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Original Paper Dermatology 2010;220:32–37 DOI: 10.1159/000254482 Received: May 28, 2009 Accepted after revision: August 4, 2009 Published online: October 29, 2009 Increased Amount of Visceral Fat in Patients with Psoriasis Contributes to Metabolic Syndrome Ali Balci a Didem Didar Balci b Zafer Yonden c Inan Korkmaz a Julide Zehra Yenin b Ebru Celik b Nese Okumus c Ertugrul Egilmez a Departments of a Radiology, b Dermatology and c Biochemistry, Faculty of Medicine, Mustafa Kemal University, Antakya, Turkey Key Words Psoriasis ⴢ Visceral fat ⴢ Metabolic syndrome Abstract Background: Psoriasis is associated with obesity and metabolic syndrome. Metabolic syndrome is associated with visceral fat accumulation. There is no study on the accumulation of visceral fat in patients with psoriasis. Objective: The aim of this study was to compare the visceral fat accumulation in patients with psoriasis and controls. Subjects and Methods: 46 patients with psoriasis and 46 sex- and agematched control patients were included in this study. The abdominal fat area [visceral fat area (VFA), subcutaneous fat area (SFA) and total fat area (TFA)] at the level of the umbilicus was evaluated by computed tomography. Results: The mean VFA value and VFA/SFA ratio of the psoriasis patients were significantly higher compared with the control patients (123.4 8 80.3 vs. 81.2 8 59.8 cm2 and 0.734 8 0.593 vs. 0.491 8 0.336; p = 0.005 and p = 0.017, respectively). Fasting blood sugar levels were also found to be significantly higher in psoriasis patients, compared with the control patients (101.8 8 43.5 vs. 83.4 8 9.1 mg/dl; p = 0.005). Multiple linear regression analysis indicated that waist-to-hip ratio, age, body weight, the presence of psoriasis and metabolic syndrome were significantly associated with VFA. Conclusion: Psoriasis patients had a higher amount of VFA, compared with the control patients. Copyright © 2009 S. Karger AG, Basel © 2009 S. Karger AG, Basel 1018–8665/10/2201–0032$26.00/0 Fax +41 61 306 12 34 E-Mail [email protected] www.karger.com Accessible online at: www.karger.com/drm Introduction Psoriasis is a systemic, chronic, inflammatory skin disease that affects approximately 2% of the population [1]. Recently, associations have been recognized between psoriasis and an increased incidence of atherosclerotic diseases and metabolic syndrome (central obesity, diabetes or insulin resistance, hypertension, and dyslipidaemia) [2–5]. Abdominal obesity, which is caused by excess accumulation of visceral adipose tissue (VAT), is associated with increased risk for cardiovascular disease and diabetes mellitus [6, 7]. The visceral component of abdominal fat is the most prevalent form in insulin resistance and metabolic syndrome [8]. Studies have clearly shown that viscerally obese patients have the most disturbed metabolic risk profile. An excess and disproportionate accumulation of VAT is responsible for metabolic and atherosclerotic diseases more frequently than the excess accumulation of subcutaneous or total body fat [6–9]. The accumulation of VAT is a risk factor for carotid and coronary atherosclerosis, irrespective of body weight [10, 11]. Anthropometric measurements such as the waist-to-hip ratio (WHR) and sagittal abdominal diameter are simple and useful indicators of VAT accumulation, but these indices do not always accurately reflect visceral adiposity [12–14]. Computed tomography (CT) is an optimal, reproducible, and reliable technique for accurately assess- Didem Didar Balci Department of Dermatology, Faculty of Medicine Mustafa Kemal University TR–31100 Antakya (Turkey) Tel. +90 326 214 0649, Fax +90 326 214 4977, E-Mail didemaltiner @ yahoo.com ing visceral fat accumulation. Using CT, visceral and subcutaneous fat can be accurately quantified, with small intra- and interobserver variation, allowing the determination of their relationships with biochemical and anthropometric measurements [15, 16]. This study is the first to determine visceral fat accumulation in psoriasis patients compared with controls. We also investigated the association of visceral fat accumulation with metabolic syndrome and anthropometric measurements in patients with psoriasis. Subjects and Methods Study Patients 46 consecutive patients with psoriasis vulgaris and 46 genderand age-matched control patients attending our dermatology outpatient clinic were included in this study. Informed consent was obtained from all patients, and the study protocol was approved by the ethics committee of our institution. The diagnosis of psoriasis vulgaris was based on a clinical or histopathological examination of all patients. Controls were recruited among the patients referred for dermatological conditions other than psoriasis. The diagnoses of the controls were skin neoplasm (5 patients, 10.9%: e.g. squamous cell carcinoma, basal cell carcinoma), superficial fungal infections (17 patients, 37.0%), contact dermatitis (8 patients, 17.4%), lichen planus (3 patients, 7.0%), vitiligo (4 patients, 8.7%), and urticaria (9 patients, 20.0%). The psoriasis and control patients were of the same ethnic origin. A known endocrine, kidney, or metabolic disease other than obesity or diabetes mellitus and age younger than 18 years were exclusion criteria. Subjects who were receiving lipid-lowering therapy were also excluded from the study. Before conducting the study, a power analysis was performed based on the results of a pilot study (n = 20). Using a sample size calculator (DSS Research, Fort Worth, Tex., USA), it was estimated that 43 subjects for each group were needed to give this study a power of 90% for showing a relevant change in visceral fat area (VFA) with a 95% confidence interval. Anthropometric characteristics, including age, gender, weight, height, body mass index (BMI), and WHR, and clinical characteristics, including duration of disease, type and severity of disease, medications, blood pressure, and smoking habits, were recorded. The WHR was calculated as the ratio of the waist and hip circumferences. BMI was calculated as the ratio of the weight (kg) to the square of the height (m) (kg/m2). Morning blood pressure was measured using a mercury sphygmomanometer, after a 15min rest with the patient in the sitting position. Blood pressure was recorded as the average of two consecutive measurements. Disease severity was quantified using the Psoriasis Area and Severity Index (PASI). Laboratory Measurements To measure serum total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglyceride, uric acid, and glucose levels, blood samples were obtained in the morning after an overnight fast of at least 8 h. Serum Increased Visceral Fat in Psoriasis total cholesterol, HDL and LDL cholesterol, triglyceride, uric acid, and glucose levels were determined spectrophotometrically using an autoanalyser (Synchron LX20; Beckman Coulter, Fullerton, Calif., USA). To diagnose diabetes mellitus, subjects who had a fasting blood sugar in the range of 110–126 mg/dl underwent a standard (75 g glucose) oral glucose tolerance test, as proposed by the World Health Organization, between 8 and 11 a.m. [17]. The number of diagnostic criteria for metabolic syndrome in each study subject was recorded. The criteria of the National Cholesterol Education Program’s Adult Panel III for metabolic syndrome were used: waist circumference 1102 cm in men or 188 cm in women; hypertriglyceridaemia 1150 mg/dl; HDL cholesterol !40 mg/dl in men or !50 mg/dl in women; blood pressure 1130/85 mm Hg or antihypertensive medication; fasting plasma glucose 1110 mg/dl or known diabetes mellitus. Subjects who had three or more criteria were diagnosed with metabolic syndrome [18]. Measurement of Abdominal Fat Distribution Abdominal fat distribution was examined on one cross-sectional CT (Toshiba Aquilion 64 scanner, Tokyo, Japan) scan (120 kV, 200 mA, 5-mm section thickness) at the level of the umbilicus (fourth lumbar vertebra) with the patient in the supine position, using a previously described procedure [16]. A region of interest in the subcutaneous fat layer was defined by tracing its contour on each scan, and the attenuation range of CT numbers for fat tissue was calculated and expressed as the mean 8 2 standard deviations (SD). Intraperitoneal tissue was defined by tracing its contour on each scan; within that region of interest, tissue with attenuation within the attenuation mean 8 2 SD for fat tissue was considered VFA (fig. 1). VFA was measured as the fat tissues located in the intraperitoneal, omental, and retroperitoneal areas. Total abdominal tissue with attenuation within the mean 8 2 SD for fat tissue was considered as the total fat area (TFA) (fig. 2). The subcutaneous fat area (SFA) was calculated as TFA minus VFA. The measurements were extrapolated by one of the authors (I.K.), using a previously described procedure [16]. The subjects had fasted overnight and were studied in the morning, between 8 and 12 a.m. All laboratory parameters and anthropometric measurements were obtained on the same day as the CT examination. Statistical Analysis Continuous data are expressed as the mean 8 SD, and categorical variables are expressed as percentages. The normality of the variables was tested using the Kolmogorov-Smirnov test. Comparisons between two groups were assessed using Student’s t test for continuous variables and a 2 test for categorical variables. The Mann-Whitney U test was used for continuous variables that were not distributed normally. Correlations between variables were analyzed using the Pearson correlation analysis. Multiple linear regression analysis was used to assess independent associations between VFA and other variables. The variables significantly associated with VFA (p ! 0.05) in the Pearson correlation analysis were included as independent variables in multiple linear regression analysis models. A stepwise selection method was used in the multiple linear regression analysis. Two-sided p values of less than 0.05 were considered statistically significant. The statistical analysis was carried out using the Statistical Package for the Social Sciences (SPSS) version 16 (SPSS, Chicago, Ill., USA). Dermatology 2010;220:32–37 33 Fig. 1. A CT scan obtained at the level of the umbilicus. The area in pink is regarded as VFA. Fig. 2. A CT scan obtained at the level of the umbilicus. The area in pink shows TFA. Results 34 Dermatology 2010;220:32–37 400 300 VFA The main demographic, clinical, and laboratory features of the subjects are shown in table 1. The two groups were comparable in terms of age, gender, BMI, WHR, total cholesterol, LDL cholesterol, HDL cholesterol, triglyceride, uric acid levels, TFA, and SFA. However, the mean VFA and VFA/SFA ratio of the psoriasis patients were significantly higher than those in the control patients (123.4 8 80.3 vs. 81.2 8 59.8 cm2 and 0.734 8 0.593 vs. 0.491 8 0.336; p = 0.005 and p = 0.017, respectively) (fig. 3). The fasting blood sugar level was also significantly higher in the psoriasis patients than in the controls (101.8 8 43.5 vs. 83.4 8 9.1 mg/dl; p = 0.005). The presence of diabetes mellitus and smoking habit were significantly more frequent in psoriasis patients compared with controls. However, the prevalence of hypertension did not differ significantly between the two groups (table 1). Table 2 shows the results of multiple linear regression analyses for factors associated with VFA in the entire group of 92 study subjects and in the psoriasis patients only. Multiple linear regression analysis in all study subjects indicated that VFA was significantly associated with WHR, age, body weight, presence of psoriasis, and metabolic syndrome. Multiple linear regression analyses of the factors associated with VFA in psoriasis patients only indicated that VFA was significantly associated with WHR, age, body weight, and presence of metabolic syn- 44 2 200 100 0 Controls (n = 46) Patients (n = 46) Fig. 3. Boxplot graph of VFA in patients with psoriasis and controls. The upper and lower sides of each box show the upper and lower quartile, respectively, while the horizontal line dividing each box shows the median. Circles represent outliers. drome (table 2). BMI was not associated with VFA in the linear regression analysis. PASI score, duration or type of disease, smoking habit, and therapies were not associated with VFA (p 1 0.05). None of the laboratory findings were associated with VFA (p 1 0.05). At the time of the study, 22 (47.8%) patients were using topical corticoid or calcipotriol; 4 (8.7%) acitretin, 2 each (4.3% each) phototherapy and biologics, Balci /Balci /Yonden /Korkmaz /Yenin / Celik /Okumus /Egilmez Table 1. Demographic, clinical and laboratory features of the subjects Psoriasis patients (n = 46) Age, years Male/female Disease duration, years PASI score BMI, kg/m2 WHR, % Total cholesterol, mg/dl LDL cholesterol, mg/dl HDL cholesterol, mg/dl Triglyceride, mg/dl Fasting blood sugar, mg/dl Uric acid, mg/dl Smoking Diabetes mellitus Hypertension Metabolic syndrome VFA, cm2 TFA, cm2 SFA, cm2 VFA/SFA, % 39.5814.2 29/17 11.088.3 6.186.3 26.584.2 90.688.3 178.8836.6 107.8834.4 43.6810.5 139.78129.9 101.8843.5 4.481.3 24 (52.2) 7 (15.2) 4 (8.7) 8 (17.4) 123.4880.3 291.88148.7 168.4891.3 73.4859.3 Controls (n = 46) p values 39.8813.5 29/17 0.898a 1 26.884.1 88.187.5 170.1839.0 103.4835.6 42.1811.6 119.1874.2 83.489.1 4.681.0 14 (30.4) 1 (2.2) 5 (10.9) 5 (10.9) 81.2859.8 268.08126.0 186.8893.4 49.1833.6 0.760a 0.132a 0.310a 0.542a 0.516a 0.631b 0.005b 0.419a 0.028c 0.029c 0.500c 0.275c 0.005a 0.410a 0.342a 0.017a Figures in parentheses are percentages. a Student’s t test. b Mann-Whitney U test. c 2 test. and 1 each (2.2% each) cyclosporine, methotrexate, and salazopyrine. The remaining 13 (28.3%) were not taking any therapy. 40 (87.0%) of the psoriasis patients had the plaque type, 5 (10.9%) had the guttate type, and the remaining 1 (2.2%) had the erythrodermic type. 3 (6.5%) patients had psoriatic arthritis. This study clearly demonstrated for the first time that VFA is increased in psoriasis patients compared with control patients with similar waist circumferences. This study also clarified that VFA is independently associated with the presence of metabolic syndrome in patients with psoriasis. Several recent studies have indicated that psoriasis patients tend to develop metabolic syndrome, which is a cluster of conditions that include increased waist circumference, dyslipidaemia, hypertension, and diabetes mellitus or insulin resistance [2–5]. Other comorbidities such as smoking habit and obesity have also been reported more frequently in patients with psoriasis than in nonpsoriatic controls [19, 20]. In the present study, diabetes mellitus and smoking habit were more common in pso- riatic patients than in controls, whereas no significant difference was found in the prevalence of hypertension or metabolic syndrome between psoriasis patients and controls. However, this study did not aim to compare the prevalence of these comorbidities, and the study population was too small for an analysis of these parameters. Obesity may be accompanied by several metabolic disturbances, including diabetes mellitus, dyslipidaemia, insulin resistance, and atherosclerotic diseases. In general, the risk associated with obesity is proportional to the total amount of excess adipose tissue, but visceral obesity appears to be an important indicator of metabolic and atherosclerotic diseases [6–9]. In psoriasis, the chronic inflammation and persistent secretion of TNF-␣ and other pro-inflammatory cytokines together with comorbidities such as metabolic syndrome and smoking habit appear to be the main cause of increased atherosclerosis [2, 3, 19, 20]. A number of mechanisms have been proposed to explain the association between visceral adiposity and metabolic complications and atherosclerosis. First, visceral fat, owing to its anatomical location and peculiar metabolism (enhanced lipolytic activity), releases toxic free fatty acids (FFAs), which are delivered in high concentration Increased Visceral Fat in Psoriasis Dermatology 2010;220:32–37 Discussion 35 Table 2. Multiple linear regression analysis factors associated with VFA in the entire group and psoriasis patients only Independent variables WHR Age Body weight Presence of metabolic syndrome Presence of psoriasis R2 (multiple coefficient of determination) Standard regression coefficients () VFA in psoriasis patients only (n = 46) VFA in all study subjects (n = 92) 0.412*** 0.282** 0.219* 0.245** – 0.787*** 0.343*** 0.293*** 0.278*** 0.182** 0.222*** 0.773*** * p < 0.05; ** p < 0.01; *** p < 0.001. VFA is significantly associated with WHR (p < 0.001), age (p < 0.01), body weight (p < 0.05) and presence of metabolic syndrome (p < 0.01) in psoriasis patients only. VFA is significantly associated with WHR (p < 0.001), age (p < 0.001), body weight (p < 0.001), presence of metabolic syndrome (p < 0.01) and presence of psoriasis (p < 0.001) in all study subjects. to the liver. An excessive accumulation of FFAs in the liver impairs hepatic insulin sensitivity, resulting in peripheral hyperinsulinaemia and insulin resistance [8, 21, 22]. In addition, an increased amount of FFAs in the liver is ultimately responsible for the production of highly atherogenic small dense LDLs [8]. Second, adipose tissue functions as an endocrine organ, releasing pro-inflammatory and adipocyte-derived cytokines such as TNF-␣, leptin, resistin, and adiponectin, which are thought to constitute an important link between obesity and insulin resistance [8, 20, 23, 24]. These cytokines can also contribute to an increased risk for atherosclerotic diseases [8]. More recently, Takahashi et al. [25] reported that plasma adiponectin levels were decreased and plasma leptin levels increased in psoriasis patients compared with healthy controls. In that study, a negative correlation was also demonstrated between plasma adiponectin levels and both the PASI score and TNF- ␣ level in psoriasis patients. Adiponectin is the most abundant adipocytespecific adipokine in the circulation. This important cytokine has anti-inflammatory effects and functions in regulating insulin sensitivity [20, 26]. The adiponectin level is decreased in obese subjects, particularly in those viscerally obese [27]. Reduced adiponectin levels have also been found to be associated with metabolic syndrome, atherosclerosis, and insulin resistance [20]. Another adipocyte-specific cytokine, leptin, appears to be influenced by pro-inflammatory cytokines. It has been suggested that omental fat has more influence than subcutaneous fat on plasma leptin [28]. Similarly, TNF-␣ 36 Dermatology 2010;220:32–37 and IL-6 are secreted in adipose tissue and have important roles in the pathogenesis of psoriasis. TNF-␣ and IL-6 promote a chronic inflammatory state, angiogenesis, and oxidative stress, which contribute to the aetiology of insulin resistance, glucose intolerance, dyslipidaemia, hypertension, endothelial dysfunction, and atherogenesis [20, 29]. Viscerally obese patients are more susceptible to thrombosis and are more likely to show evidence of a chronic inflammatory state [8]. Obesity has also been suggested as a risk factor for the development of psoriasis in a large cohort study [30]. In our study, mean BMI did not differ significantly between the groups. However, our study found that the patients with psoriasis had more visceral fat than controls, even when BMI and waist circumference were similar between the two groups. Furthermore, the linear regression model showed that the presence of psoriasis was independently associated with VFA, suggesting that visceral fat is linked to the chronic inflammatory state. We failed to detect any association between VFA and PASI score or disease duration. The fact that PASI is not a stable parameter and may change over time, mainly due to therapy, may explain our failure to detect a significant association between VFA and PASI score. The therapies, particularly systemic steroids, used in psoriasis may affect the metabolic state of patients. However, no significant association was found between VFA and the therapies. None of the patients with psoriasis were receiving systemic steroids. In addition, the study Balci /Balci /Yonden /Korkmaz /Yenin / Celik /Okumus /Egilmez included few patients receiving systemic therapies such as cyclosporine, methotrexate, or biologics. In conclusion, for the first time, we demonstrated that VFA is increased in psoriasis patients and is independently associated with the presence of psoriasis. We also demonstrated that VFA is independently associated with the presence of metabolic syndrome in patients with pso- riasis. 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