PAPER Serum leptin concentration in obese patients with binge eating ...

International Journal of Obesity (2002) 26, 1125–1128 ß 2002 Nature Publishing Group All rights reserved 0307–0565/02 $25.00 www.nature.com/ijo

PAPER Serum leptin concentration in obese patients with binge eating disorder GF Adami1*, A Campostano2, F Cella3 and N Scopinaro1 1

Dipartimento di Discipline Chirurgiche e Metodologie Integrate, Universita` di Genova, Genova, Italy; 2Divisione Medicina I, Azienda Ospedaliera San Martino, Genova, Italy; and 3Dipartimento di Scienze Endocrino-Metaboliche, Universita` di Genova, Genova, Italy BACKGROUND: In steady-state conditions serum leptin concentration is directly related to body fat stores, but is also affected by changes in energy balance. This cross-sectional study investigated the serum leptin concentrations of severely obese patients with binge eating disorder (BED), in whom body fat was greater than normal and, because of eating pattern, rapid and repeated changes in energy balances took place. METHODS: A group of BED obese patients was compared to a group of obese patients with a regular eating pattern with the same body weight, body composition and resting energy expenditure. Serum leptin was measured and the eating attitudes were evaluated by Eating Inventory and Eating Disorder Inventory. RESULTS: In these patients serum leptin concentrations were only weakly correlated to body mass. Furthermore, in BED obese patients serum leptin concentration was higher than in their non bingeing counterparts. CONCLUSIONS: In obese patients both body fat size and eating behavior influence serum leptin concentration, but BED patients binge eating is not triggered by a low leptin value. International Journal of Obesity (2002) 26, 1125 – 1128. doi:10.1038/sj.ijo.0802010 Keywords: leptin; obesity; eating behavior

Introduction Leptin is recognized as a feedback signal to the central nervous system that influences feeding behavior and energy homeostasis.1 Leptin is mainly produced by adipocytes; this is reflected in a positive relationship between serum leptin concentration and body fat mass in both normal-weight and obese subjects. Furthermore, a sharp decrease in serum leptin concentration follows an acute energy restriction, suggesting an additional role of leptin in the short-term regulation of food intake.2 – 4 Leptin plasma concentrations are sharply reduced in underweight anorectic patients, mainly because of the low body weight and the reduced body fat store.5 – 7 Furthermore, a clear-cut decrease of serum leptin concentration was observed in bulimia nervosa patients despite a normal or nearly normal body weight, indicating that factors other

*Correspondence: GF Adami, Dipartimento di Discipline Chirurgiche, Universita` di Genova, largo Rosanna Benzi 8, 16132 Genova, Italy. E-mail: [email protected] Received 25 September 2001; revised 0 2001; accepted 14 January 2002

than body fat stores may play a role in regulating leptin production.8,9 It has therefore been suggested that in anorexia and bulimia nervosa patients a reduced leptin level in absolute or relative terms could explain the increased hunger sensation and could compel bulimic patients to binge eating.5 – 9 The few published investigations on leptin concentration in binge eating disorder (BED) obese patients provide conflicting results. Karhunen et al suggested no difference in serum leptin concentration between BED and non-BED obese patients, suggesting that leptin does not play a role in the short-term regulation of eating.10 In contrast, other researches showed higher leptin concentrations in BED obese patients than is normally expected for their body weight, indicating that plasma leptin might be a sensitive marker of metabolic changes occurring during bingeing episodes, and that an increased leptin value with an impaired sensitivity to the increased circulating leptin could be involved in the pathogenesis and=or in the maintenance of bingeing behavior.8,11 In order to ascertain the relationships between leptin and eating pattern in obese patients, this investigation sought to

Leptin in binge eating disorder GF Adami et al

1126 measure the serum leptin concentrations in both BED and non-BED obese patients and to correlate data to individual food- and shape-attitudes and to the patients’ weight fluctuations.

uated using the Mann – Whitney U-test for independent data, and the relationships between data were assessed using the Spearman coefficient.

Results Material and methods The investigation was carried in 30 severely obese women asking for bariatric surgery. Body weight (BW) had been stable for at least 6 months in all patients and at the time of the study none of them was on reducing diet. Fourteen women met the criteria for BED,12 and 16 women had never engaged in bingeing behavior (Table 1). Except for obesity, all patients were in completely good health and did not take any medication known to influence metabolic parameters. The height and weight of each subject was recorded and body composition determined by bioelectrical impedance analysis (RJL System, Detroit, MI, USA), deriving body fat (BF) content from appropriate equations.13 Resting energy expenditure (REE, kcal=min) was measured by indirect calorimetry (Centaurus Cosmed) and calculated by standard equations.14 Serum leptin concentration was determined in the morning after an overnight fast: measurements were made using a commercially available RIA kit (DRG Instrument, GmbH, Marburg, Germany), the interassay and intra-assay coefficient of variation being 5.7 and 3.7%, respectively.15 Patients were asked to answer a series of questions on BW variability, covering magnitude and frequency of weight reduction due to dieting during their lifetime, considering only the weight loss episodes greater than 10 kg: a continuous weight cycling index (WCI) was then computed.16 Eating behavior was evaluated by Eating Inventory (EI), which assesses the cognitive alimentary restraint, the tendency to disinhibition over food intake, and the susceptibility to hunger,17 and by Eating Disorder Inventory (EDI), developed to assess specific behavioral traits among eatingdisordered individuals and thus deemed suitable to identify characteristics associated with binge eating among obese persons.18 Due to the small number of cases, analysis was carried out by non-parametric statistical methods: differences were evalTable 1 Comparison between BED and non-BED obese women (mean s.d.)

n Body weight (kg) Body mass index (kg=m2) Body fat mass (kg) Resting energy expenditure (kcal=24 h) Serum leptin concentration (ng=ml) Serum leptin concentration normalized for body fat (ng=ml=kg) *U ¼ 41, P ¼ 0.0056. **U ¼ 54, P ¼ 0.0260.

International Journal of Obesity

BED patients

Non-BED patients

14 121.9 21.2 46.4 9.9 63.0 19.9 1471 395 81.9 21.2 1.43 0.58

16 122.6 16.4 46.5 7.8 61.0 16.0 1412 301 59.0 19.3* 0.99 0.58**

Among the obese women of this study, 14 (47%) of patients met the criteria for BED. In the BED and non-BED patients, BW, body mass index (BMI), BF and REE were essentially identical. Higher serum leptin concentrations were found in the BED patients, both as absolute values and normalized for BF (Table 1), with significance levels greater for the absolute values. Furthermore, serum leptin level was significantly associated with BF (r ¼ 0.387, P ¼ 0.045), while no correlation with BW or BMI was observed. In all patients, serum leptin concentration was not related to the measures of dietary restraint, such as EI Cognitive Restraint and EDI Drive for Thinness, whereas there was a significant positive association with the WCI values (r ¼ 0.3734, P ¼ 0.046). Furthermore, significant positive associations between serum leptin and EI Disinhibition (r ¼ 0.592, P ¼ 0.0032), EI Hunger (r ¼ 0.5086, P ¼ 0.0048) and EDI Bulimia (r ¼ 0.4064, P ¼ 0.0287) scores were observed. The other EDI subscale scores were fully unrelated to serum leptin value.

Discussion In this investigation serum leptin concentrations of BED patients were greater than those observed in their non-BED counterparts with similar BW and body fat mass. Unlike most previous data,15,19,20 the serum leptin concentrations detected in this study were unrelated to BW and BMI values. The vast majority of papers reporting the relationship between leptin and body mass have been carried out in normal or in slightly and moderately obese subjects and, since the prevalence of BED increases with increasing adiposity, it is conceivable that only a few BED patients had been included. On the contrary, this investigation focused on individuals with severe obesity, and nearly 50% of them had to be considered as having BED. Since serum leptin concentrations of BED obese patients were considerably higher than those of their non-BED counterparts, the influence of a source of variation, eg the eating pattern, in the relationship of leptin to body mass has to be hypothesized. The presence of BED and therefore of markedly high serum leptin concentration values in nearly onehalf of the subjects might explain the lack of correlation between serum leptin concentration and BMI values observed in the patients of this study. This finding is in agreement with previous results obtained in patients with obesity of extreme degree.21 However, although in severely obese patients serum leptin concentration appears to be strongly associated with eating pattern, the weakly significant positive relationship between leptin and BF mass suggests that adipose tissue still has a


1127 substantial role in determining leptin concentration. The finding of a greater level of statistical significance of the difference in leptin absolute values than that found in leptin values normalized for BF between BED patients and their non-BED counterparts concurs with this suggestion. Several studies have demonstrated that the tendency to disinhibition and the susceptibility to hunger, as evaluated by the EI, as well as the EDI bulimia score, are higher in BED than in non-BED patients.22 – 24 Furthermore, weight fluctuation due to reducing diet is more frequent in BED patients than in the non-BED individuals.24,25 Therefore, since serum leptin concentrations in BED patients were also greater than in their non-BED counterparts, the positive associations between serum leptin concentration and EI disinhibition and susceptibility to hunger score, EDI bulimia score and WCI are not surprising. One could speculate that in BED patients a low serum concentration of leptin compels the individual to binge: this hypothesis, however, is not supported by the normal or higher serum leptin concentration observed in BED patients compared to non-BED counterparts.8,10,11 Because BW, body composition and REE values were very similar in all subjects of this study, and since the physical activity was most likely comparable, a similar overall energy intake has to be assumed. In addition, since in all cases BW was essentially stable in all cases, all patients have to be considered in energy balance. BED and non-BED patients are thought to have an average similar energy intake and different serum leptin concentration: this prompts the hypothesis that in obese patients customary food consumption and serum leptin concentration are essentially independent. Hence, the higher serum leptin concentration in BED patients could simply reflect the transient positive energy balance that patients experience during binge eating episodes, confirming previous results obtained in normal subjects.26 In BED patients with a lesser degree of obesity, with BW and BF values lower than those of the subjects in this study, completely normal serum leptin concentrations were observed.10 In these patients a lower overall food intake and a less frequent bingeing with a smaller quantity of food consumed per episode have to be assumed. Therefore, it might be inferred that leptin production in BED patients is influenced by the frequency of bingeing and by the amount of food eaten during each bingeing episode. Some investigations have reported a negative association between dietary restraint and serum leptin concentration in eating disordered and in BED patients.9,10,27,28 In contrast, this study showed that serum leptin concentration was positively related only to scores indicating a tendency to lose control over food intake. This would suggest that the dietary restraint of severely obese patients is inadequate in reducing the current food intake and therefore plays no role in influencing leptin concentration. In conclusion, the findings of this study indicate that both the eating behavior and the amount of adipose tissue influence serum leptin concentration, thus confirming in

severely obese patients the findings observed in eating disordered patients and in BED individuals with a mild degree of obesity.9,10,27,28 Furthermore, the results do not support the hypothesis that in eating disordered and in BED patients a low serum leptin concentration is a primary phenomenon, which causes a restriction of food intake in anorexia nervosa patients,27 or an increased hunger sensation that compels bulimia nervosa or BED patients to binge.29 Rather, increased or decreased serum leptin concentrations merely seem to be the consequence of prolonged periods of sharply negative energy balance ensuing from frequent dieting in anorectic patients or in restricting individuals, or of frequent bouts of positive energy balances due to bingeing episodes in BED and in bulimic patients.

References 1 Wang Q, Bing C, Al-Barazanij K, Mossakowaska DE, Wang XM, McBay DL, Neville WA, Taddayon M, Pickavance L, Dryden S, Thomas MEA, McHale MT, Gloyer IS, Wilson S, Buckingham R, Arch JRS, Trayhurn P, Williams G. Interactions between leptin and hypothalamic neuropeptide Y neurons in the control of food intake and energy homeostasis in the rat. Diabetes 1997; 46: 335 – 341. 2 Jenkins AB, Markovic TP, Fleury A, Campbell LV. Carbohydrate intake and short-term regulation of leptin in humans. Diabetologia 1996; 40: 348 – 351. 3 Kolaczynsky JW, Considine RV, Ohannesian J, Marco C, Opentanova I, Nyce MR, Myint M, Caro JF. Responses of leptin to shortterm fasting and refeeding in humans. Diabetes 1996; 45: 1511 – 1515. 4 Weigle DS, Duell PB, Connor WE, Steiner RA, Soules MR, Kuijper JL. Effect of fasting refeeding and dietary fat restriction on plasma leptin levels. J Clin Endocrinol Metab 1997; 82: 561 – 565. 5 Hebebrand J, Blum WF, Barth N, Coners H, Englaro P, Juul A, Ziegler A, Warnke A, Rascher W, Remschmidt H. Leptin levels in patients with anorexia nervosa are reduced in the acute stage and elevated upon short-term weight restoration. Mol Psych 1997; 2: 330 – 334. 6 Kopp W, Blum WF, Ziegler A, Mathiak K, Lubbert H, Herpertz S, Deter HC, Hebebrand J. Serum leptin and body weight in females with anorexia and bulimia nervosa. Horm Metab Res 1998; 30: 272 – 275. 7 Mathiak K, Gowin W, Hebebrand J, Ziegler A, Blum WF, Felsenberg D, Lubbert H, Kopp W. Serum leptin levels body fat deposition and weight in females with anorexia or bulimia nervosa. Horm Metab Res 1999; 31: 274 – 277. 8 Monteleone P, Di Lieto A, Tortorella A, Longobardi N, Maj M. Circulating leptin in patients with anorexia nervosa bulimia nervosa or binge eating disorder: relationship to body weight eating pattern psychopathology and endocrine changes. Psych Res 2000; 94: 121 – 129. 9 Nakai Y, Hanagaki S, Kato S, Seino Y, Takagi R, Kurimoto F. Role of leptin in women with eating disorders. Int J Eat Disord 1999; 26: 29 – 35. 10 Karhunen L, Haffner S, Lappalainen R, Turpeinen A, Miettinen H, Uusitupa M. Serum leptin and short term regulation of eating in obese women. Clin Sci 1997; 92: 573 – 578. 11 d’Amore A, Massignan C, Montera P, Moles A, De Lorenzo A, Scucchi S. Relationship between dietary restraint, binge eating, and leptin in obese women. Int J Obes Relat Metab Disord 2001; 25: 373 – 377. 12 Spitzer RL, Yanovski SZ, Wadden TA, Wing RR, Marcus MD, Stunkard AJ, Devlin M, Mitchell JE, Hasin D, Horne RL. Binge eating disorder: its further validation in a multisite study. Int J Eat Disorder 1993; 13: 137 – 153.



1128

13 Lukaski HC, Johnson PE, Bolonchuck WW, Lykken GI. Assessment of fat-free mass using bioelectrical impedance measurements of the human body. Am J Clin Nutr 1985; 41: 810 – 817. 14 Jequier E, Acheson K, Schultz Y. Assessment of energy expenditure in man. A Rev Nutr 1987; 7: 187 – 208. 15 Maffei M, Halaas J, Ravussin E, Pratley RE, Lee GH, Zhang Y, Fei H, Kim S, Lallone R, Ranganathan S, Kern PA, Friedman JM. Leptin levels in human and rodent: measures of plasma leptin and ob RNA in obese and weight reduced subjects. Nat Med 1966; 11: 1155 – 1161. 16 Rodin J, Radke-Sharpe N, Rebuffe-Scrive M, Greenwood MRC. Weight cycling and fat distribution. Int J Obes 1990; 14: 303 – 310. 17 Stunkard AJ, Messik S. The three-factor eating questionnaire to measure dietary restraint disinhibition and hunger. J Psychosom Res 1985; 29: 71 – 83. 18 Garner MG, Olmsted P, Polivy J. Development and validation of a multidimensional eating disorder inventory for anorexia nervosa and bulimia. Int J Eat Disord 1983; 2: 15 – 34. 19 Caro JF, Sinha MK, Kolaczynski JW, Zhang PL, Considine RV. Perspectives in diabetes leptin: the tale of an obesity gene. Diabetes 1996; 45: 1455 – 1462. 20 Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR, Ohannesian JP, Marco CC, McKee LJ, Bauer TL, Caro JF. Serum immunoreactive-leptin concentrations in normalweight obese humans. New Engl J Med 1996; 334: 292 – 295. 21 Adami GF, Cordera R, Campostano A, Bressani A, Cella F, Scopinaro N. Serum leptin and weight loss in severely obese patients undergoing biliopancreatic diversion. Int J Obes Relat Metab Disord 1998; 22: 822 – 824.


22 DeZwann M, Nutzinger DO, Schoenbeck G. Binge eating in overweight women. Compreh Psych 1992; 4: 256 – 261. 23 Brody ML, Walsh BT, Devlin MJ. Binge eating disorder: reliability and validity of a new diagnostic category. J Consul Clin Psychol 1994; 62: 381 – 386. 24 Westenhoefer J, Stunkard AJ, Pudel V. Validation of the flexible and rigid control dimension of dietary restraint. Int J Eat Disord 1999; 26: 53 – 64. 25 Adami GF, Gandolfo P, Campostano A, Cocchi F, Bauer B, Scopinaro N. Obese binge eaters: metabolic characteristics, energy expenditure and dieting. Psychol Med 1995; 25: 195 – 198. 26 Taylor AE, Hubbard J, Anderson EJ. Impact of binge eating on metabolic and leptin dynamics in normal young women. J Clin Endocrinol Metab 1999; 84: 428 – 434. 27 Von Prittwitz S, Blum WF, Ziegler A, Scharmann S, Remschnidt H, Hebebrand J. Restrained eating is associated with low leptin levels in underweight females. Mol Psych 1997; 2: 420 – 422. 28 Laessle RG, Wurmser H, Pirke KM. Restrained eating and leptin levels in overweight preadolescent girls. Physiol Behav 2000; 70: 45 – 47. 29 Owen WP, Kalmi KA, Gibbs J, Smith JP. Satiety responses in eating disorders. J Psych Res 1985; 19: 279 – 284.