to the usual pain relievers or can’t tolerate drugs such as ibuprofen or opioids used for severe pain.

“The results of this study might help guide others doing clinical research into pain management,” said Wallace.

Posted by dlifenews at 02:54 PM | Comments (0)

Exercise Improves Thinking, Reduces Diabetes Risk in Overweight Children

October 23, 2007 (EurekAlert) - Just three months of daily, vigorous physical activity in overweight children improves their thinking and reduces their diabetes risk, researchers say.

Studies of about 200 overweight, inactive children ages 7-11 also showed that a regular exercise program reduces body fat and improves bone density.

“Is exercise a magic wand that turns them into lean, healthy kids? No. They are still overweight but less so, with less fat, a healthier metabolism and an improved ability to handle life,” says Dr. Catherine Davis, clinical health psychologist at the Medical College of Georgia and lead investigator.

All study participants learned about healthy nutrition and the benefits of physical activity; one-third also exercised 20 minutes after school and another third exercised for 40 minutes. Children played hard, with running games, hula hoops and jump ropes, raising their heart rates to 79 percent of maximum, which is considered vigorous.

“Aerobic exercise training showed dose-response benefits on executive function (decision-making) and possibly math achievement, in overweight children,” researchers write in an abstract being presented during The Obesity Society’s Annual Scientific Meeting Oct. 20-24 in New Orleans. “Regular exercise may be a simple, important method of enhancing children’s cognitive and academic development. These results may persuade educators to implement vigorous physical activity curricula during a childhood obesity epidemic.”

Functional magnetic resonance imaging studies, which show the brain at work, were performed on a percentage of children in each group and found those who exercised had different patterns of brain activity during an executive function task.

“Look what good it does when they exercise,” says Dr. Davis. “This is an important public health issue we need to look at as a nation to help our children learn and keep them well.”

Unprecedented obesity and inactivity rates in America’s children are impacting health, including dramatic increases in the incidence of type 2 diabetes, a disease formerly known as adult-onset diabetes.

Overweight children also have slightly lower school achievement, on average.

“We hope these findings will help persuade policymakers, schools and communities that time spent being physically active enhances, rather than detracts, from learning,” says Dr. Davis.

“There have been several studies that have shown that exercise produces kind of a selective effect, particularly with older adults, in cognitive tasks that require regulation of behaviors,” says Dr. Phillip D. Tomporowski, experimental psychologist at the University of Georgia and a key collaborator.

For this study, researchers gave the children tests that look at their decision-making processes. In the first such studies in children, the researchers found small to moderate improvements in children who exercised as well as a hint of increased math achievement.

“We have a number of studies conducted with animals that examined what influence physical activity has on blood flow, metabolic activity, brain function, glucose regulation, and they all demonstrate the same theme: that physical activity done on a regular basis has a protective effect,” says Dr. Tomporowski. “It doesn’t take too much to make the leap that it might influence developing children as well.”

Looking at the children’s insulin resistance, a precursor of type 2 diabetes in which it takes more insulin to convert glucose into energy, researchers found levels dropped 15 percent in the 20-minute exercise group and 21 percent in the 40-minute group. The control group stayed about the same.

“Increasing volume of regular aerobic exercise shows increased benefits on insulin resistance in overweight children, indicating reduced risk of type 2 diabetes, regardless of sex or race,” they write.
“We also know that if you stop exercising, you lose all the benefits,” adds Dr. Davis. “Exercise works if you do it.”

Adult studies have yielded comparable findings regarding exercise’s impact on insulin resistance and cognition.

The researchers tested oral glucose tolerance, measuring insulin response after children drank a small amount of glucose, before and after the studies. “Once your glucose levels start to rise, it’s called impaired glucose tolerance and that is a precursor of diabetes. It’s called pre-diabetes now,” says Dr. Davis, noting that overweight children typically have higher insulin resistance than their leaner peers. Insulin resistance is an early sign of diabetes risk that appears before glucose levels start to rise. Growth associated with puberty can temporarily increase insulin resistance, Dr. Davis notes, so because some of the children were beginning puberty, they made adjustments for the level of sex hormones.

DEXA scanning, which uses a small amount of radiation to quantify bone, tissue and fat, was used to accurately assess body composition. Executive function was measured using the Cognitive Assessment System and math skills using the Woodcock Johnson Test of Achievement III.

“If physical education were ideal, which it’s not – it’s not daily and it’s not active – then children could achieve this within the school day,” Dr. Davis says, pointing to benefits derived by children exercising just 20 minutes a day. “We are not there. To achieve maximum benefit, we were able to show it will take more than PE.”

Posted by dlifenews at 03:54 PM | Comments (0)

Chewing Gum May Help Reduce Cravings and Control Appetite

New research shows chewing gum may help reduce cravings and control appetite

October 23, 2007 (EurekAlert) –

WHAT: A research study to be presented at the 2007 Annual Scientific Meeting of The Obesity Society, found that chewing gum before an afternoon snack helped reduce hunger, diminish cravings and promote fullness among individuals who limit their overall calorie intake. Calorie intake from snacks was significantly reduced by 25 calories. Overall, this study demonstrates the benefits of chewing gum and highlights the potential role of chewing gum in appetite control and weight management. Nutritionists say that even small changes in calories can have an impact in the long term. This research study supports the role of chewing gum as an easy, practical tool for weight management.

WHO: Marion Hetherington, D.Phil., Professor of Biopsychology, Glasgow Caledonian University in Glasgow, Scotland led the research study and can discuss the potential role of chewing gum on appetite control.

Gilbert Leveille, Ph.D., Executive Director, Wrigley Science Institute, will also be available to discuss study findings and research on the benefits of chewing gum related to weight management and other areas including oral health, stress relief, and focus, alertness and concentration.

WHEN: Study to be presented as a poster on Monday, October 22, 5:30 p.m. CST; Hall G – Level 1, Ernest N. Morial Convention Center, New Orleans, La.

STUDY BACKGROUND: In the 60-person study, participants aged 18 to 54 were asked to consume a sweet and salty afternoon snack after chewing a sweetened gum or not chewing gum. Hunger, appetite and cravings were rated immediately after lunch, and then hourly.

• Chewing gum significantly reduced caloric intake by 25 calories and specifically reduced sweet snack intake by 39 calories; salty snacks were decreased by 11 calories.

• Hunger and desire to eat were significantly suppressed by chewing gum at one, two and three hour intervals after lunch.

• Participants reported that chewing gum improved their mood by reducing anxiety and stress, and increasing contentment and relaxation.

• In a similar study among individuals not actively trying to manage their weight, chewing gum reduced snack intake by average of 36 calories.

• Data combined from both studies found that chewing gum reduced intake of the sweet snack in particular by an average of 47 calories.

WRIGLEY SCIENCE INSTITUTE AWARDS:

As part of its commitment to advancing and sharing scientific research that explores the benefits of chewing gum, this year, the Wrigley Science Institute (WSI) will award its first two $25,000 grants to further examine the impact of chewing gum on food intake, regulation of appetite and diet, weight loss and/or prevention of weight gain.

The WSI will also award two grants through The Obesity Society in 2008 and will announce an official call for proposals early next year.

Posted by dlifenews at 03:48 PM | Comments (0)

Study Explains How Exercise Lowers Cardiovascular Risk

October 23, 2007 (EurekAlert) - It is well known that physical activity can improve cardiovascular health. But it's the impact exercise has on specific known risk factors that accounts for about 60 percent of that improvement, researchers reported in Circulation: Journal of the American Heart Association.

In a major study of over 27,000 women in the Women's Health Study, researchers assessed a variety of risk factors and different levels of exercise in women who were followed for 11 years for new diagnosis of heart attack and stroke.

"Regular physical activity is enormously beneficial in preventing heart attack and stroke," said Samia Mora, M.D., lead author of the study and instructor of medicine at Harvard Medical School in the divisions of preventive and cardiovascular medicine at Brigham and Women's Hospital, Boston Mass. "We found that even modest changes in risk factors for heart disease and stroke, especially those related to inflammation/hemostasis and blood pressure, can have a profound impact on preventing clinical events.

This study is the first to examine the importance of a variety of known risk factors in explaining how physical activity prevents heart disease and stroke."

The women ranged from 45 to 90 years old (average age 55) and were assessed for a full range of risk factors and different levels of exercise. There was a 40 percent reduction in heart attack and stroke between the highest and lowest exercise groups. The women self-reported physical activity, weight, height, hypertension and diabetes.

The long-term benefits of exercise start at a relatively low level, 600 kilocalories per week, equivalent to about two hours of physical activity per week, Mora said.

The study measured levels of a variety of traditional and novel risk factors to help understand the mechanisms that reduce risk for heart attack and stroke. Novel risk factors are emerging clinical, biochemical, and genetic markers that researchers have studied in order to better understand the development of a disease, to improve disease risk prediction, and to identify new targets for treatment.
Inflammatory and hemostatic biomarkers -- fibrinogen, C-reactive protein and intracellular adhesion molecule-1 -- together made the largest contribution to lower risk, 33 percent.

Blood pressure was the next major contributor to lower risk, 27 percent, followed by lipids, body mass index, glucose abnormalities, with minimal contribution from measures of renal function or homocysteine.

Inflammatory and hemostatic biomarkers are novel risk factors that relate to blood vessel function and inflammation of the arteries.

"Inflammatory and hemostatic factors as a group have overlapping functions and roles and, in our study, had the biggest effect in mediating exercise-related cardioprotection, more so than blood pressure or body weight," Mora said. The study population was divided into four groups by levels of exercise:

• The highest level expended greater than or equal to 1,500 kilocalories per week (kcal/week) representing greater than five hours of moderately intense physical activity (such as brisk walking) per week.

• The next group expended from 600 to 1,499 kcal/week which reflected about two to five hours of physical activity per week.

• A third group represented an expenditure of 200 to 599 kcal/week, which is about one to two hours of physical activity per week.

• The reference group had less than 200 kcal per week (less than one hr per week).

The risk of cardiovascular disease events decreased with higher levels of physical activity. Compared to the reference group, relative risk reductions were associated with ¡Ý1,500, 600 to 1,499, 200 to 599 kcal/wk of 41 percent, 32 percent and 27 percent, respectively.

Posted by dlifenews at 03:43 PM | Comments (0)

FDA Issues Exanatide (Byetta) Safety Alert

October 19, 2007 (FDA) - FDA has reviewed 30 postmarketing reports of acute pancreatitis in patients taking Byetta, a drug used to treat adults with type 2 diabetes. An association between Byetta and acute pancreatitis is suspected in some of these cases.

Healthcare professionals should instruct patients taking Byetta to seek prompt medical care if they experience unexplained persistent severe abdominal pain which may or may not be accompanied by vomiting. If pancreatitis is suspected, Byetta should be discontinued. If pancreatitis is confirmed, Byetta should not be restarted unless an alternative etiology is identified.

FDA has asked and the maker of Byetta, Amylin Pharmaceuticals, Inc. has agreed to include information about acute pancreatitis in the PRECAUTIONS section of the product label.

This information reflects FDA’s current analysis of data available to FDA concerning this drug. FDA is not advising practitioners to discontinue prescribing the product. FDA intends to update this sheet when additional information or analyses become available.

Posted by dlifenews at 01:56 PM | Comments (0)

Cross-Species Transplant in Rhesus Macaques is Step Toward Diabetes Cure for Humans

Oct. 18, 2007 (Eurekalert) — With an eye on curing diabetes, scientists at Washington University School of Medicine in St. Louis have successfully transplanted embryonic pig pancreatic cells destined to produce insulin into diabetic macaque monkeys – all without the need for risky immune suppression drugs that prevent rejection.

The transplanted cells, known as primordia, are in the earliest stages of developing into pancreatic tissues. Within several weeks of the transplants, the cells became engrafted, or established, within the three rhesus macaque monkeys that received them. The cells also released pig insulin in response to rising blood glucose levels, as would be expected in healthy animals and humans.

"The approach reduced the animals' need for insulin injections and has promise for curing diabetes in humans," says senior investigator Marc Hammerman, M.D., the Chromalloy Professor of Renal Diseases in Medicine. "The transplants worked without a need for immune suppression and that is a major obstacle we have overcome."

The researchers' results appear online and will be published in the journal Xenotransplantation in November.

Although the transplants fell short of producing sufficient insulin to cure the macaques' diabetes, Hammerman predicts that with additional research, including the transplantation of additional embryonic pig cells into the animals, he will be able to reduce their need for insulin injections entirely.

The new research follows on the heels of reports by Hammerman and his colleagues demonstrating that transplanted pig pancreatic primordia can cure both type 1 and type 2 diabetes in rats, without using immune suppression drugs. Other scientists have tried different types of pancreatic cell transplants – in animals and humans – as a stepping stone to curing diabetes, but they all require anti-rejection drugs. These drugs must be taken daily to stave off rejection and have adverse effects of their own that limit the success of the transplants.

As a treatment for diabetes in people, pig insulin typically works as well as the human form. Before recombinant DNA technology enabled pharmaceutical companies to manufacture human insulin in the 1980s, pig and cow insulin were routinely given to diabetic patients.

The primates in the current study had type 1 diabetes, the form that occurs when islet cells in the pancreas stop producing insulin all together. The Washington University researchers transplanted 19 embryonic pig pancreatic primordia into each diabetic monkey. Each primordium is smaller than the diameter of a period that ends a sentence and is transplanted into a membrane that envelops the intestines and other digestive organs.

The transplanted cells were retrieved from the pig embryos early in their development, which is believed to render them "invisible" to the primates' immune system or induce a state of tolerance, either of which eliminates the need for immune suppression.

The researchers determined by multiple methods that the transplanted cells became established within the primates. And as the cells matured, they began to release pig insulin. "We found using every method that the cells engraft long-term and, thus, are not rejected by the animals' immune systems," Hammerman says. "It's been more than two years since our first transplant was carried out. That particular primate doesn't produce any primate insulin, but has pig insulin circulating in its bloodstream that has reduced by more than 50 percent the amount of injected insulin the animal needs, compared to levels before the transplant. The animals have never received immune suppression drugs."

Two of the macaques remain healthy. One, however, became anemic about six weeks post-transplant and was euthanized a month later after developing acute respiratory distress. The researchers could not find a link between this animal's illness and the pancreatic cell transplants.

The two remaining macaques have each received two transplants of embryonic pancreatic cells. One of the animals has been followed for 23 months after his first transplant, and the amount of insulin he needs to have injected has declined by some 55 percent over baseline levels. The other macaque has been followed for 10 months after his initial transplant, and his need for injected insulin continues to decline over time.

Hammerman and his colleague Sharon Rogers, research instructor in medicine, are leaders in the emerging field of organogenesis, which focuses on growing organs from transplanted embryonic organ precursors known as primordia. Unlike embryonic stem cells, which can become virtually any cell type, primordia are locked into becoming cells of a particular organ.

"We are encouraged by these results," Rogers says. "The absence of a need for immune suppression in diabetic rats gave us hope that we were on the right track. But many findings in rats do not hold true for species that are more closely related to humans, such as non-human primates. This one did."

The team will now determine how best to eliminate the need for injected insulin in the diabetic macaques that receive transplants, thus demonstrating long-term effectiveness of the technique, and establish the absolute safety of pancreatic primordia transplants. If these experiments succeed, the researchers plan to conduct clinical trials in humans with diabetes.

"We hope to find out how to apply our findings to human type 1 and type 2 diabetics because the embryonic pig primordia would represent an unlimited source of tissue for transplantation," Hammerman says.

Posted by dlifenews at 04:42 PM | Comments (0)

Pfizer Reports Third-Quarter 2007 Results: Announces Company Will Exit Exubera Inhaled Insulin Business

October 18, 2007 (BUSINESS WIRE) -- Pfizer: Pfizer Inc posted third-quarter 2007 revenues of $12.0 billion, a 2% decline from the same period last year. The Company’s reported net income was $761 million in the third quarter of 2007, a decrease of 77% from the same period last year, primarily reflecting pre-tax charges of $2.8 billion related to the decision to exit Exubera, our inhaled insulin product to treat diabetes. Adjusted income(1) for the third quarter of 2007 increased 1% to $4.0 billion compared to the third quarter of 2006.

“We are encouraged by our operating results in the third quarter, and we remain on track to achieve our full-year 2007 revenues and adjusted diluted EPS(1) goals. Meanwhile, we made an important decision regarding Exubera, a product for which we initially had high expectations,” said Jeff Kindler, Chairman and Chief Executive Officer. “Despite our best efforts, Exubera has failed to gain the acceptance of patients and physicians. We have therefore concluded that further investment in this product is unwarranted.”

“We will work with physicians to transition Exubera patients to other treatment options in the next three months. We remain committed to investing significant resources in the development of new and innovative medicines to manage diabetes, including monitoring inhalation technologies and other innovative delivery systems for insulin and other medicines.”

Frank D’Amelio, Chief Financial Officer, added, “The Exubera pre-tax charges of $2.8 billion related primarily to the write-off of assets associated with this product, as well as the accrual of other exit costs. More specifically, these charges are comprised of approximately $1.1 billion of intangible assets, $661 million of inventory, $454 million of fixed assets and $584 million of other exit costs.”

Commenting on the financial performance in the just-ended quarter, Mr. Kindler said, “We are achieving our operational goals in the face of major revenue losses due to patent expirations in the U.S. Most of our new products(3) along with the favorable impact of foreign exchange are contributing significantly toward offsetting these losses as evidenced by our year-to-date results.”

Mr. Kindler continued, “While optimizing revenues from our in-line products(2) and generating strong growth from our new products(3), we remain focused on driving a series of fundamental changes in the Company to improve our performance and achieve a lower, more flexible cost base. We are making substantial progress on these priorities. For example, our reduction in adjusted selling, informational and administrative expenses(1) this year is expected to exceed our previous forecast on a constant currency basis(8).”

“However, we need to deliver better results, continue to make tough decisions about allocating our capital wisely, and bring more new products to the market as quickly as possible. Doing all of this will put Pfizer on the right course and build value for our shareholders.”

Read the rest of the Pfizer Third Quarter Earnings Release Here

Posted by dlifenews at 12:17 PM | Comments (0)

FDA Approves Supplemental New Drug Applications for JANUVIA™ (sitagliptin)

Oct. 17, 2007 (Merck) – Merck & Co. Inc. today announced that the U.S. Food and Drug Administration (FDA) has approved expanded labeling for JANUVIA™ (sitagliptin), the only DPP-4 inhibitor available in the United States for the treatment of type 2 diabetes. JANUVIA is indicated, as an adjunct to diet and exercise, to improve glycemic control in adult patients with type 2 diabetes. JANUVIA should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis. JANUVIA has not been studied in combination with insulin. The new regimens with JANUVIA described in the updated labeling include, as an adjunct to diet and exercise, initial therapy in combination with metformin; add-on therapy to a sulfonylurea (glimepiride) when the single agent alone does not provide adequate glycemic control; and, add-on therapy to the combination of a sulfonylurea (glimepiride) and metformin when dual therapy does not provide adequate glycemic control.

New data contained in three studies support the efficacy and safety of JANUVIA. Initial therapy with the combination of JANUVIA and metformin provided substantial A1C reductions. JANUVIA demonstrated similar efficacy to a sulfonylurea (glipizide) in patients inadequately controlled on metformin. JANUVIA also provided significant placebo-adjusted A1C reductions in patients being treated with a sulfonylurea (glimepiride), with or without metformin.

The expanded labeling for JANUVIA was also updated, within Warnings and Precautions, to include post-marketing reports of hypersensitivity reactions in patients treated with JANUVIA. These reactions include anaphylaxis, angioedema and exfoliative skin conditions including Stevens-Johnson syndrome. Because these reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The expanded labeling also includes a contraindication for patients with history of a serious hypersensitivityreaction to sitagliptin, including anaphylaxis and angioedema.

Since its initial approval in October 2006, over two million prescriptions have been written for JANUVIA. In controlled clinical studies as both monotherapy and combination therapy with metformin or pioglitazone, the overall incidence of adverse reactions, hypoglycemia, and discontinuation of therapy due to clinical adverse reactions with JANUVIA were similar to placebo. In these clinical studies, the most common adverse reactions reported with JANUVIA (greater than or equal to 5 percent and higher than placebo) were stuffy or runny nose and sore throat, upper respiratory infection and headache. In clinical trials in combination with a sulfonylurea (glimepiride), with or without metformin, JANUVIA demonstrated an overall incidence of adverse reactions higher than that seen with placebo, in part related to a higher
incidence of hypoglycemia.

Initial therapy with the combination of JANUVIA and metformin provides significantly greater A1C reductions with a similar GI tolerability profile compared to metformin alone

JANUVIA as initial therapy in combination with metformin is supported by a randomized, double-blind, placebo-controlled factorial study in 1,091 patients with type 2 diabetes who experienced inadequate glycemic control with diet and exercise alone. In this study, the mean reduction of A1C relative to placebo at 24 weeks was 2.1 percent with initial therapy combining JANUVIA 100 mg daily and metformin 2000 mg dailyi (n=178) from a mean baseline A1C of 8.8 percent (p <0.001). The mean placebo-adjusted A1C reductions in the other arms of the study were 1.6 percent with JANUVIA 100 mg daily and metformin 1000 mg dailyii (n=183); 1.3 percent with metformin 2000 mg dailyiii (n=177); 1.0 percent with metformin 1000 mgiv daily (n=178); and 0.8 percent with JANUVIA (n=175), (p<0.001 for all treatment groups versus placebo).

At 24 weeks, 66 percent of patients treated with the initial combination of JANUVIA 100 mg daily and metformin 2000 mg daily achieved the American Diabetes Association's (ADA) goal A1C level of <7 percent vs. 38 percent of patients treated with metformin 2000 mg daily alone. In the other arms of the study, 43 percent of patients treated with JANUVIA 100 mg daily and metformin 1000 mg daily, 23 percent of patients treated with metformin 1000 mg daily, and 20 percent of patients treated with JANUVIA achieved the ADA goal A1C level of <7 percent.

This study also included an open label cohort of an additional 117 patients with severely elevated baseline A1C (mean: 11.2 percent). These patients experienced a significant mean A1C reduction from baseline of 2.9 percent at 24 weeks with initial therapy combining JANUVIA 100 mg daily and metformin 2000 mg daily.

This study also compared the efficacy of JANUVIA to two common doses of metformin in a subset of patients not on any anti-hyperglycemic agent at study entry. In this patient population, patients treated with JANUVIA experienced a mean A1C reduction from baseline of 1.1 percent compared to 1.1 percent in patients treated with metformin 1000 mg daily and 1.2 percent in patients treated with metformin 2000 mg daily.

“The substantial A1C reductions that are seen when JANUVIA is used in combination with metformin as first-line therapy in patients with type 2 diabetes are meaningful to me as a clinician. The data show that this approach helped many patients achieve their A1C goal and the rate of gastrointestinal side effects was similar to that seen with metformin alone,” said Barry J. Goldstein, M.D., Ph.D., professor of medicine, Biochemistry and Molecular Pharmacology; director, Division of Endocrinology, Diabetes and Metabolic Diseases, Jefferson Medical College, Philadelphia, PA.

Initial combination therapy or maintenance of combination therapy may not be appropriate for all patients. These management options are left to the discretion of the physician.

In the factorial study, initial therapy with JANUVIA and metformin was not associated with an increased risk of gastrointestinal adverse reactions beyond those commonly seen with metformin alone. In a pooled analysis of four other placebo-controlled clinical studies with JANUVIA, not including initial therapy with JANUVIA and metformin, the incidence of selected gastrointestinal adverse reactions in patients treated with JANUVIA was abdominal pain (2.3 percent JANUVIA; 2.1 percent placebo); nausea (1.4 percent JANUVIA; 0.6 percent placebo); and diarrhea (3.0 percent JANUVIA; 2.3 percent placebo).

The incidence of hypoglycemia was similar across treatment groups (0.6 percent in patients on placebo, 0.6 percent in patients given JANUVIA alone, 0.8 percent in patients given metformin alone, and 1.6 percent in patients given JANUVIA in combination with metformin).

The most common adverse reactions reported with JANUVIA and metformin as initial therapy (greater than or equal to 5 percent) compared to metformin alone were upper respiratory infection (6.2 percent vs. 5.2 percent) and headache (5.9 percent vs. 3.8 percent).

JANUVIA demonstrated similar efficacy compared to a sulfonylurea (glipizide) with significantly less hypoglycemia, and patients treated with JANUVIA experienced mean weight loss from baseline of 1.5 kg

The efficacy of JANUVIA was also evaluated in a 52-week, double-blind, glipizidecontrolled
noninferiority trial predominantly in patients with mildly to moderately elevated A1C levels (mean baseline A1C 7.5 percent). Patients were treated with either JANUVIA 100 mg daily or glipizide up to 20 mg daily (mean daily dose 10 mg daily). This study showed that JANUVIA achieved the pre-specified bounds for noninferiority vs. a sulfonylurea (glipizide).

After one year, the mean A1C reduction from baseline was 0.5 percent for JANUVIA and 0.6 percent for glipizide in the intent-to-treat patient populationv and 0.7 percent for JANUVIA and 0.7 percent for glipizide in the per protocol analysisvi, confirming the similar efficacy of JANUVIA compared to glipizide.

Patients treated with JANUVIA experienced significant weight loss (mean -1.5 kg) from baseline at 52 weeks, while patients treated with glipizide experienced significant weight gain (mean +1.1 kg) from baseline at 52 weeks. Additionally, patients treated with JANUVIA experienced a lower incidence of hypoglycemia than patients treated with glipizide (4.9 percent vs. 32.0 percent, respectively, p<0.001). The noninferiority of JANUVIA to glipizide may be limited to patients with A1C levels comparable to those included in this study (over 70 percent of patients had a baseline A1C <8 percent and over 90 percent had a baseline A1C <9 percent).

JANUVIA provides significant additional A1C reductions, even in patients on triple therapy

The new regimens for adding JANUVIA to a sulfonylurea (glimepiride) with or without metformin are supported by a 24-week, randomized, double-blind, placebo-controlled study examining the efficacy and safety of JANUVIA in 441 patients with type 2 diabetes and inadequate glycemic control (A1C 7.5 percent to 10.5 percent) on a sulfonylurea (glimepiride) and metformin or on a sulfonylurea (glimepiride) alone. In this study, JANUVIA demonstrated a significant mean difference from placebo in A1C of -0.9 percent when added to patients on glimepiride and metformin and -0.6 percent when added to patients on glimepiride alone (p<0.001 for both comparisons versus placebo).

In this study, the overall incidence of clinical adverse reactions with JANUVIA was higher than that seen with placebo, in part related to a higher incidence of hypoglycemia with JANUVIA compared to placebo (12.2 percent vs. 1.8 percent, respectively). The higher rate of hypoglycemia is commonly seen when antihyperglycemic agents are used in combination with sulfonylurea agents. After 24 weeks, patients treated with JANUVIA had a mean increase in body weight of 1.1 kg versus placebo (+0.8 kg vs. -0.4 kg).

As is typical with other anti-hyperglycemic agents used in combination with a sulfonylurea, when JANUVIA is used in combination with a sulfonylurea, a class of medications known to cause hypoglycemia, the incidence of hypoglycemia was increased over that of placebo. Therefore, a lower dose of sulfonylurea may be required to reduce the risk of hypoglycemia.

Dosing of JANUVIA

The recommended dose of JANUVIA is 100 mg once daily, with or without food, for all approved indications. No dosage adjustment is needed for patients with mild to moderate hepatic insufficiency or in patients with mild renal insufficiency (CrCl ≥50 mL/min). To achieve plasma concentrations of JANUVIA similar to those in patients with normal renal function, lower dosages are recommended in patients with moderate and severe renal insufficiency as well as in end-stage renal disease (ESRD) patients requiring hemodialysis. For patients with moderate renal insufficiency (CrCl ≥30 to <50 mL/min), the dose of JANUVIA is 50 mg once daily. For those with severe renal insufficiency (CrCl <30 mL/min) or with ESRD requiring dialysis, the dose of JANUVIA is 25 mg once daily. Because there is a need for dosage adjustment based upon renal function, assessment of renal function is recommended prior to initiation of JANUVIA and periodically thereafter.

Selected cautionary information for JANUVIA

Because JANUVIA is renally eliminated, and to achieve plasma concentrations of JANUVIA similar to those in patients with normal renal function, a dosage adjustment is recommended in patients with moderate renal insufficiency and in patients with severe renal insufficiency or with ESRD requiring hemodialysis or peritoneal dialysis. Safety and effectiveness of JANUVIA in pediatric patients have not been established. There are no adequate and well-controlled studies in pregnant women. JANUVIA should be used during pregnancy only if clearly needed. It is not known whether sitagliptin is excreted in human milk.

Because many drugs are excreted in human milk, caution should be exercised when JANUVIA is administered to a nursing woman. There have been post-marketing reports of hypersensitivity reactions in patients treated with JANUVIA. These reactions include anaphylaxis, angioedema, and exfoliative skin conditions including Stevens-Johnson syndrome.

Because these reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Onset of these reactions occurred within the first three months after initiation of treatment with JANUVIA, with some reports occurring after the first dose. If a hypersensitivity reaction is suspected, discontinue JANUVIA, assess for other potential causes for the event and institute alternative treatment for diabetes.

Expanding clinical development program for sitagliptin family

Merck’s clinical development program for sitagliptin is robust and continues to expand with 49 studies completed or underway. Five additional studies are set to begin this year. It is estimated that there have been more than 9,400 patients in the Company’s clinical studies, with about 6,000 of these patients being treated with sitagliptin. Additionally, about 2,300 patients have been treated with sitagliptin for more than a year and, of these, approximately 400 patients have been treated for at least two years.

Posted by dlifenews at 04:30 PM | Comments (0)

Women with High or Increasing Blood Pressure are Up to Three Times More Likely to Develop Diabetes

October 11, 2007 (EurekAlert) - One of the largest studies to investigate the relationship between blood pressure and type 2 diabetes has found that women who have high blood pressure levels are three times more likely to develop diabetes than women with low blood pressure levels. This effect was independent of body mass index and other conditions that are known to predispose people to cardiovascular disease and diabetes.

Writing in the European Heart Journal today [1], the authors say that clinicians should be aware of the relationships between blood pressure and type 2 diabetes to optimise the management of patients at increased risk for cardiovascular disease.

The researchers from the Brigham and Women’s Hospital, Harvard Medical School and the Harvard School of Public Health, USA, followed over 38,000 female health professionals for ten years. At the start of the study in 1993, all the women were free of diabetes and cardiovascular disease. Follow-up continued to the end of March 2004, at which point data were nearly 100% complete (97.2% for morbidity and 99.4% for mortality).

The lead author, Dr David Conen, a cardiologist and research fellow, explained: “Despite several studies finding a close relationship between hypertension and type 2 diabetes, little information exists on the relationship between blood pressure levels and the subsequent development of type 2 diabetes. Data for women are particularly limited. Finding an independent association between blood pressure and new-onset diabetes is important, because it suggests that women with increasing blood pressure levels should have their blood glucose levels monitored. Individuals at high risk for cardiovascular disease may benefit from early intervention.”

The researchers divided the women into four groups: those with optimal blood pressure (BP), below 120 mmHg systolic, 75 mmHg diastolic; those with normal BP (120-129 mmHg systolic, 75-84 mmHg diastolic); those with high normal BP (130-139 mmHg systolic, 85-89 diastolic); and those with established hypertension (at least 140 mmHg systolic, 90 mmHg diastolic, and/or self-reported history of hypertension or treatment for the condition).

After 10 years of follow-up 1.4, 2.9, 5.7 and 9.4% of women in the four categories respectively had developed type 2 diabetes. After adjusting for various factors such as age, ethnicity, smoking, alcohol intake, body mass index (BMI), exercise, family history of diabetes etc, the researchers found that women with hypertension had a three-fold risk of developing diabetes compared with women with optimal BP.

Dr Conen said: “We found that obesity was also a strong and independent risk factor for the development of type 2 diabetes. However, statistical analyses showed that the relationship between blood pressure and the onset of type 2 diabetes was similar among women who were normal weight, overweight or obese. There was a three-fold increase in risk from the lowest to the highest BP category within all three weight categories. This analysis showed that the association between blood pressure and diabetes was not explained by weight alone.”

Women who had an increase in BP during the study also had an increased risk of developing diabetes. Those whose BP rose but who remained within the range of normal BP had an increased risk of 26% compared to women who had stable or decreasing BP. Women who progressed to hypertension had a 64% increased risk.

Dr Conen said: “Compared with an overall rate of 4.5 events per 1,000 person-years, the incidence rates in the optimal BP category was 1.5 events per 1,000 person-years, showing that these women have a very low risk of developing diabetes. On the other hand, women with high normal BP had a much higher risk compared with women with normal BP, and the risk among those with established hypertension was substantial: after ten years almost 10% of these women had diabetes, a rate of ten events per 1,000 person-years. Taken together, our study demonstrates that BP and BP progression are strong predictors of incident type 2 diabetes, an effect independent of BMI and other components of the metabolic syndrome.” [2]

The authors suggest a possible mechanism for the relation between BP and diabetes may be endothelial dysfunction – a dysfunction of the normal biochemical processes carried out by the layer of cells that line the inner surfaces of blood vessels. “It may be a precursor of both hypertension and diabetes,” said Dr Conen. “Thus, the progression of endothelial dysfunction may cause worsening of both BP and blood glucose. This is in line with the fact that both BP and blood glucose occur together as part of the metabolic syndrome.”

He concluded: “Our findings provide strong evidence that BP and progression of BP are associated with an increased risk of diabetes. They highlight the fact that cardiovascular risk factors are interrelated and occur in clusters. Thus, an important message for physicians and future guidelines is that none of the cardiovascular risk factors should be looked at individually. The combination of all risk factors should be used to make treatment decisions.”

Posted by dlifenews at 03:13 PM | Comments (0)

Diabetic Neuropathy Costs Billions Per Year in Lost Work Time

October 5, 2007 (Newswise) - A recent study in the Journal of Occupational and Environmental Medicine finds that workers who have diabetes with neuropathic symptoms such as tingling in feet or hands lose the equivalent of 1.4 hours a week or $3.65 billion per year in health-related lost productive time.

Dr. Walter "Buzz" Stewart of the Geisinger Center for Health Research in Danville, Pa. can discuss the study's implications for the care of diabetic patients and for the workplace.

J. of Occupational and Environmental Medicine --Geisinger Health System

Posted by dlifenews at 09:58 AM | Comments (1)

FDA Announces Initiative to Bolster Generic Drug Program

Effort will streamline generic drug approval process; provide more options for consumers, health professionals

October 4, 2007 (FDA) - The U.S. Food and Drug Administration today outlined a program aimed at increasing the number and variety of generic drug products available to consumers and health care providers. Generic drugs generally cost less than their brand-name counterparts and competition among generics has been a key factor in lowering drug prices. The Generic Initiative for Value and Efficiency, or GIVE, will help the FDA modernize and streamline its generic drug approval process.

The agency approved or tentatively approved a record of 682 generic drugs products in fiscal year 2007, over 30 percent more than the previous year.

“To keep pace with the increasing number of generic drug applications, FDA will implement some changes to the generic drug approval process,” said Gary Buehler, director of FDA’s Office of Generic Drugs. “The GIVE plan outlines ways to maximize the use of our resources so that FDA can review and approve even more high quality generic drugs during the upcoming fiscal year than it did in 2007.”

As part of the GIVE efforts, FDA is revising the review order for certain drug applications. For example, first generic products, for which there are no blocking patents or exclusivity protections on the reference listed drug, are identified at the time of submission for expedited review. This will mean that these products, for which there are currently no generic products on the market, may reach the consumer much faster.

FDA now has about 215 full-time staff working on the review of generic drug applications. Under GIVE, FDA will hire and train new generic drug reviewers and focus on enhanced use of electronic programs for handling drug submissions and internal documents. When possible, resources from other FDA departments will be engaged in the effort. As well, FDA will increase its communications with generic drug manufacturers and provide training on proper application submission to the industry in meetings and Webcasts.

Generic drugs undergo a rigorous scientific review to ensure that they are of high quality, safe, and effective. Generic drug manufacturers must demonstrate that a generic drug has the same dosage form, strength, route of administration, and conditions of use as the approved brand-name product. Generic drug manufacturers also must demonstrate bioequivalence, meaning they show that the drug delivers the same amount of its active ingredient in the same amount of time as the brand-name counterpart. Bioequivalence is a critical requirement for concluding that the original and generic drugs will produce the same therapeutic results.

Posted by dlifenews at 04:57 PM | Comments (1)

Botched Production of Insulin Molecule May Lead to Diabetes

October 2, 2007 (EurekAlert) — Picture a pretzel factory production line, with conveyer belts carrying the dough, formed into unbaked pretzels, down to the oven to be cooked.

Now imagine what would happen if pretzel dough started to overflow the mixer and oozed as a blob onto the conveyor, misshapen, and sticking fast to the dough of the other fully formed, unbaked pretzels. The result: a mess. And if that mess could no longer be conveyed into the oven, the backup of messy dough in the system would get worse and worse, and might eventually shut down the whole factory.

That’s essentially what might be happening in a much smaller kind of factory: the cells that make insulin in the body of people with diabetes.

According to new findings by a team from the University of Michigan Medical School, those tiny factories may shut down because of glitches in the production of a molecule called proinsulin — the precursor, or “dough”, out of which insulin is made.

The insulin factories are called beta cells, and they normally churn out large quantities of insulin within the pancreas. This insulin supply can be released into the bloodstream as needed, to help the body turn sugars from food into energy for cells.

But in people with diabetes, the beta cell factories don’t keep up with the demand for insulin, and sugar builds up in the blood, wreaking havoc on nerves, blood vessel walls and kidneys. And just like a factory that can’t fill a growing number of orders for a hot product, the situation just keeps getting worse and the diabetes progresses.

Scientists have been working to understand why insulin production falters in people with diabetes, and the U-M team has focused on the production and folding of the proinsulin molecule deep within the beta cell. Using a tag that can make proinsulin glow green, they have now found a way to watch proinsulin being made within animal cells, and folded into a shape that can then be turned into insulin. Of course, this also allows them to study what happens when that process goes awry.

In the new paper, published online before print publication in the Proceedings of the National Academy of Sciences, the team details its findings and proposes that proinsulin 'blobs' might lead to beta cell dysfunction and death, which in turn can lead to the start, or progression, of diabetes.

Senior author Peter Arvan, M.D., Ph.D., says, "We believe that in the insulin production factory, misfolded copies of newly-made proinsulin can gum up the works in several ways. This paper shows that one of the first things that can happen is that misfolded proinsulin can stick to other proinsulin in the very first stages of production within the endoplasmic reticulum,” the area of the cell where proteins are made.

Arvan, who is chief of Metabolism, Endocrinology and Diabetes at the U-M Medical School and director of the Michigan Comprehensive Diabetes Center, explains that this chain reaction can start with just a few misfolded proinsulin molecules. It can then lead to beta cell shutdown and an insulin shortage. “The misfolded proinsulin does not get exported from the factory, and neither does the normally folded proinsulin made after it,” he says. “Pretty soon, pancreatic beta cells are running out of insulin to secrete in response to the customer's demand for the product – that is, an increase in blood glucose.” And that is a key hallmark of diabetes.

Arvan, who is the William and Delores Brehm Professor of Type 1 Diabetes Research, and first author Ming Liu, M.D., Ph.D., led the research team in developing the techniques needed to visualize proinsulin production and then study problems with the process by following misfolded molecules through the production pathway.

First, the team engineered the gene for human proinsulin to insert a tag that makes the protein fluorescent, but does not interfere with the production, function or secretion of insulin. They inserted the human gene into rat pancreas cells, which allows them to see the human proinsulin being made in live rat cells under the microscope.

Next, the team introduced a mutation into the tagged human insulin gene that causes the proinsulin molecule to fold incorrectly. This allowed them to see what happened when the misfolded human proinsulin and the normal rat proinsulin were produced together inside the same cell.

What they saw was misfolded fluorescent proinsulin getting stuck in the endoplasmic reticulum, so it could not move along normal ‘conveyor belt’ to make insulin. Simultaneously, this blocked the traffic of the normal proinsulin in the same cells. This ‘protein mess’ in the endoplasmic reticulum directly inhibits insulin production in the beta cells, even including insulin production that comes from the otherwise normal rat proinsulin. The beta cells begin to suffer from this, and they ultimately die.

The Arvan lab is also collaborating with other groups to identify new mutations in the proinsulin gene of people with congenital diabetes, and to understand how these mutations may cause a similar “protein mess.”

These mutations are apparently the second most common genetic cause of congenital diabetes, which is a relatively rare genetic illness. Congenital diabetes differs from Type 1 diabetes because congenital diabetes is not caused by an attack by the immune system on the body’s own beta cells, and because it is passed down from parent to child. Arvan and his team suspect that congenital diabetes in babies mirrors the proinsulin misfolding seen in their new study, and in a strain of mice known as Akita mice, which develop diabetes spontaneously after birth.

“The big question -- still to be determined -- is how much of the more common forms of diabetes also involve proinsulin misfolding in beta cells that are stressed to the max to make all the insulin they can,” Arvan notes. “This is a question that we are actively pursuing.”

Posted by dlifenews at 04:53 PM | Comments (0)

Genetic 'Roadblock' Hoped to Inspire Future Type 2 Diabetes Research

October 2, 2007 (EurekAlert) – A team of Mount Sinai Hospital researchers has found that a “genetic roadblock” identified in a recent study could pave the way toward novel treatments for type 2 diabetes.

In the study, researchers from the Samuel Lunenfeld Research Institute of Mount Sinai Hospital found the first genetic evidence that the elimination of the gene for glycogen synthase kinase-3 (GSK-3) in mice sensitizes the animals to insulin.

Insulin is a hormone that helps control sugar (glucose) levels in the blood. In people with type 2 diabetes, the pancreas does not produce enough insulin, or it is not properly used. As a result, sugar accumulates in the blood rather than being absorbed, stored or burned for energy. The study found that by eliminating GSK-3 in mouse models, more sugar became stored in the liver in response to increased insulin sensitivity, indicating that insulin had become more effective.

The study from the laboratory of Dr. Jim Woodgett, Director of the Lunenfeld, and the first scientist to isolate the GSK-3 genes in 1990, made the cover of the October 3 edition of Cell Metabolism.

“We created a ‘genetic roadblock’ by knocking out this particular gene and this made the mice far more efficient in their ability to use insulin to regulate their blood-sugar levels,” said Dr. Woodgett. “Research creates the best medicine and while potential human treatments are likely still years down the road, this study provides strong evidence that chemical inhibitors of this enzyme will be useful for increasing the effective potency of insulin.“

The study was co-authored by Drs. Katrina MacAulay and Bradley Doble. Dr. MacAulay was inspired to become a medical researcher specializing in diabetes because her sister, Ailsa MacAulay, suffers from this disease.

“I hope our findings will inspire other researchers around the world to develop treatments that will reduce symptoms of this epidemic disease as well as its associated complications, such as heart disease, liver disease or limb amputation,” said Dr. MacAulay.

Currently, more than two million people in Canada suffer from diabetes. It is one of the fastest growing diseases in the country with more than 60,000 new cases diagnosed each year.

Type 2 diabetes makes up about 90 per cent of all cases, with most evidence suggesting that it could be prevented or delayed by maintaining a healthy lifestyle.

“With this research, another piece in the puzzle has been put in place. It advances our understanding of how the complex mechanisms activated by insulin work. Understanding the details of this picture is central to developing new drugs that can help people with diabetes control their blood sugar,” says Dr. Diane T. Finegood, Scientific Director of the CIHR-Institute of Nutrition, Metabolism and Diabetes.

Posted by dlifenews at 04:50 PM | Comments (0)

Joslin Researchers Uncover Potential Role of Leptin in Diabetes

October 1, 2007(Joslin) - A new Joslin-led study has shown that leptin, a hormone known mainly for regulating appetite control and energy metabolism, plays a major role in islet cell growth and insulin secretion. This finding opens up new avenues for studying leptin and its role in islet cell biology, which may lead to new treatments for diabetes. This study appears in the October 2007 issue of The Journal of Clinical Investigation.

Previous in vitro studies suggested that leptin receptors, which are found in tissues throughout the body including the pancreas as well as the brain, mediate leptin-induced inhibition of insulin secretion in islet cells, also known as beta cells. "We wanted to further our understanding of leptin and its role in beta cells independent of its effects in the brain," said Rohit N. Kulkarni, M.D., Ph.D., principal investigator at Joslin Diabetes Center and Assistant Professor of Medicine at Harvard Medical School, who led this study. It is currently not known why obese individuals exhibit a high incidence of diabetes despite high levels of both insulin and leptin circulating in the bloodstream.

To understand the role of leptin in the islets, researchers developed a mouse model (known as a "knock out" or KO mouse) genetically engineered not to produce leptin receptors in the pancreas, while maintaining the receptors in the brain and the rest of the body. Researchers found that the mice lacking leptin receptors in the pancreas showed improved glucose tolerance and greater insulin secretion and beta cell growth. "Since the normal function of leptin is to keep insulin levels from getting too high, the lack of leptin enhances insulin action in the beta cells and promotes insulin secretion, which was the result we expected," said Dr. Kulkarni.

In the second part of the study, the KO mice and a control group of mice with intact leptin receptors were placed on a high-fat diet. Although both the control and KO mice became obese, only the KO mice developed severe glucose intolerance and insulin resistance, a precursor to the development of diabetes. "These novel results indicate that in the presence of obesity, the combination of insulin resistance in the beta cell and the lack of leptin signaling leads to poor beta cell growth and function leading to glucose intolerance. Interactions between leptin and insulin signaling in the beta cell need to be considered to understand the relationship between diabetes and obesity," said Dr. Kulkarni.
Obesity is a major risk factor for the development of type 2 diabetes, the most common form of the disease. Other risk factors are age (over 40) and a family history of diabetes, although today it is increasing prevalent in younger people, including adolescents. In type 2 diabetes, islet cells malfunction and the body is unable to compensate by growing more beta cells. By investigating the cellular mechanisms that affect islet cell development and growth, Joslin researchers hope to find better ways to prevent and treat the disease.

Follow-up studies will focus on examining the interactions between insulin and leptin signaling in beta cells and identifying the key proteins found in the pathways that regulate beta cell growth and activity. This could lead to the development of therapeutic drugs that manipulate these proteins to influence beta cell growth and function. "Unraveling the role of leptin in the regulation of beta cell biology will be especially useful in understanding the mechanisms that contribute to beta cell growth with implications for the treatment of both type 1 and type 2 diabetes," said Dr. Kulkarni.

Funding for the study was provided by the National Institutes of Health.
Other researchers participating in the study include: Tomoaki Morioka, M.D., Ph.D., Jiang Hu, M.D., Amarnath J. Kurpad, M.D., and Hui Li, Ph.D., Research Division, Joslin Diabetes Center; Esra Asilmaz, B.S., Laboratory of Molecular Genetics, The Rockefeller University; John F. Dishinger, B.S., and Robert T. Kennedy, Ph.D., Departments of Chemistry and Pharmacology, University of Michigan; and Carol F. Elias, Ph.D. and Joel K. Elmquist, Ph.D., Center for Hypothalamic Research and Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Texas Southwestern Medical Center.

Posted by dlifenews at 05:08 PM | Comments (0)

Clinical Trials for Diabetes Drugs Should Measure Outcomes Important to Patients

October 1, 2007 (Newswise) — Most clinical trials for new diabetes drugs do not consider the impact medication will have on a patient’s quality of life or other outcomes that are important to patients, such as the risk of developing complications associated with diabetes, according to a Mayo Clinic commentary in the current issue of The Lancet. Rather, drug trials focus on the effect of a particular medication on blood sugar levels. The result is smaller, shorter and cheaper trials that lead to more drug choices more quickly, but are not necessarily better or safer for patients.

“The apparent benefits of these trials are a mirage and the apparent savings represent false economy,” writes Victor Montori, M.D., an endocrinologist at Mayo Clinic, along with Gunjan Gandhi, M.D., of Mayo Clinic, and Gordon Guyatt, M.D., of McMaster University in Canada. “Any savings are quickly overwhelmed by expenses associated with potentially ineffective, or even harmful, expensive therapies and the incremental costs of treating the harms these interventions might cause. Patients and society may end up paying dearly for medications that cause more harm than good.”

The medical community is increasingly aware of the need to engage patients with chronic conditions in decisions about their care. For example, clinicians and patients need to know the extent to which diabetes medications can help patients feel better and live longer. Despite this need, only one in five randomized trials in diabetes published in top medical journals measured the effect of drugs on quality of life and on the risk of complications associated with diabetes, such as death, heart attack, stroke, amputation, blindness and dialysis. Ongoing trials do not promise much more, the author states.
Dr. Montori and colleagues call for clinical trials that consider and measure the impact of diabetes medications on outcomes that are important to patients.

“The medical community should insist that we invest the resources needed to do trials that ascertain the effect of interventions on patient-important outcomes,” the authors state. “This policy will prevent the premature dissemination of therapies that ultimately prove harmful, facilitate patients’ participation in decision making, and speed the day when we can confidently offer safe treatments that can provide important benefit to patients with diabetes.”

In summary, the authors say:

1. Diabetes medications have been approved without requiring proof of reducing the risk of complications associated with diabetes, such as heart attack, stroke, amputation, blindness and kidney dialysis.

2. The majority of diabetes trials focus on the ability of medications to reduce blood sugar, not on outcomes that matter to patients.

3. Diabetes medications may reduce the risk of complications, but we do not know this with confidence.

4. The focus should shift from getting new drugs to market to testing the effect of diabetes medications against outcomes important to patients.

Dr. Montori is a lead investigator with the Knowledge and Encounter Research Unit at Mayo Clinic. His research team seeks to improve the care and outcomes of patients with diabetes by studying ways to promote health care decisions that are more consistent with research findings and the values and preferences of informed patients.

Posted by dlifenews at 11:46 AM | Comments (0)

FDA Approves SYMLIN Pen-Injector Devices Offering Convenience and Accuracy for SYMLIN Use

October 1, 2007 (PRNewswire-FirstCall) -- Amylin Pharmaceuticals, Inc. (Nasdaq: AMLN) announced today that the U.S. Food and Drug Administration (FDA) has approved the SymlinPen(TM) 120 and the SymlinPen(TM) 60 pen-injector devices for administering SYMLIN(R) (pramlintide acetate) injection. These new pre-filled pen-injector devices feature simple, fixed dosing to improve mealtime glucose control.

"SymlinPen 120 and SymlinPen 60 offer patients improved convenience and accuracy," said Daniel M. Bradbury, President and CEO, Amylin Pharmaceuticals. "For people with diabetes using mealtime insulin, the addition of SYMLIN can enhance glucose control with the potential for weight loss."

SymlinPen(TM) 60 features fixed dosing to deliver 15, 30, 45, or 60 micrograms per dose. SymlinPen(TM) 120 features fixed dosing to deliver 60 or 120 micrograms per dose. Both pen-injector devices can be conveniently stored at room temperature not to exceed 86 degrees F (30 degrees C) after first use. The pens are expected to be available to patients by December 2007.

"Not Approvable" Letter Received for SYMLIN Use with Basal Insulin Alone

Amylin also announced today that the FDA has issued a "Not Approvable" letter for SYMLIN use with basal insulin (without mealtime insulin) in patients with type 2 diabetes who have not achieved desired glucose control. SYMLIN is currently approved in the U.S. for patients with type 2 or type 1 diabetes who use mealtime insulin and need improved glucose control.

"SYMLIN remains an important therapeutic option for people with diabetes who use mealtime insulin therapy," Bradbury added. "We will initiate discussions with the FDA to clarify their response for its use with basal insulin alone."

About SYMLIN

SYMLIN is the first and only amylin mimetic for use in patients with diabetes treated with mealtime insulin. SYMLIN is a synthetic analog of human amylin, a naturally occurring hormone that is made in the beta cells of the pancreas, the same cells that make insulin. In patients with type 2 diabetes who use insulin, and in patients with type 1 diabetes, those cells in the pancreas are either damaged or destroyed, resulting in reduced secretion of both insulin and amylin after meals. The use of SYMLIN contributes to glucose control after meals.

Healthcare professionals and people with diabetes may obtain more information, including the complete Prescribing Information and the Medication Guide, at http://www.SYMLIN.com.

Important Safety Information

SYMLIN is not intended for all patients with diabetes. SYMLIN is used with insulin and has been associated with an increased risk of insulin-induced severe hypoglycemia, particularly in patients with type 1 diabetes. When severe hypoglycemia associated with SYMLIN use occurs, it is seen within three hours following a SYMLIN injection. If severe hypoglycemia occurs while operating a motor vehicle, heavy machinery, or while engaging in other high- risk activities, serious injuries may occur. Appropriate patient selection, careful patient instruction, and insulin dose adjustments are critical elements for reducing this risk. This information is highlighted in a boxed warning in the SYMLIN Prescribing Information for healthcare professionals and in a Medication Guide for patients, which will be distributed by pharmacists.

Other adverse events commonly observed with SYMLIN when co-administered with insulin were mostly gastrointestinal in nature, including nausea, which was the most frequently reported. The incidence of nausea was higher at the beginning of SYMLIN treatment and decreased with time in most patients. The incidence and severity of nausea are reduced when SYMLIN is gradually increased to the recommended doses.

Posted by dlifenews at 09:00 AM | Comments (1)