Diurnal variation of the serum leptin concentration in patients with anorexia nervosa

In rodents, leptin is involved in regulating eating behaviour, fat storage, and reproductive function. In humans, the serum leptin concentration in obese and normal weight subjects correlates with body mass index, reflecting the body fat store. The serum leptin exhibit diurnal variation, however, this has been reported to be absent in normal weighted amenorrheic athletes. Anorexia nervosa is associated with multiple endocrine abnormalities. Hypothalamic amenorrhoea often precedes the weight loss and may persist after weight recovery. We hypothesized that leptin could be involved in the regulation of eating behaviour and gonadal function in anorexia nervosa.

We measured the concentration of leptin in serum samples taken after an overnight fast in 18 female anorexia nervosa patients and 11 controls. To study diurnal variation, eight patients and 11 controls were hospitalized for 24 h and had a standardized diet at regular times. Seven blood samples were obtained at 4 h intervals from each subject.

The patients fulfilled the DSM-IV criteria for anorexia nervosa. The mean body mass index for the patients was 14.2 +/- 2.3 kg/m2 and for controls 20.3 +/- 1.7 kg/m2.

The mean fasting leptin concentration as well as the 24 h mean concentration were significantly lower in the anorectic group than in the control group (2.5 +/- 0.9 vs 10.1 +/- 6.1 micrograms/l, P < 0.01 and 2.7 +/- 1.5 vs 10.6 +/- 7.1 micrograms/l, P < 0.01 respectively). In the whole group of subjects (n = 28) a significant positive correlation 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 0100 h respectively. However, the individual coefficients of variance were significantly lower in the anorectic group compared to the group of healthy women.

In patients with anorexia nervosa the leptin level is low, reflecting the low body fat mass, and the relative diurnal variation is strikingly reduced. The similarity to that of normal weighted women with hypothalamic amenorrhoea suggest that altered leptin oscillations may be of particular significance in the hypothalamic regulation of reproductive function.