Improved pancreatic beta-cell function in type 2 diabetic patients after lifestyle-induced weight loss is related to glucose-dependent insulinotropic polypeptide

Thomas P J Solomon, Jacob M Haus, Karen R Kelly, Michael Rocco, Sangeeta R Kashyap, John P Kirwan

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77 Citations (Scopus)


OBJECTIVE: Restoration of insulin secretion is critical for the treatment of type 2 diabetes. Exercise and diet can alter glucose-induced insulin responses, but whether this is due to changes in beta-cell function per se is not clear. The mechanisms by which lifestyle intervention may modify insulin secretion in type 2 diabetes have also not been examined but may involve the incretin axis.

RESEARCH DESIGN AND METHODS: Twenty-nine older, obese (aged 65 +/- 1 years; BMI 33.6 +/- 1.0 kg/m(2)) subjects, including individuals with newly diagnosed type 2 diabetes (obese-type 2 diabetic) and individuals with normal glucose tolerance (obese-NGT), underwent 3 months of nutritional counseling and exercise training. beta-Cell function (oral glucose-induced insulin secretion corrected for insulin resistance assessed by hyperinsulinemic-euglycemic clamps) and the role of glucose-dependent insulinotropic polypeptide (GIP) were examined.

RESULTS: After exercise and diet-induced weight loss (-5.0 +/- 0.7 kg), oral glucose-induced insulin secretion was increased in the obese-type 2 diabetic group and decreased in the obese-NGT group (both P < 0.05). When corrected for alterations in insulin resistance, the change in insulin secretion remained significant only in the obese-type 2 diabetic group (1.23 +/- 0.26 vs. 2.04 +/- 0.46 arbitrary units; P < 0.01). Changes in insulin secretion were directly related to the GIP responses to oral glucose (r = 0.64, P = 0.005), which were augmented in the obese-type 2 diabetic group and only moderately suppressed in the obese-NGT group.

CONCLUSIONS: After lifestyle-induced weight loss, improvements in oral glucose-induced insulin secretion in older, obese, nondiabetic subjects seem to be largely dependent on improved insulin sensitivity. However, in older obese diabetic patients, improved insulin secretion is a consequence of elevated beta-cell function. We demonstrate for the first time that changes in insulin secretion after lifestyle intervention may be mediated via alterations in GIP secretion from intestinal K-cells.

Original languageEnglish
Pages (from-to)1561-6
Number of pages6
JournalDiabetes Care
Issue number7
Publication statusPublished - Jul 2010


  • Aged
  • Blood Glucose
  • Diabetes Mellitus, Type 2
  • Diet, Reducing
  • Exercise
  • Female
  • Gastric Inhibitory Polypeptide
  • Glucose Clamp Technique
  • Humans
  • Hyperinsulinism
  • Insulin
  • Insulin Resistance
  • Insulin-Secreting Cells
  • Life Style
  • Male
  • Middle Aged
  • Obesity
  • Physical Fitness
  • Weight Loss


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