DIURNAL-VARIATION OF THE SERUM LEPTIN CONCENTRATION IN PATIENTS WITH ANOREXIA-NERVOSA

OBJECTIVE In rodents, leptin is involved in regulating eating behaviou r, fat storage, and reproductive function. In humans, the serum leptin concentration in obese and normal weight subjects correlates with bod y mass index, reflecting the body fat store. The serum leptin exhibit diurnal variation, however, this has been reported to be absent in nor mal weighted amenorrheic athletes. Anorexia nervosa is associated with multiple endocrine abnormalities. Hypothalamic amenorrhoea often prec edes the weight loss and may persist after weight recovery. We hypothe sized that leptin could be involved in the regulation of eating behavi our and gonadal function in anorexia nervosa, DESIGN We measured the c oncentration of leptin in serum samples taken after an overnight fast in 18 female anorexia nervosa patients and 11 controls. To study diurn al variation, eight patients and 11 controls were hospitalized for 24 h and had a standardized diet at regular times. Seven blood samples we re obtained at 4h intervals from each subject. PATIENTS The patients f ulfilled the DSM-IV criteria for anorexia nervosa, The mean body mass index for the patients was 14.2 +/- 23 kg/m(2) and for controls 20.3 /- 1.7 kg/m(2). RESULTS The mean fasting leptin concentration as well as the 24 h mean concentration were significantly lower in the anorect ic group than in the control group (2.5 +/- 0.9 vs 10.1 +/- 6.1 mu g/l , P<0.01 and 2.7 +/- 1.5 vs 10.6 +/- 7.1 mu g/l, P<0.01 respectively). In the whole group of subjects (n=28) a significant positive correlat ion between the leptin level and body mass index was found (r = 0.63, P < 0.001). In the anorectic group it was found that the leptin level correlated better with body fat percentage than with body mass index. In normalized data the time course of the mean leptin levels showed a monophasic Variation with nadir and zenith at about 0900 and 100h resp ectively. However, the individual coefficients of variance were signif icantly lower in the anorectic group compared to the group of healthy women, CONCLUSION In patients with anorexia nervosa the leptin revel i s low, reflecting the low body fat mass, and the relative diurnal Vari ation is strikingly reduced. The similarity to that of normal weighted women with hypothalamic amenorrhoea suggest that altered leptin oscil lations may be of particular significance in the hypothalamic regulati on of reproductive function,