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The study, led by Dr. Theodore Mazzone, professor of medicine at UIC, is posted online and will appear in the Dec. 6 print issue of JAMA. The results will also be presented at the American Heart Association scientific session in Chicago.

Patients with type 2 diabetes are known to have an increased risk of heart attack and other cardiovascular events. Some evidence suggests that a class of oral drugs used to treat type 2 diabetes called thiazolidinediones may be useful in reducing the progression of atherosclerosis, a thickening and hardening of the arteries that can lead to cardiac events.

Mazzone and colleagues conducted a Chicago-area multicenter trial to test a potential new approach for slowing the thickening of artery walls in diabetic patients.

They enrolled 462 racially and ethnically diverse adults with type 2 diabetes. The 289 men and 173 women, whose average age was 60, were randomly assigned to receive either pioglitazone (a thiazolidinedione sold as Actos), a drug that increases the body’s sensitivity to insulin, or glimepiride (sold as Amaryl), another type of diabetes drug that stimulates the pancreas to make more insulin.

Patients received a baseline ultrasound to measure the thickness of the lining and middle layers of the carotid arteries, which carry blood to the brain. The arteries’ thickness is a marker for coronary atherosclerosis and a predictor of future heart attack. The patients were then evaluated at 24, 48 and 72 weeks to measure the progression of thickenening.

“The less the thickening, and the slower the rate of thickening, the less risk of heart attack in general,” said Mazzone.

By the end of the study, patients taking pioglitazone had an artery thickness that decreased an average of 0.001 millimeters, while in those taking glimepiride it increased 0.012 millimeters. About 70 percent of all patients were able to complete the 72-week trial.

The study, Mazzone said, showed that pioglitazone significantly slowed the thickening of the carotid artery wall compared to the other diabetes drug.

“We showed this for both the average thickness of the wall, as well as the maximum thickness of the wall,” he said.

The beneficial effect of pioglitazone was uniform regardless of age, sex, duration of diabetes, blood pressure, blood cholesterol levels or blood glucose control.

The study also monitored cardiovascular clinical events. There were four adverse events in the pioglitazone treated group, including three patients who required coronary revascularization. There were 10 adverse events in the glimepiride treated group, including eight who required coronary revascularization.

“Additional data needs to be brought to bear,” said Mazzone, “however this is very helpful for suggesting that pioglitazone could be a useful, novel approach for managing cardiovascular risk in patients with diabetes.”

Periodontal disease is a chronic infection of the gums and mouth. Gestational diabetes is an inability to process dietary sugars normally during pregnancy. Gestational diabetes puts women and their babies at increased risk of injury and illness.

The team of researchers analyzed health data from 256 pregnant women who participated in the National Health and Nutrition Examination Study III. Based on their analysis, the researchers recommend that dental care during pregnancy should be considered as a way to help prevent gestational diabetes.

The study, published in The Journal of Clinical Endocrinology & Metabolism, highlights the effect of ethnicity and obesity on insulin resistance during late pregnancy. While a high body mass index and ethnicity have already independently been linked to onset of diabetes, this study is the first to point out that ethnicity can further magnify obesity’s effect on insulin sensitivity. Researchers tested healthy pregnant women – 116 Caucasian, 31 South Asian and 28 Asian – who had been referred to ambulatory obstetrics clinics with an abnormal response to a 50 grams of glucose screening test. Using the data from diagnostic oral glucose tolerance tests, the researchers were able to demonstrate that ethnicity was an independent determinant of insulin sensitivity.

The findings further emphasize the need for ethnicity-specific thresholds for overweight and obesity, says the study’s senior author, Professor Bernard Zinman of the Faculty of Medicine’s Division of Endocrinology. “This appears to be particularly relevant for women in the reproductive age group,” Zinman says. “Obesity during pregnancy can affect races differently and we’ve found that it’s particularly important for Asian and South Asian women to enter pregnancy at an ideal weight to avoid complications such as gestational diabetes.”

The study was funded by the Canadian Institutes of Health Research and the Canadian Diabetes Association. South Asian participants were defined as having ancestry from India, Pakistan, Sri Lanka and Bangladesh; Asian participants were defined as having ancestry from East and Southeast Asian, including China, Japan, Korea, Vietnam and the Philippines.

Zinman’s group is also working on a diabetes prevention study. Individuals who have a family history of Type 2 DM or are overweight may be eligible to participate in the CANOE diabetes prevention study.

“Both diet and exercise provide profound benefits to reduce the risk of diabetes. Both those who restrict calories and those who exercise benefit from weight loss,” says Edward Weiss, Ph.D., lead author and assistant professor of nutrition and dietetics at Saint Louis University’s Doisy College of Health Sciences.

“We thought exercise probably would produce greater benefits. But both of these are providing beneficial health improvements.”

Weiss said the scientists looked at markers for developing diabetes because the disease is one of the main causes of premature death.

The researchers studied 50 to 60 year olds whose body mass index was between 23 and 30. That places them at the high end of normal weight or overweight, but not obese.

“People weren’t way out of whack in terms of their body composition,” Weiss says.

The study participants were divided into three groups – with 18 each in the diet and exercise groups and 10 in the control group. The year long study was funded by the National Institutes of Health.

All participants had their insulin action and glucose tolerance, which both are markers for diabetes, evaluated at the beginning and end of the study. In addition, their weight, body composition and energy intake were measured at the beginning of the study and at one, three, six, nine and 12 month intervals.

Those who restricted calories met weekly with a dietitian who helped them develop individualized menu plans and guided them to reduce portion sizes and replace high calorie foods with lower caloric choices.

Their goal was to reduce their calorie consumption by 16 percent the first three months and by 20 percent for the next nine. Their progress was tracked by keeping food diaries and the doubly-labeled water test, which is the gold standard in measuring the rate of a person’s metabolism or the amount of energy expended.

Exercisers — or those who expended more calories — had the goal of burning 16 percent more calories for the first three months, increasing to 20 percent the next nine months. They met weekly with an exercise trainer and had open access to a fitness center. To meet their goal, they exercised for between an hour and 90 minutes a day and tracked their progress on a heart rate monitor that recorded calories burned.

“As they got fit, the treadmill could be speeded up. They could exercise on a steeper grade and they could burn more calories,” Weiss says. “All of them learned very quickly the most efficient way to burn more calories was through cardio. If they pushed themselves, the numbers added up quickly.”

While those in the control group could request general advice on eating a healthy diet and free passes to a yoga class, few did, Weiss says.

Glucose tolerance and insulin levels improved at about the same levels in both the dieters and exercisers. They also lost weight. Those in the control group didn’t lose weight or have changes to their glucose tolerance or insulin levels.

“The next step is to determine what happens when you exercise and diet to lose weight,” Weiss says. “We don’t know if the combination is going to provide greater benefits.”

In patients with type 1 diabetes, the autoimmune response destroys insulin-producing cells (beta cells) in pancreatic islets, thereby subjecting these individuals – often children or young adults – to a lifetime of insulin injections. To prevent disease, autoreactive immune cells need to be suppressed or eliminated without negative side-effects. One treatment strategy that has been shown to suppress beta cell killing is the delivery of an antibody against the CD3 molecule expressed on most T cells. This antibody promotes the function of regulatory T cells (Tregs), which put the brakes on an overaggressive immune response. However, chronic “body-wide” suppression of the immune system in this way puts patients at risk for malignancies or reactivation of dormant viral infections, consequently dampening enthusiasm for this monotherapeutic approach.

One of the critical questions that has remained is how do we prevent immune responses against only insulin-producing cells? Promising data in animal models has shown that it is possible to deliver beneficial immune modulatory molecules to the pancreatic islets by inducing islet antigen-specific Tregs. However, this intervention only appears effective early in the pre-diabetic stage.

In their JCI study, von Herrath and colleagues show that combination treatment with a low-dose, orally-delivered CD3epsilon-specific antibody as well as an intranasally-delivered proinsulin peptide synergizes to reverse recent-onset type 1 diabetes in mice, with much greater efficacy than monotherapy with anti-CD3 or peptide alone. As the induced Tregs acted to specifically shield islets from autoimmune destruction, and only a low dose of anti-CD3 antibody was required, this strategy is also expected to reduce the potential for adverse side effects resulting from the immune suppression. Suppression of the immune response in this way promotes pancreatic beta cell regeneration through the natural regenerative process. If similar success is observed in humans, this dynamic therapeutic duo may hold great potential for the treatment of individuals with recent-onset type 1 diabetes.

Professors Eisenbarth and Chatenoud were selected for their outstanding contributions to fundamental research that has increased the understanding of the autoimmune mechanisms in type 1 diabetes (also known as insulin-dependent or autoimmune diabetes). In both cases, the research has the potential to offer a new therapeutic approach to the disease and transform the lives of millions of patients worldwide.

“The winners of this important prize have revolutionized the concept of the pathophysiology of type 1 diabetes and offer hope for the prevention and improved treatment of this condition in the future”, says Professor Pierre Lefebvre, President of the International Federation of Diabetes and member of the independent prize selection jury.

The Pasteur-Weizmann / Servier Prize, given once every three years, focuses on medical themes of common interest to the Pasteur, Weizmann and Servier Institutes. The theme for the 2006 award is ‘Diabetes and Autoimmunity: from fundamental mechanisms to therapeutic applications’.

George Eisenbarth

George Eisenbarth, awarded the ‘senior prize’ of €100,000, is an internationally-recognised pioneer in the fields of diabetes and immunology research with a long and highly distinguished career in advancing the understanding of the pathophysiology of type 1 diabetes. “Professor Eisenbarth is one of the ‘greats’ of diabetes research”, says Professor Pierre Godeau, Chairman of the Scientific Committee of the Servier Institute. “His meticulous research over the last 25 years has shown us that, in genetically predisposed individuals, type I diabetes is an autoimmune disease that follows a defined path with a series of different stages. This important work has led to the development of a potential ‘vaccine’ against type 1 diabetes in high risk individuals. This work is still ongoing, but has opened up a number of research avenues for the prevention of the disease.”

“Receiving this award is a great honour to me and all my research collaborators over the past years”, says Professor Eisenbarth. “Type I diabetes is a huge global health problem and more research in this area is crucial. I believe it will be possible to develop an immunologic vaccine using response to insulin to prevent this disease and our work to achieve this aim will continue.”

Lucienne Chatenoud

Lucienne Chatenoud is the ‘junior’ winner and recipient of €50,000. Although still young, she has made a huge contribution to the understanding of the autoimmune mechanisms involved in type 1 diabetes and has shown how immunotherapy with monoclonal antibodies can preserve residual insulin secretion in newly diagnosed patients with type 1 diabetes and reduce the need for injected (endogenous) insulin in these patients.

“Professor Chatenoud is a brilliant immunologist whose work on CD3 monoclonal antibodies has recently shown how short-term treatment with these agents can prevent further decline of beta-cell function in recent-onset type 1 diabetic patients for up to 18 months”, says prize judge Professor J-P Soulillou, Director of the Institute of Transplantation and Transplantation Research, Nantes University, France.

“Her work is an excellent example of how fundamental research can lead to new therapies for type 1 diabetics and exemplifies the philosophy behind the Pasteur/Weizmann / Servier Prize”, adds judge Professor Pierre Freychet, Emeritus Professor of Endocrinology and Metabolism, University of Nice, France.

“I am delighted to have won this prestigious award and plan to continue my research in this area”, points out Professor Chatenoud. “Given the very encouraging results we have obtained to date, we hope to achieve more widespread use of CD3 antibodies in type 1 diabetes patients in the near future.”

Type 1 diabetes is a growing health problem among European children. European data indicate that the disease incidence has increased five-six-fold among children under the age of 15 years after World War II, and there are no signs that the increase in incidence is levelling off. The most conspicuous increase has been seen among children under the age of 5 years.

The TRIGR study is the first study ever aimed at primary prevention of type 1 diabetes. The study is designed to answer to the question whether excluding cow’s milk protein from the infant’s diet decreases the risk of fu-ture diabetes. All subjects are followed for 10 years to get information on whether the dietary recommendations for infants at increased genetic risk of type 1 diabetes should be revised.

Starting in May 2002, 76 study centres from 15 countries (Australia, Canada, the Czech Republic, Estonia, Finland, Germany, Hungary, Italy, Luxembourg, the Netherlands, Poland, Spain, Sweden, Switzerland and USA) have been recruiting families for the study. To be eligible the newborn infant has to have at least one family member (mother, father and/or sib) affected by type 1 diabetes and carry a HLA genotype conferring increased risk for type 1 diabetes. The initial recruitment target of 2032 eligible infants was reached at the be-ginning of September 2006, but the Study Group has decided to continue recruitment till the end of December 2006 (when the EU contribution will finish) to make the study even more powerful statistically.

A majority of the study participants (52%) have been recruited in Europe. The International Coordinating Cen-tre (ICC) is located at the University of Helsinki, Helsinki, Finland and the Data Management Unit (DMU) at the University of South Florida, Tampa, Florida, USA. The trial has logistically been a true challenge for both the ICC and DMU. DMU has been successful in establishing a secure, real-time, web-based, interactive data management system that works extremely well. This system can be directly applied to future international mul-ticentre studies.

The TRIGR study is generating a wealth of information on breast-feeding practices, infant nutrition and growth in young children in various countries. At 2 weeks of age almost all the participating infants were breast-fed. Exclusive breast-feeding continued longer in Europe than in North America. More than one third of the infants (35 %) received other foods in addition to breast milk and/or infant formulas at the age of 4 months, while WHO recommends that supplementary food should be introduced at the earliest by the age of 6 months. In Europe the first foods to be introduced are typically vegetables and fruits, whereas gluten-free cereals are most commonly introduced in North America.

Newborn infants in Northern Europe (NE) had a higher birth weight but a shorter birth length than infants in Central and Southern Europe (CSE). The NE children remained heavier than those from CSE at least up to the age of 18 months. The NE children were also taller than the CSE children starting already from the age of 3 months up to the age of 18 months. Accelerated growth in infancy has been identified as a risk factor for type 1 diabetes later in childhood. Accordingly the observed growth pattern may contribute to the higher incidence of type 1 diabetes in NE compared to CSE.