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: yalcinbasak@yahoo.com

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