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

Diabet Med. 2000 Oct;17(10):713-9. doi: 10.1046/j.1464-5491.2000.00367.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Glucose / metabolism*
  • Diabetes Mellitus / blood*
  • Diabetes Mellitus, Type 2 / blood*
  • Glucagon / blood*
  • Glucagon-Like Peptide 1
  • Glucose Clamp Technique
  • Glucose Tolerance Test
  • Glycated Hemoglobin / analysis
  • Humans
  • Hyperinsulinism
  • Insulin / administration & dosage
  • Insulin / blood
  • Insulin / pharmacology
  • Leptin / blood*
  • Male
  • Middle Aged
  • Obesity / blood*
  • Peptide Fragments / blood*
  • Protein Precursors / blood*


  • Blood Glucose
  • Glycated Hemoglobin A
  • Insulin
  • Leptin
  • Peptide Fragments
  • Protein Precursors
  • Glucagon-Like Peptide 1
  • Glucagon