According to new research presented at ADA, after more than half a century of living with type 1 diabetes, a significant number of patients appear to have residual beta-islet cell function. In a study of these relatively long-lived type 1 patients about 13% had evidence of C-peptide secretion, indicating that they were still producing insulin, reported Hillary Keenan, Ph.D., of the Joslin Diabetes Center in Boston at the American Diabetes Association meeting.
"It is surprising that some medalists [50-year survivors] 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 of mass still is present," said George L. King, M.D., the study’s lead author.
The findings suggested that instead of islet cell or pancreas transplants in people with type 1 diabetes, it might be possible in the future to stimulate the growth of native, residual islet cells to restore insulin secretion and glucose regulatory functions to normal levels, Dr. King said.
In the study, about half the patients had little or no microvascular complications present, suggesting that diabetes duration does not always equate to complications.
The 50-year Medalist Study followed the clinical, physiological, and genetic characteristics of 326 patients. "The findings are phenomenal," Dr. Keenan said. "This is the first study to look at the specific biomarkers of islet cell presence in people with a 50-year duration of insulin-dependent diabetes."
In a subset of 125 of these patients, the investigators found that 12.7% of the patients had a C-peptide level above 0.3 ng/mL, indicating that they still had a population of active islet cells and some degree of residual insulin production, despite being dependent on exogenous insulin for most of a lifetime.
Still, most of the 50-year survivors had clinical characteristics typical of type 1 diabetics, regardless of the presence or absence of the C-peptide.
Among those patients who were positive for C-peptide, 23.2% produced either of two common anti-islet antibodies: GADA (glutamic acid decarboxylase) or IA2 (a tyrosine phosphatase-like protein). The presence of these antibodies is another indicator that a small pool of islet cells may still be present and possibly functioning. Otherwise, the antibodies would presumably have vanished when their target cells died off.
In addition to looking at C-peptide, the investigators examined cholesterol and triglycerides levels, body mass index, and daily insulin requirements, and found that there were no significant differences in these clinical parameters when controlling for C-peptide presence.
The lack of microvascular complications in about half of the patients is particularly intriguing, Dr. King said.
"If we could find out the reason for their lack of complications, we could perhaps prevent kidney or eye disease," he commented. "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," he said.
2006 American Diabetes Association Scientific Sessions: Keenan HA et al. "Positivity of C-Peptide, GADA and IA2 Antibodies in Type 1 Diabetic Patients with Extreme Duration." Abstract 278-OR, presented June 11, 2006.
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