Insulin resistance in obesity can be reliably identified from fasting plasma insulin

BACKGROUND/OBJECTIVES: Insulin resistance is the major contributor to cardiometabolic complications of obesity. We aimed to (1) establish cutoff points for insulin resistance from euglycemic hyperinsulinemic clamps (EHCs), (2) identify insulin-resistant obese subjects and (3) predict insulin resistance from routinely measured variables. SUBJECTS/METHODS: We assembled data from non-obese (n = 112) and obese (n = 100) men who underwent two-step EHCs using [6,6-H-2(2)] glucose as tracer (insulin infusion dose 20 and 60 mUm(-2) min(-1), respectively). Reference ranges for hepatic and peripheral insulin sensitivity were calculated from healthy non-obese men. Based on these reference values, obese men with preserved insulin sensitivity or insulin resistance were identified. RESULTS: Cutoff points for insulin-mediated suppression of endogenous glucose production (EGP) and insulin-stimulated glucose disappearance rate (R-d) were 46.5% and 37.3 mu mol kg(-1) min(-1), respectively. Most obese men (78%) had EGP suppression within the reference range, whereas only 12% of obese men had R-d within the reference range. Obese men with R-d < 37.3 mu mol kg(-1) min(-1) did not differ from insulin-sensitive obese men in age, body mass index (BMI), body composition, fasting glucose or cholesterol, but did have higher fasting insulin (110 +/- 49 vs 63 +/- 29 pmol l(-1), P < 0.001) and homeostasis model assessment of insulin resistance (HOMA-IR) (4.5 +/- 2.2 vs 2.7 +/- 1.4, P = 0.004). Insulin-resistant obese men could be identified with good sensitivity (80%) and specificity (75%) from fasting insulin >74 pmol l(-1). CONCLUSIONS: Most obese men have hepatic insulin sensitivity within the range of non-obese controls, but below-normal peripheral insulin sensitivity, that is, insulin resistance. Fasting insulin (>74 pmol l(-1) with current insulin immunoassay) may be used for identification of insulin-resistant (or metabolically unhealthy) obese men in research and clinical settings.