Effect of obesity and insulin resistance on resting and glucose-induced thermogenesis in man.

OBJECTIVE: to assess the impact of obesity and insulin sensitivity on resting (REE) and glucose-induced thermogenesis (GIT). DESIGN: Data from 322 studies carried out in non-diabetic subjects of either gender, covering a wide range of age (18 ± 80 y) and body mass index (BMI, 18 ± 50 kg=m2). MEASUREMENTS: Insulin sensitivity and thermogenesis were measured by combining the euglycaemic insulin clamp technique with indirect calorimetry. RESULTS: REE was inversely related to age (P 0.001) and the respiratory quotient (P 0.03), and positively related to BMI, lean body mass (LBM), fat mass, and percentage fat mass (all p<0.0001). In a multiple regression model, LBMadjusted REE was estimated to decline by 9% between 18 and 80 y, independently of obesity and insulin sensitivity. In contrast, GIT was strongly associated with insulin sensitivity (P<0.0001) but not with gender, age or BMI. By multiple regression analysis, GIT was linearly related to insulin sensitivity after controlling for gender, age, BMI and steadystate plasma insulin levels. Furthermore, both of the main components of insulin-mediated glucose disposal (glucose oxidation and glycogen synthesis) correlated with GIT independently of one another. In the subset of subjects (n 89) in whom waist-to-hip ratio (WHR) measurements were available, GIT was inversely associated with WHR (P<0.001 after adjustment by gender, age, BMI, insulin sensitivity and steady-state plasma insulin concentration). In this model, a significant interaction between WHR and gender indicated a stronger adverse effect on GIT of a high WHR in women than in men. CONCLUSIONS: In healthy humans, age, lean mass and respiratory quotient are the main independent determinants of resting thermogenesis. In contrast, insulin sensitivity and, to a lesser extent, abdominal obesity are the principal factors controlling glucose-induced thermogenesis.