Leptin and Variables of Body Adiposity , E n e rgy Balance , and Insulin Resistance in a Population-Based Study

1097 T he recent discovery of leptin is potentially important for re s e a rch into obesity and related diseases (1). Leptin is a hormone produced by the fat cells, and is thought to play a key role in the control of body weight (2,3). Leptin is hypothetically involved in a feedback loop linking fat and a satiety/energy expenditure center in the hypothalamus. This feedback loop appears to be disturbed in obesity (4,5). Obesity is also often accompanied by disturbances in blood pre s s u re or lipid metabolism re l a t e d to insulin resistance (decreased tissue sensitivity to insulin) (6,7). Recent studies suggest a complex interrelationship between leptin and insulin or insulin resistance (2). Experimental studies in mice and rats show that insulin affects leptin concentrations (4) and that recombinant leptin influ e n c e s insulin resistance and triglyceride metabolism (8,9). Human studies confirm a re l a-tionship between insulin and leptin (10,11), but are controversial with re g a rd to the involvement of leptin in insulin re s i stance or triglyceride metabolism (3,12–16). This controversy might partly be explained by the selection of specific study populations or by small sample sizes. Another explanation might be the role of leptin in a feedback loop, which would diff e re n t i a t e cause and effect. For example, some investigators have hypothesized that leptin has an influence on insulin resistance (12), others that insulin resistance has an influence on leptin (17). The purpose of the p resent study was to gain insight into the regulation of leptin concentrations. We t h e re f o re explored, in a large cro s s-sectional population-based study, the i n fluence on serum leptin concentrations of potential determinants related to body adiposity, energy balance, and insulin re s i s t a n c e. Subjects A random sample of 50-to 74-year-old subjects was taken from the population re g i s t e r of the town of Hoorn in the Netherlands (57,000 inhabitants). Of the 3,553 subjects invited, 2,540 (71.5%) participated, of whom 56 were excluded from the analyses because they were non-Caucasian. Thus, the fin a l c o h o rt consisted of 2,484 subjects (18). Subjects who re p o rted having diabetes (n = 104) w e re excluded from the present analyses to …