High serum leptin levels subsequent to weight gain predict renewed weight loss in patients with anorexia nervosa

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Abstract

It has repeatedly been shown that high serum leptin levels at target weight ensue from therapeutically induced weight gain in patients with anorexia nervosa (AN). It was hypothesized that elevated leptin levels may be an important factor underlying the difficulties of maintaining the target-weight in AN patients after re-feeding. The aim of this study was to examine if serum leptin levels at discharge from inpatient treatment predict renewed weight loss within 2 months after discharge and upon a 1 yr follow-up.

Univariate variance analysis (ANOVA) revealed that 60% (cor. R2=0.60, P=0.002) of the variance in the BMI standard deviation score (BMI-SDS) 2 months after discharge was explained by the model consisting of the independent variables lg10 leptin levels at discharge (P=0.019) and at admission (P=0.069) and BMI-SDS at admission (P=0.002) and delta BMI between admission and discharge (P=0.047). Similarly, 60% (cor. R2=0.60, P=0.005) of the variance in BMI-SDS 1 yr after discharge was explained by lg10 leptin levels at discharge (P=0.046) and at admission (P=0.052) and BMI-SDS at admission (P=0.008) and 2 months after discharge (P=0.007) and delta BMI between admission and discharge (P=0.933). Patients with a poor outcome after 1 yr (n=9, ANCOVA, group: descriptive P=0.041), but not recovered patients (n=9, P=0.649), had lg10 leptin levels at discharge higher than those of controls when adjusted for BMI and % body fat at discharge.

In conclusion, high serum leptin levels at discharge from inpatient treatment may indicate a risk for renewed weight loss and an unfavorable 1 yr outcome in AN.

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).

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