To investigate a possible role of an enteroinsular axis involvement in the pathogenesis of type 2 diabetes, plasma glucagon-like peptide 1 (GLP-1) 7-36 amide response to nutrient ingestion was evaluated in type 2 diabetics affected by different degrees of β-cell dysfunction.

Methods: 14 patients on oral hypoglycaemic treatment (group A: HbA1C= 8.1±1.8%) and 11 age-matched diabetic patients on diet only (group B: HbA1C= 6.4±0.9) participated in the study. 10 healthy volunteers were studied as controls. In the postabsorptive state, a mixed meal (700 kCal) was administered to all subjects, and blood samples were regularly collected up to 180′ for plasma glucose, insulin, glucagon, and GLP-1 determination.

Results: In the control group, the test meal induced a significant increase in plasma GLP-1 at 30′ and 60′(p< 0.01); the peptide concentrations then returning toward basal levels. β-cell function estimation by HOMA score confirmed a more advanced involvement in group A than in group B (p< 0.01). In contrast, the insulin resistance degree showed a similar result in the two groups (HOMA-R). In group A, first-phase postprandial insulin secretion (0-60’) resulted, as expected, in being significantly reduced compared to healthy subjects (p< 0.001). In the same patients the mean fasting GLP-1 value was similar to controls, but the meal failed to increase plasma peptide levels, which even tended to decrease during the test (p< 0.01). In group B, food-mediated early insulin secretion was higher than in group A (p< 0.001), although significantly reduced when compared to controls (p< 0.01). Like group A, no GLP-1 response to food ingestion occurred in group B patients in spite of maintained basal peptide secretion. Whereas the test-meal did not significantly modify plasma glucagon levels in the control group, glucagon concentrations increased at 30’and 60’in both diabetic groups (p< 0.01).

Conclusions: 1) The functional integrity of GLP-1 cells results as being seriously impaired even in the condition of mild diabetes; 2) the early peptide failure could contribute to the development of β-cell deterioration which characterizes overt type 2 diabetes.