Determinants of postabsorptive endogenous glucose output in non-diabetic subjects

Aims/hypothesis. To gain insight into the physiologic determinants of posta bsorptive endogenous glucose output (EGO) in humans. Methods. We analysed the data of 344 non-diabetic subjects (212 men and 132 women) with a wide range of age (18-85 years) and body mass index (15-55 k g/m(2)) who participated in the European Group for the Study of Insulin Res istance (EGIR) project. Whole-body endogenous glucose output was measured b y tracer ([H-3]glucose) dilution at steady-state, peripheral insulin sensit ivity (a glucose clearance/partial derivative insulin) was measured by the euglycaemic insulin (7 pmol x min(-1) x kg(-1)) clamp technique. Results. Whole-body endogenous glucose output showed a large variability (m ean = 768 +/- 202 mu mol.min(-1), range 209-1512) and was strongly related to lean body mass (r = 0.63,p < 0.0001). This association entirely explaine d the endogenous glucose output being higher in men than in women (827+/-18 9 vs 674 x 187 mu mol x min(-1), p < 0.0001), its relation to body mass (10 +/- 2 per unit of body mass index, p < 0.0001) and its trend to decline with age (-1.1 +/- 0.7 mu mol.min(-1) per year, p = 0.10). Although inverse ly related to one another (r = -0.41, p < 0.0001), peripheral insulin sensi tivity and fasting plasma insulin were both independently associated with e ndogenous glucose output in an inverse fashion (with partial r's of 0.19 an d 0.21, respectively, after adjusting for lean body mass and centre, p < 0. 0001 for both). Conclusion/interpretation. Among non-diabetic subjects in the postabsorptiv e condition, total body endogenous glucose output variability is wide and i s largely explained by the amount of lean mass; this, in turn, explains dif ferences in total endogenous glucose output due to sex, obesity and age. In dependently of the amount of lean mass, peripheral insulin resistance is as sociated with a higher endogenous glucose output independently of fasting p lasma insulin concentration, suggesting coupled regulation of insulin actio n in peripheral tissues and the liver.