Improvement in β-cell function after diet-induced weight loss is associated with decrease in pancreatic polypeptide in subjects with type 2 diabetes

Objective: The aim of our study was to evaluate the effect of a lifestyle intervention program on beta-cell function and to explore the role of gastrointestinal peptides in subjects with T2D. Methods: Subjects with T2D (n = 74) received 24 weeks of intervention: 12 weeks of slimming diet (-500 kcal/day) and the subsequent 12 weeks of diet were combined with aerobic exercise. All subjects were examined at weeks 0, 12 and 24. beta-cell function was assessed during standard meal tests. Insulin secretory rate (ISR) was calculated by C-peptide deconvolution, and beta-cell function was quantified with a mathematical model. Plasma concentrations of gastrointestinal peptides were measured in a fasting state and during hyperinsulinemia induced by hyperinsulinemic isoglycemic clamp. Results: Mean weight loss was 5.03 +/- 4.38 kg (p<0.001) in weeks 0-12. Weight did not change significantly in weeks 12-24. Both insulin secretion at the reference level and glucose sensitivity increased in weeks 0-12 (by 33% +/- 54% and by 26% +/- 53%, respectively, p<0.001) and remained unchanged in weeks 12-24. Both fasting and hyperinsulinemic plasma concentrations of pancreatic polypeptide (PP) decreased in weeks 0-12 (p<0.05 for both) and did not change significantly in weeks 12-24. Changes in insulin secretion at the reference level correlated negatively with plasma concentrations of PP during hyperinsulinemia (r = -0.36; p<0.001). Changes in glucose sensitivity correlated negatively with changes in plasma concentrations of PP, both in fasting and during hyperinsulinemia (r = -0.2; p = 0.01 for both). The correlations remained significant after adjustment for changes in body-mass-index. Conclusions: After diet-induced weight loss, beta-cell function improved in T2D subjects and remained unchanged after the addition of exercise. We demonstrate for the first time that these changes are associated with a decrease in PP secretion. (C) 2012 Elsevier Inc. All rights reserved.