Impaired glucose tolerance (IGT) is associated with reduced insulin-induced suppression of glucagon concentrations

Aims/hypothesis. We aimed to examine whether impaired glucose tolerance is associated with reduced suppression of glucagon concentrations. Methods. Eighty-four non-diabetic women of Caucasian origin and 61 years of age, of whom 48 had normal glucose tolerance (NGT) and 36 had IGT, underwent a 75 g OGTT and a hyperinsulinaemic, euglycaemic clamp with measurement of glucagon, insulin and glucose concentrations. Results. At 2 h after 75 g oral glucose, glucagon concentrations were reduced by 7.1 +/- 1.1 ng/l in NGT vs 8.0 +/- 1.4 ng/l in IGT, (NS). However, the 2 h reductions in glucagon per mmol/l increase in 2 h glucose or per pmol/l increase in 2 h insulin were both impaired in IGT (p = 0.002 and p = 0.043, respectively) because the 2 h increases in glucose and insulin were higher in IGT than in NGT. Furthermore, suppression of glucagon concentrations during a euglycaemic clamp at hyperinsulinaemic concentrations (NGT: 607 +/- 19 pmol/l. IGT. 561 +/- 21 pmol/l) was lower in IGT (13.6 +/- 1.6 ng/l) than in NGT (23.1 +/- 1.2 ng/l; p < 0.001). The suppression of glucagon concentrations during the hyperinsulinaemic, euglycaemic clamp correlated with insulin sensitivity (r = 0.24, p = 0.027) and with the 2 h glucose value during the OGTT (r = -0.52, p < 0.001). Conclusion/interpretation. Impaired glucose tolerance is associated with reduced insulin-induced suppression of glucagon secretion, which could be caused by A-cell insulin resistance. Inappropriately high glucagon secretion could therefore contribute to the metabolic perturbations in IGT.