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

J Diabetes Complications. Sep-Oct 2012;26(5):442-9. doi: 10.1016/j.jdiacomp.2012.05.003. Epub 2012 Jun 4.


Objective: The 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.

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. 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.

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, 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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Body Mass Index
  • C-Peptide / blood
  • Combined Modality Therapy
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Diet, Reducing*
  • Down-Regulation*
  • Exercise
  • Female
  • Humans
  • Insulin-Secreting Cells / metabolism*
  • Life Style
  • Male
  • Middle Aged
  • Models, Biological
  • Obesity / complications
  • Obesity / diet therapy*
  • Obesity / therapy
  • Overweight / complications
  • Overweight / diet therapy*
  • Overweight / therapy
  • Oxygen Consumption
  • Pancreatic Polypeptide / blood*
  • Pancreatic Polypeptide / metabolism
  • Protein Precursors / blood*
  • Protein Precursors / metabolism
  • Weight Loss


  • C-Peptide
  • PPY protein, human
  • Protein Precursors
  • Pancreatic Polypeptide