Prospective studies have shown a relationship between hyperinsulinaemia, an indirect index of insulin resistance, and IHD in men with normal glucose tolerance. In NIDDM this association is less clear possibly due to the poor significance of insulin and C-peptide concentrations as an index of insulin resistance. Therefore, only a direct measurement of insulin sensitivity could clarify the possible relationship between insulin resistance and IHD in NIDDM. We have evaluated insulin sensitivity, by means of an ITT, and some risk factors for IHD in 72 men with NIDDM, 36 with and 36 without IHD, attending our out-patient Diabetic Clinic. The two groups were of similar age, duration of diabetes, glycaemic control and body composition. Subjects with IHD were more insulin resistant (K(ITT) index 2.45 +/- 0.18 vs 3.12 +/- 0.13% per min, in patients with and without IHD, respectively, p < 0.004), had higher total (p = 0.011) and LDL serum cholesterol levels (p = 0.010) and greater prevalence of hypertension (p = 0.001) compared to subjects without IHD. Using step-wise logistic regression analysis, insulin resistance (odds ratio 2.57, 95% CI 1.87-3.28, p = 0.008), hypertension (odds ratio 8.17, 95% CI 6.86-9.48, p = 0.002), total serum cholesterol levels (odds ratio 1.02, 95% CI 1.005-1.035, p = 0.015) and BMI (0.79, 95% CI 0.67-0.97, p = 0.049) were independently associated with IHD. After adjustment for age and duration of diabetes, only insulin sensitivity was directly related to the age of onset of IHD, independently from other clinical and metabolic parameters (p < 0.015).(ABSTRACT TRUNCATED AT 250 WORDS)