Insulin resistance and beta-cell function were assessed by a continuous infusion of glucose in the following three groups of white subjects at risk of developing impaired glucose tolerance and diabetes: 41 subjects who were the offspring of patients with type II diabetes, 26 general-population subjects with an increased fasting plasma glucose level of at least 5.6 mmol/L on screening, and 22 subjects who had had gestational diabetes but were now nondiabetic. Subjects had a mean (+/- 1 SD) age of 43 +/- 9 years and a body mass index (BMI) of 27 +/- 5 kg/m2. Subjects with previously increased fasting glucose levels were significantly more insulin resistant than a control group, taking into account BMI, age, and gender (% normal insulin sensitivity [%], 59 [50 to 79] v 87 [73 to 96]; P < .005), and previously gestationally diabetic subjects showed greater impairment of beta-cell function (% normal beta-cell function [% beta], 69 [60 to 87] v 97 [89 to 105]; P < .005). Diabetes (defined by World Health Organization criteria) or impaired glucose tolerance (defined as an achieved plasma glucose concentration [APG] > 95th percentile of an age- and weight-matched population) was identified in 22% of family members, 31% of fasting hyperglycemic subjects, and 41% of previously gestationally diabetic subjects.(ABSTRACT TRUNCATED AT 250 WORDS)