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ORIGINAL RESEARCH ARTICLE
Prevalence of Metabolic Syndrome in Behcet Disease:A Case-Control Study in Turkey
Basak Yalcın • Gunes Gur • Ferda Artuz •
Nuran Allı
Published online: 13 June 2013
� Springer International Publishing Switzerland 2013
Abstract
Background Chronic inflammatory diseases such as
psoriasis, rheumatoid arthritis, and inflammatory bowel
diseases have been reported to be associated with the
development of metabolic syndrome (MetS), which is
characterized by central obesity, elevated triglycerides
(TG), reduced high-density lipoproteins (HDL), impaired
fasting blood glucose (FBG), and hypertension. Behcet
disease (BD) is a chronic, immuno-inflammatory disease
with multisystemic involvement.
Objective The aim of this study was to investigate the
prevalence and risk factors for MetS in patients with BD.
Methods All patients had BD according to the criteria of
the International Study Group. Diagnosis of MetS was
established according to National Cholesterol Education
Program Adult Treatment Panel III (NCEP ATP III) cri-
teria. Mean waist circumference, body mass index (BMI),
FBG, erythrocyte sedimentation rate (ESR), C-reactive
protein (CRP), total cholesterol, HDL, very low-density
lipoprotein (VLDL), low-density lipoprotein (LDL), TG,
systolic BP, and diastolic BP were measured and analyzed.
Results A total of 86 patients and 72 healthy controls
were included. MetS was detected in 35.4 % of patients
and 20 % of controls (p = 0.04). Patients with BD had a
2.67-fold higher risk for MetS than healthy controls
(p \ 0.05). Significant risk factors for developing MetS
according to multivariate analyses were BD, age, and BMI.
Age at onset of the disease, duration of disease, BMI,
gastrointestinal system involvement, and neurological
involvement were correlated with increased MetS risk
(p \ 0.05). MetS tended to increase with age and the
duration of the disease and was higher in women under the
age of 40 years compared with healthy controls in the same
age group.
Conclusion All BD patients should be closely monitored
for hypertension, hyperlipidemia, and diabetes mellitus to
avoid MetS development.
1 Introduction
Behcet disease (BD) is a chronic, multisystemic, immuno-
inflammatory disease with a wide spectrum of clinical
manifestations including mucocutaneous, ocular, vascular,
musculoskeletal, gastrointestinal (GI) and central nervous
system involvement [1]. Although the etiopathogenesis of
BD still needs to be further illuminated, innate and adap-
tive immune dysregulation resulting from some genetic and
environmental factors are implicated in the pathogenesis of
the disease [2, 3]. An uncontrolled, innate-related inflam-
mation may cause activation of the adaptive immune sys-
tem in BD [2, 4].
Metabolic syndrome (MetS) is a combination of disor-
ders, including central obesity, elevated triglycerides (TG),
reduced high-density lipoproteins (HDL), impaired fasting
blood glucose (FBG), and hypertension [5]. According to
the updated National Cholesterol Education Program Adult
Treatment Panel III (NCEP ATP III) from 2005, MetS is
diagnosed when an individual has at least three of the
B. YalcınDepartment of Dermatology, Yıldırım Beyazıt University,
Ankara, Turkey
B. Yalcın (&)
Ikizdere sok. C19/1 GOP, 06670 Ankara, Turkey
e-mail: [email protected]
G. Gur � F. Artuz � N. AllıDepartment of Dermatology, Ankara Numune Educational
and Research Hospital, Ankara, Turkey
Am J Clin Dermatol (2013) 14:421–425
DOI 10.1007/s40257-013-0034-8
following five conditions: (i) FBG 100 mg/dL or greater
(or receiving a drug for hyperglycemia); (ii) blood pressure
(BP) 130/85 mmHg or higher (or receiving a drug for
hypertension); (iii) TG 150 mg/dL or higher (or receiving a
drug for hypertriglyceridemia); (iv) HDL \40 mg/dL in
men or\50 mg/dL in women (or receiving a drug for low
HDL); and (v) waist circumference C102 cm in men or
C88 cm in women [6].
Recently, chronic inflammatory diseases such as psori-
asis, rheumatoid arthritis, and inflammatory bowel diseases
have been suggested to be associated with the development
of MetS, which consequently increases the risk of cardio-
vascular diseases (CVD) such as coronary artery disease
and stroke, fatty liver disease, and certain types of malig-
nancies [7–9].
In this study, we investigated the prevalence of MetS in
patients with BD. Increased insulin resistance has been
reported in BD previously [10]; however, this is the first
study to investigate the relationship between BD and the
risk of MetS development.
2 Patients and Methods
Patients were consecutive patients admitted to the
Department of Dermatology, Ankara Numune Educational
and Research Hospital with a diagnosis of BD according to
the criteria of the International Study Group [11]. Control
subjects were age- and sex-matched healthy people or
patients without any severe or chronic inflammatory skin
disease such as acne vulgaris, superficial fungal or bacterial
infections, verruca vulgaris, or melasma. Exclusion criteria
were: age \18 years old, patients who had a disease
duration of\1 year, and patients and controls who had any
other chronic systemic disease.
The study protocol was approved by the institutional
ethics committee and written informed consent was
received from all patients and control subjects.
2.1 Data Collection
The age, gender, and smoking habits of patients and con-
trols were noted. Height, weight, body mass index (BMI),
waist circumference (which was measured midway between
the lower costal margin and iliac crest), BP after 5 min of
rest, FBG, TG, total cholesterol, low-density lipoprotein
(LDL), very low-density lipoprotein (VLDL), HDL,
erythrocyte sedimentation rate (ESR), and C-reactive pro-
tein (CRP) levels were measured in the study subjects when
they were admitted to our clinic during the study period. In
addition, patients were further investigated for age at onset
of the disease, duration of the disease, clinical manifesta-
tions of the disease, and medications used for BD.
The diagnosis of MetS was made using the criteria set
out by the NCEP ATP III guidelines.
2.2 Statistical Analysis
Chi-square tests and Fisher’s exact test were used for
comparisons of categorical data. Differences in the means
of continuous measurements were tested by using Student’s
t test.
Univariate analyses to identify variables associated with
MetS were investigated using chi-square, Fisher’s exact
and Student’s t tests, where appropriate. For the multivar-
iate analyses, the possible factors identified with univariate
analyses were further entered into the logistic regression
analysis to determine independent predictors of patient
outcome. Hosmer–Lemeshow goodness-of-fit statistics
were used to assess model fit. A 5 % type I error level was
used to infer statistical significance.
3 Results
A total of 86 patients (32 male, 54 female) and 72 healthy
controls (23 male, 49 female) were included. Mean age
(± standard deviation) of the patients was 39.05 ± 10.1 years
and for controls was 38.96 ± 11.4 years. There was no
statistical difference between patient and control groups
according to sex and age (p = 0.96). Subjects were
grouped according to their age: those below 40 years of
age were included in group I and those 40 years of age or
older were included in group II. In group I there were 44
patients (31 female and 13 male) and 38 controls (26
female and 12 male). In group II there were 42 patients (23
female and 19 male) and 34 controls (23 female and 11
male).
Clinical characteristics of the patients are shown in
Table 1. Ocular and cardiovascular involvement were more
prevalent in males than females, which was statistically
significant (p \ 0.05).
Mean waist circumference, BMI, FBG, ESR, CRP, lipid
levels, and BP according to gender are shown in Table 2.
ESR levels of male patients were statistically higher than
male control subjects (p = 0.03). Systolic BP and diastolic
BP of female patients were statistically higher than female
controls (p = 0.05; p = 0.03, respectively).
Mean waist circumference, BMI, FBG, ESR, CRP, lipid
levels, and BP according to age groups are shown in
Table 3. Mean ESR was statistically higher in patients than
controls of group I; and diastolic BP was statistically
higher in patients than controls of group II. There were no
significant differences for other parameters.
MetS was detected in 35.4 % of patients and 20 %
of controls; this difference was statistically significant
422 B. Yalcın et al.
(p = 0.04). In women, MetS was present in 40.4 % of the
patients and 21.7 % of the controls (p = 0.05). In men,
26 % of patients and 15.8 % of controls developed MetS;
this difference was not significant (p = 0.5). When we
compared patients with controls according to age groups,
22 % of patients and 15 % of controls in group I developed
MetS (not statistically significant; p = 0.4). However, in
group II, 48.5 % of patients and 25 % of controls devel-
oped MetS; this difference was statistically significant
(p = 0.05).
Multiple logistic regression analysis revealed that the
risk of MetS development was increased by 2.67-fold in
BD (95 % confidence interval 1.1–6.7). Relative risks of
possible risk factors according to multivariate analysis are
shown in Table 4.
In BD patients, age, age at onset of the disease, duration
of disease, BMI, GI involvement, and neurological
involvement were correlated with the development of MetS
(p \ 0.05). However, presence of family history for BD,
high CRP levels, smoking, treatment with corticosteroids
or immunosuppressive drugs, mucocutaneous, ocular,
articular and cardiovascular involvement did not correlate
with MetS development (p [ 0.05).
4 Discussion
BD remains a significant health problem along the historical
Silk Road. The incidence of BD is highest in Turkey, where
the prevalence reaches 42 per 100,000. The prevalence of
Table 1 Comparison of clinical characteristics of the female and
male patients
Characteristics Total
(n = 86)
Female
(n = 54)
Male
(n = 32)
p Value
Mean age at
onset of the
disease (years)
29.6 ± 8.8 28.3 ± 7.4 31.9 ± 10.5 [0.5
Mean duration of
the disease
(years)
9.5 ± 6.6 9.9 ± 6.9 8.6 ± 6.1 [0.5
Aphthous
stomatitis (%)
100 100 100 1
Genital ulcer (%) 91.7 90.7 93.7 0.7
Papulopustular
lesions (%)
71.4 70.4 73.3 0.8
Erythema
nodosum (%)
63.1 68.5 53.1 0.1
Pathergy
positivity (%)
52.1 53.1 50.0 0.8
Eye involvement
(%)
29.4 16.7 51.6 0.001
Arthritis/
arthralgia (%)
20.5/60.1 22.6/64.2 16.7/53.3 0.5
Gastrointestinal
involvement
(%)
7.1 3.7 13.3 0.1
Cardiovascular
involvement
(%)
20.2 5.6 46.7 \0.001
Neurological
involvement/
headache (%)
11.9/44.0 11.1/48.1 13.3/36.7 0.6
Table 2 Characteristics of patients and control subjects according to gender
Characteristics Female Male
Patients (n = 54) Controls (n = 49) p Value Patients (n = 32) Controls (n = 23) p Value
Waist (cm) 92.9 ± 16.6 92.1 ± 14.9 0.8 95.1 ± 9.6 96.6 ± 8.6 0.8
BMI 27.8 ± 7.9 27.4 ± 5.6 0.8 25.9 ± 3.9 25.9 ± 4.0 0.9
FBG (mg/dL) 93.1 ± 21.6 94.0 ± 23.2 0.8 90.5 ± 11.8 95.6 ± 12.5 0.1
ESR (mm/h) 16.8 ± 13.3 13.0 ± 14.3 0.2 12.2 ± 16.2 3.4 ± 2.1 0.03
CRP (mg/L) 40.3 ± 62.3 49.5 ± 74.8 0.5 73.2 ± 134.5 41.3 ± 59.6 0.3
T. Cholesterol (mg/dL) 180.1 ± 36.7 183.8 ± 37.2 0.6 186.8 ± 47.5 195.0 ± 45.3 0.5
HDL (mg/dL) 53.5 ± 15.5 51.9 ± 13.2 0.5 47.1 ± 14.9 43.1 ± 10.7 0.3
VLDL (mg/dL) 21.4 ± 10.5 23.3 ± 11.5 0.4 30.0 ± 16.0 37.8 ± 18.8 0.1
LDL (mg/dL) 103.1 ± 30.4 108.6 ± 32.2 0.5 110.7 ± 42.3 115.0 ± 41.5 0.7
TG (mg/dL) 110.7 ± 52.5 114.9 ± 56.9 0.7 151.1 ± 80.5 196.1 ± 116.0 0.1
Systolic BP (mmHg) 122.4 ± 16.3 116.3 ± 12.7 0.05 119.0 ± 10.0 117.5 ± 15.5 0.7
Diastolic BP (mmHg) 76.8 ± 10.3 72.2 ± 9.3 0.03 74.0 ± 1.0 73.0 ± 10.0 0.7
BMI body mass index, BP blood pressure, CRP C-reactive protein, ESR erythrocye sedimentation rate, FBG fasting blood glucose, HDL high-
density lipoprotein, LDL low-density lipoprotein, T. Cholesterol total cholesterol, TG triglyceride, VLDL very low-density lipoprotein
Metabolic Syndrome in Behcet Disease 423
BD in Japan, Korea, China, Iran, and Saudi Arabia ranges
from 13.5–22 cases per 100,000 population [12]. BD is
associated with important morbidity and mortality risks
[13]. The overall mortality rate is 3.2–5 % within 7 years.
Coronary/pulmonary arterial aneurysm rupture, neurologi-
cal involvement, and thrombosis are the main causes of
death in the disease [14]. However, to our knowledge, the
rate of MetS and the morbidity and mortality related to
MetS have not yet been studied thoroughly in relation to
BD.
MetS itself is a major worldwide health problem. It is an
important risk factor for CVD and type 2 diabetes mellitus.
MetS increases the risk of CVD morbidity three-fold,
mortality two-fold, and type 2 diabetes five-fold [15].
Increasing obesity due to the development of Western-style
eating habits throughout the world and decreased physical
activity are the main causes of MetS [16]. In addition to
these, the long-term cumulative effects of inflammation
resulting from chronic inflammatory diseases are also an
important cause of MetS. Insulin resistance and abnormal
adipose tissue functions are responsible for MetS in these
diseases [17]. Patients with rheumatoid arthritis, psoriasis,
and inflammatory bowel diseases (especially ulcerative
colitis) develop MetS more often than the general popu-
lation. It was suggested that chronically elevated free fatty
acids (FFA) along with increased tumor necrosis factor
alpha (TNFa) and interleukin (IL)-6 lead to increased
glucose production in the liver, reduced glucose uptake in
the muscle and, consequently, impaired glucose tolerance
[18]. Additionally, TNF may promote insulin resistance by
changing the structure of the insulin receptor substrate [19].
BD is a chronic inflammatory disease characterized by
overactivation of the cytokine cascade, including TNFa,
IL-1, and IL-6, which play an important role in the path-
ogenesis of the disease [2]. In the present study, patients
with BD had a 2.67-fold higher risk for MetS. MetS tended
to increase with age and duration of the disease, and was
more prevalent in females under the age of 40 years
compared with the healthy controls in the same age group.
Furthermore, systolic and diastolic BPs were higher in
female BD patients than in female controls. MetS in BD
was not correlated with smoking, immunosuppressive
drugs, or systemic corticosteroid use. We found that MetS
was correlated with BMI in BD patients but not in controls.
In addition, the presence of gastrointestinal and neurologic
involvement were associated with an increased risk for
MetS in BD.
Serious involvement of BD such as ocular and cardio-
vascular involvement is seen more often in male patients
than female patients, which was also seen in the present
study. However, female patients (especially those younger
than 40 years of age) were more prone to develop MetS
and hypertension compared with the healthy controls.
Young obese female patients seem to be at even higher risk
for MetS. Exercise, training, and dietary-induced weight
loss may improve the MetS by diminishing insulin
Table 3 Characteristics of patients and control subjects according to the age groups
Characteristics Group I (\40 years) Group II (C40 years)
Patients (n = 44) Controls (n = 38) p Value Patients (n = 42) Controls (n = 34) p Value
Waist (cm) 88.5 ± 15.6 88.5 ± 13.0 0.9 98.5 ± 11.2 98.0 ± 11.4 0.8
BMI 25.5 ± 7.9 25.2 ± 4.8 0.8 28.6 ± 5.0 28.7 ± 5.0 0.9
FBG (mg/dL) 86.9 ± 13.3 90.3 ± 11.6 0.2 97.1 ± 21.2 99.2 ± 27.1 0.7
ESR (mm/h) 175.0 ± 17.3 8.9 ± 12.8 0.01 12.9 ± 10.8 12.0 ± 12.8 0.7
CRP (mg/L) 49.3 ± 100.9 38.7 ± 57.5 0.5 56.0 ± 92.4 59.6 ± 85.6 0.8
T. Cholesterol (mg/dL) 168.5 ± 35.8 175.7 ± 31.4 0.3 196.9 ± 40.9 200.6 ± 4.7 0.7
HDL (mg/dL) 50.4 ± 14.3 48.2 ± 12.1 0.4 51.9 ± 16.8 50.5 ± 14.1 0.7
VLDL (mg/dL) 22.3 ± 14.6 26.4 ± 15.6 0.2 26.7 ± 11.8 29.0 ± 15.5 0.4
LDL (mg/dL) 95.7 ± 27.1 101.0 ± 29.6 0.4 116.3 ± 39.4 121.7 ± 38.0 0.5
TG (mg/dL) 112.3 ± 72.3 139.5 ± 98.3 0.1 138.5 ± 57.3 139.0 ± 72.0 0.9
Systolic BP (mmHg) 119.4 ± 13.9 116.4 ± 12.3 0.4 122.5 ± 16.1 116.8 ± 14.7 0.1
Diastolic BP (mmHg) 75.1 ± 10.9 74.8 ± 8.4 0.9 76.4 ± 10.7 70.4 ± 9.8 0.01
BMI body mass index, BP blood pressure, CRP C-reactive protein, ESR erythrocye sedimentation rate, FBG fasting blood glucose, HDL high-
density lipoprotein, LDL low-density lipoprotein, T. Cholesterol total cholesterol, TG triglyceride, VLDL very low-density lipoprotein
Table 4 Risk factors for metabolic syndrome according to multi-
variate analysis
Risk factor RR (95 % CI) p Value
Behcet disease 2.67 (1.1–6.7) 0.03
Age 1.05 (1.0–1.1) 0.04
BMI 1.16 (1.0–1.3) 0.001
BMI body mass index, RR relative risk
424 B. Yalcın et al.
resistance, increasing glucose tolerance, and decreasing
BP [20]. All BD patients, especially women, should be
encourged to adopt a healthier lifestyle including decreased
calorie intake and more physical activity and should be
closely monitored for hypertension, hyperlipidemia, and
diabetes.
5 Conclusion
BD is a chronic inflammatory disease that may be associ-
ated with an increased risk for the development of MetS.
Female BD patients in particular seem more prone to MetS
development. In order to prevent MetS-related morbidity
and mortality, BD patients should be encourged to adopt a
healthier lifestyle including decreased calorie intake and
more physical activity and should be closely monitored for
hypertension, hyperlipidemia and diabetes.
Acknowledgments No sources of funding were used to conduct this
study. The authors have no conflict of interest that are directly rele-
vant to the content of this study.
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Metabolic Syndrome in Behcet Disease 425