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

ObjectiveThe aim of our study was to evaluate the effect of a lifestyle intervention program on β-cell function and to explore the role of gastrointestinal peptides in subjects with T2D.MethodsSubjects 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. β-cell function was assessed during standard meal tests. Insulin secretory rate (ISR) was calculated by C-peptide deconvolution, and β-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.ResultsMean 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.ConclusionsAfter diet-induced weight loss, β-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.