INSULIN-RESISTANCE AND HYPERSECRETION IN OBESITY

Insulin resistance and insulin hypersecretion are established features of obesity. Their prevalence, however, has only been inferred from pl asma insulin concentrations. We measured insulin sensitivity (as the w hole-body insulin-mediated glucose uptake) and fasting posthepatic ins ulin delivery rate (IDR) with the use of the euglycemic insulin clamp technique in a large group of obese subjects in the database of the Eu ropean Group for the Study of Insulin Resistance (1,146 nondiabetic, n ormotensive Caucasian men and women aged 18-85 yr, with a body mass in dex (BMI) ranging from 15 to 55 kg . m(-2)). Insulin resistance, defin ed as the lowest decile of insulin sensitivity in the lean subgroup (6 08 subjects with BMI less than or equal to 25 kg m(-2)), was present i n 26% of the obese subgroup (538 subjects with a mean BMI of 29 kg . m (-2)). Insulin sensitivity declined linearly with BMI at an age-and se x-adjusted rate of 1.2 mu mol . min(-1). kg FFM-1 per Bhn unit (95% co nfidence intervals = 1.0-1.4). Insulin hypersecretion, defined as the upper decile of IDR, was significantly (P < 0.0001) more prevalent (38 %) than insulin resistance in the obese group. In the whole dataset, I DR rose as a function of both BMI and insulin resistance in a nonlinea r fashion. Neither the waist circumference nor the waist-to-hip ratio, indices of body fat distribution, was related to insulin sensitivity after adjustment for age, gender, and BMI; both, however, were positiv ely associated (P < 0.001) with insulin hypersecretion, particularly i n women. In nondiabetic, normotensive obese subjects, the prevalence o f insulin resistance is relatively low, and is exceeded by the prevale nce of insulin hypersecretion, particularly in women with central obes ity. In the obese with preserved insulin sensitivity, risk for diabete s, cardiovascular risk, and response to treatment may be different tha n in insulin resistant obesity.