Glucagon-like peptide (GLP)-1 and leptin concentrations in obese patients with Type 2 diabetes mellitus

Aims To assess differences in circulating leptin and glucagon-like peptide (GLP)-1 concentrations before and after an oral glucose load, in euglycaemi c and isoinsulinaemic conditions, between obese patients with and without T ype 2 diabetes mellitus. Methods Ten male obese (body mass index (BMI) > 30 kg/m(2)) patients with T ype 2 diabetes and 20 matched non-diabetic subjects were studied. Leptin, G LP-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 beginn ing of a euglycaemic hyperinsulinaemic clamp. Results GLP-1(7-36)amide concentrations before the glucose load were signif icantly 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 w as observed in baseline GLP-1(7-37). In non-diabetic subjects, GLP-1(7-36)a mide 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 i n 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 Ty pe 2 diabetic patients. GLP-1(7-36)amide baseline concentrations are reduce d 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 insulina emia during assessment, could contribute to the pathogenesis of hyperglycae mia in Type 2 diabetes mellitus.