New Theories of Type 2 Diabetes as an Inflammatory, Autoimmune Disease to be Investigated in Major Study

BUFFALO, N.Y. -- A study centering on two emerging theories on the causes of diabetes in adults will be conducted by researchers at the University at Buffalo over the next three years, funded by a $1.6 million grant from the National Institutes of Health.

The research has the promise to provide the most definitive information to date on a disease that currently afflicts 16 million people in the U.S. and is the nation's seventh leading cause of death.

"The world's diabetic population is estimated to reach 221 million by the year 2010," said lead researcher Richard P. Donahue, Ph.D., professor of social and preventive medicine in the UB School of Medicine and Biomedical Sciences. "The public health consequences are enormous. We think the findings from this study will be very useful in fighting this disease and saving lives."

The research will concentrate on two new ideas concerning the underlying mechanisms that lead to the disease that have come to light through recent basic science work and small clinical and epidemiological studies, Donahue said.

Researchers now hypothesize that most diabetes in adults (sometimes called adult-onset diabetes, or more often, type 2 diabetes) is caused by chronic inflammation. Meanwhile, preliminary studies have shown that in 10-15 percent of adult diabetics, the disease shows characteristics of a slow-developing form of type 1 diabetes, an autoimmune disorder formerly thought to occur only in children.

The chronic inflammation hypothesis arises from the known link between adult diabetes and obesity.

"We know that 80-90 percent of people with type 2 diabetes are obese," Donahue said. "A sustained 15-pound weight loss is associated with a 60 percent reduction in risk. But it's not clear why obesity and diabetes are so closely linked. We do know that insulin resistance (a major symptom of type 2 diabetes) and obesity go hand-in-hand.

"Fat cells don't just store fat; they secrete various components into the blood stream, including cytokines, which cause inflammation," Donahue said. "We think cytokines interfere with insulin receptors, which would account for insulin resistance and point to the inflammatory process as an important underlying cause of type 2 diabetes."

The autoimmune hypothesis is based on the fact that some adults diagnosed with diabetes are found to have antibodies in their blood to the insulin-producing islet cells and consequently must begin receiving insulin soon after diagnosis.

A lack of insulin is the primary symptom of type 1 diabetes, also called juvenile diabetes, an autoimmune disease caused by destruction of the islet cells in the pancreas by the body's own immune system.

Donahue noted that historically, adult-onset diabetes has been characterized by too much insulin in the blood, not too little. This excess of insulin results from the inability of muscle to take up insulin from the blood and break down sugar, protein and fat consumed in the diet. The fact that some adults diagnosed with type 2 diabetes require insulin soon after their diagnosis suggests they actually have a latent autoimmune disease, a slow-developing form of type 1 diabetes, Donahue said.

Studying participants from an unrelated UB study conducted from 1996-2000 and analyzing its bank of fasting blood samples taken at the study's start, UB researchers will be able to provide the most definitive results to date on the relationship between type 2 diabetes, the inflammatory process and autoimmunity.

The 3,000 participants will be recontacted to determine current health status and identify those who have developed type 2 diabetes in the interim. Researchers will analyze baseline blood samples from these cases for the presence of islet-cell antibodies and specific markers of inflammation, as well as indicators of impaired functioning of cells lining the blood vessels. These data will be compared with baseline blood samples from participants who didn't develop diabetes.

"If the findings turn out as we hope, this study will lead to better understanding of the underlying causes of diabetes," said Donahue. "The results also could point to ways to identify people at risk of developing diabetes by looking for these inflammatory and autoimmune biomarkers. These people then could be treated to prevent development of full-blown diabetes.

"Our study results also should lead to better diagnosis of those who have the latent form of type 1 diabetes so that they can receive proper therapy from the start."

Additional researchers on the study are Jacek Dmochowski, Ph.D., research assistant professor in the UB Department of Social and Preventive Medicine; Russel Tracy, Ph.D., at the University of Vermont, and Massimo Pietrapaolo, M.D., at the University of Pittsburgh.