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 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.
Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
H
H
Kahleova
A
A
Mari
V
V
Nofrate
M
M
Matoulek
L
L
Kazdova
M
M
Hill
T
T
Pelikanova
D015992:Body Mass Index; D002096:C-Peptide / Q000097:blood; D003131:Combined Modality Therapy; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D004038:Diet, Reducing; D015536:Down-Regulation; D015444:Exercise; D005260:Female; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008019:Life Style; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009765:Obesity / Q000150:complications / Q000178:diet therapy* / Q000628:therapy; D050177:Overweight / Q000150:complications / Q000178:diet therapy* / Q000628:therapy; D010101:Oxygen Consumption; D010191:Pancreatic Polypeptide / Q000097:blood* / Q000378:metabolism; D011498:Protein Precursors / Q000097:blood* / Q000378:metabolism; D015431:Weight Loss
D002096:C-Peptide; C043710:PPY protein, human; D011498:Protein Precursors; D010191:Pancreatic Polypeptide