Secretion of incretin hormones (GIP and GLP-1) and incretin effect after oral glucose in first-degree relatives of patients with type 2 diabetes

Aims/Hypothesis: Since insulin secretion in response to exogenous gastric inhibitory polypeptide (GIP) is diminished not only in patients with type 2 diabetes, but also in their normal glucose-tolerant first-degree relatives, it was the aim to investigate the integrity of the enteroinsular axis in such subjects. Methods: Sixteen first-degree relatives of patients with type 2 diabetes (4 male, 12 female, age 50 12 years, BMI 26.1 +/- 3.8 kg/m(2)) and 10 matched healthy controls (negative family history, 6 male, 4 female, 45 +/- 13 years, 26.1 +/- 4.2 kg/m(2)) were examined with an oral glucose load (75 g) and an "isoglycaemic" intravenous glucose infusion. Blood was drawn over 240 min for plasma glucose (glucose oxidase), insulin, C-peptide, GIP and glucagon-like peptide 1 (GLP-1; specific immunoassays). Results: The pattern of glucose concentrations could precisely be copied by the intravenous glucose infusion (p = 0.99). Insulin secretion was stimulated significantly more by oral as compared to intravenous glucose in both groups (p < 0.0001). The percent contribution of the incretin effect was similar in both groups (C-peptide: 61.9 +/- 5.4 vs. 64.4 +/- 5.8%; p = 0.77; insulin: 74.2 +/- 3.3 vs. 75.8 +/- 4.9; p = 0.97; in first-degree relatives and controls, respectively). The individual responses of GIP and GLP-1 secretion were significantly correlated with each other (p = 0.0003). The individual secretion of both GIP and GLP-1 was identified as a strong predictor of the integrated incremental insulin secretory responses as a,ell as of the incretin effect. Conclusion/Interpretation: Despite a lower insulin secretory response to exogenous GIP, incretin effects are similar in first-degree relatives of patients with type 2 diabetes and control subjects. This may be the result of a B cell secretory defect that affects stimulation by oral and intravenous glucose to a similar degree. Nevertheless, endogenous secretion of GIP and GLP-1 is a major determinant of insulin secretion after oral glucose. (C) 2004 Elsevier B.V. All rights reserved.