AIMS/HYPOTHESIS: The aim of this study was to evaluate the separate impact of insulin resistance and impaired glucose tolerance (IGT) on the incretin effect. METHODS: Twenty-one healthy glucose-tolerant first-degree relatives of patients with type 2 diabetes underwent a 75 g OGTT, an isoglycaemic i.v. glucose test and a mixed meal to evaluate the incretin effect before and after treatment with dexamethasone to increase insulin resistance. Beta cell glucose sensitivity, beta cell index and fasting proinsulin were measured as indices of beta cell function. RESULTS: After dexamethasone, ten individuals had increased insulin resistance but normal glucose tolerance (NGT), while 11 individuals with an equal increase in insulin resistance developed IGT. In the NGT and IGT groups, the incretin effects were 71¿±¿3.2% and 67¿±¿4.6% (p¿=¿0.4) before treatment, but decreased significantly in both groups to 58¿±¿5.2% and 32¿±¿8.8% (p¿