ORIGINAL ARTICLE. Abstract. Introduction

Transcription

1 ORIGINAL ARTICLE Impact of the Visceral Fat Area Measured by Dual Impedance Method on the Diagnostic Components of Metabolic Diseases in a Middle-aged Japanese Population Koji Sakamaki 1, Yuko Maejima 2, Yoshiharu Tokita 3, Yasuhiro Masamura 1, Kensuke Kumamoto 4, Masako Akuzawa 1, Nobuo Nagano 1, Katsuyuki Nakajima 1, Kenju Shimomura 2, Seiichi Takenoshita 4 and Yohnosuke Shimomura 1 Abstract Objective The aim of this study was to examine the associations between the visceral fat area (VFA) and the subcutaneous fat area (SFA) as estimated by the dual impedance method with a body composition monitor (BCM) and the diagnostic components of metabolic syndrome in a middle-aged Japanese population. Methods The subjects included 303 men (average age 51.3±9.0 years old) and 345 women (average age 40.0±9.4 years old). The VFA and SFA were estimated by BCM, and the associations among the components of metabolic syndrome (waist circumference, blood pressure and related blood sample tests) were evaluated. Results VFA showed positive correlations with waist circumference, HbA1c, high-density lipoprotein (HDL)/low-density lipoprotein (LDL) cholesterol, triglyceride and uric acid level in men, while showing positive correlations with waist circumference, HDL cholesterol, triglyceride and HbA1c in women. The estimated SFA showed positive correlations with systolic blood pressure, HDL/LDL cholesterol and triglyceride in men, and HDL cholesterol and triglyceride in women. A receiver operating characteristic (ROC) analysis showed the estimated VFA to be as effective as WC to identify subject with metabolic syndrome. Conclusion By estimating the VFA using BCM, it may be possible to identify patients at risk of developing metabolic syndrome and hyperuricemia. Key words: metabolic syndrome, visceral fat, subcutaneous fat, body composition monitor (Intern Med 55: , 2016) () Introduction It is considered that visceral fat accumulation, rather than subcutaneous fat accumulation, contributes to the development of metabolic syndrome and metabolic diseases (1-3). Based on these findings, the waist circumference (WC) corresponding to a visceral fat area (VFA) of over 100 cm 2 is the basic criteria for diagnosing metabolic syndrome in Japan (WC 85 cm for men and WC 90 cm for women; are the cut-off points suggested by the Japanese Committee for the Definition of Metabolic Syndrome). However, WC is only a surrogate criterion of visceral fat accumulation. Although WC has a strong correlation with visceral fat, it is only an estimation based on a statistical analysis. Since it is visceral fat that contributes to the development of metabolic syndrome and diseases, it is more appropriate to only measure VFA. A computerized tomography (CT) scan is known to be the most effective way to measure VFA (4). However, CT scans require the patient s cooperation (sedation and radiation) and they are also time consuming. Another way is to Centre for Health Control, Hidaka Hospital, Japan, Department of Electrophysiology and Oncology, Fukushima Medical University School of Medicine, Japan, Department of Laboratory Sciences, Gunma University Graduate School of Health Sciences, Japan and Department of Organ Regulatory Surgery, Fukushima Medical University School of Medicine, Japan Received for publication July 1, 2015; Accepted for publication September 27, 2015 Correspondence to Dr. Kenju Shimomura, shimomur@fmu.ac.jp 1691

2 A y= 3.231x r=0.791 p metabolic disease. Materials and Methods Visceral fat area (cm 2 ) Participants The participants consisted of those who underwent health check ups at Hidaka Hospital, Gunma, Japan. A total of 648 subjects (male: n=303; average 51±9 years old, female: n= 345; average 40±9 years old) participated in this study. B Visceral fat area (cm 2 ) y = 1.906x r=0.618 p Waist circumference (cm) Waist circumference (cm) Figure. Relationship between the estimated visceral fat area and waist circumference in men (A) and women (B). use a body composition monitor (BCM). This system uses the dual impedance method, which can estimate fat composition (both VFA and subcutaneous fat area: SFA) without radiation exposure and in less than 5 minutes. Previous reports based on small sample sizes showed that BCM has a good correlation with the anthropometric parameters of central obesity (5). However, it is not clear whether VFA measured by BCM is able to replace WC as diagnostic criteria for identifying metabolic syndrome. Furthermore, the impact of VFA measured using BCM on the diagnostic components of metabolic syndrome has not yet been well investigated. We herein used BCM for the measurement of VFA to investigate the correlation between WC and its impact on the diagnostic components of metabolic syndrome. Our results suggest that BCM-measured VFA has a good correlation with WC, according to the currently used diagnostic criteria for metabolic syndrome, and it is therefore considered to be effective in the diagnosis of metabolic syndrome. Moreover, we found that VFA estimated by BCM has an impact on the uric acid level. The present data indicate the usefulness of using BCM to diagnose metabolic syndrome at an early stage or to identify subjects who are at risk of developing Data collection The health check included a physical examination, anthropometric measurements, WC and a serum blood analysis, which included fasting glucose, glycated haemoglobin (HbA 1c: National Glycohemoglobin Standardization Program values), total cholesterol, HDL-cholesterol, LDL-cholesterol, triglyceride levels, and uric acid. Height and weight were measured using a standard stadiometer and scale with the participants in light clothing. The WC was measured midway between the lowest rib and the iliac crest with flexible anthropometric tape (6). The body mass index was calculated as weight/height 2 (kg/m 2 ), and blood pressure was measured using a standard mercury sphygmomanometer. The body fat composition was measured by the dual impedance method using an OMRON HDS-2000 BCM (Omron, Kyoto, Japan). All measurements were performed by trained staff. Statistical evaluation Data are expressed as the mean ± SD. A multiple regression analysis was used to identify which parameters predicted the VFA, SFA, and body fat rate. A comparison of WC and VFA as factor for the diagnosis of metabolic syndrome was made using a receiver operating characteristic (ROC) analysis. The area under the ROC curve was used as an index of accuracy. All statistical analyses were performed using the Stat Flex version 5.0 software program for Windows (Artec, Osaka, Japan). A value of p<0.05 was considered to be statistically significant. Results The mean ages of the participants were 51.3±9.0 years for men (n=303) and 40.0±9.4 years for women (n=345). Since WC is one of the main diagnostic components of metabolic syndrome and is considered to reflect VFA, we analysed the correlation between WC and VFA estimated by BCM. The estimated VFA was found to be positively correlated with WC in both men and women (men: r=0.791, p< 0.001, women: r=0.618, p, Figure) indicating that VFA estimated by BCM is similar to WC measurements, and it is therefore considered to be a useful indicator of diagnosing metabolic syndrome. Table 1 shows the clinical characteristics of the subjects and a comparison of all the factors between the male and 1692

3 Table 1. Clinical Characteristics of Study Subjects and Comparisons between Men and Women in Each Factor. Male (n=303) Female (n=345) Age, years 51.3 ± ± 9.4 Body weight (kg) 71.3 ± ± 8.6 Body mass index (kg/m 2 ) 24.5 ± ±3.3 Waist circumference (cm) 86.8 ± ± 9.0 VFA (cm 2 ) 84.7 ± ± 24.2 SFA (cm 2 ) ± ± 72.3 Body fat percentage (%) 24.1 ± ± 7.2 Systolic blood pressure (mmhg) ± ± 12.5 Diastolic blood pressure (mmhg) 77.2 ± ± 19.5 Uric acid (mg/dl) 6.3 ± ± 0.9 Total cholesterol (mg/dl) ± ± 36.4 HDL cholesterol (mg/dl) 55.2 ± ± 15.9 LDL cholesterol (mg/dl) ± ± 31.7 Triglyceride (mg/dl) ± ± 84.5 Fasting blood glucose (mg/dl) ± ± 11.1 HbA1c (%) 5.4 ± ± 0.4 female subjects. Next, we evaluated whether VFA and SFA, as estimated by BCM, have any impact on the other diagnostic components of metabolic syndrome. A stepwise multiple regression analysis of the data identified triglyceride, HDL/LDL cholesterol, HbA1c and the uric acid level as significant explanatory variables from estimated VFA in the male subjects. While in the female subjects, HDL cholesterol, triglyceride and HbA1c level were identified as significant explanatory variables from VFA (Table 2). On the other hand, regarding estimated SFA, systolic blood pressure, HDL/LDL cholesterol, triglyceride for males and HDL cholesterol, and triglyceride were identified in females as significant explanatory variables (Table 2). The ratio of VFA and SFA (VFA/SFA), HDL cholesterol and triglyceride level were identified as significant explanatory variables only in male subjects (Table 2). A comparison of the accuracy of diagnosing metabolic syndrome by WC and estimated VFA were evaluated by an ROC analysis with the area under the curve (AUC). In the present study, only the male participants had significantly enough subjects who met the diagnostic criteria of metabolic syndrome for the analysis. When analysed in male subjects, AUC for WC and VFA was and respectively. Therefore, the estimated VFA was considered to be as effective as the WC measurement. Discussion The present study demonstrated that VFA estimation by BCM has a good correlation with WC, which is currently used in the diagnosis of metabolic syndrome. Although there is a report that indicated the usefulness of BCM for diagnosing and monitoring metabolic syndrome based on a relatively small group of subjects (5), this is the first report to present its usefulness based on a large number of Japanese subjects. The ultimate goal of diagnosing and treating metabolic syndrome is to prevent its progression into more severe states such as diabetes and cardiovascular disease. There are a number of reports showing visceral fat being more pathogenic compared to subcutaneous fat (3, 7-10). This is because metabolically active adipose tissues, which secrete active substances, such as inflammatory markers and adipocytokines, are mostly found in the visceral area (11-13). Our present study showed that the estimated VFA by BCM positively correlated with WC in both men and women. In addition, the ROC analysis revealed the estimated VCM to be as effective as WC to identify subjects with metabolic syndrome. These results reemphasize the effectiveness of measuring WC to diagnose metabolic syndrome. However, an epidemiological study by Kuk et al. showed that correlation of WC and VFA is influenced by age and sex (14). In addition, WC measurement is reported to show variation between measurements (15, 16). The most accurate and reliable method to measure VFA is using CT. However, due to the risk of radiation, CT measurements cannot be used as a regular measurement modality. Because the estimated VFA by BCM is reported to have a good correlation with VFA measured by CT (17), the estimation of VFA by BCM may provide accurate information equal to CT measurements. Clinically, visceral fat is also strongly associated with diabetes and the development of insulin resistance (18). Consistently, the present study s results also indicate that the estimated VFA is associated with HbA1c in both males and females. Recent studies indicate that ectopic fat accumulation in organs such as the liver and heart may predict the future development of diabetes (19, 20). The increase of visceral 1693

4 Table 2. Results of Multiple Regression Analysis for VFA and SFA for Men (upper Table) and Women (lower Table). VFA SFA VFA/SFA Male (n=303) Systolic blood pressure (mmhg) Diastolic blood pressure (mmhg) Uric acid (mg/dl) HDL cholesterol (mg/dl) LDL cholesterol (mg/dl) Trigliceride (mg/dl) HbA1c (%) VFA SFA VFA/SFA Female (n=345) Systolic blood pressure (mmhg) Diastolic blood pressure (mmhg) Uric acid (mg/dl) HDL cholesterol (mg/dl) LDL cholesterol (mg/dl) Trigliceride (mg/dl) HbA1c (%) VFA: visceral fat area, SFA: subcutaneous fat area, : standardized regression coefficient fat reflects the increase of ectopic fat accumulation and can be considered as a maker of ectopic fat (20, 21). Taking these findings into consideration, VFA estimation by BCM can therefore be powerful tool to identify patients with ectopic fat accumulation. There are numerous reports indicating the reliability of BCM estimation of VFA (5, 17, 22, 23). However, one must take into account that the VFA value from BCM is based on completely different technology compared to the CT-based VFA measurement, which is the most accurate method. BCM can only estimate the VFA by measuring impedance by two different pathways of current through abdominal fat (17, 22). Ida et al. reported that when comparing the time dependent change of VFA after weight reduction therapy by CT and BCM measurement, BCM measurement tend to show more significant change (23). This may be due to the difference between the principle method of CT and BCM. Further detailed study is therefore required. Interestingly, we found that VFA was associated with the uric acid level in men. Although uric acid is not included in the diagnostic components of metabolic syndrome, recent studies have revealed that increased uric acid leads to the development of atherosclerosis, which ultimately results in hypertension and leads to increased mortality (24-27). The contribution of visceral fat accumulation to the development of hyperuricemia is well reported (28, 29). In the present study, we found that the impact of VFA on the diagnostic components of metabolic syndrome is larger in men than in women. Previously, when we evaluated the impact of self-awareness of fast eating on the diagnostic components of metabolic syndrome among middle-aged Japanese subjects, we also found that women are less affected (30). It is possible to speculate that, similar to selfawareness of fast eating, VFA may have less impact on such diagnostic components in women compared to men. However, since there are contradictory reports regarding gender difference and the impact of VFA on metabolic factors (8), further studies are required. Usually, when considering the pathophysiology of metabolic syndrome, VFA is focused on as the main contributor (11-13). In the present study we found that VFA, rather than SFA, significantly affects the diagnostic components of metabolic syndrome. However, when analysed with the ratio of VFA and SFA (VFA/SFA) its impact was found to be smaller. This result indicate that VFA alone has strong impact on the diagnostic components of metabolic syndrome. On the other hand, the subcutaneous adipose cell size is reported to have a direct correlation with WC (31). The hypertrophy of subcutaneous adipose cells is a consequence of impaired adipogenesis. Importantly, a recent report has shown that individuals with a genetic predisposition for type 2 diabetes demonstrated an impaired ability for recruiting new adipose cells for subcutaneous adipose tissue (32). In this study, although less than that of VFA, we found the estimated SFA also has an impact on the diagnostic components of metabolic syndrome. It is possible that this data is reflecting the impaired adipogenesis of subcutaneous fat tissue, thus suggesting the importance of evaluating SFA for the diagnosis of metabolic syndrome. Further studies are required to clarify to what extent the SFA contributes to the development of metabolic syndrome. Although we have shown the effectiveness of VFA estimation by BCM, there are some limitations associated with our design. The number of female participants with metabolic syndrome was limited and was not sufficient to evaluate the effectiveness for diagnosing metabolic syndrome. In 1694

5 addition, the important factor of diagnosing/treating metabolic syndrome patient is to follow-up the patient condition. Our present study did not perform any follow-up of the participants and therefore the long term evaluation of BCM as estimated by VFA is required. Since the number of patients with diabetes and obesity is showing epidemic increases, it is important to identify subjects who are at risk of developing metabolic syndrome, or to diagnose it at an early stage. Therefore, an accurate, simple and inexpensive method to evaluate the risk of metabolic syndrome is urgently needed. As for such a method, we proposed in our previous study that asking about selfawareness of fast eating was a simple and effective way to detect patients who are at risk for developing metabolic syndrome (30). In the present study, we demonstrated that estimating VFA using BCM is also a simple, useful and inexpensive method. Therefore, in clinical practice, the combination of asking about self-awareness of fast eating and use of BCM may be a powerful tool to diagnose metabolic syndrome and it related metabolic diseases. The authors state that they have no Conflict of Interest (COI). References 1. Fujioka S, Matsuzawa Y, Tokunaga K, Tarui S. Contribution of intra-abdominal fat accumulation to the impairment of glucose and lipid metabolism. Metabolism 36: 54-59, Kanai H, Matsuzawa Y, Kotani K, et al. Close correlation of intraabdominal fat accumulation to hypertension in obese women. Hypertension 16: , Matsuzawa Y, Funahashi T, Nakamura T. The concept of metabolic syndrome: contribution of visceral fat accumulation and its molecular mechanism. J Atheroscler Thromb 18: , Lee SY, Gallagher D. Assessment methods in human body composition. Curr Opin Clin Nutr Metab Care 11: , Baudrand R, Dominguez JM, Tabilo C, et al. The estimation of visceral adipose tissue with a body composition monitor predicts the metabolic syndrome. J Hum Nutr Diet 26: , Takahashi M, Shimomura K, Proks P, et al. A proposal of combined evaluation of waist circumference and BMI for diagnosis of metabolic syndrome. Endocr J 56: , Fox CS, Massaro JM, Hoffman U, et al. Abdominal visceral and subcutaneous adipose tissue compartments. Association with metabolic risk factors in the Framingham heart study. Circulation 116: 39-48, Ryo M, Funahashi T, Nakamura T, et al. Fat accumulation and obesity-related cardiovascular risk factors in middle-aged Japanese men and women. Intern Med 53: , Yamashita S, Nakamura T, Shimomura I, et al. Insulin resistance and body fat distribution. Diabetes Care 19: , Nagaretani H, Nakamura T, Funahashi T, et al. Visceral fat is a major contributor for multiple risk factor clustering in Japanese men with impaired glucose tolerance. Diabetes Care 24: , Funahashi T, Nakamura T, Shimomura I, et al. Role of adipocytokines on the pathogenesis of atherosclerosis in visceral obesity. Intern Med 38: , Halleux CM, Takahashi M, Delporte ML, et al. Secretion and regulation of apm1 gene expression in human visceral adipose tissue. Biochem Biophys Res Commun 288: , Shimomura I, Funahashi T, Takahashi M, et al. Enhanced expression of PAI-1 in visceral fat: Possible contribution to vascular disease in obesity. Nat Med 2: 1-5, Kuk JL, Lee S, Heymsfield SB, Ross R. Waist circumference and abdominal adipose tissue distribution: influence of age and sex. Am J Clin Nutr 81: , Dhaliwal SS, Welborn TA. Measurement error and ethnic comparisons of measures of abdominal obesity. Prev Med 49: , Yamada S, Tsukamoto Y, Irie J. Waist circumference in the metabolic syndrome. Lancet 370: , Yamakagge H, Ito R, Tochiya M, et al. The utility of dual bioelectrical impedance analysis in detecting intra-abdominal fat area in obese patients during weight reduction therapy in comparison with waist circumference and abdominal CT. Endocr J 61: , Hayashi T, Boyko EJ, McNeely MJ, Leonetti DL, Kahn SE, Fujimoto WY. Visceral adiposity, not abdominal subcutaneous fat area, is associated with an increase in future insulin resistance in Japanese Americans. Diabetes 57: , Neeland IJ, Turner AT, Ayers CR, et al. Dysfunctional adiposity and the risk of prediabetes and type 2 diabetes in obese adults. JAMA 308: , Graner M, Siren R, Nyman K, et al. Cardiac steatosis associates with visceral obesity in nondiabetic obese men. J Clin Endocrinol Metab 98: , Smith U. Abdominal obesity: a marker of ectopic fat accumulation. J Clin Invest 125: , Browning LM, Muqridge O, Chatfield MD, et al. Validity of a new abdominal bioelectrical impedance device to measure abdominal and visceral fat: comparison with MRI. Obesity (Silver Spring) 18: , Ida M, Hirata M, Odori S, et al. Early changes of abdominal adiposity detected with weekly dual bioelectrical impedance analysis during calorie restriction. Obesity (Silver Spring) 21: E350-E353, Kang DH, Park SK, Lee IK, Johnson RJ. Uric acid-induced C- reactive protein expression: implication on cell proliferation and nitric oxide production of human vascular cells. J Am Soc Nephrol 16: , Kanellis J, Watanabe S, Li JH, et al. Uric acid stimulates monocyte chemoattractant protein-1 production in vascular smooth muscle cells via mitogen-activated protein kinase and cyclooxygenase- 2. Hypertension 41: , Mazzali M, Kanellis J, Han L, et al. Hyperuricemia induces a primary renal arteriolopathy in rats by a blood pressure-independent mechanism. Am J Physiol Renal Physiol 282: F991-F997, Hakoda M, Masunari N, Yamada M, et al. Serum uric acid concentration as a risk factor for cardiovascular mortality: a long term cohort study of atomic bomb survivors. J Reumatol 32: , Tamba S, Nishizawa H, Funahashi T, et al. Relationship between the serum uric acid level, visceral fat accumulation and serum adiponectin concentration in Japanese men. Intern Med 47: , Hikita M, Ohno I, Mori Y, Ichida K, Yokose T, Hosoya T. Relationship between hyperuricemia and body fat distribution. Intern Med 46: , Nohara A, Maejima Y, Shimomura K, et al. Self-awareness of fast eating and its impact on diagnostic components of metabolic syndrome among middle-aged Japanese males and females. Endocr Regul 49: 91-96, Hammarstedt A, Hedjazifar S, Jenndahl L, et al. WISP2 regulates preadipose commitment and PPARgamma activation by BMP4. Proc Natl Acad Sci USA 110: , Arner P, Arner E, Hammarstedt A, Smith U. Genetic predisposi- 1695

6 tion for type 2 diabetes, but not for overweight/obesity, is associ- ated with restricted adipogenesis. PLoS One 6: e18284, The Japanese Society of Internal Medicine