Separate Impact Of Obesity And Glucose Tolerance On The Incretin Effect In Normal Subjects And Type 2 Diabetic Patients

摘要

Potentiation of β-cell function by the route of nutrient administration has been defined as incretin effect which is mainly caused by the glucagon-like peptide-1 (GLP-1) and the glucose-dependent insulinotropic polypeptide (GIP). An impaired incretin effect contributes to β-cell dysfunction in type 2 diabetes (T2D). Although T2D is strongly associated with obesity, the result of the separate impact of obesity and hyperglycemia on the incretin effect is uncertain.rnIn 51 patients (24 with normal [NGT], 17 with impaired glucose tolerance [IGT], and 10 with T2D) with a wide range of BMI (20-61 kg/m~2), a 3-h oral glucose tolerance test with measurements of plasma glucose at 10-min intervals was reproduced the next day as an isoglycemic profile with a variable intravenous glucose (20%) infusion. In both studies, venous blood was sampled at -30, 0, 10, 20, 30, 40, 60, 90, 120, 150, and 180 min for plasma insulin, C-peptide, glucagon, GLP-1 (R1A for C-terminal amidated GLP-1) and NH_2-terminal GIP (RIA). β-cell glucose sensitivity was determined by the slope of the insulin secretion/ glucose concentration dose-response curve. In 8 subjects with NGT and 10 with T2D, oral glucose appearance was measured by the double-tracer technique.