help button home button Endocrine Society JCEM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2005-1018
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
90/11/6214    most recent
Author Manuscript (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Allison, K. C.
Right arrow Articles by Stunkard, A. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Allison, K. C.
Right arrow Articles by Stunkard, A. J.
Related Collections
Right arrow Neuroendocrinology and Pituitary
Right arrow Metabolism
The Journal of Clinical Endocrinology & Metabolism Vol. 90, No. 11 6214-6217
Copyright © 2005 by The Endocrine Society

Neuroendocrine Profiles Associated with Energy Intake, Sleep, and Stress in the Night Eating Syndrome

Kelly C. Allison, Rexford S. Ahima, John P. O’Reardon, David F. Dinges, Vibhavasu Sharma, David E. Cummings, Moonseong Heo, Nicole S. Martino and Albert J. Stunkard

Department of Psychiatry, Weight and Eating Disorders Program (K.C.A., J.P.O., N.S.M., A.J.S.), and Division of Sleep and Chronobiology (D.F.D.); and Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism (R.S.A., V.S.), University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104; Department of Medicine, Division of Metabolism, Endocrinology, and Nutrition (D.E.C.), University of Washington, Seattle, Washington 98195; and Department of Psychiatry (M.H.), Weill Medical College of Cornell University, White Plains, New York 10605

Address all correspondence and requests for reprints to: Kelly C. Allison, Ph.D., University of Pennsylvania School of Medicine, Department of Psychiatry, Weight and Eating Disorders Program, 3535 Market Street, Suite 3021, Philadelphia, Pennsylvania 19104. E-mail: kca{at}mail.med.upenn.edu.


   Abstract
Top
 Abstract
Introduction
 Subjects and Methods
 Results
 Discussion
 References
 
Context: Night eating syndrome (NES) is characterized by evening hyperphagia and frequent awakenings with ingestion of food. It is associated with obesity and depressed mood. Greater understanding of hormonal influences on NES is desirable.

Objective: Our objective was to evaluate 25-h profiles of hormones involved in energy balance, sleep, and stress in NES.

Design: Blood assays for glucose, insulin, ghrelin, leptin, melatonin, cortisol, TSH, and prolactin were sampled repeatedly among NES and control subjects. Food intake and depressive symptoms were assessed.

Setting and Participants: Fifteen NES and 14 matched control participants stayed three nights in a General Clinical Research Center.

Main Outcome Measures: We assessed differences between NES and control participants in the 25-h profiles of eight hormones.

Results: Nocturnal food intake was higher among NES participants, although their daily calorie intake was similar to that of controls. Reflecting their increased nocturnal intake, insulin (P < 0.001) and glucose levels (P = 0.07) among NES participants were higher than those of controls. Ghrelin levels were significantly lower in NES participants than in controls from 0100–0900 h (P = 0.003). Levels of plasma cortisol, melatonin, leptin, and prolactin did not differ between groups, but there was a trend for TSH levels (P = 0.07) to be higher during the 25 h in NES. NES participants had greater depressive symptoms than controls (P < 0.001). The differences in the levels of glucose, insulin, and ghrelin between NES and controls are closely associated with nocturnal food intake.


   Introduction
Top
 Abstract
 Introduction
Subjects and Methods
 Results
 Discussion
 References
 
THE NIGHT EATING syndrome (NES) is conceptualized as a delay in the circadian pattern of food intake, characterized by evening hyperphagia and awakenings with ingestion of small amounts of food (1, 2, 3). The circadian sleep-wake pattern remains intact in NES (3, 4). NES is often accompanied by morning anorexia, depressed mood, and obesity (1, 2, 3).

We evaluated 25-h profiles of circulating glucose and seven hormones in relation to food intake, sleep, and stress among NES subjects and matched controls. Leptin falls in response to fasting or weight loss. Its daily nadir occurs before noon, and it peaks during the night, presumably to suppress appetite during sleep (5, 6, 7, 8). Ghrelin increases before meals in normal subjects (9) and is suppressed by feeding (10). Melatonin peaks during the first half of the night and entrains sleep to the dark phase (11). Cortisol and prolactin are both increased by stress. Cortisol peaks in the morning, whereas prolactin peaks during the latter part of the sleep period and declines upon awakening (12, 13). TSH peaks in the late evening and is suppressed by sleep (14). The biological basis of NES is unknown; thus, we sought to determine whether these hormones are affected by NES.


   Subjects and Methods
Top
 Abstract
 Introduction
 Subjects and Methods
Results
 Discussion
 References
 
Subject recruitment and screening

Fifteen female NES subjects (eight Caucasian-American and seven African-American) and 14 female controls (six Caucasian-American and eight African-American), ages 40.8 ± 8.7 vs. 38.6 ± 9.5 yr (P = 0.5), with body mass index of 36.1 ± 7 vs. 38.7 ± 7 kg/m2 (P = 0.6), were studied. The participants were assessed with the Night Eating Questionnaire (15) and a clinical interview. NES patients who reported eating about half of their caloric intake after the evening meal and who awoke to eat three or more times per week and control subjects who reported eating less than a quarter of their intake after the evening meal and no nocturnal ingestions completed a 10-d outpatient study during which they kept food and sleep diaries to confirm the presence or absence of NES, as described in our previous outpatient study (3). Diaries revealed that NES patients consumed 35.9 ± 7.9% of their calories after the evening meal and woke to eat 1.5 ± 1.0 times per night, whereas controls consumed 8.5 ± 6.2% (P < 0.0001) and did not wake to eat (P < 0.0001). Histories and physical examinations, blood chemistries, electrocardiogram, blood count, urinalysis, and urine pregnancy test were performed and were within normal limits for both groups.

Inclusion criteria consisted of age 18–65 yr and body mass index at least 27 kg/m2. Exclusion criteria are noted in our previous report (3). Depressive symptoms were assessed by the Beck Depression Inventory (BDI) (16). Polysomnography detected no sleep disorders in either group. The Human Subjects Institutional Review Board at the University of Pennsylvania approved the study, and subjects gave informed consent to participate. All subjects were paid.

Inpatient study

Participants were housed in private rooms with unrestricted mobility at the National Institutes of Health General Clinical Research Center (GCRC) of the Hospital of the University of Pennsylvania for 3 consecutive days. Lights were limited to 20 lux from 1900 h the night before blood draws began until study completion 38 h later. Supervising nursing staff documented times for lights off at night and lights on upon morning awakening. Subjects were served three meals a day plus ad libitum access to snacks. Snacks were brought from home or provided by the GCRC and were available at the bedside for ready access during all nocturnal awakenings.

Measurements

Participants arrived at the GCRC at 1500 h on the first day and underwent polysomnography on the first two nights (4). They slept according to their usual schedules. Food intake was recorded by subjects in diaries and weighed before and after meals by metabolic kitchen staff. Caloric and macronutrient content of ingested food was calculated with the ESHA Food Processor (version 8; Salem, OR). On the third day, a catheter was placed in the antecubital vein at 0730 h, and blood samples were collected every 2 h from 0800–2000 h, then hourly from 2100–0900 h. Samples were centrifuged after collection and stored frozen at –80 C until assayed. The vendors and precision of assays were as follows: cortisol from Diagnostic Products Inc. (Los Angeles, CA), with a coefficient of variation (CV) of 6.94, melatonin from Alpco (Windham, NH) with a CV of 9.2, leptin from Linco Research (St. Charles, MO) with a CV of 4.62, prolactin from Alpco with a CV of 5.25, and TSH from M.P. Biomedical (Irvine, CA) with a CV of 5.1. Ghrelin was measured with a modification of a commercial RIA (Phoenix Pharmaceuticals, Belmont, CA) with a CV of 7.67 (17). All samples for individual subjects were measured together to minimize variability. Insulin and glucose were also assayed across the 25-h period.

Statistical analyses

Baseline demographic and clinical data and food and macronutrient intake were compared by t test, two-sided. P < 0.05 was considered significant. Levels of hormones were analyzed using linear mixed-effects models in the following form: dependent variable = intercept + group + time + group x time. The intercept was taken as random to account for within-subject temporal correlations of the dependent variables for statistical inference, and group and time variables were taken as fixed and discrete. The effect of particular interest was the interaction between group and time because this interaction represents differences between NES and control groups in trends of the dependent variables over time (18). We used SAS version 8.2 (SAS Institute, Inc., Cary, NC) for statistical analyses.


   Results
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
Discussion
 References
 
Energy intake and demographic information

NES participants consumed more calories during the phlebotomy period between 2000 and 0800 h than controls (779.1 ± 376.6 vs. 288.7 ± 225.2 kcal; P < 0.001), and there was a trend for fewer calories from 0800–1959 (2179.8 ± 463.7 vs. 2604.1 ± 756.2 kcal by NES and control subjects, respectively; P = 0.09). Total caloric intake did not differ (P = 0.8). All 15 NES subjects recorded eating episodes during at least two of the three nights at the GCRC. Only one control subject ate twice at night. Similar macronutrients were consumed by each group from 0800–2000 h. NES participants consumed double the amount of carbohydrates (111.0 ± 63.8 vs. 58.2 ± 59.9 g; P = 0.03) and protein (16.6 ± 13.2 vs. 7.7 ± 9.9 g; P < 0.05) as the controls and four times the fat (35.5 ± 16.9 vs. 9.7 ± 12.4 g; P < 0.001) from 2000–0800 h. NES participants reported more depressive symptoms on the BDI than controls (19.7 ± 10 vs. 3.9 ± 3.6; P < 0.001). All control subjects scored 12 or below on the BDI, so controlling for depressed mood in additional analyses was not appropriate given its exclusivity to the NES group.

Neuroendocrine analyses

There was a trend for glucose to be higher in NES subjects at night, consistent with their increased nocturnal carbohydrate intake (F(19,473) = 1.5; P = 0.07) (Fig. 1AGo). In parallel with the increase in glucose, insulin was higher at night and lower in the morning for NES subjects (F(19,443) = 2.96; P < 0.001) (Fig. 1BGo). Ghrelin levels showed a pattern opposite to that of insulin, lower in the early morning hours (F(19,436) = 2.17; P = 0.003) (Fig. 1CGo).



View larger version (22K):
[in this window]
[in a new window]
  		FIG. 1. Twenty-four-hour profiles of glucose (A), insulin (B), and ghrelin (C) in NES (•) and control subjects ({circ}). Data are mean ± SE; *, P < 0.05 vs. control.

 
Leptin and melatonin levels increased at night in both NES and control subjects (Fig. 2Go, A and B). Cortisol was highest in the morning and declined at night (Fig. 2CGo). None differed between groups.



View larger version (22K):
[in this window]
[in a new window]
  		FIG. 2. Twenty-four-hour profiles of leptin (A), melatonin (B), cortisol (C), and TSH (D) in NES (•) and control subjects ({circ}). Data are mean ± SE; *, P < 0.05 vs. control.

 
There was a trend for TSH levels to be higher in NES subjects than in controls (F(1,25) = 3.62; P < 0.07) across the 25 h, especially in the early morning (Fig. 2DGo). Prolactin profiles did not differ from those of control subjects (not shown).


   Discussion
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
References
 
In accordance with their diagnosis, NES subjects ate significantly more at night than did the controls. The total caloric intake of the two groups, however, did not differ, supporting our previous finding that NES involves a shift in the timing of food intake rather than an increase in total caloric intake (3).

Appetite-regulating hormones were a key focus of this study, and we found that ghrelin levels were lower in NES than in control subjects in the early morning hours, when awakenings are most likely for NES sufferers (3). Thus, the lower ghrelin levels at 0200 h in NES participants are consistent with evidence that ingested food suppresses ghrelin dose dependently (19) and that the lower nocturnal levels were a consequence of increased nocturnal eating, not a cause of it. The awakenings of NES subjects could also have blunted the usual nocturnal rise in ghrelin, because such blunting has been demonstrated in healthy subjects during periods of sleep deprivation (20). The trend for TSH levels to be higher than controls could be a result of their nighttime awakenings, which have been associated with elevated TSH (14). Prolactin levels, not tested before in NES, did not differ between groups.

It should be noted that the results of the present study differ from those of an earlier study of NES with seven overweight and five normal-weight night eaters compared with 10 overweight and 11 normal-weight controls, all Norwegians (2). That earlier study reported that the usual nighttime rise in melatonin and leptin was blunted in night eaters, and their cortisol values were higher than control values. In contrast to the previous study where control subjects had markedly elevated melatonin levels compared with NES (110 vs. 30 pg/ml), the nighttime values of melatonin in controls and NES in the current study were similar (50 pg/ml in both groups). Similarly, leptin and cortisol patterns did not differ between controls and NES at any time of day or on average across the 25-h period. The reasons for these differences are not clear.

In the present study, insulin levels were significantly higher and glucose levels marginally higher at night in NES compared with control subjects, which was consistent with the timing of food intake. Three large meals and ad libitum snacks yielded a daily intake of about 2900 kcal. In the earlier study, insulin and glucose levels between NES and control subjects were similar, but in response to only four meals of 300 kcal each, spaced 4 h apart. These findings suggest that the insulin regulation of night eaters is intact, producing lower insulin levels on a calorically restricted diet and elevated levels in response to a large carbohydrate load at night.

The earlier study suggested the NES resulted from a failure to maintain sleep by melatonin and to limit nighttime hunger by leptin (2). This conceptualization is not supported by the present study. We conclude that differences in neuroendocrine profiles between NES and control subjects are likely to be the result, not the cause, of the altered timing of food intake.


   Acknowledgments
 
We thank our collaborators at the University of Pennsylvania, Heather Collins, Ph.D. (Diabetes Center RIA Core); Lisa Basel-Brown, M.S., R.D., and the nursing and metabolic kitchen staff (General Clinical Research Center); and Claire Fox (Division of Sleep and Chronobiology, Department of Psychiatry) for their work on this study. We also thank Richard Wurtman, M.D., and his laboratory at the Massachusetts Institute of Technology for performing the melatonin assays and R. Scott Frayo of University of Washington for performing the ghrelin assays.


   Footnotes
 
This work was supported by Grant RO1 DK56735 from the National Institute of Diabetes and Digestive and Kidney Diseases and by a General Clinical Research Center grant from National Institutes of Health/National Center for Research Resources Grant M01 RR00040. R.S.A. is supported by Grant PO1-DK49250. D.F.D. is supported by National Institutes of Health Grants NR04281 and HL70154 and by the Institute for Experimental Psychiatry Research Foundation.

First Published Online August 30, 2005

Abbreviations: BDI, Beck Depression Inventory; CV, coefficient of variation; NES, night eating syndrome.

Received May 11, 2005.

Accepted August 18, 2005.


   References
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
 References
 

  1. Stunkard AJ, Grace WJ, Wolff HG 1955 The night-eating syndrome: a pattern of food intake among certain obese patients. Am J Med 19:78–86[CrossRef][Medline]
  2. Birketvedt GS, Florholmen J, Sundsfjord J, Osterud G, Dinges D, Bilker W, Stunkard A 1999 Behavioral and neuroendocrine characteristics of the night-eating syndrome. JAMA 282:657–663[Abstract/Free Full Text]
  3. O’Reardon JP, Ringel BL, Dinges DF, Allison KC, Rogers NS, Martino NS, Stunkard AJ 2004 Circadian eating and sleeping patterns in the night eating syndrome. Obes Res 12:1789–1796[Medline]
  4. O’Reardon JP, Allison KC, Fox CG, Martino NS, Dinges DF, Stunkard AJ 2003 Comparison of in-lab polysomnography in night eating syndrome and overweight controls. Sleep 26(Suppl):A378
  5. Campfield LA, Smith FJ, Guisez Y, Devos R, Burn P 1995 Recombinant mouse OB protein: evidence for a peripheral signal linking adiposity and central neural networks. Science 269:546–549[Abstract/Free Full Text]
  6. Ahima RS, Prabakaran D, Mantzoros C, Qu D, Lowell B, Maratos-Flier E, Flier JS 1996 Role of leptin in the neuroendocrine response to fasting. Nature 382:250–252[CrossRef][Medline]
  7. Friedman M, Halaas JL 1998 Leptin and the regulation of body weight in mammals. Nature 395:770–773
  8. Sinha MK, Ohannesian JP, Heiman ML, Kriauciunas A, Stephens TW, Magosin S, Marco C, Caro JF 1996 Nocturnal rise of leptin in lean, obese and non-insulin-dependent diabetes mellitus subjects. J Clin Invest 97:1344–1347[Medline]
  9. Cummings DE, Weigle DS, Frayo RS, Breen PA, Ma MK, Dellinger EP, Purnell JQ 2002 Plasma ghrelin levels after diet-induced weight loss and gastric bypass surgery. N Engl J Med 346:1623–1630[Abstract/Free Full Text]
  10. Tschop M, Smiley DL, Heiman ML 2000 Ghrelin induces adiposity in rodents. Nature 407:908–913[CrossRef][Medline]
  11. Zhdanova I, Lynch HJ, Wurtman R 1997 Melatonin: a sleep promoting hormone. Sleep 20:899–907[Medline]
  12. Czeisler CA, Klerman EB 1999 Circadian and sleep-dependent regulation of hormone release in humans. Recent Prog Horm Res 54:97–132
  13. Sassin JF, Frantz GF, Weitzman ED, Kapen S 1972 Human prolactin: 24-hour pattern with increased release during sleep. Science 177:1205–1207[Abstract/Free Full Text]
  14. Allan JS, Czeisler CA 1994 Persistence of the circadian thyrotropin rhythm under constant conditions and after light-induced shifts of circadian phase. J Clin Endocrinol Metab 79:508–512[Abstract]
  15. Marshall H, Allison KC, O’Reardon JP, Birketvedt G, Stunkard AJ 2004 Night eating syndrome among nonobese persons. Int J Eat Disord 35:217–222[CrossRef][Medline]
  16. Beck AT, Steer R 1987 Manual for revised Beck Depression Inventory. New York: Psychological Corp.
  17. McLaughlin T, Abbasi F, Lamendola R, Frayo RS, Cummings DE 2004 Plasma ghrelin concentrations are decreased in insulin-resistant obese adults relative to equally obese insulin-sensitive controls. J Clin Endocrinol Metab 89:630–635
  18. Verbeke G, Molenberghs G 1997 Linear mixed models in practice: a SAS-oriented approach. New York: Springer
  19. Callahan HS, Cummings DE, Pepe MS, Breen PA, Matthys CC, Weigle DS 2004 Postprandial suppression of plasma ghrelin level is proportional to ingested caloric load but does not predict intermeal interval in humans. J Clin Endocrinol Metab 89:1319–1324[Abstract/Free Full Text]
  20. Dzaja A, Dalal MA, Himmerich M, Uhr M, Pollmächer T, Schuld A 2004 Sleep enhances nocturnal plasma ghrelin levels in healthy subjects. Am J Physiol Endocrinol Metab 286:E963–E996



This article has been cited by other articles:


Home page
 J. Clin. Endocrinol. Metab.Home page
J. Z. Kasa-Vubu, A. Rosenthal, E. G. Murdock, and K. B. Welch
Impact of Fatness, Fitness, and Ethnicity on the Relationship of Nocturnal Ghrelin to 24-Hour Luteinizing Hormone Concentrations in Adolescent Girls
J. Clin. Endocrinol. Metab., August 1, 2007; 92(8): 3246 - 3252.
[Abstract] [Full Text] [PDF]

Home page
 Diabetes CareHome page
S. A. Morse, P. S. Ciechanowski, W. J. Katon, and I. B. Hirsch
Isn't This Just Bedtime Snacking?: The potential adverse effects of night-eating symptoms on treatment adherence and outcomes in patients with diabetes
Diabetes Care, August 1, 2006; 29(8): 1800 - 1804.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
90/11/6214    most recent
Author Manuscript (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Allison, K. C.
Right arrow Articles by Stunkard, A. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Allison, K. C.
Right arrow Articles by Stunkard, A. J.
Related Collections
Right arrow Neuroendocrinology and Pituitary
Right arrow Metabolism

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals