We characterised 62 non-diabetic, middle-aged, Caucasians with and without the T risk allele of rs7903146 in TCF7L2 with regard to secretion of insulin, glucagon, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1) as well as insulin sensitivity and endogenous glucose production. All participants had a 3-hour oral glucose tolerance test (OGTT), an intravenous glucose tolerance test, and a euglycaemic, hyperinsulinaemic clamp. After adjustment for age and sex, risk T allele carriers had higher HbA(1c) levels (P=0.030), reduced first-phase insulin response (P=0.048), higher peripheral insulin sensitivity (P=0.050) and lower fasting GIP concentrations (P=0.003) than CC allele carriers. The latter was also reflected by lower total GIP secretion during the OGTT (P=0.018). We found no significant differences in endogenous glucose production, hepatic insulin sensitivity or fasting concentrations of glucose, insulin, glucagon, and GLP-1 between the groups. The findings suggest that the effect of TCF7L2 on diabetes risk may include reduced secretion of GIP.
Diabetes, Obesity and Metabolism Online, 2012, Vol 15, Issue 1, p. 91-95