High serum leptin levels subsequent to weight gain predict renewed weight loss in patients with anorexia nervosa
Introduction
Anorexia nervosa (AN) is a psychiatric disorder with a high mortality. Re-feeding therapies are efficient in weight rehabilitation but rates of short-term relapses are nevertheless high (Herpertz-Dahlmann et al., 2001). Between 50 and 100% of relapses occur within the first year after discharge (Eckert et al., 1995, Strober et al., 1997). Besides psychological factors (Channon and de Silva, 1985, Strober et al., 1997) physiological processes tend to perpetuate the disorder and make recovery more difficult. It is assumed that an elevated caloric requirement and increased resting energy expenditure upon attainment of target weight coupled with a food intake too low to meet this elevated metabolic requirement may particularly contribute to relapse in AN patients (Kaye et al., 1986, Weltzin et al., 1991, Scalfi et al., 1993, Krahn et al., 1993, Obarzanek et al., 1994).
More recently, it has been hypothesized that elevated levels of the adipocyte hormone leptin may be an important factor in the difficulties of maintaining target-weight in AN patients after re-feeding (Hebebrand et al., 1997a, Mantzoros et al., 1997, Holtkamp et al., 2003). Previously, we demonstrated (Hebebrand et al., 1997a, Holtkamp et al., 2003) that hyperleptinemia at target weight is likely to ensue as a result of both large and rapid weight gains. Indeed, administration of leptin increases energy expenditure in rodents (Scarpace et al., 1997, Hwa et al., 1997) and leads to a loss of weight and fat in lean, obese and genetically leptin deficient humans (Heymsfield et al., 1999, Farooqi et al., 2002) and in leptin-deficient and wild type animals (for a review see van Dijk, 2001).
The aim of this study was to investigate if elevated leptin levels at discharge from inpatient treatment indicate a risk for renewed weight loss directly after discharge and predict 1-yr outcome of BMI in patients with anorexia nervosa.
Section snippets
Methods
Eighteen medication-free adolescent females (mean 14.1±1.2 yr) with a DSM-IV diagnosis of AN (14 restricting, four binge eating/purging type) were followed up after discharge from inpatient treatment. This patient sample and the control group of 18 normal-weight, age-matched, and weight stable female controls without a history of eating disorder have been previously described by Holtkamp and co-workers (2003); in the respective study we confirmed the occurrence of hyperleptinemia upon
Results
Leptin levels, BMI and % body fat of patients and controls are shown in Table 1. Controls (14.1±1.2 yr) and patients (13.9±0.8) did not differ in age (descriptive P-value >0.05). Mean duration of inpatient treatment was 16±5 weeks. Pearson correlation coefficients between lg10 leptin levels at discharge and BMI-SDS at different time points are depicted in Table 2. Descriptive analyses revealed that there was no correlation between lg10 leptin levels at discharge and % body fat at discharge (P
Discussion
For the first time, this study provides evidence that high lg10 serum leptin levels at discharge may predict renewed weight loss after discharge and an unfavorable 1-yr outcome of AN. We found an inverse correlation between lg10 leptin levels at discharge and BMI-SDS at both the 2 and 12 month follow-up assessments (Fig. 1). The effect of lg10 leptin levels on BMI-SDS 2 months after discharge was significant after controlling for BMI-SDS and lg10 leptin levels at admission and delta BMI between
Acknowledgments
We thank the patients for their participation. This research was supported by the Christina Barz Foundation (Essen, Germany), the START program of the Technical University of Aachen (Aachen, Germany), German Research Society (DFG RE 471/ 11-2), and the Federal Ministry for Education and Research (NeuroNet Marburg, NGFN; 01 GS 0168 and 01 GS 0118).
References (36)
- et al.
Psychological correlates of weight gain in patients with anorexia nervosa
J. Psychiatr. Res.
(1985) - et al.
Chronic leptin administration promotes lipid utilization until fat mass is greatly reduced and preserves lean mass of normal female rats
Regul. Pept
(2000) - et al.
Outcome prediction by MMPI in subtypes of anorexia nervosa
Psychosomatics
(1988) - et al.
The effect of therapeutically induced weight gain on plasma leptin levels in patients with anorexia nervosa
J. Psychol. Res.
(2003) - et al.
Caloric intake necessary for weight maintenance in anorexia nervosa: nonbulimics require greater caloric intake than bulimics
Am. J. Clin. Nutr.
(1986) - et al.
Changes in resting energy expenditure and body composition in anorexia nervosa patients during refeeding
J. Am. Diet. Assoc.
(1993) - et al.
Leptin rapidly lowers food intake and elevates metabolic rates in lean and ob/ob mice
J. Nutr.
(1997) - et al.
Resting metabolic rate of anorexia nervosa patients during weight gain
Am. J. Clin. Nutr.
(1994) - et al.
Measurement of body fat by dual-energy x-ray absorptiometry and bioimpedance analysis in men with prostate cancer
Nutrition
(2002) - et al.
Effects of weekly administration of pegylated recombinant human OB protein on appetite profile and energy metabolism in obese men
Am. J. Clin. Nutr.
(2001)
The reliability of bioelectrical impedance analysis for measuring changes in the body composition of patients with anorexia nervosa. Int
J. Eat. Disord.
Ten-year follow-up of anorexia nervosa: clinical course and outcome
Psychol. Med
Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/ metabolic dysfunction of human congenital leptin deficiency
J. Clin. Invest.
Leitlinien zur Diagnostik und Therapie von psychischen Störungen im Säuglings- Kindes- und Jugendalter
Weight-reducing effects of the plasma protein encoded by the obese gene
Science
Leptin levels in patients with anorexia nervosa are reduced in the acute stage and elevated upon short-term weight restoration
Mol. Psychiat
Prediction of low body weight at long-term follow-up in acute anorexia nervosa by low body weight at referral
Am. J. Psychiat
Prospective 10-year follow-up in adolescent anorexia nervosa—course, outcome, psychiatric comorbidity, and psychosocial adaptation
J. Child Psychol. Psychiat
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