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Serum Insulin Is Significantly Related to Components of the Metabolic Syndrome in Japanese Working Men Tomoyuki Kawada, MD, PhD; Hirofumi Inagaki, PhD; Yoko Wakayama, PhD; Qing Li, MD, PhD; Masao Katsumata, PhD
The aim of this study was to examine the association between serum insulin levels and components of the metabolic syndrome (MS). The target participants were 3054 working men. MS was diagnosed based on the modified criteria of the International Diabetes Federation and was present in 12.9% of the study patients. Serum lipid profiles, uric acid, insulin, plasma glucose, and hemoglobin A1c were measured. Stepwise multiple regression analysis showed that all the components of MS were significantly associated with log-transformed values of the serum insulin. The standardized regression coefficient for the waist circumference was 5-fold higher than that for fasting plasma glucose, being 0.40 and 0.08, respectively. The standardized regression coefficients for diastolic blood pressure, log-transformed values of serum triglyceride, high-density lipoprotein cholesterol, and age were 0.09, 0.13, )0.16, and )0.11, respectively. A statistically significant relationship existed between the components of MS, especially abdominal obesity, and
From the Department of Hygiene and Public Health, Nippon Medical School, Tokyo, Japan Address for correspondence: Tomoyuki Kawada, MD, PhD, Department of Hygiene and Public Health, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-Ku, Tokyo 113-8602, Japan E-mail:
[email protected] Manuscript received September 30, 2008; revised February 1, 2009; accepted June 10, 2009
doi: 10.1111/j.1751-7176.2009.00239.x
VOL. 12 NO. 4 APRIL 2010
the serum insulin levels. J Clin Hypertens (Greenwich) 2010;12:309–314. 2009 Wiley Periodicals, Inc. ª
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nsulin resistance (IR) plays a crucial role in diseases such as glucose intolerance, hypertension and dyslipidemia characterized by increased plasma triglyceride (TG) and ⁄ or decreased highdensity lipoprotein cholesterol (HDL-C), all of which are associated with the future development of coronary artery disease.1,2 The World Health Organization designated the concept of IR representing the risk of cardiovascular and metabolic risk factors as ‘‘metabolic syndrome (MS)’’ in 1998,3 and the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) proposed a clinical definition for MS based on popularly measured parameters in routine clinical practice in 2001.4 Furthermore, the most frequently adopted definition in Japan is the one proposed by the International Diabetes Federation (IDF) in 2005.5 Although there are several definitions for MS, it is mainly characterized by the following major risk factors: central obesity, glucose intolerance, hypertension, and dyslipidemia. Among these, glucose intolerance6 is the secondary factor to contribute to the occurrence of MS. It has been clarified that MS is a risk factor for cardiovascular diseases7,8 and the development of diabetes mellitus.9 Although the underlying pathophysiology of the MS is complicated and modified by many factors, IR plays a crucial role in the development of MS.1,10 Therefore, we consider that early detection of MS by measurement of the IR is logical and reasonable.
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As the definition of central obesity as a criterion for MS differs among different ethnic groups, it would be of significance to conduct a survey by measuring the insulin levels in relation to the presence of components of MS in middle-aged Japanese patients. The purpose of this cross-sectional study was to identify the components of MS independently related to the serum insulin and the strength of the associations, which may serve as valuable information for the control ⁄ prevention of cardiovascular diseases. METHODS Study Population We studied a population of 3692 Japanese workers (3584 men and 144 women) ranging in age from 34 to 64 years at a workplace in Gunma Prefecture, Japan, who responded to a self-administered questionnaire containing questions to determine the current medical and treatment history and the status of some lifestyle factors in the patients. Because the number of women was relatively small, they were excluded from the analysis. The participants underwent a health checkup, including measurement of height, weight, waist circumference (WC), and systolic and diastolic blood pressure (measured in the sitting position after the patients had rested for 3 minutes), and fasting blood samples were collected from all of the patients. The number of participants with a current history of treatment for diabetes, hypertension, dyslipidemia, hyperuricemia, or coronary and ⁄ or cerebrovascular disease were 94, 314, 112, 47, and 33, respectively. There were many patients with comorbidities, and 530 with a current history of treatment for chronic diseases were excluded. Finally, the data of 3054 participants, after excluding the 530 patients above, were finally included for the analysis. While patients receiving medication were excluded, untreated patients were included in this study. Informed consent was obtained from all of the study participants, and the study protocol was approved by the ethics committee of the company. Biochemical Analysis and Definition of MS Venous blood samples were drawn from each participant after they had fasted for 9 hours, and the samples were stored at )80C until the assays were analyzed. Serum TG and total cholesterol levels were determined by the enzymatic method, and serum HDL-C was measured by the phosphotungstate method. Serum uric acid was measured by uricase-peroxidase method. Plasma glucose was
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determined by the hexokinase method, and hemoglobin A1c (HbA1c) was measured by the latex agglutination method. Serum insulin was measured by a chemiluminescent enzyme immunoassay (Fujirebio, Inc, Tokyo, Japan), with a detection sensitivity of the assay technique of 0.3 uIU ⁄ mL.11 Intra-assay coefficient of variation for insulin for repeated measurements was 2.05% for values using the National Institute for Biological Standards and Control (1st IRP NIBSC code: 66 ⁄ 304). Intra-assay for total cholesterol, TG, HDL-C, fasting plasma glucose (FPG), HbA1c, and uric acid in this study were 0.71%, 1.31%, 0.44%, 0.67%, 0.54%, and 0.64%, respectively. They were repeated 20 times except insulin (n=10). Unfortunately, inter-assay coefficient of variation cannot be presented here because of information loss. We adopted the definition of MS that is widely accepted by the Japanese Society of Internal Medicine and 7 other special societies of medicine in Japan.12 The criteria in this study were based on the International Diabetes Federation, in which WC is appropriately assessed according to the nation of origin or ethnicity of the patient. Central obesity was defined as a WC 85 cm. Dyslipidemia was judged by the presence of a high TG (150 mg ⁄ dL) and ⁄ or low HDL-C (
