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The Journal of Clinical Endocrinology & Metabolism 88(11):5387–5391
Copyright © 2003 by The Endocrine Society
doi: 10.1210/jc.2003-030956
Opposite Changes in Circulating Adiponectin in Women
With Bulimia Nervosa or Binge Eating Disorder
PALMIERO MONTELEONE, MICHELE FABRAZZO, VASSILIS MARTIADIS, ANTONIO FUSCHINO,
CRISTINA SERRITELLA, NICOLA MILICI, AND MARIO MAJ
Departments of Psychiatry (P.M., M.F., V.M., A.F., C.S., M.M.) and Biochemistry and Biophysics (N.M.), University of
Naples SUN, 80138 Naples, Italy
Adiponectin is a recently discovered peripheral peptide that
is secreted exclusively by differentiated adipocytes. It has
been shown to enhance insulin sensitivity, control body
weight, regulate lipid homeostasis, and prevent atherosclerosis. Dysregulation of both lipid and glucose metabolism and
changes in body weight and body fat mass have been reported
in bulimia nervosa (BN) and/or binge eating disorder (BED);
hence, investigation of adiponectin secretion is of obvious
interest in these eating disorders. To this purpose, we measured plasma levels of adiponectin, glucose, cholesterol, triglycerides, and thyroid hormones in 60 drug-free women, including 20 patients with BN, 20 patients with BED, and 20
healthy controls. Compared with healthy women, BN women
exhibited significantly increased circulating adiponectin levels (P < 0.002) and cholesterol concentrations (P < 0.005),
whereas BED women had significantly reduced plasma levels
A
DIPOSE TISSUE HAS been traditionally considered an
inert storage depot for lipids to be released in conditions of hardship such as starvation. Now it is becoming
more and more clear that adipocytes operate as endocrine
cells that release a number of peptide hormones actively
involved in the regulation of body weight (BW) and energy
homeostasis. These peptides share some structural properties of cytokines and are therefore referred to as adipocytokines (1). One of the latest arrivals in the family of adipocytokines is adiponectin, a 30-kDa protein that is secreted
exclusively by differentiated adipocytes (2).
Several recent studies suggest that adiponectin plays an
important role in the metabolic homeostasis of the organism.
In vitro, adiponectin facilitates reduction of hepatocyte glucose production by insulin (3) and attenuates TNF-␣ signal
transduction in macrophages, and TNF-␣ is one factor that
potentially induces insulin resistance (4). In vivo, the administration of purified adiponectin to obese mice improves
glucose metabolism and fatty acid utilization in the liver and
skeletal muscles (3, 5, 6). Moreover, serum levels of adiponectin have been found to be significantly decreased in
obese humans (7) and in patients with type 2 diabetes mellitus (8, 9), conditions commonly associated with insulin
resistance. Similarly, reduced adiponectin concentrations
have been detected in women with dyslipidemia (10). Taken
together, all these data suggest that maintenance of stable
Abbreviations: BED, Binge ED; BMI, body mass index; BN, bulimia
nervosa; BW, body weight; ED, eating disorder; FT3, free T3; FT4, free T4.
of adiponectin (P < 0.005) and increased concentrations of
glucose (P < 0.01), cholesterol (P < 0.05), and triglycerides (P <
0.02). Moreover, plasma levels of adiponectin were significantly correlated to the frequency of binge/vomiting episodes
(r ⴝ 0.65, P ⴝ 0.002) in bulimics but not to the frequency of
bingeing in BED patients. Because we did not include a group
of obese patients who did not binge eat, the specificity of our
findings in the BED should be considered cautiously. However, on the basis of present results, it is tempting to speculate
that the increased production of adiponectin in BN may represent a compensatory mechanism to counteract the possible
development of insulin resistance, whereas the decreased secretion of adiponectin in individuals with BED may be a risk
factor for the development of glucose intolerance. (J Clin Endocrinol Metab 88: 5387–5391, 2003)
systemic adiponectin levels might be critical to glucose and
lipid homeostasis and modulation of insulin sensitivity.
Bulimia nervosa (BN) and binge eating disorder (BED) are
two relatively recently categorized eating disorders (EDs).
BN is characterized by multiple binge episodes followed by
compensatory behaviors, such as purging, excessive exercising, and prolonged starvation, which aim to prevent the
BW increase that would follow the massive calorie ingestion
in the binge episodes. As a consequence of the abnormal
eating patterns and compensatory behaviors, multiple physiological aberrations occur in BN. In particular, although
normal glucose and insulin responses to oral glucose (11, 12)
have been elicited in bulimic patients, exaggerated insulin
peaks after test meals (13, 14), reduced insulin sensitivity
(15), and glucose intolerance (16) have all been reported.
Similarly, either increased or normal levels of cholesterol and
triglycerides have been detected in symptomatic bulimic individuals (17–21).
BED is characterized by multiple binge episodes, as in BN,
but with no compensatory behaviors; therefore, patients with
this disorder incur BW gain and fat accumulation. This considerable increase of adipose tissue is expected to be associated with changes in adiponectin secretion in BED patients.
Furthermore, an intriguing association has been reported
between BED and type 2 diabetes mellitus (22). Finally, alterations in the physiology of other adipose-borne peptide
hormones, such as leptin, have been clearly documented in
both BN and BED (23–26). Therefore, investigation of circulating adiponectin in patients with BN or BED seems to be
of obvious interest.
5387
5388
J Clin Endocrinol Metab, November 2003, 88(11):5387–5391
Monteleone et al. • Circulating Adiponectin in BN and BED
In the present study, we measured circulating adiponectin
and investigated its relationships to anthropometrics and
metabolic and hormonal parameters in a cohort of subjects
including patients with BN, patients with BED, and healthy
controls.
Subjects and Methods
Subjects
A total of 60 women were recruited for the study. Forty women were
outpatients attending the Eating Disorder Center in the Department of
Psychiatry (University of Naples, Naples, Italy), and 20 women were
healthy controls. According to the criteria of the Diagnostic and Statistical
Manual of Mental Disorders, Fourth Edition (DSM-IV) (27), 20 patients
fulfilled the diagnosis of BN (five of the patients had a previous history
of anorexia nervosa), and 20 fulfilled the diagnosis of BED. Diagnostic
assessment was made by a trained interviewer using the Structured
Clinical Interview for DSM-IV (28). Moreover, all the patients underwent
a structured clinical interview that is used in our department to collect
information about the patients’ demographic and historical characteristics and to specifically assess past and/or current eating-related symptomatology, including the number of daily objective bingeing and purging episodes in the 4 wk preceding the assessment. Patients with BN
were all of the purging subtype, with binge episodes always followed
by self-induced vomiting; five of the patients also abused laxatives, one
abused diuretics, and two exercised excessively. Five bulimic patients
were amenorrheic; the remaining patients with BN and the patients with
BED had normal, regular menses. At the time of the study, all patients
had been drug free for more than 6 wk.
The control women were mentally healthy, as assessed by the M.I.N.I.
International Neuropsychiatric Interview (29), and had no positive family history of mental disorders, as assessed by the Family History Research Diagnostic Criteria (30). The control subjects were regularly menstruating, had normal diets, and took no medication for at least 6 wk
before the study.
Both patients and healthy volunteers had normal physical examinations, normal values of routine blood and urine tests, and normal electrocardiograms. Female controls and patients who were normally menstruating were tested in the follicular phase of their menstrual cycle (d
5–10 from menses). None of the subjects was taking oral contraceptives
or had a past history of alcohol or drug abuse.
Procedure
The study was approved by the local ethics committee, and subjects
gave written informed consent before study participation.
Each subject underwent a blood sample collection in the morning,
between 0800 and 0900 h, after an overnight fast. Patients were instructed to not binge from 2000 h of the day before blood sampling, and
their behavior was carefully checked by a relative. Blood was collected
in tubes with lithium heparin as anticoagulant. Plasma was separated by
centrifugation and stored at ⫺20 C.
In each subject, BW and height were measured, and the body mass
index (BMI) was calculated. Moreover, body composition was evaluated
by means of a bioelectrical impedance analyzer (STA/BIA, Akern Srl,
Florence, Italy).
Biochemical analyses
Plasma adiponectin values were determined by a sandwich ELISA
using a commercial kit purchased from B-Bridge International, Inc. (San
Jose, CA). The sensitivity of the method was 23.4 pg/ml, and the intraand interassay coefficients of variation were 4.6 and 7.3%, respectively.
Plasma free T3 (FT3) and free T4 (FT4) levels were determined by an
ELISA using commercial kits purchased from Adaltis Italia (Bologna,
Italy). The sensitivities of the assays were 0.05 pg/ml for FT3 and 0.05
ng/dl for FT4, and the intra- and interassay coefficients of variation were
4.1 and 5.2% for FT3, and 6.1 and 9.6% for FT4, respectively.
Plasma glucose, cholesterol, and triglycerides were determined by
commercial enzymatic colorimetric methods (Roche Diagnostics GmbH,
Mannheim, Germany) on an automated clinical chemistry analyzer (Hitachi 717, Boheringer Biochemia Robin, Monza, Italy).
Data analysis
The BMDP statistical software package (University of California,
Berkeley, CA) was used for data analysis (31). In each subject group,
adiponectin values were analyzed for normality of distribution; because
there were no significant deviations from normality in the data, parametric statistical analyses were used. Where one-way ANOVA showed
significant differences among the groups, the post hoc Tuckey’s test was
used to assess differences between patients and controls. The Pearson’s
product ⫻ moment correlation test was used to examine the relationships between adiponectin values and demographic, metabolic, or hormonal data.
Results
Demographic and clinical data
ANOVA showed significant intergroup differences in
mean age [F(2,57) ⫽ 10.19, P ⬍ 0.0001], BW [F(2,57) ⫽ 44.03, P ⬍
0.0001], BMI [F(2,57) ⫽ 43.39, P ⬍ 0.0001], body fat mass [F(2,57)
⫽ 48.92, P ⬍ 0.0001], and body lean mass [F(2,57) ⫽ 20.52, P ⬍
0.0001]. With respect to healthy women, patients with BED
had significantly higher mean age, BW, BMI, body fat mass,
and body lean mass. No significant differences in these variables were observed between patients with BN and healthy
women (Table 1).
For the BN group, the mean binge/vomiting frequency
and the mean duration of the illness were 17.8 ⫾ 8.2 episodes/wk and 5.9 ⫾ 2.8 yr, respectively. For the BED group,
the mean binge frequency and the mean duration of the
illness were 15.4 ⫾ 9.3 episodes/wk and 8.9 ⫾ 6.5 yr,
respectively.
Biochemical data
ANOVA showed significant intergroup differences in
plasma levels of adiponectin [F(2,57) ⫽ 23.53, P ⬍ 0.0001],
cholesterol [F(2,57) ⫽ 6.71, P ⬍ 0.003], triglycerides [F(2,57) ⫽
TABLE 1. Anthropometrics and metabolic parameters of healthy female controls and women with BN or BED
Age (yr)
BW (kg)
BMI (kg/m2)
Body fat mass (kg)
Body lean mass (kg)
Glucose plasma levels (nmol/liter)
Cholesterol plasma levels (mmol/liter)
Triglycerides plasma levels (mmol/liter)
Plasma FT3 (pmol/liter)
Plasma FT4 (pmol/liter)
a
P ⬍ 0.001;
b
P ⬍ 0.01; c P ⬍ 0.005;
d
Healthy women
Women with BN
Women with BED
22.6 ⫾ 2.7
58.9 ⫾ 5.6
21.8 ⫾ 1.7
15.7 ⫾ 3.8
42.5 ⫾ 3.0
3.9 ⫾ 0.4
3.95 ⫾ 0.82
0.84 ⫾ 0.30
2.4 ⫾ 1.8
12.8 ⫾ 2.1
24.3 ⫾ 2.6
60.3 ⫾ 6.7
22.2 ⫾ 3.5
15.7 ⫾ 5.2
44.5 ⫾ 3.5
4.1 ⫾ 0.4
4.90 ⫾ 0.97c
1.10 ⫾ 0.37
1.9 ⫾ 1.3
11.9 ⫾ 3.0
30.6 ⫾ 9.4a
90.5 ⫾ 18.9a
33.9 ⫾ 7.0a
38.5 ⫾ 13.0a
51.5 ⫾ 6.4a
4.4 ⫾ 0.7b
4.64 ⫾ 0.72d
1.19 ⫾ 0.44e
1.8 ⫾ 0.3
9.0 ⫾ 1.5a
P ⬍ 0.05; e P ⬍ 0.02 vs. healthy women (post hoc Tukey’s test).
Monteleone et al. • Circulating Adiponectin in BN and BED
4.58, P ⬍ 0.02], glucose [F(2,57) ⫽ 4.68, P ⬍ 0.02], and FT4 [F(2,57)
⫽ 13.78, P ⬍ 0.0001] but not in plasma levels of FT3 [F(2,57) ⫽
2.09, P ⫽ 0.1].
Compared with healthy women, BN patients exhibited
significantly increased plasma levels of adiponectin (Fig. 1)
and cholesterol but similar plasma concentrations of triglycerides, glucose, FT3 and FT4 (Table 1). Circulating adiponectin was higher in the five patients with BN who had a previous history of anorexia nervosa than in BN patients
without this history (15.8 ⫾ 5.6 ␮g/ml vs. 11.8 ⫾ 3.4 ␮g/ml,
respectively), although this difference did not reach a statistical significance [F(1,18) ⫽ 3.63, P ⫽ 0.07]. After excluding
these five patients, in BN patients, plasma adiponectin levels
were still higher than in healthy controls [F(1,33) ⫽ 6.43,
P ⫽ 0.01].
Women with BED had significantly reduced blood concentrations of adiponectin (Fig. 1) and FT4 but increased
plasma levels of cholesterol, triglycerides, glucose, and normal levels of FT3 (Table 1). Regarding cholesterol data, eight
women with BN (40% of the sample) and five women with
BED (25% of the sample), but none of the healthy controls,
showed plasma concentrations of cholesterol above the desirable value of 5.172 mmol/liter, as defined by the National
Cholesterol Education Program Expert Panel (31). Regarding
triglycerides, only one BED patient exhibited plasma levels
above the normal value of 1.80 mmol/liter.
To evaluate whether differences in adiponectin levels
among the groups persisted after adjustments for age, BW,
and plasma levels of glucose, cholesterol, and triglycerides,
analyses of covariance were performed with adiponectin as
the dependent variable. These analyses showed that age
[F(2,56) ⫽ 0.06, P ⫽ 0.8], BW [F(2,56) ⫽ 1.54, P ⫽ 0.2], and plasma
levels of glucose [F(2,56) ⫽ 0.016, P ⫽ 0.9], cholesterol [F(2,56)
⫽ 1.63, P ⫽ 0.2], and triglycerides [F(2,56) ⫽ 0.07, P ⫽ 0.8] were
not significantly associated with adiponectin.
FIG. 1. Plasma adiponectin concentrations in healthy women,
women with BN, and women with BED. Data are expressed as
mean ⫾ SD. *, P ⬍ 0.005; and **, P ⬍ 0.002 compared with healthy
women (post hoc Tukey’s test).
J Clin Endocrinol Metab, November 2003, 88(11):5387–5391 5389
Correlations
Adiponectin levels were negatively correlated with BW
(r ⫽ ⫺0.50, P ⬍ 0.001), BMI (r ⫽ ⫺0.53, P ⬍ 0.001), and body
fat mass (r ⫽ ⫺0.50, P ⬍ 0.001) in the entire population (i.e.,
the BN, BED, and control groups combined). These correlations were no longer observed when data were assessed in
each group separately. This may be explained by the narrow
ranges of anthropometrics values within each group. Moreover, no significant correlations emerged between plasma
levels of adiponectin and metabolic or hormonal variables in
both the entire population and each diagnostic group. To the
contrary, a strong positive correlation emerged between circulating adiponectin and the frequency of bingeing/vomiting in the BN group (r ⫽ 0.65, P ⫽ 0.002) but did not emerge
between the hormone and the frequency of bingeing in the
BED group (r ⫽ 0.29, P ⫽ 0.2, Fig. 2). Finally, no significant
correlations emerged between cholesterol or triglycerides
plasma levels and thyroid hormone concentrations.
Given the significant inverse correlations between adiponectin levels and BW, BMI, and body fat mass in the whole
group and the positive correlation between adiponectin and
the frequency of bingeing/purging in the BN group, a stepwise multiple regression analysis was carried out to clarify
the simultaneous effect of nutritional and clinical variables
on circulating adiponectin in women with BN. This analysis
showed that the bingeing/purging frequency was the only
variable significantly associated with circulating adiponectin
[F(1,18) ⫽ 13.19, P ⫽ 0.001], which explains 42% of the variability in plasma adiponectin concentrations (R2 ⫽ 0.42).
After removing this effect, no further variable entered into
the analysis.
Discussion
There most original and striking primary results from this
study are: 1) normal-weight patients with BN had circulating
adiponectin higher than normal-weight healthy women of
similar age, whereas obese women with BED had significantly decreased plasma levels of this adipocytokine; and 2)
circulating adiponectin strongly correlated with the frequency of binge/purging episodes in BN patients but not
with the frequency of binge eating in women with BED.
Secondary results of this investigation were the finding of
significantly enhanced plasma levels of cholesterol in bulimic
individuals and the presence of significantly increased
plasma concentrations of cholesterol, triglycerides, and glucose in BED patients.
At present, we are not aware of studies exploring adiponectin production in people with BN or BED; therefore, we
cannot compare our data with those of other research groups.
However, the finding of decreased levels of circulating adiponectin in our obese binge eaters does agree with studies
reporting decreased plasma levels of this adipocytokine in
obese individuals (7, 33). It has been shown that adipose
tissue produces a factor that destabilizes adiponectin mRNA
(34), thus exerting a negative feedback on its own adiponectin production. Therefore, the increased fat mass in our obese
women with BED could enhance such a negative feedback,
contributing to hypoadiponectinemia.
Two studies have reported increased concentrations of
5390
J Clin Endocrinol Metab, November 2003, 88(11):5387–5391
Monteleone et al. • Circulating Adiponectin in BN and BED
FIG. 2. Correlation between plasma
adiponectin values and the frequency of
binge/vomiting in women with BN (left
panel) and correlation between plasma
adiponectin values and the frequency of
binge episodes in women with BED
(right panel).
adiponectin in underweight women with anorexia nervosa
(35, 36). Therefore, our findings of enhanced plasma levels of
adiponectin in BN suggest that a similar derangement in the
production of this adipocytokine occurs in both EDs. This is
not surprising because analogous findings have been reported for other hormones, including cortisol (37, 38), neuroactive steroids (39), and leptin (23–26). The finding of similar biochemical alterations in anorexia nervosa and BN
likely suggests that common pathophysiological mechanisms could underlie these dysfunctions. In particular, malnutrition and energy restriction have been claimed to be the
major determinants of physiological aberrations in EDs, and
it is well known that, despite no significant BW change in BN
patients, bulimics do incur malnutrition and energy restriction because of their abnormal eating patterns, purging behaviors, prolonged starvation, and incorrect selection of
food. Furthermore, in those bulimics with a previous history
of anorexia nervosa, which likely implies a more severe malnutrition, circulating adiponectin was higher than in bulimics
without such a history. Finally, it has been recently reported
that a significant increase in plasma adiponectin occurs in
young women in response to 7-d energy restriction (39).
It has been shown that, in both healthy subjects and bulimic patients, experimental binge eating dramatically increases insulin plasma levels despite a normal glucose response (13, 16, 40), which suggests an incoming insulin
resistance. Therefore, it is possible to speculate that in our
bulimic patients, who binged with a frequency ranging from
7 to 28 times a wk, a persistent insulin resistance could
develop. Because adiponectin has been shown to have insulin-sensitizing properties (2, 3), its increased production
might counteract the occurrence of such a persistent insulin
resistance, thus preserving bulimic patients from dysregulation of glucose metabolism. In support of this idea, a strong
positive correlation was found in our BN women between
circulating adiponectin values and the frequency of bingepurging episodes, and no significant difference emerged in
the mean fasting levels of plasma glucose between BN patients and healthy controls.
Because of the association of bingeing and purging, bulimics do not gain BW or incur body fat accumulation as BED
patients do. Therefore, it is likely that in the condition of
increased fat mass, as in BED individuals, the negative feed-
back exerted by the adipose tissue on adiponectin biosynthesis (34) leads to a decreased adiponectin production with
a consequent increase in the risk for glucose dismetabolism.
Therefore, there have been suggestions that binge eating may
contribute to the onset of diabetes mellitus (41), possibly via
its impact on BW (42). Indeed, it has been proposed that BED
is more typical of the population with type 2 diabetes mellitus, and it has been shown that, in this population, binge
eating started, on average, at a significantly earlier age than
the age at diagnosis of type 2 diabetes (22). Furthermore, a
recent article focusing on adiponectin levels during the progression of type 2 diabetes in Rhesus monkeys genetically
predisposed to develop insulin resistance evidentiated that
adiponectin levels decreased at the onset of the obesity and
that this decrease preceded overt hyperglycemia (9). Therefore, we can suggest that, in women with BED, the decrease
in circulating adiponectin may represent a risk factor for the
development of glucose intolerance.
A secondary finding of the present investigation was that,
compared with healthy controls, both women with BN and
those with BED exhibited significantly enhanced mean
plasma levels of cholesterol, with 40% of BN patients and
25% of BED patients showing circulating cholesterol concentrations above the desirable value of 5.172 mmol/liter
(32). These findings agree with those of previous studies that
found enhanced blood levels of cholesterol in nonfasted bulimic subjects (17–20) but disagree with the results of a single
study reporting normal morning levels of cholesterol in 12-hr
fasted bulimic women (21). However, in the latter study, only
10 bulimics and 10 healthy controls older than our subjects
were studied; differences in the sample sizes and age of the
subjects may explain these discrepancies. Therefore, present
findings do extend the knowledge in the field because they
confirm that increased blood concentrations of cholesterol
also occur in fasted bulimic patients.
Some limitations of the present study need to be discussed.
First, we did not assess plasma insulin concentrations and
oral glucose tolerance or undertake sensitive tests of insulin
resistance; therefore, we can only speculate about the compensatory role of hypoadiponectinemia in BN subjects and
the putative diabetic risk of hypoadiponectinemia in BED
individuals. Second, we did not include a BMI-matched control group for the BED subjects. Therefore, although a decrease
Monteleone et al. • Circulating Adiponectin in BN and BED
in circulating adiponectin has been consistently reported in
obese non-binge-eating individuals (7, 32), we cannot conclude
that the changes observed in BED patients were attributable
exclusively to their obesity rather than to their behaviors.
Notwithstanding these limitations, our findings show for
the first time that fasting adiponectin levels are increased in
the blood of drug-free symptomatic women with BN,
whereas they are decreased in the blood of women with BED.
The pathophysiological significance of these alterations
awaits further studies to be clarified. However, these data,
together with other findings showing changes in the physiology of other adipocytokines in people with EDs, suggest
the need to deeply investigate peripheral mechanisms in
disordered eating.
Acknowledgments
Received June 3, 2003. Accepted July 22, 2003.
Address all correspondence and requests for reprints to: Palmiero
Monteleone, M.D., Department of Psychiatry, University of Naples
SUN, Largo Madonna delle Grazie, 80138 Naples, Italy. E-mail:
[email protected].
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