Signs Of Residual Islet Cell Function In People With Long-term Type 1 Diabetes

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

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

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

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

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

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

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

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

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

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

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

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