Residual Insulin Production and Pancreatic β-Cell Turnover After 50 Years of Diabetes: Joslin Medalist Study

摘要: OBJECTIVE To evaluate the extent of pancreatic β-cell function in a large number insulin-dependent diabetic patients with disease duration 50 years or longer (Medalists). RESEARCH DESIGN AND METHODS Characterization clinical and biochemical parameters 411 Medalists correlation postmortem morphologic findings 9 Medalists. RESULTS The Medalist cohort, mean ± SD age 56.2 5.8 67.2 7.5 years, respectively, has phenotype similar to type 1 diabetes (type diabetes): onset at 11.0 6.4 BMI 26.0 5.1 kg/m2, insulin dose 0.46 0.2 u/kg, ∼94% positive for DR3 and/or DR4, 29.5% either IA2 glutamic acid decarboxylase (GAD) autoantibodies. Random serum C-peptide levels showed that more than 67.4% participants had minimal (0.03–0.2 nmol/l) sustained range (≥0.2 nmol/l). Parameters associated higher random were lower hemoglobin A1C, older onset, frequency HLA genotype, responsiveness mixed-meal tolerance test (MMTT). Over half fasting >0.17 nmol/l responded MMTT by twofold greater rise over course compared fasting. Postmortem examination pancreases from nine all insulin+ β-cells some TUNEL staining, indicating apoptosis. CONCLUSIONS Demonstration persistence insulin-producing cells suggests possibility steady state turnover which stimuli enhance endogenous β could be viable therapeutic approach significant diabetes, even those chronic duration.