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

Abstract

OBJECTIVE: to assess the impact of obesity and insulin sensitivity on resting (REE) and glucose-induced thermo-genesis (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, LBM-adjusted 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 steady-state 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.