RELATIONSHIP BETWEEN INSULIN SENSITIVITY AND PLASMA LEPTIN CONCENTRATION IN LEAN AND OBESE MEN

Alterations in the production of or the sensitivity to leptin, the pro tein encoded by the ob gene, cause obesity and diabetes in rodents, We evaluated the isolated relationship between leptin and insulin sensit ivity in lean and obese humans, Three groups of subjects who were care fully matched for either insulin sensitivity (determined by the modifi ed intravenous glucose tolerance test and minimal model analysis) or a diposity (determined by hydrodensitometry) were studied: 1) lean insul in-sensitive men (percentage body fat, 15 +/- 1%); 2) lean insulin-res istant men (percentage body fat, 16 +/- 1%), matched on percentage bod y fat and fat mass with the lean insulin-sensitive group; and 3) obese insulin-resistant men (percentage body fat, 31 +/- 3), matched on ins ulin sensitivity with the lean insulin-resistant group, Basal plasma l eptin concentrations were significantly lower in the lean insulin-sens itive than in the lean insulin-resistant men (1.90 +/- 0.4 vs, 4.35 +/ - 1.21 ng/ml, P < 0.05) despite identical body composition, Plasma lep tin in the obese men (9.27 +/- 1.4 ng/ml) was significantly higher tha n values in the two lean groups (P < 0.01), Marked alterations in plas ma glucose and insulin concentrations induced by glucose and tolbutami de injection did not cause any change in plasma leptin levels, These r esults demonstrate that insulin resistance is associated with elevated plasma leptin levels independent of body fat mass, However, plasma in sulin itself does not acutely regulate leptin production.