Relation of direct and surrogate measures of insulin resistance to cardiovascular risk factors in nondiabetic Finnish offspring of type 2 diabetic individuals

Context: Methods to directly measure insulin resistance are invasive, complex, and costly. Surrogate indexes derived from the oral glucose tolerance test (OGTT) have been developed, but few studies have systematically analyzed these indexes. Objective: We examined the relation of surrogate and direct measures of insulin resistance to metabolic variables. Design and Setting: We conducted a cross-sectional analysis of the validation cohort of the Metabolic Syndrome in Men study. Participants: Participants included 272 nondiabetic Finnish offspring of type 2 diabetic individuals (age, 24-50 yr; 55% female). Intervention: Surrogate indexes of insulin resistance were computed according to published formulas. Insulin sensitivity was also directly measured by the euglycemic-hyperinsulinemic clamp. Results: The strength of the correlation of the Matsuda index with directly measured insulin sensitivity (r = 0.77) was similar to that of Avignon's insulin sensitivity index (r = 0.76; P = 0.581) and simple index assessing insulin sensitivity using OGTT measurements (r = 0.74; P = 0.060) and stronger than that of indexes derived from fasting measurements [e.g. fasting insulin (r = 0.72; P = 0.011) and homeostasis model assessment of insulin resistance (r = 0.71; P = 0.001)]. Surrogate indexes were similar to directly measured insulin sensitivity in their relationships with metabolic abnormalities including definitive measures of fat distribution. Some indexes, however, had distinctive correlations: McAuley index with lipoproteins and Avignon insulin sensitivity and Stumvoll indexes with adiposity and fibrinogen. Conclusions: Surrogate indexes are valid measures of insulin resistance. Multiple sampling times during an OGTT may not be mandatory to adequately estimate insulin resistance in clinical and epidemiological studies.