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- Title
Demonstration of Islet Cell Function in Patients with 50 years or Longer of Diabetes.
- Authors
Keenan, Hillary A.; Berger, Alysha; Sun, Jennifer K.; Eisenbarth, George; Doria, Alessandro; King, George L.
- Abstract
In 1972, Joslin Diabetes Center began awarding a medal to individuals (Medalists) who had documented insulin dependent diabetes for 50 or more years. To date, 218 have been enrolled in the Medalist Study, with a mean current age of 68 ±7.1 years, average age at diagnosis of 12.4 ±7 years, mean duration 57 ± 6 years, median HbA1c6.9%, BMI 124.5 ± 4.5 kg/m² and mean insulin dose per kilogram 0.46 (±0.16) u/kg. Complications evaluated were: retinopathy (fundus photos), nephropathy (albumin creatinine ratios), and peripheral neuropathy (monofilament examination, reflex measurements and Michigan neuropathy assessment questionnaire). Approximately 40% (n=88) patients did not have significant diabetic retinopathy, neuropathy or nephropathy. About 22% of Medalists were positive for auto-antibodies to IA2 or GAD65. A surprisingly high percentage of Medalist patients (18%) had a random c-peptide value greater than 0.3 ng/mL. No differences were found between c-peptide positive v. negative groups with respect to presence of complications, HbA1C levels, autoantibodies, TIDM HLA risk alleles or insulin dose. To determine whether the presence of c-peptide over 0.3 ng/ml had any significance with respect to insulin secretion, eleven participants whose random c-peptide levels were over 0.3 ng/mL were studied with a Mixed Meal Tolerance Test. Five of these individuals had a substantial increase (at least 100%) in c-peptide level during the test; their initial random c-peptide levels were all above 0.5 ng/mL. Medalists with c-peptide levels over 0.5 ng/mL (n=6) were older at diagnosis (20.5 ± 7.2 v. 10.0 ± 5.5 years, p=0.002), and were slightly heavier (26.9±2.9 v. 24.5 ±3.5 kg/m²⋅ p=0.08) than those with c-peptide levels below 0.5 ng/mL. Again, no differences in the presence of microvascular complications, GAD and IA2 autoantibodies, or the presence of TIDM HLA risk alleles were observed between those with c-peptide levels above and below 0.5 ng/mL. These findings suggest that residual and responsive islets still exist in patients with c-peptide levels >0.5 ng/mL even after 50 years of diabetes. Future therapeutic interventions to increase regeneration or reduce the destructive process of beta cells may eliminate the need for exogenous insulin even in diabetic patients with extreme duration of disease.
- Subjects
ISLANDS of Langerhans; PEOPLE with diabetes; DIABETES complications; DIABETIC retinopathy; DIABETIC nephropathies; DIABETIC neuropathies; INSULIN
- Publication
Diabetes, 2007, Vol 56, pA386
- ISSN
0012-1797
- Publication type
Article