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Keywords:

  • euglycaemic hyperinsulinaemic clamp;
  • glucagon-like peptide-1;
  • leptin;
  • obesity;
  • Type 2 diabetes mellitus

SUMMARY

Aims  To assess differences in circulating leptin and glucagon-like peptide (GLP)-1 concentrations before and after an oral glucose load, in euglycaemic and isoinsulinaemic conditions, between obese patients with and without Type 2 diabetes mellitus.

Methods  Ten male obese (body mass index (BMI) > 30 kg/m2) patients with Type 2 diabetes and 20 matched non-diabetic subjects were studied. Leptin, GLP-1(7–36)amide and GLP-1(7–37) concentrations were measured 0, 30, 60, and 90 min after a 50-g oral glucose load administered 90 min after the beginning of a euglycaemic hyperinsulinaemic clamp.

Results  GLP-1(7–36)amide concentrations before the glucose load were significantly lower in diabetic patients than in controls (median (quartiles): 50.5 (44.7–53.2) vs. 128.7(100–172.5) pg/ml; P < 0.01), while no difference was observed in baseline GLP-1(7–37). In non-diabetic subjects, GLP-1(7–36)amide and GLP-1(7–37) concentrations increased significantly after the oral glucose load, while no glucose-induced increase in GLP-1 concentration was observed in diabetic patients. GLP-1(7–36)amide at 30, 60, and 90 min, and GLP-1(7–37) at 30 min, of the glucose challenge, were significantly lower in diabetic patients. Leptin concentrations were not significantly different in diabetic patients when compared to non-diabetic subjects, and they did not change after the oral glucose load.

Discussion  Leptin concentrations are not significantly modified in obese Type 2 diabetic patients. GLP-1(7–36)amide baseline concentrations are reduced in Type 2 diabetes; moreover, diabetic subjects show an impaired response of GLP-1 to oral glucose in euglycaemic, isoinsulinaemic conditions. This impairment, which is not the result of differences in glycaemia or insulinaemia during assessment, could contribute to the pathogenesis of hyperglycaemia in Type 2 diabetes mellitus.