Abnormal incretin effect in subjects with "silent" type I diabetes
PURPOSE:The incretin effect is defined as the augmentation in insulin secretion seen when the glucose is administered orally as compared to intravenously. A group of asymptomatic subjects have been identified through the Diabetes Prevention Trial - Type 1 (DPT-1) but have been excluded from participation in the intervention trial due to abnormal oral glucose tolerance tests (normal fasting glucose, but >200 mg/dl at 2 hours). We asked whether these subjects with "silent" type 1 diabetes have an abnormal incretin response since incretin factors account for a large percentage of post-prandial insulin secretion. METHODS: Subjects (n=10) and controls (n=4) underwent standard oral glucose tolerance testing with samples for glucose and insulin obtained at -10, 0, 30, 60, 90, and 120 min. On a separate day these individuals were administered glucose IV to match the serum glucose values obtained during their OGTT. The percentage difference in insulin values between each individual's oral and intravenous glucose test were determined and compared between subjects and controls. RESULTS: (a) Glucose values on IV glucose testing were 95+/-10% of glucose values on OGTT. (b) Percentage difference between oral and IV insulin values at each time point (p=0.05 ANOVA between subjects and controls): 30 min 60 min 90 min 120 min Subjects 35% 26% 34% 29% Controls 53% 58% 48% 57% SUMMARY: (1) Glucose values were well matched between oral and intravenous glucose tolerance tests. (2) Subjects have an impaired incretin response as compared to controls. CONCLUSION: Subjects with "silent" type 1 diabetes have an impaired incretin response. Investigations as to whether this is due to abnormal GLP-1 or GIP secretion are underway.
Greenbaum, CJ; Prigeon, RL; D'Alessio, DA
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