Insulin resistance is associated with atherosclerosis, and hyperinsulinemia is predictive of coronary heart disease. However, a quantitative estimation of in vivo insulin sensitivity in juvenile myocardial infarction is still lacking and the mechanism of hyperinsulinemia is unknown. We estimated insulin sensitivity, beta-cell secretion, and hepatic insulin extraction using the minimal model analysis of a frequently sampled intravenous glucose tolerance test (FSIGT) in 25 normal-weight subjects without glucose intolerance and hypertension who had an acute myocardial infarction before the age of 40 years, and 10 control subjects comparable for age, sex, body mass index, and blood pressure. All patients underwent a coronary angiography. Insulin sensitivity was significantly lower in patients than in control subjects (mean +/- SEM, 4.6 +/- 0.6 v8.5 +/- 1.2 10(-4). min(-1)(microU/mL), P = .002). The basal C-peptide secretion rate (P = .02), total C-peptide secretion (P = .005), area under the curve (AUC) of insulin (P = .04) and C-peptide (P = .01), and hepatic insulin extraction (P = .04) were higher in patients versus control subjects. In conclusion, insulin resistance is evident in subjects with early myocardial infarction accurately selected to avoid the influence of other factors known to reduce insulin sensitivity, and hyperinsulinemia is due to an increase in beta-cell secretion rather than a decrease in hepatic insulin extraction.