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 [6,6-2H2]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 (Rd) 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 Rd within the reference range. Obese men with Rd < 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.