Preventative Care the Standard to Treat New Diabetics

June 26, 2008 (Newswise) - The Centers for Disease Control and Prevention recently reported that the number of Americans with diabetes has grown to 24 million - a surge of more than 3 million people in the past two years.

That surge is evident at Temple University’s School of Podiatric Medicine, where podiatrists have seen a spike in recently diagnosed diabetic patients who have been referred by their primary care physician as part of a heightened awareness of the disease.

“Diabetes has reached epidemic proportions, and health care providers are becoming more proactive in their approach to care,” said Temple podiatrist Kathya Zinszer, who specializes in diabetic wound care. “In years past, patients would come to their doctor with chronic foot wounds, and would be so far gone that the only option would be to amputate. Now, that’s not the case, thanks to the push for preventative care.”

Temple’s approach to preventative care is two fold: at the Foot and Ankle Institute, newly diagnosed diabetics undergo a number of baseline tests including shoe fittings and gait analysis, to determine and correct any problem areas before they develop into chronic ulcers or wounds.

In addition, Zinszer and her colleagues stress the need for patients to make foot care a part of their everyday lives. She suggests wearing good, supportive slippers in the house, never going barefoot outdoors and checking inside the shoes to make sure there are no foreign objects that could rub or cut the foot.

“I tell all my patients to get in the habit of checking their shoes now, because while they may have good feeling in their feet today, in 10 years, they might not,” said Zinszer.

“Our goal is to do everything we can to salvage limbs and help our diabetic patients maintain a good quality of life,” she said.

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

Seniors With Type 2 Diabetes May Experience Memory Declines Immediately After Eating Unhealthy Meal

June 26, 2008 (Science Daily) - Adults with type 2 diabetes who eat unhealthy, high-fat meals may experience memory declines immediately afterward, but this can be offset by taking antioxidant vitamins with the meal, according to new research from Baycrest.

There is already growing evidence linking diabetes to cognitive complications in humans. Adults with type 2 diabetes are especially vulnerable to acute meal-induced memory deficits after eating unhealthy foods.

This latest study, led by Baycrest and published in the July issue of Nutrition Research, suggests that taking high doses of antioxidant vitamins C and E with the meal may help minimize those memory slumps.

"Our bottom line is that consuming unhealthy meals for those with diabetes can temporarily further worsen already underlying memory problems associated with the disease,"said lead author Michael Herman Chui, who conducted the research as a University of Toronto pathobiology undergraduate in the Kunin-Lunenfeld Applied Research Unit (KLARU) at Baycrest. "We've shown that antioxidant vitamins can minimize oxidative stress from the meal and reduce those immediate memory deficits."

Type 2 diabetes is associated with chronic oxidative stress, a major contributor to cognitive decline and Alzheimer disease. Consuming unhealthy foods can induce this type of stress which is triggered by acute elevations of free radicals -- unstable molecules that can damage tissue, including brain tissue. These destructive molecule reactions typically occur over a one-to-three hour period after food ingestion.

Dr. Carol Greenwood, senior author of the study and a nationally recognized expert in how diet impacts brain function, cautioned that relying on antioxidant vitamins at meal time is not a quick fix. "While our study looked at the pill form of antioxidants, we would ultimately want individuals to consume healthier foods high in antioxidants, like fruits and vegetables," said Dr. Greenwood, a KLARU senior scientist at Baycrest.

Maintaining a healthy lifestyle that includes regular exercise, a low fat diet rich in antioxidants, and staying mentally active and socially engaged in a variety of activities, is the best medicine for optimizing cognitive health during the lifespan, she said.

In the study, 16 adults (aged 50 years and older) with type 2 diabetes participated in an unblinded trial where they attended three weekly sessions that involved consuming a different test meal. One meal consisted of high fat products -- a danish pastry, cheddar cheese and yogurt with added whipped cream; the second meal consisted of only water consumption; and the third test meal was the high-fat meal plus high doses of vitamins C (1000 mg) and E (800 IU) tablets.

Fifteen minutes after starting meal ingestion, participants completed a series of neuropsychological tests lasting 90 minutes that measured their recall abilities for words they had heard and paragraph information they had read. These cognitive skills are associated with the brain's memory centre -- the hippocampus.

Researchers found that vitamin supplementation consistently improved recall scores relative to the meal alone. Participants who ate the high fat meal without vitamin supplements showed significantly more forgetfulness of words and paragraph information in immediate and time delay recall tests, relative to those who had the water meal or the meal with antioxidant vitamins. Those on water meal and meal with vitamins showed similar levels in cognitive performance.

Dr. Greenwood and medical student M.H. Chui emphasize that their findings require further replication in larger studies with more participants. Future studies will need to look at whether antioxidant vitamins are directly targeting oxidative stress reactions or triggering an independent memory-enhancing ability which is simply masking the detrimental effects.

The study was funded by a grant from the Natural Sciences and Engineering Research Council of Canada.

Posted by dlife at 09:32 AM | Comments (1)

Insulin Analogs No Better than the Real Deal, According to Latest Research

June 25, 2008 (Newswise) - Efforts to make diabetes care more manageable, and easier on the patient, have led to the introduction of insulin “analogs” – medicines that act similarly to ordinary insulin, but which are supposed to provide additional benefits. Recent research from Generex Biotechnology, a company focused on advanced insulin delivery and diabetes vaccine research, shows that the advantages of insulin analogs may be illusory. Investigators from the company presented their data at the recently completed Endocrine Society 90th Annual Meeting, held in San Francisco from June 15 through 18. The presentation was co-authored by researchers from the Institute for Endocrinology IEMYR, Quito, Ecuador, and the University of Florida, Gainsville.

The year-long study examined 26 subjects with type 1 diabetes, which is normally treated with “basal” injected injection once or twice a day to provide baseline glycemic control, and additional insulin injections before meals. The control study group received insulin glargine (an insulin analog) once a day as their basal dose, and a faster-acting insulin analog before meals. The treatment group received a non-analog long-acting insulin twice a day as their basal insulin; before meals the they took Oral-lyn™, a liquid formulation of human insulin, developed by Generex, that is absorbed through the lining of the mouth. All subjects were monitored for three standard measures of glycemic control: Hemoglobin A1c and fructosamine levels were recorded every two weeks by investigators, and pre-meal glucose levels were taken by patients themselves. Together, these readings assess the effectiveness of diabetes treatment regimens better than any test alone. Higher readings generally indicate less-effective glucose control.

At the end of the study all three measures were found to be consistently and significantly lower in the group that received the human insulin regimen that included the Oral-lyn product before meals. Oral-lyn uses a formulation that allows insulin to pass through the “buccal” mucosa – the soft tissues lining the inside of the mouth – and into the bloodstream rapidly and safely, without injection. Oral-lyn is delivered to the mouth using Generex’s proprietary RapidMist™ spray device. Unlike inhaled insulin products which have enjoyed limited success, the combination of Oral-lyn insulin and RapidMist delivery technology allows patients to deliver their insulin dose as needed, and do not deposit insulin into the lungs.

People with diabetes, and physicians treating them, have become excited in recent years by insulin analogs due to their rapid window of action. Several studies have also claimed that analogs improve glycemic control. Insulin analogs can cost up to three times as much as insulin, however, which can place serious financial strains on families that pay for their own insulin. Even families with comprehensive drug coverage will find that plans charge a significantly higher co-pay for insulin analogs than for “regular” human insulin.

“Our results clearly show that over the course of a year-long study the advantage of these analogues is equaled or improved upon by the use of Oral-lyn. When Oral-lyn is absorbed through the buccal mucosa its rapid entry into the blood stream mimics and improves upon the rapid acting analogues.” commented Dr. Jaime Guevara, a study author and clinician that has conducted studies for Generex’s Oral-lyn. “Claims that analogs provide superior convenience do have some merit when these agents are compared with insulin injected before meals. However, when compared with Oral-lyn, which is not injected, even those arguments fail to make the case for drugs that cost three times as much as standard insulin.”

Oral-lyn is currently approved in two countries, and is currently undergoing clinical testing for U.S. approval.

For more information, log on to http://www.generex.com

Posted by dlife at 10:28 AM | Comments (1)

Living Cell Technologies Confirms Insulin Delivery From Implants in Diabetes Clinical Trial

June 24, 2008 (MarketWire) - Living Cell Technologies Limited (ASX: LCT) (PINKSHEETS: LVCLY) today reported that patients in the DiabeCell® phase I/IIa diabetes clinical trial had porcine insulin in their blood samples providing additional scientific confirmation that implants of DiabeCell® actively produce insulin and directly contribute to clinical benefit.

Professor Bob Elliott, LCT Medical Director, said, "The early clinical response in the first two patients showed that following DiabeCell® treatment they were able to control their diabetes with reduced insulin dose. By detecting porcine insulin in blood samples, we have demonstrated with certainty that the reduced insulin requirement is due to the implanted cells."

"Porcine insulin was present in the circulation of the first patient at 11 months follow up and in the second patient 6 months after receiving the implant. In the second patient it was detected after she stopped insulin injections clearly demonstrating the effect of the implants," continued Professor Elliott.

Dr Paul Tan, LCT Chief Executive Officer, said, "This recent information is consistent with LCT's published research which demonstrated presence of porcine insulin in a patient 10 years after a similar implant. This has now been validated again after 11 months without use of immunosuppressive drugs in the current trial and at the lowest dose of DiabeCell®. The long term functioning of the encapsulated cells is important and we expect LCT's current encapsulation technology to keep the cells alive and functioning long term."

"The preliminary data from this world-first diabetes clinical trial of encapsulated porcine insulin-producing cells gives us increasing confidence as we advance DiabeCell® to larger scale trials with higher doses," continued Dr Tan. LCT announced earlier this month that it would be expanding the Russian trial.

This preliminary data from the first two patients will be followed by results from the other patients in the trial. All 5 patients who have received transplants are participating in the follow-up programme. All remain well and without complication. The first two have received their second implant while the other three are to be scheduled for their second implants.

Professor Bob Elliott is travelling to Russia in July to review all patients with their personal physicians and to collate clinical data. LCT expects to be able to provide a complete trial update in late July.

DiabeCell®, encapsulated porcine insulin producing cells, is the Company's lead product. It is currently undergoing phase I//IIa clinical trials for insulin dependent type 1 diabetes.

Posted by dlife at 10:18 AM | Comments (2)

Marijuana May Be Effective for Neuropathic Pain

June 25, 2008 (Newswise) - The growing body of evidence that marijuana (cannabis) may be effective as a pain reliever has been expanded with publication of a new study in The Journal of Pain reporting that patients with nerve pain showed reduced pain intensity from smoking marijuana.

Researchers at University of California Davis examined whether marijuana produces analgesia for patients with neuropathic pain. Thirty-eight patients were examined. They were given either high-dose (7%), low-dose (3.5%) or placebo cannabis.

The authors reported that identical levels of analgesia were produced at each cumulative dose level by both concentrations of the agent. As with opioids, cannabis does not rely on a relaxing or tranquilizing effect, but reduces the core component of nociception and the emotional aspect of the pain experience to an equal degree. There were undesirable consequences observed from cannabis smoking, such as feeing high or impaired, but they did not inhibit tolerability or cause anyone to withdraw from the study. In general, side effects and mood changes were inconsequential.

It was noted by the authors that since high and low dose cannabis produced equal analgesic efficacy, a case could be made for testing lower concentrations to determine if the analgesic profile can be maintained while reducing potential cognitive decline.

In addition, the authors said further research could probe whether adding the lowest effective dose of cannabis to another analgesic drug might lead to more effective neuropathic pain treatment for patients who otherwise are treatment-resistant.

Source: A Randomized, Placebo-Controlled, Crossover Trial of Cannibis Cigarettes in Neuropathic Pain; Barth Wilsey, Thomas Marcotte, Alexander Tsodikov, Jeanna Millman, Heather Bentley, Ben Gouaux and Scott Fishman, University of California Davis

Posted by dlife at 10:16 AM | Comments (6)

Number of People with Diabetes Increases to 24 Million

June 24, 2008 (CDC Press Release) - Diabetes now affects nearly 24 million people in the United States, an increase of more than 3 million in approximately two years, according to new 2007 prevalence data estimates released today by the Centers for Disease Control and Prevention (CDC). This means that nearly 8 percent of the U.S. population has diabetes.

In addition to the 24 million with diabetes, another 57 million people are estimated to have pre-diabetes, a condition that puts people at increased risk for diabetes. Among people with diabetes, those who do not know they have the disease decreased from 30 percent to 25 percent over a two-year period.

“These new estimates have both good news and bad news,” said Dr. Ann Albright, director of the CDC Division of Diabetes Translation. “It is concerning to know that we have more people developing diabetes, and these data are a reminder of the importance of increasing awareness of this condition, especially among people who are at high risk. On the other hand, it is good to see that more people are aware that they have diabetes. That is an indication that our efforts to increase awareness are working, and more importantly, that more people are better prepared to manage this disease and its complications.”

Diabetes is a disease associated with high levels of blood glucose resulting from defects in insulin production that causes sugar to build up in the body. It is the seventh leading cause of death in the country and can cause serious health complications including heart disease, blindness, kidney failure, and lower-extremity amputations.

Among adults, diabetes increased in both men and women and in all age groups, but still disproportionately affects the elderly. Almost 25 percent of the population 60 years and older had diabetes in 2007. And, as in previous years, disparities exist among ethnic groups and minority populations including Native Americans, blacks and Hispanics. After adjusting for population age differences between the groups, the rate of diagnosed diabetes was highest among Native Americans and Alaska Natives (16.5 percent). This was followed by blacks (11.8 percent) and Hispanics (10.4 percent), which includes rates for Puerto Ricans (12.6 percent), Mexican Americans (11.9 percent), and Cubans (8.2 percent). By comparison, the rate for Asian Americans was 7.5 percent with whites at 6.6 percent.

The data are an update of diabetes prevalence estimates last reported two years ago and now published in the 2007 National Diabetes Fact Sheet developed by CDC in collaboration with multiple agencies under the U.S. Department of Health and Human Services and other federal agencies.

CDC also is releasing estimates of diagnosed diabetes for all counties in the United States. Derived from the agency's Behavioral Risk Factor Surveillance Survey (BRFSS) and census data, the estimates provide a clearer picture of areas within states that have higher diabetes rates. Nationally, the data indicate increased diabetes rates in areas of the Southeast and Appalachia that have traditionally been recognized as being at higher risk for many chronic diseases, including heart disease and stroke.

“These data are an important step in identifying the places in a state that have the greatest number of people affected by diabetes,” said Dr.Albright. “If states know which communities or areas have more people with diabetes, they can use that information to target their efforts or tailor them to meet the needs of specific communities.”

CDC, through its Division of Diabetes Translation, funds diabetes prevention and control programs in all 50 states, as well as the District of Columbia and eight U.S. territories and island jurisdictions. The National Diabetes Education Program, co-sponsored by CDC and the National Institutes of Health (NIH), provides diabetes education to improve the treatment and outcomes for people with diabetes, promote early diagnosis, and prevent or delay the onset of diabetes.

For more information on diabetes, please visit www.cdc.gov/diabetes. To access the National Diabetes Fact Sheet and county-level estimates of diagnosed diabetes, click on the "data and trends" link at the left.

Posted by dlife at 02:28 PM | Comments (0)

Low Vitamin D Levels Associated With Death from Cardiovascular, All Causes

June 23, 2008 (JAMA & Archives) CHICAGO – Individuals with lower blood levels of vitamin D appear to have an increased risk of death overall and from cardiovascular causes, according to a report in the June 23 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.

A recent consensus panel estimated that about 50 percent to 60 percent of older individuals in North America and the rest of the world do not have satisfactory vitamin D status, and the situation is similar for younger individuals, according to background information in the article. Blood levels of 25-hydroxyvitamin D, a measure of blood vitamin D levels, lower than 20 to 30 nanograms per milliliter have been associated with falls, fractures, cancer, immune dysfunction, cardiovascular disease and hypertension. These effects are thought to be mediated by the compound 1,25-dihydroxyvitamin D, which is produced by the body and also converted from 25-hydroxyvitamin D.

Harald Dobnig, M.D., of Medical University of Graz, Austria, and colleagues studied 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels in 3,258 consecutive patients (average age 62 years) who were scheduled for coronary angiography testing at a single medical center between 1997 and 2000.

During about 7.7 years of follow-up, 737 (22.6 percent) of participants died, including 463 (62.8 percent) who died of cardiovascular causes. Death rates from any cause and from cardiovascular causes were higher among individuals in the lower one-half of 25-hydroxyvitamin D levels and the lowest one-fourth of 1,25-dihydroxyvitamin D levels.

These associations remained when the researchers accounted for other factors, including coronary artery disease, physical activity level and co-occurring diseases.

Low 25-hydroxyvitamin D levels also were correlated with markers of inflammation such as C-reactive protein, as well as signs of oxidative (oxygen-related) damage to cells, the authors note.

“Apart from the proved effects that vitamin D has on bone metabolism and neuromuscular function, appropriate serum levels (that may also be higher than in the present investigation) are associated with a decrease in mortality,” they conclude. “Although not proved, it seems possible that at least part of this effect may be due to lowering of a risk profile promoting atherosclerosis [narrowing of the arteries] and preventing cardiovascular end points.”

“Based on the findings of this study, a serum 25-hydroxyvitamin D level of 20 nanograms per milliliter or higher may be advised for maintaining general health.”

Posted by dlifenews at 03:19 PM | Comments (0)

Common Cooking Spice Shows Promise In Combating Diabetes And Obesity

June 20, 2008 (EurekAlert) - Turmeric, an Asian spice found in many curries, has a long history of use in reducing inflammation, healing wounds and relieving pain, but can it prevent diabetes? Since inflammation plays a big role in many diseases and is believed to be involved in onset of both obesity and Type 2 diabetes, Drew Tortoriello, M.D., an endocrinologist and research scientist at the Naomi Berrie Diabetes Center at Columbia University Medical Center, and his colleagues were curious what effect the herb might have on diabetic mice.

Dr. Tortoriello, working with pediatric resident Stuart Weisberg, M.D., Ph.D., and Rudolph Leibel, M.D., fellow endocrinologist and the co-director of the Naomi Berrie Diabetes Center, discovered that turmeric-treated mice were less susceptible to developing Type 2 diabetes, based on their blood glucose levels, and glucose and insulin tolerance tests. They also discovered that turmeric-fed obese mice showed significantly reduced inflammation in fat tissue and liver compared to controls. They speculate that curcumin, the anti-inflammatory, anti-oxidant ingredient in turmeric, lessens insulin resistance and prevents Type 2 diabetes in these mouse models by dampening the inflammatory response provoked by obesity.

Their findings are the subject of a soon-to-be published paper in Endocrinology and were presented at ENDO 2008, the Endocrine Society's annual meeting in San Francisco this week.

Turmeric (Curcuma longa) has no known dose-limiting toxicities in doses of up to at least 12 grams daily in humans. The researchers tested high-doses of a dietary curcumin in two distinct mouse models of obesity and Type 2 diabetes: high-fat-diet-fed male mice and leptin-deficient obese female mice, with lean wild-type mice that were fed low-fat diets used as controls.

The inflammation associated with obesity was shown several years ago by researchers in the Naomi Berrie Diabetes Center to be due in part to the presence of immune cells called macrophages in fat tissues throughout the body. These cells produce "cytokine" molecules that can cause inflammation in organs such as the heart, and islets of the pancreas, while also increasing insulin resistance in muscle and liver. Researchers hypothesized that by suppressing the number and activity of these cells, with turmeric or a drug with similar actions, it may be possible to reduce some of the adverse consequences of obesity.

Curcumin administration was also associated with a small but significant decline in body weight and fat content, despite level or higher calorie consumption, suggesting that curcumin beneficially influences body composition.

"It's too early to tell whether increasing dietary curcumin [through turmeric] intake in obese people with diabetes will show a similar benefit," Dr. Tortoriello said. "Although the daily intake of curcumin one might have to consume as a primary diabetes treatment is likely impractical, it is entirely possible that lower dosages of curcumin could nicely complement our traditional therapies as a natural and safe treatment."

For now, the conclusion that Dr. Tortoriello and his colleagues have reached is that turmeric – and its active anti-oxidant ingredient, curcumin – reverses many of the inflammatory and metabolic problems associated with obesity and improves blood-sugar control in mouse models of Type 2 diabetes.

In addition to exploring novel methods of curcumin administration to increase its absorption, they are also interested in identifying novel anti-inflammatory processes invoked by curcumin and in adapting those processes in the development of more potent curcumin analogues.

Posted by dlife at 11:16 AM | Comments (6)

Some Adults With Type 1 Diabetes Have Beta Cells, Live Complication-free Even 50 Years After Diagnosis

June 19, 2008 (Science Daily) - Research findings and innovative approaches offer the promise of new therapies and the potential for cures for adults living with type 1 diabetes, according to researchers at the Juvenile Diabetes Research Foundation's (JDRF's) Global Research Forum in Washington D.C.

Type 1 diabetes is an autoimmune disease that results in the destruction of insulin-producing beta cells in the pancreas. It renders people insulin-dependent for life and carries the constant threat of debilitating and life-threatening complications. Half of those diagnosed each year with type 1 diabetes are adults. Overall, adults with diabetes may have lived with the disease for more than 90% of their lives.

Still Capable of Producing Insulin

Among the research presented at the JDRF conference were insights of the Medalist Study from the Joslin Diabetes Center in Boston. George King, MD, Senior Vice President, Director of Research at the Joslin Center and director of the study, said that individuals with established type 1 diabetes (even those who have lived with it for 50 years or more) are still capable of producing insulin. The Joslin Study also found that even after 50 years about 30% of the patients studied didn't experience common complications such as eye, kidney or nerve disease. These findings have potential implications for improved treatment for all type 1 diabetes sufferers.

Potential for Islet Cell Regeneration

Mark Atkinson, M.D., Director of The Diabetes Center of Excellence at the University of Florida, presented initial findings from nPOD; the Network for Pancreatic Organ Donors with Diabetes. Organized and funded by JDRF, the network was established last August to procure and characterize, in a collaborative manner, pancreatic and related tissues from organ donors with long-standing type 1 diabetes as well as those who are islet autoantibody positive. These tissues would be used to study how type 1 diabetes develops with the hope of finding a means to cure the disease.

Dr. Atkinson presented findings from nPOD, which have enabled researchers to assess the potential for islet cell regeneration. "Contrary to common dogma, what we've learned so far is that some pancreata from subjects with long-standing type 1 diabetes have insulin positive beta cells and some have many intact islets. This finding gives hope for islet cell regeneration or restoration," Atkinson noted. He pointed out another key finding: that some islets have beta cells that don't produce insulin. "If we know beta cells are there, then we can focus on finding ways to get them to produce insulin," Dr. Atkinson explained.

JDRF's Chief Medical Officer, Paul Strumph, MD, also presented findings that showed how beta cell mass expands in response to increased metabolic demands such as growth during the first decade of life, obesity, and pregnancy - leading to possible therapeutics that mimic the biological mechanisms that increase insulin-producing cells in this instances. "A little bit of insulin is not a cure, but it can be significant to reduce the complications of diabetes," Strumph noted.

A New Era of Diabetes Research Has Begun

All of the presenters agreed that researchers are on the cusp of a new era in diabetes research, one in which advanced technology and human clinical research should enhance the development of new therapeutics and an ultimate cure.

"Much of what we've known regarding the pathogenesis of type 1 diabetes has dated back to studies performed with the human pancreas' in the 1970s -- before microwaves, the internet and cell phones, and before modern day medical research technology. Now we're looking at this disease in whole new ways," explained Atkinson.

Strumph added that there is more of an emphasis on looking at the natural history of the disease to guide research opportunities for those with established type 1 diabetes. JDRF is currently devoting a significant portion of its $160 million in research funding to science involving people with established type 1 diabetes, with a particular emphasis on areas such as autoiummunity and regeneration; the organization and plans to fund as much as $195 million on research in the coming 12 months.

Posted by dlife at 09:07 AM | Comments (3)

Lifestyle Can Alter Gene Activity, Lead To Insulin Resistance

June 19, 2008 (EurekAlert) - A Finnish study of identical twins has found that physical inactivity and acquired obesity can impair expression of the genes which help the cells produce energy. The findings suggest that lifestyle, more than heredity, contributes to insulin resistance in people who are obese. Insulin resistance increases the chance of developing diabetes and heart disease.

The study, "Acquired obesity and poor physical fitness impair expression of genes of mitochondrial oxidative phosphorylation in monozygotic twins discordant for obesity," appears in the online edition of the American Journal of Physiology-Endocrinology and Metabolism, published by The American Physiological Society (www.the-aps.org).

The study was carried out by Linda Mustelin and Kirsi Pietiläinen, of Helsinki University Central Hospital and the University of Helsinki; Aila Rissanen, Anssi Sovijärvi and Päivi Piirilä of Helsinki University Central Hospital; Jussi Naukkarinen, Leena Peltonen and Jaakko Kaprio, University of Helsinki and National Public Health Institute; and Hannele Yki-Järvinen of Helsinki University Central Hospital and Minerva Medical Research Institute.

Environment can influence genes

Recent studies have suggested that defects in expression of genes involved in the body's conversion of food to energy, known as mitochondrial oxidative phosphorylation, can lead to insulin resistance. The researchers wanted to know if defects in the expression of these genes are primarily a result of heredity or lifestyle. Because the twins in the study were identical, any differences that were found could be attributed to environmental factors, the researchers reasoned.

Twenty four pairs of identical twins, born in Finland between 1975 and 1979, took part in the study. Fourteen pairs (eight male and six female) were discordant for obesity, that is, one twin was obese, while the other was not. The control group consisted of five male and five female twin pairs who were concordant for weight. Some of the concordant pairs were normal-weight while some pairs were overweight.

The researchers measured whole body insulin sensitivity, body composition and cardiorespiratory fitness. They also obtained a needle biopsy of abdominal subcutaneous fat tissue, although they were unable to obtain this measurement for one of the discordant pairs.

Among the discordant pairs, the study found the obese twin had significantly lower:

* Insulin sensitivity, indicating the body has a harder time using glucose to produce energy.

* Fitness levels, as measured by maximum oxygen uptake and maximum work capacity.

* Transcription levels of genes that help cells convert food to energy (the genes of mitochondrial oxidative phosphorylation). Transcription is a multi-step process in which information in the genes is used to manufacture proteins. Proteins, in turn, direct cell activity. This suggests that the impaired expression of the genes may make it more difficult to lose excess weight, or may make additional weight gain more likely.

Heredity may still play role

"These data suggest that physical inactivity may have contributed to the defects in mitochondrial oxidative phosphorylation described in type 2 diabetic patients and prediabetic subjects," the authors wrote. The authors also noted that, although environment plays a role in how these genes work, there still may be a hereditary component.

"Although we found that the reduced transcript levels of genes encoding mitochondrial oxidative phosphorylation in obesity is influenced by environmental and acquired factors, it does not exclude the possibility that genetic factors contribute to regulation of mitochondrial oxidative metabolism," lead author Linda Mustelin noted.

The next step is to do a clinical study to see if exercise and other lifestyle changes can increase the expression of these genes.

Posted by dlife at 09:03 AM | Comments (0)

Science, Hope For Adults With Type 1 Diabetes Focus Of JDRF's Annual Global Diabetes Research Forum

June 18, 2008 (EurekAlert) - Research findings and innovative approaches offer the promise of new therapies and the potential for cures for adults living with type 1 diabetes, according to researchers at the Juvenile Diabetes Research Foundation's (JDRF's) Global Research Forum in Washington D.C.

Type 1 diabetes is an autoimmune disease that results in the destruction of insulin-producing beta cells in the pancreas. It renders people insulin-dependent for life and carries the constant threat of debilitating and life-threatening complications. Half of those diagnosed each year with type 1 diabetes are adults. Overall, adults with diabetes may have lived with the disease for more than 90% of their lives.

Still Capable of Producing Insulin

Among the research presented at the JDRF conference were insights of the Medalist Study from the Joslin Diabetes Center in Boston. George King, MD, Senior Vice President, Director of Research at the Joslin Center and director of the study, said that individuals with established type 1 diabetes (even those who have lived with it for 50 years or more) are still capable of producing insulin. The Joslin Study also found that even after 50 years about 30% of the patients studied didn't experience common complications such as eye, kidney or nerve disease. These findings have potential implications for improved treatment for all type 1 diabetes sufferers.

Potential for Islet Cell Regeneration

Mark Atkinson, M.D., Director of The Diabetes Center of Excellence at the University of Florida, presented initial findings from nPOD; the Network for Pancreatic Organ Donors with Diabetes. Organized and funded by JDRF, the network was established last August to procure and characterize, in a collaborative manner, pancreatic and related tissues from organ donors with long-standing type 1 diabetes as well as those who are islet autoantibody positive. These tissues would be used to study how type 1 diabetes develops with the hope of finding a means to cure the disease.

Dr. Atkinson presented findings from nPOD, which have enabled researchers to assess the potential for islet cell regeneration. "Contrary to common dogma, what we've learned so far is that some pancreata from subjects with long-standing type 1 diabetes have insulin positive beta cells and some have many intact islets. This finding gives hope for islet cell regeneration or restoration," Atkinson noted. He pointed out another key finding: that some islets have beta cells that don't produce insulin. "If we know beta cells are there, then we can focus on finding ways to get them to produce insulin," Dr. Atkinson explained.

JDRF's Chief Medical Officer, Paul Strumph, MD, also presented findings that showed how beta cell mass expands in response to increased metabolic demands such as growth during the first decade of life, obesity, and pregnancy - leading to possible therapeutics that mimic the biological mechanisms that increase insulin-producing cells in this instances. "A little bit of insulin is not a cure, but it can be significant to reduce the complications of diabetes," Strumph noted.

A New Era of Diabetes Research Has Begun

All of the presenters agreed that researchers are on the cusp of a new era in diabetes research, one in which advanced technology and human clinical research should enhance the development of new therapeutics and an ultimate cure.

"Much of what we've known regarding the pathogenesis of type 1 diabetes has dated back to studies performed with the human pancreas' in the 1970s -- before microwaves, the internet and cell phones, and before modern day medical research technology. Now we're looking at this disease in whole new ways," explained Atkinson.

Strumph added that there is more of an emphasis on looking at the natural history of the disease to guide research opportunities for those with established type 1 diabetes. JDRF is currently devoting a significant portion of its $160 million in research funding to science involving people with established type 1 diabetes, with a particular emphasis on areas such as autoiummunity and regeneration; the organization and plans to fund as much as $195 million on research in the coming 12 months.

Posted by dlife at 10:08 AM | Comments (1)

Depression and Diabetes: Fellow Travelers, Researchers Say

June 17, 2008 (EurekAlert) - Researchers have long known that type-2 diabetes and depression often go hand in hand. However, it's been unclear which condition develops first in patients who end up with both. Now, a new study led by Johns Hopkins doctors suggests that this chicken-and-egg problem has a dual answer: Patients with depression have an increased risk of developing type-2 diabetes, and patients with type-2 diabetes have an increased risk of developing depression.

For the study, published in the June 18 Journal of the American Medical Association, diabetes expert Sherita Hill Golden, M.D., M.H.S., and her colleagues took advantage of data generated by the Multi-Ethnic Study of Atherosclerosis (MESA), which examined risk factors for atherosclerosis, or hardening of the arteries, in an ethnically diverse group of 6,814 men and women between ages 45 to 84. Participants in the MESA study identified themselves when they enrolled as white, black, Hispanic or Chinese.

During MESA, participants made three visits to clinics over the course of three years to be examined for various atherosclerosis risk factors, including type-2 diabetes and symptoms of depression, which could serve as a precursor for full-blown clinical depression.

The study also collected information on other atherosclerosis risk factors, such as participants' body-mass indices, blood pressure, diet and exercise patterns, and smoking habits, as well as information correlated with health in general, such as income and socioeconomic factors.

Mining the data for their own purposes, Golden and her colleagues excluded from their analysis all participants who had high fasting glucose, an indication of diabetes, at the initial clinic visit. They then looked to see whether participants who initially had elevated symptoms of depression, as indicated through a questionnaire, were more likely than those who didn't to develop high fasting glucose at the end of the three-year study period.

Results showed that those with elevated depressive symptoms were 42 percent more likely overall to develop diabetes by the end of the study than those without these symptoms. Moreover, the stronger the symptoms, the higher the risk of diabetes, a "dose response" that lends strength to the findings.

Even when the researchers accounted for such factors as overweight, lack of exercise, and smoking, the risk of developing diabetes was still 34 percent higher for patients with depressive symptoms.

To investigate whether diabetes could lead to depression, Golden and her colleagues used the same pool of MESA information and excluded those who had elevated depressive symptoms at the initial clinic visit. Then, they looked to see whether those who had high fasting glucose—with or without a formal diagnosis of diabetes—were more likely to develop depressive symptoms by the end of the study.

The researchers found that patients treated for diabetes, about 9 percent of the group, were about 54 percent more likely to develop elevated depressive symptoms than those without diabetes.

Surprisingly, those with prediabetes or untreated diabetes were about 25 percent less likely to develop elevated depressive symptoms than people with normal fasting glucose, a finding Golden's team cannot explain at this time.

Golden, an associate professor of medicine and epidemiology at the Johns Hopkins University School of Medicine, speculates that depression may lead patients to develop behaviors that trigger diabetes or make it worse, such as overeating, not exercising or smoking. Similarly, keeping up with the often extensive treatment regimens to care for their diabetes may make patients' depression worse. Understanding how one condition might lead to another could improve treatments for both problems, she says.

"Having both diabetes and depression can make it difficult for patients to get the good clinical outcomes that we like to see for each of these conditions," says Golden. "To make sure that patients with diabetes and depression receive the best care, we wanted to get to the bottom of the connection between these two conditions.

"It's important that doctors be attuned to look for both conditions in patients at risk for either diabetes or depression," Golden adds. "We may want to develop interventions for both treatments, instead of just one or the other."

Posted by dlife at 01:31 PM | Comments (0)

Testosterone Replacement Therapy Reduces Cardiovascular Risk in Men with Diabetes or Metabolic Syndrome

June 17, 2008 (Newswise) — Testosterone replacement therapy reduces insulin resistance, which is associated with high cardiovascular risk, in men with type 2 diabetes and metabolic syndrome, a new study found. The results will be presented Tuesday, June 17, at The Endocrine Society’s 90th Annual Meeting in San Francisco.

“Approximately three quarters of men with diabetes die as a result of cardiovascular disease,” said lead author Professor Hugh Jones, MD, of Barnsley Hospital and the University of Sheffield in the, United Kingdom. “The finding that testosterone replacement therapy improves insulin sensitivity in a placebo-controlled study and that the effect persists over the 12 month treatment period is a very important clinical finding.”

Insulin resistance is a major biochemical defect in diabetes and metabolic syndrome and is associated with the development of high blood sugars, hypertension, and several other factors which combined lead to an increased cardiovascular risk.

Drugs commonly used to treat diabetes also improve insulin sensitivity, but testosterone may have one other benefit. In addition to the effect on insulin sensitivity, the study found that testosterone can also help men with erectile dysfunction. This demonstrates the key importance of testosterone in the erectile process of diabetic men, said Jones.

Patients in the study were testosterone deficient men with type 2 diabetes or metabolic syndrome. They were treated with either 3g 2 percent testosterone gel (Tostran®) per day or a placebo. At 14 days, all patients underwent peak serum testosterone measurement and dose titration.

This is the first large study (220 men) looking at the use of testosterone replacement therapy in men with metabolic syndrome or type 2 diabetes, said Jones. The study involved 40 centers throughout Europe and lasted 12 months.

Metabolic syndrome is a cluster of metabolic risk factors that increase the chances of developing heart disease, stroke, and diabetes. To receive this diagnosis, patients must have three of the following five risk factors: increased waist circumference (abdominal fat), low HDL (“good”) cholesterol, high triglycerides (fats in the blood), high blood pressure, and high blood sugar.

Posted by dlife at 10:05 AM | Comments (0)

New Study: Hearing Impairment Is Common Among Adults With Diabetes

June 17, 2008 (EurekAlert) - Hearing impairment is common in adults with diabetes, and diabetes seems to be an independent risk factor for the condition according to a study published today on the Web site of Annals of Internal Medicine.

"We found that hearing loss was much more common in people with diabetes than people without the disease," says Kathleen E. Bainbridge, PhD, the study's lead researcher. "The hearing loss we detected did not seem to be caused by other factors such as exposure to loud noises, certain medicines, and smoking."

Using the National Health and Nutrition Examination Survey, collected by the National Center for Health Statistics from 1999 to 2004, the researchers analyzed data from 5,140 adults aged 20 to 69 who completed an audiometric examination and a diabetes questionnaire.

Hearing impairment was more prevalent among adults with diabetes. Age-adjusted prevalence of low- or mid-frequency hearing impairment of mild or greater severity assessed in the worse ear was 21.3 percent among 399 adults with diabetes compared to 9.4 percent among 4,741 adults without diabetes. These differences in hearing between people with and without diabetes were present in both sexes; all groups of race or ethnicity, education, and income; and all age groups but the oldest.

Similarly, age-adjusted prevalence of high-frequency hearing impairment of mild or greater severity assessed in the worse ear was 54.1 percent among adults with diabetes compared to 32 percent among adults without diabetes.

Diabetes, which can damage small blood vessels and nerves in the body, affects an estimated 9.6 percent of the U.S. adult population.

"It is possible that high blood sugar levels damage the small blood vessels and nerves of the inner ear, resulting in hearing impairment," says Bainbridge. "People with diabetes might benefit from having their hearing checked."

Hearing impairment was assessed from the pure tone average of thresholds over low or mid-frequencies (500; 1,000; and 2,000 Hz) and high frequencies (3,000; 4,000; 6,000; and 8,000 Hz) and was defined as mild or greater severity (pure tone average greater than 25 decibels hearing level and moderate or greater severity (pure tone average greater than 40 decibels hearing level). Hearing loss is reported by more than 17 percent of the U.S. adult population.

The editors of Annals of Internal Medicine caution that diabetes was self-reported and was verified in only a small fraction of participants, and the researchers did not distinguish between type 1 and type 2 diabetes. Noise exposure was based on participant recall.

In an accompanying editorial, Keiko Hirose, MD, of Washington University, writes, "We have few current therapeutic options for progressive hearing loss from any cause, and the study of hearing loss in diabetic patients could lead to important progress in new techniques of studying and treating microvascular disease of the inner ear."

Posted by dlife at 10:03 AM | Comments (0)

Some Patients May Not Need Insulin For Long-Term Control Of Type 2 Diabetes

June 15, 2008 (EurekAlert) - Some patients with type 2 diabetes can control their disease for years yet avoid insulin injections by using multiple classes of oral diabetic medications, a new study found. The results were presented Sunday, June 15, at The Endocrine Society's 90th Annual Meeting in San Francisco.

Findings from the study contradict common beliefs about non-insulin diabetic medications, said principal investigator Arthur Swislocki, MD, of the Veterans Affairs (VA) Northern California Health Care System in Martinez. Oral diabetes medications help control blood glucose, or sugar, levels in people whose bodies still produce some insulin, as is true for many patients with type 2 diabetes.

"Generally, both patients and physicians believe that long-term use of oral diabetic medications is not possible because these drugs lose their effectiveness over time as the patient's pancreas fails," Swislocki said. "Our data suggest that some patients can remain in good glucose control for years using non-insulin, oral diabetic agents."

The study result is good news for people who need medical therapy for type 2 diabetes, according to Swislocki. "They may be able to delay or avoid the use of insulin," he said.

Some patients prefer pills over insulin injections because they are easier to use or because the patient fears needles or getting low blood sugar, as is possible with insulin treatment, he said.

Swislocki and his coworkers studied the VA medical records of 191 veterans (188 men and 3 women) with type 2 diabetes who received treatment beginning in 1992 and received follow-up for 15 consecutive years. Of these patients, 96 began treatment solely with oral drugs. The researchers found that 55 percent of the patients (53 of 96) who started treatment with oral diabetic agents were able to continue using them 15 years later and achieve good blood sugar control. A measure of long-term blood sugar control—hemoglobin A1c—improved from an average of nearly 8 percent to about 7 percent 15 years later in this group.

Of the 96 patients, 45 percent eventually switched to insulin, either alone or in combination with oral drugs. At the beginning of the study, the duration of diabetes was similar between these patients and those who remained on an oral drug regimen. However, the group of patients who stayed on oral medications throughout the study had a lower beginning A1c and were less obese than patients in the other group, the authors reported. They also were more likely to be white. Past studies show minorities have poorer blood sugar control than do whites.

Swislocki said the long-term effectiveness of oral diabetic medications seen in their study may reflect the wider range of oral drugs now available for treating type 2 diabetes, compared with 15 years ago. Therefore, if one class of drugs became less effective, other classes could be added in combination.

The study, however, did not specifically address whether or not oral diabetic drugs lose their effectiveness over a long time, according to Swislocki. Rather, it mainly tracked the prescribing practices of VA primary care providers. "Deductions about drug effectiveness need to be made cautiously," he said.

Posted by dlife at 10:36 AM | Comments (2)

Current Screening Test For Prediabetes In Children Misses The Diagnosis Too Often

June 15, 2008 (EurekAlert) - Obese children, who are at increased risk for prediabetes and type 2 diabetes, may not be getting the most appropriate test to screen for these conditions, a new Canadian study found. Results were presented Sunday, June 15, at The Endocrine Society's 90th Annual Meeting in San Francisco.

The standard screening test for high blood sugar in children with risk factors—a blood test called the fasting plasma (or blood) glucose test—identified nearly 3 times fewer the children with prediabetes than did a longer blood test, said the study's lead author.

Katherine Morrison, MD, from the pediatrics department of McMaster University, Hamilton, Ontario, said the more accurate test was the glucose stress test, also called the oral glucose tolerance test. This test takes longer because the patient has blood drawn after fasting and again 2 hours after drinking a sugary solution.

Compared with the glucose stress test, the fasting blood glucose test also was not as sensitive in detecting metabolic syndrome. This syndrome is a cluster of risk factors for heart disease and diabetes, including a high blood sugar level.

"Prediabetes and metabolic syndrome are common in obese children but are not readily identified with the currently recommended test," Morrison said. "They require a glucose stress test."

The authors studied 172 obese children, ages 5 to 17, who joined a program to help attain a healthy weight. All children had evaluation of risk factors for diabetes (or its precursor, prediabetes) and metabolic syndrome, including testing of blood sugar. Using the glucose stress test, the researchers found that 25 percent of the children met the diagnostic criteria for prediabetes. But when they relied on results of the fasting blood glucose test, as recommended by the American and Canadian diabetes associations, they found that only 8 percent of the children had prediabetes.

"A large proportion of the children with prediabetes would not have had their condition recognized," Morrison said.

The same was true for the metabolic syndrome. Of the children in the study, 12.8 percent had a diagnosis of this syndrome (based on International Diabetes Federation pediatric criteria) using the glucose stress test, compared with just 5.2 percent using the standard test, the authors reported.

Prediabetes and the metabolic syndrome usually cause no obvious symptoms. Early detection is important because changes in diet, regular exercise, and moderate weight loss can help prevent or delay diabetes and the metabolic syndrome. Although adults receive diabetes screening with either blood test, children typically do not get the 2-hour glucose stress test, Morrison said.

"The commonest reasons are the increased time, inconvenience, and cost required for 2-hour testing," she said. "But this research suggests that the recommended test for screening obese children for prediabetes and metabolic syndrome should be changed."

Posted by dlife at 10:30 AM | Comments (0)

Severe Insulin Resistance may Increase Rate of Pregnancy and Birth Complications

June 15, 2008 (Newswise) - Testing pregnant women for insulin resistance with a simple blood test may be a new tool for predicting problems during pregnancy, according to a new study. The results will be presented at The Endocrine Society’s 90th Annual Meeting in San Francisco.

Insulin resistance is a condition in which the body blocks the effects of the hormone insulin. As a result, glucose, or sugar, builds up in the blood, and diabetes can develop. Insulin resistance lies behind the development of gestational diabetes—diabetes that develops during pregnancy—which increases the risk of pregnancy and birth complications. Therefore, the authors aimed to find out whether insulin resistance is linked to poor outcomes in pregnant women and newborns, said the lead author, Weerapan Khovidhunkit, MD, PhD, of Chulalongkorn University, Bangkok, Thailand.

It is standard for pregnant women to get a blood test for gestational diabetes between the 24th and 28th weeks of pregnancy, according to The Hormone Foundation, the public education affiliate of The Endocrine Society. This test is called the glucose challenge test or glucose challenge screening. If this test result is positive, the woman then has an oral glucose tolerance test (OGTT), in which her blood sugar levels are tested 3 hours after she drinks a glucose drink.

“The OGTT is time-consuming,” Khovidhunkit said. “Also, many women cannot tolerate an OGTT due to nausea and vomiting.”

It is possible for women to have high insulin resistance without having gestational diabetes, according to Khovidhunkit. A special test of insulin resistance, called HOMA, is not part of standard pregnancy tests, but it is quick and easy, he said. This test relies on a fasting blood test of glucose and insulin levels.

The authors studied 538 pregnant women who had positive glucose challenge tests and then underwent the OGTT. The researchers also assessed insulin resistance using HOMA. They tracked pregnancy complications, including preeclampsia, a condition involving high blood pressure; excess amniotic fluid (called polyhydramnios); premature rupture of the membranes, in which the woman’s water breaks before she goes into labor; and need for a cesarean section.

Even if women did not have gestational diabetes, those who had the highest degree of insulin resistance (above 2.44) had nearly 1.5 times the rate of pregnancy complications than those with the lowest insulin resistance, the authors found. The most common maternal complication was need for a cesarean section, according to Khovidhunkit.

Similarly, babies born to women in the group that had the highest degree of insulin resistance had a complication rate at birth 1.75 times higher than babies born to women with the lowest insulin resistance. The most common newborn complications were macrosomia—an abnormally large size—as well as low blood sugar (hypoglycemia), the authors reported.

The study tested only pregnant women who were at increased risk of pregnancy complications because they had high blood glucose levels, as shown by a positive glucose challenge test. Therefore, Khovidhunkit said, “Before we can advise pregnant women to undergo this testing, further studies are needed in other patient populations.”

Posted by dlife at 12:24 PM | Comments (0)

Weight Gain Main Factor In Falling Beta Cell Function In Hispanic Women

June 10, 2008 (Newswise) - A study by researchers at the University of Southern California (USC) found that weight gain was the strongest factor associated with falling beta cell function in Hispanic women, a condition that often leads to diabetes.

The results of the study were presented as an oral presentation on Monday, June 9 at the American Diabetes Association meeting 68th Scientific Sessions held in San Francisco.

“We know that type 2 diabetes in young Hispanic women occurs when pancreatic beta cells, the cells that make insulin to regulate blood sugar levels, fail progressively over time in people who are overweight, and thus resistant to their body’s insulin,” says Anny Xiang, Ph.D., associate professor in the Department of Preventive Medicine at the Keck School of Medicine of USC and the lead author of the study. “In this study, we looked for factors that might contribute to the failing beta cell function in a cohort of women who we followed with detailed metabolic measurements over five years.”

The study examined 60 women (28 with normal glucose tolerance and 32 with impaired tolerance) who had oral and intravenous glucose tolerance tests 15-30 months postpartum. Results showed that weight gain appeared to negatively impact beta cell function in two ways—it worsened insulin resistance, which places increased demands on beta cells to make more insulin, and it led to changes in some hormones from fat cells that may be damaging to beta cells, she says.

“The results highlight the importance of reducing the negative effects of excess fat if we want to prevent or delay diabetes,” Xiang notes. “The bad effects could be reduced by weight loss, or at least the prevention of weight gain, and by creating a better hormonal pattern from fat cells.”

Further follow-up data will allow researchers to examine the long-term pathogenesis in diabetes development, as well as look for genetics determinants of beta cell failure in Hispanic Americans in a separate study.

The study was funded by the National Institutes of Health-National Institute of Diabetes and Digestive and Kidney Diseases.

Posted by dlife at 11:16 AM | Comments (2)

Belly Fat May Affect Liver Function

June 10, 2008 (Newswise) - A study by the University of Southern California (USC) suggests the release of lipids from abdominal fat, which drains directly to the liver, increases overnight, providing additional insight as to how abdominal fat is associated with type 2 diabetes risk. The results of the study were presented at an oral session Monday, June 9 at the American Diabetes Association 68th Scientific Sessions held in San Francisco.

“It has been shown that people who store body fat in their abdomens are at greater risk to develop diabetes and other chronic illnesses, but why this happens has remained unclear,” says Lisa Nicole Harrison, B.S., Master’s candidate, at the Keck School of Medicine of USC and lead author on the study. “Our study found lipid release from abdominal fat was substantially elevated during the night, which may be a primary mechanism leading to insulin resistance, a strong risk factor for type 2 diabetes.”

The observed lipids drain directly to the liver, a key center of glucose and insulin metabolism, where they may accumulate as triglyceride and cause dysregulation of these important metabolic processes, Harrison says. The results highlight the importance of abdominal obesity in the pathogenesis of type 2 diabetes.

“Further studies in this area should look at the cause of overnight elevation of abdominal fat release as well as clarifying the role this plays in the development of obesity and insulin resistance,” suggests Harrison.

The study was funded by grants from the National Institutes of Health.

Lisa N. Harrison, Maya Lottati, Cathryn M. Kolka, Isabel R. Hsu, Vahe Mooradian, Justin Dittmann, Edward Zuniga, Edgardo Paredes, Richard N. Berman, “Nocturnal Outpouring of FFA from Visceral Fat Depot.” Presented at 2:15pm. PT, Monday June 9.

Posted by dlife at 11:03 AM | Comments (6)

Unique Drug Combination May Hold The Key To Reversing Type 1 Diabetes

June 10, 2008 (EurekAlert) - Norfolk, Virginia – Promising results from a study that tested a new approach for reversing Type 1 diabetes are being presented this week at the American Diabetes Association's 68th Annual Scientific Session in San Francisco.

The study tested the combination of Lisofylline (LSF), a drug that is being developed to halt immune damage to insulin producing cells, and Islet Neogenesis Associated Protein peptide (INGAP), a drug based on a naturally occurring protein produced by the pancreas. (ADA abstract number: 1620-P Unique Drug Combination for Reversal of Type 1 Diabetes, by Tersey, Carter, Kropf, Rosenberg, Nadler, available online at http://scientificsessions.diabetes.org)

The study was conducted at the University of Virginia by a team of scientists led by Jerry L. Nadler, M.D. Currently Director of Endocrinology and Metabolism at the University of Virginia, Nadler will join the faculty at Eastern Virginia Medical School (EVMS) in July as chair of the Department of Internal Medicine and head of the EVMS Strelitz Diabetes Center.

INGAP was discovered in 1997 at the EVMS Strelitz Diabetes Center by Aaron I. Vinik, M.D., Ph.D., Professor of Internal Medicine and the Strelitz Center's Director of Research.

Diabetes is caused by the body's inability to produce or process insulin, a hormone that cells need to convert food into energy. Uncontrolled diabetes causes serious complications throughout the body, including cardiovascular disease, blindness, kidney failure, and nerve disease. Type 1 diabetes is an autoimmune disease, caused when the body's own immune system mistakenly attacks and destroys the insulin-producing cells of the pancreas. This damage was once thought to be irreversible, however, new evidence suggests that the pancreas has an innate ability to repair and regenerate the insulin-producing cells. In Type 1 diabetes, however, the pancreas' ability to self-repair cannot keep pace against the autoimmune response that is causing the diabetes.

In this study, diabetic mice were either given a placebo (saline) or treated with LSF, INGAP peptide, or LSF and INGAP together. The remission rate was most striking when mice were first treated with LSF in an effort to dampen the autoimmune system and then treated with the combination of LSF and INGAP peptide. This novel therapy resulted in a remission of diabetes in 70% of the mice after all treatments were withdrawn, including animals with very high blood glucose levels prior to treatment. Mice treated with INGAP peptide alone or INGAP peptide/LSF combinations averaged markedly higher levels of serum insulin after treatment than saline treated controls and were similar to non-diabetic mice. It was only when the combination of LSF and INGAP was used that a reversal of hyperglycemia was observed.

"These are very encouraging results," Nadler said. "Since both LSF and INGAP are already known to be safe, we should soon be able to begin testing the combination of LSF and INGAP in the clinic as a potential therapy for Type 1 diabetes in people soon."

Nadler was recruited to EVMS as part of a strategic initiative to expand the medical school's research capabilities in four areas where the state's eastern region has specific health needs and EVMS has existing research strengths, including: diabetes, cardiovascular disease, women's health/infant development, and cancer.

"Our ultimate goal is to improve the health of individuals by discovering novel approaches to the kinds of diseases that take a serious toll on the quality of life in our community and around the world," said Gerald J. Pepe, Ph.D., Dean and Provost of Eastern Virginia Medical School. "Dr. Nadler's work with LSF and INGAP is exactly the kind of innovative new therapy that we want to bring to fruition. Imagine the impact it would have to be able to reverse diabetes."

Posted by dlife at 10:16 AM | Comments (2)

Diabetes Medication Associated With Slower Progression Of Retina Disease

June 9, 2008 (EurekAlert) - Patients with diabetes who take the medication rosiglitazone may be less likely to develop the eye disease proliferative diabetic retinopathy or to experience reductions in visual acuity (sharpness), according to a report in the June issue of Archives of Ophthalmology, one of the JAMA/Archives journals.

Proliferative diabetic retinopathy occurs when existing blood vessels in the retina are blocked or damaged and new, tiny blood vessels form, according to background information in the article. It one of is the most common causes of severe vision loss among working-age Americans, and few effective therapies exist to delay its progression.

Lucy Q. Shen, M.D., of the Jules Stein Eye Institute, University of California–Los Angeles, and colleagues reviewed the medical records of 124 patients who were treated with rosiglitazone and who were receiving medical and ophthalmic care at the Joslin Diabetes Center in Boston between May 2002 and May 2003. They compared these patients to 158 patients who also had diabetes but were not taking rosiglitazone or a similar medication.

At the beginning of the study, 14 eyes of those in the rosiglitazone group (6.4 percent) and 24 eyes of those in the control group (9.3 percent) had severe non-proliferative diabetic retinopathy, an earlier stage of the disease in which new blood vessels have not yet developed. Among those, 7.7 percent of those in the rosiglitazone group and 29.2 percent of those in the control group progressed to proliferative diabetic retinopathy after one year. After three years, 19.2 percent in the rosiglitazone group and 47.4 percent in the control group had progressed from non-proliferative to proliferative diabetic retinopathy—a 59.5 percent relative risk reduction in the rosiglitazone group.

In addition, fewer eyes in the rosiglitazone group than in the control group experienced a loss in visual acuity of three or more lines on the vision chart (.5 percent vs. 14.5 percent) during an average of 2.8 years of follow-up.

Rosiglitazone may delay the progression of retinopathy and preserve vision by reducing the formation of new blood vessels, a process known as angiogenesis, the authors note. "However, because this study does not rigorously prove that rosiglitazone either reduces the incidence of proliferative diabetic retinopathy or prevents loss of visual acuity, and because there may be adverse effects from therapy, rosiglitazone treatment of patients with diabetes specifically to reduce these ophthalmic complications is not advocated at this time," they write. Known adverse effects include fluid build-up, abnormal liver function test and the worsening of congestive heart failure.

"Determination of the full efficacy and clinical role of rosiglitazone in the treatment of proliferative diabetic retinopathy and other angiogenic conditions awaits confirmation of risks and benefits and possibly large-scale definitive studies," the authors conclude.

Posted by dlife at 10:57 AM | Comments (0)

Researchers Identify Gene that Regulates Glucose Levels and Increases Risk for Diabetes

June 9, 2008 (Newswise) — Researchers at the University of Southern California (USC) have helped identify a genetic variant that regulates glucose levels and also increases the risk of type 2 diabetes. The results of the study were presented as an oral presentation on Saturday, June 7, at the American Diabetes Association 68th Scientific Sessions held in San Francisco.

“We tested for an association between genetic variants across the human genome and fasting glucose and insulin,” says Richard M. Watanabe, Ph.D., associate professor of preventive medicine and physiology & biophysics at the Keck School of Medicine of USC and lead author of the paper. “We found a novel association between fasting glucose and the melatonin receptor 1B (MTNR1B). It’s novel because this is the first time a genetic variant has been associated with both glucose and increased risk of diabetes.”

The study examined genetic information from 6,543 people participating in three independent genome-wide association studies for fasting glucose and insulin. The studies included Finland-United States Investigation of Non-insulin-dependent Diabetes Mellitus (FUSION) study and the SardiNIA study of aging and the Diabetes Genetics Initiative.

“The MTNR1B finding is interesting because melatonin is involved with regulating circadian rhythms, like sleep cycles, and people with sleep disorders, like sleep apnea, tend to develop obesity and insulin resistance, which are risk factors for type 2 diabetes,” continues Watanabe. “More studies will be needed to understand how MTNR1B is involved in regulating glucose and associated risk for diabetes.”

Richard M. Watanabe, Wei-Min Chen, Michael R. Erdos, Richa Saxena, Anne U. Jackson, Valerie Lyssenko, Manuela Uda, Thomas A. Buchanan, David Schlessinger, Leif Groop, Francis S. Collins, David Altshuler, Goncalo Abecasis, Micheal Boehnke, Angelo Scuteri, “Novel Genetic Loci for Fasting Glucose and Insulin Identified by Genome-wide Association in Caucasians.” Abstract # 137-OR.

Posted by dlife at 10:26 AM | Comments (0)

NASTECH Announces Positive Intranasal Insulin Data at American Diabetes Association Meeting

June 9, 2008 (Press Release) - Nastech Pharmaceutical Company Inc. (Nasdaq: NSTK) announced today data from a Phase II clinical trial demonstrating that its ultra rapid acting intranasal insulin was both superior to usual therapy (oral anti-diabetic medicines and/or basal insulin) and non-inferior to insulin aspart (NovoLog®), a rapid-acting injectable insulin, in maintaining glucose control at both 60 and 90 minutes following a meal. The data also demonstrated a statistically significant reduction in the incidence of hypoglycemia (low blood sugar <70 mg/dL) compared with insulin aspart in the four hours following the meal. The data were reported at the 68th Scientific Sessions meeting of the American Diabetes Association in San Francisco in an oral presentation by Professor Lutz Heinemann, Ph.D., of the Profil Institute for Metabolic Research Ltd., and in a Nastech poster presentation.

“The data from our Phase II intranasal insulin study show a combination of very desirable attributes: efficacy similar to that of the best mealtime insulin treatment, the safety advantage of lower rates of post-meal hypoglycemia, the further safety advantage of not getting into the lungs, and the convenience of a nasal spray,” said Steven C. Quay, M.D, Ph.D., Chairman and CEO of Nastech.

As noted by Dr. Sherwyn Schwartz, Principal Investigator with dgd Research, now a member of Cetero Research, “Currently, Type 2 diabetic patients’ mealtime glucose is less well controlled than it needs to be to attain good diabetes control. Patients avoid rapidly acting injected mealtime insulin for a variety of reasons, including a fear of needles, the perception that having to inject medication indicates a more serious disease, and concerns over hypoglycemia. The characteristics of Nastech’s intranasal insulin may represent an important advantage for doctors and patients attempting to gain better control of mealtime glucose.”

Results of the trial demonstrated that both intranasal insulin and NovoLog were significantly better at 60 and 90 minute glucose control than the patient’s usual therapy, which typically consisted of oral diabetic medications. The study’s primary endpoint was proven: that intranasal insulin was non-inferior for 60 and 90 minute glucose change from baseline compared with insulin aspart. Importantly, intranasal insulin demonstrated a significantly lower incidence (three percent, or one of 29 patients) of hypoglycemia (glucose level <70 mg/dl) compared to insulin aspart (21 percent or six of 29 patients; p=0.025) during the four hours post meal. In addition, the time to maximum concentration for intransal insulin was faster (30 minutes) than for insulin aspart (90 minutes), which further demonstrates the ultra rapid-acting nature of the product.

“The study results are also very important in the context of concerns about inhaled insulin. Our product is different from recently cancelled pulmonary insulin programs because there is little to no
pulmonary exposure,” Dr. Quay continued. “In addition, our intranasal insulin product does not require refrigeration, is easy to use and provides convenience for patients.”

The Phase II study involved 29 Type 2 diabetics, mean aged 57, with an average duration of diabetes of 7.3 years. The patients ate a standard meal on each study day. On day one of the study, they took their usual therapy and glucose levels were monitored. During subsequent days, patients were randomized to receive either an optimized insulin aspart dose or an optimized intranasal insulin before the meal.

About Diabetes and Insulin

In the United States, approximately 21 million people have diabetes and 1.5 million new patients are diagnosed every year, according to the American Diabetes Association. Type 2 diabetes accounts for an estimated 90 to 95 percent of all cases. Complications can include cardiovascular disease, kidney disease, blindness and diseases of the central nervous system. Injectable insulin has been used to treat diabetes since the early 1920s and continues to be the definitive treatment for diabetes worldwide. Branded insulin product sales were approximately $9 billion worldwide in 2006. The total direct and indirect economic cost related to diabetes in 2002 was estimated to be $132 billion annually in the United States.

About Nastech

Nastech is a clinical stage biopharmaceutical company focusing on the development and commercialization of innovative therapeutic products based on its proprietary ribonucleic acid interference technology and its proprietary molecular biology-based drug delivery technologies. Nastech and its collaboration partners are developing products for multiple therapeutic areas including diabetes, obesity, osteoporosis, autism, respiratory diseases and inflammatory conditions. Additional information about Nastech is available at http://www.nastech.com.

Nastech Forward Looking Statement

Statements made in this news release may be forward-looking statements within the meaning of Federal Securities laws that are subject to certain risks and uncertainties and involve factors that may cause actual results to differ materially from those projected or suggested. Factors that could cause actual results to differ materially from those in forward-looking statements include, but are not limited to: (i) the ability of Nastech or a subsidiary to obtain additional funding; (ii) the ability of Nastech or a subsidiary to attract and/or maintain manufacturing, research, development and commercialization partners; (iii) the ability of Nastech, a subsidiary and/or a partner to successfully complete product research and development, including preclinical and clinical studies and commercialization; (iv) the ability of Nastech, a subsidiary and/or a partner to obtain required governmental approvals; and (v) the ability of Nastech, a subsidiary and/or a partner to develop and commercialize products that can compete favorably with those of competitors. Additional factors that could cause actual results to differ materially from those projected or suggested in any forward-looking statements are contained in Nastech's most recent periodic reports on Form 10-K and Form
10-Q that are filed with the Securities and Exchange Commission. Nastech assumes no obligation to update and supplement forward-looking statements because of subsequent events.

Posted by dlife at 10:11 AM | Comments (0)

Promising Advances In Islet Cell Transplants For Diabetes

June 9, 2008 (EurekAlert) - University of Illinois at Chicago researchers have modified the procedure for islet cell transplantation and achieved insulin independence in diabetes patients with fewer but better-functioning pancreatic islet cells.

The study results are published in the June issue of the American Journal of Transplantation.

UIC is one of only a few centers worldwide able to achieve reproducible and consistent insulin independence in severe type 1 diabetes patients.

In the UIC study, 10 patients with diabetes received between one and three islet cell transplants and were followed for 15 months.

Four received the Edmonton protocol, developed at the University of Alberta, which uses a combination of two immunosuppressants and a monoclonal antibody drug, daclizumab.

Six patients received the UIC protocol -- a combination of etanercept (an anti-inflammatory drug developed to treat rheumatoid arthritis) and exenatide (a drug approved for use in type 2 diabetes to improve glucose control) -- and the Edmonton regimen.

The new procedure allowed patients to get off insulin after a single transplant versus the two to four transplants that were needed using the older protocol, said Dr. José Oberholzer, director of cell and pancreas transplantation at UIC and lead author of the study.

All patients in the study achieved insulin independence, but those who received the UIC protocol required fewer than half the number of islets as those who were treated under the Edmonton protocol.

The four patients who received the Edmonton protocol needed either two or three sequential islet cell transplants to achieve insulin-independence.

The six patients who were treated using the UIC protocol initially achieved insulin-independence after only one islet transplant. Two of these patients required a second islet cell transplant, and one resumed insulin five months after the second transplant due to other complications.

Progress in islet cell transplantation has been limited by the shortage of donor organs, said Oberholzer, who is associate professor of surgery, bioengineering and endocrinology at UIC.

"This study is extremely promising and shows that we can achieve success with fewer islet cells, freeing patients from the need to check their insulin, even after 20 or 30 years of suffering from diabetes," he said.

UIC is one of seven federally funded National Institutes of Health Islet Cell Resource Centers across the country that provides researchers with human pancreatic islet cells for transplantation into diabetic patients and for basic science research on diabetes.

"We have proven that if you have the right team and the right environment you can achieve islet cell transplantation success in a very short time," said Oberholzer, who has led UIC's program since 2003.

Building on results from Oberholzer's study, UIC is participating in the Clinical Islet Transplant Consortium, funded by the NIH to identify the most effective combination of anti-rejection drugs to maximize islet engraftment while reducing toxic side-effects.

Posted by dlife at 09:45 AM | Comments (1)

Racial Disparities Exist Among Diabetes Patients Treated By The Same Physician

June 9, 2008 (EurekAlert) - Black patients with diabetes are less likely than white patients to achieve long-term control of their blood glucose, blood cholesterol and blood pressure levels, even when they are treated by the same physician, according to a report in the June 9 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.

Racial disparities in the quality of diabetes care have been previously documented, according to background information in the article. Black patients with diabetes are less likely to receive recommended components of care, including hemoglobin A1C testing (HbA1C, a measure of blood glucose control over time) and lipid testing, and to achieve treatment goals, such as controlled blood pressure, cholesterol and blood glucose levels. In addition, black patients are more likely than white patients to develop diabetes-related eye and kidney disease and to have amputations of their lower extremities. "Identifying the underlying reasons and potential solutions for these differences in quality of care and outcomes is a high priority," the authors write.

Thomas D. Sequist, M.D., M.P.H., of Harvard Vanguard Medical Associates, Boston, and colleagues analyzed electronic medical records from 4,556 white patients and 2,258 black patients with diabetes treated by 90 primary care physicians in eastern Massachusetts. Each physician treated at least five black patients and five white patients; all patients were age 18 or older and had visited the physician within the last two years.

Black patients and white patients received tests of low-density lipoprotein (LDL or "bad") cholesterol and HbA1C at similar rates. However, white patients were more likely than black patients to reach commonly accepted benchmarks for controlled levels of HbA1C (47 percent vs. 39 percent), LDL cholesterol (57 percent vs. 45 percent) and blood pressure (30 percent vs. 24 percent).

"Patient sociodemographic factors explained 13 percent to 38 percent of the racial differences in these measures, whereas within-physician effects accounted for 66 percent to 75 percent of the differences," the authors write. "Thus, racial differences in outcomes were not related to black patients differentially receiving care from physicians who provide a lower quality of care, but rather that black patients experienced less ideal or even adequate outcomes than white patients within the same physician panel."

The variation in diabetes care was not related to overall performance or the volume of black patients treated by individual physicians, the authors note. "Our data suggest that the problem of racial disparities is not characterized by only a few physicians providing markedly unequal care, but that such differences in care are spread across the entire system, requiring the implementation of system-wide solutions," they write. "Efforts to eliminate these disparities, including race-stratified performance reports and programs to enhance care for minority patients, should be addressed to all physicians."

(Arch Intern Med. 2008;168[11]:1145-1151. Available pre-embargo to the media at www.jamamedia.org.)

Editor's Note: This study was funded by the Robert Wood Johnson Foundation Finding Answers: Disparities Research for Change National Program. Dr. Sequist serves as a consultant on the Aetna External Advisory Committee for Racial and Ethnic Equality. Co-author Dr. Ayanian serves as a consultant to RTI International and DxCG Inc. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Posted by dlife at 09:03 AM | Comments (0)

Gene That Regulates Glucose Levels And Increases Risk For Diabetes Identified

June 9, 2008 (Science Daily) - Researchers at the University of Southern California (USC) have helped identify a genetic variant that regulates glucose levels and also increases the risk of type 2 diabetes. The results of the study were presented as an oral presentation on Saturday, June 7, at the American Diabetes Association 68th Scientific Sessions held in San Francisco.

"We tested for an association between genetic variants across the human genome and fasting glucose and insulin," says Richard M. Watanabe, Ph.D., associate professor of preventive medicine and physiology & biophysics at the Keck School of Medicine of USC and lead author of the paper. "We found a novel association between fasting glucose and the melatonin receptor 1B (MTNR1B). It's novel because this is the first time a genetic variant has been associated with both glucose and increased risk of diabetes."

The study examined genetic information from 6,543 people participating in three independent genome-wide association studies for fasting glucose and insulin. The studies included Finland-United States Investigation of Non-insulin-dependent Diabetes Mellitus (FUSION) study and the SardiNIA study of aging and the Diabetes Genetics Initiative.

"The MTNR1B finding is interesting because melatonin is involved with regulating circadian rhythms, like sleep cycles, and people with sleep disorders, like sleep apnea, tend to develop obesity and insulin resistance, which are risk factors for type 2 diabetes," continues Watanabe. "More studies will be needed to understand how MTNR1B is involved in regulating glucose and associated risk for diabetes."

Richard M. Watanabe, Wei-Min Chen, Michael R. Erdos, Richa Saxena, Anne U. Jackson, Valerie Lyssenko, Manuela Uda, Thomas A. Buchanan, David Schlessinger, Leif Groop, Francis S. Collins, David Altshuler, Goncalo Abecasis, Micheal Boehnke, Angelo Scuteri, "Novel Genetic Loci for Fasting Glucose and Insulin Identified by Genome-wide Association in Caucasians." Abstract # 137-OR.

Posted by dlife at 02:47 PM | Comments (0)

Large, Long-Term Veterans Affairs Diabetes Trial (VADT) Reveals Important Cardiovascular Safety News on AVANDIA(R)

June 8, 2008 (PRNewswire) - Findings from the Veterans Affairs Diabetes Trial (VADT), a large, long-term and independent cardiovascular (CV) outcomes study in high-risk diabetes patients were released today at the 68th Scientific Sessions of the American Diabetes Association (ADA). According to news announced by the ADA, AVANDIA(R) (rosiglitazone maleate) was used in a majority of patients in the study and was not associated with increased deaths. These safety data are consistent with results from other long-term studies with AVANDIA. The primary result of VADT did not show that intensive blood sugar control (HbA1c levels below 7%) had a statistically significant effect on reducing major CV events associated with diabetes. However, it was found that there was a favorable trend in reducing all CV events, except CV death, among the patients in the intensive arm.

"Given the size and duration of this trial, the data on AVANDIA offer important safety information to physicians treating patients with type 2 diabetes," said Farhad Zangeneh, MD, FACP, FACE, assistant clinical professor of medicine at the George Washington University in Washington, DC and medical director of the Endocrine, Diabetes & Osteoporosis Clinic in Sterling, VA.

Dr. Zangeneh added, "While the VADT did not meet its primary endpoint, it is critical that these results do not detract from what we already know about the benefits of long-term blood sugar control on other serious and potentially life-threatening complications of diabetes, such as kidney failure, blindness and amputation."

In VADT, the patient population was considered at higher risk for CV disease since more than 40% had prior CV events. Further, trial participants had other risk factors, including hypertension (80%), lipid abnormalities (50%) and the majority were obese. Due to this high-risk patient population, the investigators predicted that there would be 650-700 CV events among the patients. However, there were significantly fewer CV events in the trial - 263 in the standard group and 231 in the intensive group.

Use of AVANDIA in VADT

AVANDIA was used along with other treatment options in the intensive arm to achieve tight glycemic goals. AVANDIA was the most commonly prescribed drug in the first year of the study - 85% and 78% in the intensive and standard arms, respectively. By the third year, use of AVANDIA decreased to 72% in the intensive arm and to 62% in the standard arm. The investigators noted that some of the reasons for this decrease relate to the known side effects of weight gain and edema associated with AVANDIA. There were no increased deaths in the study that were associated with AVANDIA.

VADT Study Design

VADT is a prospective, two-arm, randomized clinical trial designed to evaluate whether intensification of glucose control can reduce major CV events in patients with type 2 diabetes. A total of 1,791 mostly male veterans aged 41 and older with type 2 diabetes who were no longer responding to a maximum dose of at least one oral antidiabetic agent and/or daily insulin injections were enrolled over two years and followed up for a period of five to seven years, with clinician visits scheduled every 1.5 months; and were randomized to receive either intensive glycemic therapy (HbA1c less than 7%) or standard glycemic therapy (HbA1c = 8-9%).

Diabetes and the Role of Improved Blood Sugar Control

More than 19 million Americans have type 2 diabetes - a chronic, progressive and serious disease that occurs either when the body does not produce enough insulin or when the body does not respond properly to its natural insulin.

Improving blood sugar control in people with type 2 diabetes can help reduce the risk of diabetes-related complications, which include heart disease, stroke, eye damage, kidney failure and foot problems that lead to amputations. An epidemiological analysis from the United Kingdom Prospective Diabetes Study (UKPDS) showed that every one percent drop in HbA1c is associated with a significant reduction in risk of death related to diabetes by 21 percent, heart attack by 14 percent and diabetes-related microvascular complications by 37 percent.

Posted by dlife at 02:37 PM | Comments (0)

World's Largest Trial of Intensive Glucose Control in Type 2 Diabetes Finds Significant Reduction in Serious Complications - 21% Reduced Kidney Disease

June 6, 2008 (ADA) - The world’s largest diabetes trial has shown intensive blood glucose control in type 2 diabetes reduces the risk of complications – notably a 21% reduction in risk for kidney disease. The study also showed no evidence of any increased risk of death when blood glucose was intensively controlled, according to reports presented here today at the American Diabetes Association’s 68th Annual Scientific Sessions.

“The results clearly demonstrate that intensive control of blood glucose, as recommended by most current clinical guidelines, has an important role in the prevention of renal complications of type 2 diabetes. The other major finding of the trial was that major macrovascular events – heart attack, stroke and death from cardiovascular disease – were not significantly reduced with intensive glucose control, although there was a trend towards improvement in these outcomes. However, the results suggest that a multifactorial approach addressing all the major risk factors including blood pressure and blood lipids is required to prevent macrovascular disease,” said Anushka Patel, MBBS, SM, PhD, Study Director of the ADVANCE trial, and Director, Cardiovascular Division, The George Institute for International Health, which conducted the study, in a recent interview. “The key message is that the study confirms the current approach that intensively controlling blood glucose has an important role in the prevention of the microvascular complications of diabetes.”

There was no evidence of an increased risk of death among ADVANCE patients receiving intensive treatment to lower blood glucose, in contrast to the similar ACCORD trial in the U.S., which was discontinued prematurely earlier this year due to an increased rate of death in its intensive arm.

“Overall, we found that the intensive control strategy reduced the combined risk of macrovascular and
microvascular complications by 10%, but that was driven largely by the microvascular results,” said Dr Patel. “Further, the 14% reduction in microvascular risk was driven mainly by nephropathy rather than retinopathy. We found that intensively controlling blood glucose reduces risk of the development or progression of kidney disease by 21%.”

ADVANCE did not show a statistically significant effect of intensive glucose control on cardiovascular
disease (10% in the intensively treated group vs., 10.6% in the standard group). “We believe a protective effect remains plausible since we were aiming for a 1% difference in A1C levels between the standard and intensive groups, but achieved an average of a 0.7% difference over the course of the trial,” said Dr. Patel. “Further, the rate of cardiovascular events was only 2.2% per year rather than the expected 3% per year, possibly due to more aggressive treatment of blood pressure and lipids.” She also noted that the wide confidence interval in the trial’s results does not exclude the benefits that epidemiologic evidence predicts.

A1C is a measure of blood glucose over the prior two to three months.

Trial Design
The ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron-MR Controlled Evaluation) trial was an international study involving 11,140 high-risk patients with type 2 diabetes based at 214 centers in 20 countries worldwide.

“ADVANCE was designed to address two of the major uncertainties in the prevention of the vascular
complications of diabetes: whether important clinical benefits would result from reducing A1C to 6.5% or lower and from intensive blood pressure lowering, whether or not the patient had had hypertension,” said Stephen MacMahon, DSc, PhD, MPH, Co-Principal Investigator of the study, Principal Director of The George Institute for International Health. He is also a Professor of Cardiovascular Medicine and Epidemiology at the University of Sydney. In a factorial design, patients received blood-pressure-lowering treatment with a fixed-dose combination of the angiotensin-converting enzyme inhibitor perindopril and the diuretic indapamide or a placebo, and diabetes
treatment with gliclazide MR, plus other anti-diabetic drugs as needed.

The average age of participants was 66, with 46% coming from Europe, 37% from Asia, 13% from
Australia and New Zealand, and 4% from North America. At the outset, 32% of the participants had already had a cardiovascular event, such as a stroke or heart attack, and the balance were already at high risk due to such risk factors as a history microalbuminuria (protein in the urine), proliferative diabetic retinopathy, current cigarette smoking, elevated total cholesterol, or low HDL (the “good” cholesterol).
“The key objective was to get the intensive group patients down to an A1C of 6.5%, which the trial achieved,” said Dr. MacMahon. The investigators did not have a particular target for the standard group so they did not have control of what the standard group would achieve.

“At baseline, the average A1C of all participants was 7.5%,” said Dr. MacMahon. “Physicians treating
those in the standard group could give them any medications they chose according to the guidelines in the local country. Physicians