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- 2 H 2 ]glucose as tracer (insulin infusion dose 20 and 60 mU m −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 μmol 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 μmol 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.