Decrement of postprandial insulin secretion determines the progressive nature of type-2 diabetes

Objective: Type-2 diabetes is a progressive disease. However, little is known about whether decreased fasting or postprandial pancreatic β-cell responsiveness is more prominent with increased duration of diabetes. The aim of this study was to evaluate the relationship between insulin secretion both during fasting and 2 h postprandial, and the duration of diabetes in type-2 diabetic patients. Design: Cross-sectional clinical investigation. Methods: We conducted a meal tolerance test in 1466 type-2 diabetic patients and calculated fasting (M_o) and postprandial (M_l) β-cell responsiveness. Results: The fasting C-peptide, postprandial C-peptide, M_o, and M₁ values were lower, but HbA_lc values were higher, in patients with diabetes duration > 10 years than those in other groups. There was no difference in the HbA_lc levels according to the tertiles of their fasting C-peptide level. However, in a group of patients with highest postprandial C-peptide tertile, the HbA_1c values were significantly lower than those in other groups. After adjustment of age, sex, and body mass index (BMI), the duration of diabetes was found to be negatively correlated with fasting C-peptide (γ=-0.102), postprandial C-peptide (γ=-0.356), M_o (γ=-0.263), and M₁ (γ=-0.315; P<0.01 respectively). After adjustment of age, sex, and BMI, HbA_1c was found to be negatively correlated with postprandial C-peptide (γ=-0.264), M_o (γ=-0.379), and M₁ (γ=-0.522), however, positively correlated with fasting C-peptide (γ=0.105; P < 0.01 respectively). In stepwise multiple regression analysis, M_O, M₁, and homeostasis model assessment for insulin resistance (HOMA-IR) emerged as predictors of HbA_1c after adjustment for age, sex, and BMI (R² =0.272, 0.080, and 0.056 respectively). Conclusions: With increasing duration of diabetes, the decrease of postprandial insulin secretion is becoming more prominent, and postprandial β-cell responsiveness may be a more important determinant for glycemic control than fasting β-cell responsiveness.