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The Journal of Clinical Endocrinology & Metabolism Vol. 90, No. 12 6418-6423
Copyright © 2005 by The Endocrine Society

Association of Testosterone, Insulin-Like Growth Factor-I, and C-Reactive Protein with Metabolic Syndrome in Chinese Middle-Aged Men with a Family History of Type 2 Diabetes

Peter C. Y. Tong, Chung-Shun Ho, Vincent T. F. Yeung, Maggie C. Y. Ng, Wing-Yee So, Risa Ozaki, Gary T. C. Ko, Ronald C. W. Ma, Emily Poon, Norman N. Chan, Christopher W. K. Lam and Juliana C. N. Chan

Departments of Medicine and Therapeutics (P.C.Y.T., M.C.Y.N., W.-Y.S., R.O., R.C.W.M., E.P., J.C.N.C.) and Chemical Pathology (C.-S.H., C.W.K.L.), Qualigenics Diabetes Centre (N.N.C.), Postgraduate Education Centre, School of Public Health, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong; Our Lady of Maryknoll Hospital (V.T.F.Y.), Wong Tai Sin, Hong Kong; Alice Ho Nethersole Hospital (G.T.C.K.), Tai Po, Hong Kong; and Howard Hughes Research Institute (M.C.Y.N.), University of Chicago, Chicago, Illinois 60637

Address all correspondence and requests for reprints to: Dr. Peter Tong, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong. E-mail: ptong{at}cuhk.edu.hk.


   Abstract
Top
 Abstract
Introduction
 Subjects and Methods
 Results
 Discussion
 References
 
Context: Age-related declines in testosterone and IGF-I are associated with deposition of visceral fat, a component of the metabolic syndrome (MES).

Objective: Testosterone and IGF-I may interact with familial disposition to diabetes mellitus to increase the association with MES.

Design: We conducted a cross-sectional cohort study.

Setting: The study was conducted in a university teaching hospital.

Subjects: Study subjects included 179 middle-aged men with a family history of diabetes (FH) (aged 39.1 ± 8.1 yr) and 128 men without FH (aged 43.8 ± 8.5 yr).

Main Outcome Measures: Clinical characteristics, frequency of MES using the World Health Organization criteria with Asian definitions of obesity (body mass index ≥ 25 kg/m2), and serum levels of total testosterone, IGF-I, and high-sensitive C-reactive protein (hs-CRP) were measured.

Results: Men with FH had higher frequency of MES than those without FH [39.1 vs. 23.4% (P = 0.004)]. On multivariate analysis, smoking (former and current smokers), low total testosterone, and IGF-I but elevated hs-CRP levels explained 35% of the MES variance in men with FH. The frequency of MES increased with declining tertiles of total testosterone and IGF-I but increasing tertiles of hs-CRP. After adjustment for age and smoking history, subjects with all three risk factors had a 13-fold increase in risk association with MES compared with those without hormonal and inflammatory risk factors. These risk associations were not found in men without FH in whom only smoking (ex and current) and low total testosterone level were independent predictors for MES, which explained 14% of the variance.

Conclusions: Clustering of FH, hormonal abnormalities, and high hs-CRP is associated with MES in Chinese middle-aged men.


   Introduction
Top
 Abstract
 Introduction
Subjects and Methods
 Results
 Discussion
 References
 
ASIA IS IN the forefront of the global epidemic of diabetes and obesity. Hong Kong, a cosmopolitan city in Greater China with a population of 6 million southern Chinese, has an age-adjusted prevalence of diabetes of 12%, one of the highest in the world (1, 2). Apart from age and obesity, a family history of diabetes (FH) is a major predictor for diabetes in Chinese (3). There is now a consensus that diabetes is a complex disease with genetic-environmental interactions further influenced by socioeconomic and cultural factors (4).

The association between aging, acculturation, and diabetes may be related to age-associated decline in testosterone and GH, thence IGF-I, as well as stress-induced hypercortisolemia. These hormonal perturbations are associated with deposition of visceral fat, which is metabolically more active than sc fat. Under the influence of stress-induced lipolytic hormones such as catecholamines, visceral adipocytes release large amounts of free fatty acids leading to insulin resistance through fuel competition with glucose. The consequence is a constellation of cardiovascular risk factors including glucose intolerance, insulin resistance, high blood pressure, dyslipidemia, and albuminuria (5, 6).

Against this background, we hypothesize that men with a family history of diabetes (FH) have higher incidence of metabolic syndrome (MES) than men without. We further hypothesize that low serum total testosterone and IGF-I as well as high serum cortisol levels are associated with MES. In this study, we examined the association between hormonal parameters, hs-CRP, and MES in a cohort of young to middle-aged men with or without FH.


   Subjects and Methods
Top
 Abstract
 Introduction
 Subjects and Methods
Results
 Discussion
 References
 
Subjects with FH were recruited from the Hong Kong Diabetes Family Study (7). The Hong Kong Diabetes Family Study was initiated to study the risk association of environmental and genetic factors for type 2 diabetes in families using a genome-wide scan approach. The family study included 179 extended pedigrees with a proband of diabetes diagnosed before the age of 40 yr after excluding monogenic forms of diabetes. The recruitment lasted between 1997 and 2000, and all male siblings were included in the present analysis. From a community health screening program targeted at people of working age, which lasted between 1999 and 2002, male subjects without FH (n = 128) were recruited consecutively to serve as control. All subjects had no known past medical history and were not receiving any chronic medications at the time of the study.

All subjects attended the study unit between 0800 and 1000 h after an overnight fast. Body weight (kilograms), body height (meters), and waist and hip circumferences were measured with the subject wearing light clothing and no shoes. Waist circumference was taken as the narrowest measurement midway between the xiphoid sternum and umbilicus, whereas the hip circumference was taken as the widest measurement at the level of the greater trochanters. Sitting blood pressure (BP) was measured twice, 1 min apart, after the subject had rested for 5 min, using the Critikon Dinamap blood pressure machine (Critikon, Inc., Tampa, FL). All subjects underwent a 75-g oral glucose tolerance test for ascertainment of glycemic status using the 1998 World Health Organization (WHO) criterion.

Fasting blood was taken for measurements of plasma glucose (PG), insulin, hematology, and biochemistry including total cholesterol, high-density lipoprotein-cholesterol (HDL-C), triglyceride (TG), total testosterone, SHBG, IGF-I, hs-CRP, and cortisol. Homeostasis model assessment-insulin resistance index (HOMA-IR) was estimated using the HOMA formula with insulin in picomoles per liter and PG in millimoles per liter (8). A random spot urine sample was collected for measurement of urinary albumin:creatinine ratio (ACR) after exclusion of urinary tract infection. All subjects gave written informed consent. The study was approved by the Clinical Research Ethics Committee of the Chinese University of Hong Kong.

Laboratory assays

PG, total cholesterol, HDL-C, TG, and ACR concentrations were measured on a Hitachi 911 automated analyzer (Roche Molecular Biochemicals, Mannheim, Germany). Low-density lipoprotein-cholesterol was calculated by the Friedewald’s equation (9). Plasma creatinine concentration was measured on a Dimension AR system (Dade Behring, Deerfield, IL). Serum cortisol, hs-CRP, insulin, IGF-I, SHBG, and total testosterone concentrations were measured on an Immulite 1000 semiautomated immunoassay analyzer (Diagnostic Products Corporation, Los Angeles, CA). These measurements were performed using standard reagent kits supplied by the analyzer manufacturers. The analytical performance of these methods was within the specifications of the analyzers.

Definitions of MES

MES was defined using the Asian definition of obesity [waist circumference ≥ 90 cm in men and body mass index (BMI) ≥ 25 kg/m2] (10, 11). For the WHO criteria, HOMA-IR was used as an index of insulin resistance for epidemiological purpose (12, 13, 14), and spot urine ACR was used to define albuminuria. Other criteria were: 1) central obesity, defined as waist-to-hip ratio greater than 0.9 and/or BMI at least 25 kg/m2; 2) dyslipidemia, defined as raised TG (≥1.7 mmol/liter) and/or low HDL-C (<0.9 mmol/liter); 3) hypertension, defined as treatment with antihypertensive medications and/or BP at least 140/90 mm Hg; and 4) microalbuminuria, defined as urinary ACR at least 3.5 mg/mmol.

A person with diabetes or impaired glucose tolerance was considered to have MES if two of the criteria listed above were fulfilled. In subjects with normal glucose tolerance, MES was present if he or she had two of the above criteria in addition to having insulin resistance, defined as the highest quartile of the HOMA-IR index.

The frequency of MES was also examined using the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) criteria (15) and the International Diabetes Federation (IDF) consensus worldwide definition of MES (http://www.idf.org/webdata/docs/IDF_Metasyndrome_definition.pdf).

The NCEP-ATP III definition requires three or more of the following: 1) abdominal obesity, defined as waist circumference of at least 90 cm; 2) a high plasma TG of at least 1.69 mmol/liter; 3) a low plasma HDL-C less than 1.03 mmol/liter; 4) high BP (systolic ≥ 130 mm Hg or diastolic ≥ 85 mm Hg); and 5) a high fasting PG concentration of at least 6.1 mmol/liter.

The IDF consensus worldwide definition of the MES requires central obesity (with ethnic relevant definition) plus any two of the following factors: 1) raised TG level, at least 1.7 mmol/liter or specific treatment for this lipid abnormality; 2) reduced HDL-C level, less than 1.03 mmol/liter in men or specific treatment for this lipid abnormality; 3) raised systolic BP of at least 130 mm Hg or diastolic BP of at least 85 mmHg, or treatment for previously diagnosed hypertension; and 4) raised fasting PG of at least 5.6 mmol/liter or previously diagnosed type 2 diabetes.

Statistical analysis

All statistical analyses were performed using the Statistical Package for Social Sciences (version 11; SPSS, Inc., Chicago, IL). White blood cell count (WCC), TG, insulin, HOMA-IR, cortisol, IGF-I, hs-CRP, SHBG, total testosterone, and ACR were logarithmically transformed due to skewed distributions. Results are expressed as mean ± SD or median (interquartile range), as appropriate. Student’s t test was used for between-group comparisons, and ANOVA was used to examine the relationships between occurrence of MES and tertiles of different variables. Categorical variables were examined by {chi}2 analysis. Logistic regression analysis was used to identify the independent predictors for MES expressed as odds ratio with 95% confidence interval. A P value < 0.05 (2-sided) was considered significant.


   Results
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
Discussion
 References
 
In this combined cohort of 307 young to middle-aged men, the overall frequency of MES was 32.6, 25.7 and 20.2% if the WHO, NCEP-ATP III, and IDF criteria were used, respectively. Obesity and dyslipidemia were the leading components of the MES in these subjects (Table 1Go). Using the WHO criteria, men with a FH had higher frequencies of MES (39.1 vs. 23.4%; P = 0.004) and abnormal glucose tolerance: diabetes (26.3 vs. 9.4%), impaired fasting glycemia (1.7 vs. 0.8%) and impaired glucose tolerance (17.9 vs. 14.8%) (P = 0.001) than those without FH. Having a positive FH conferred an increased risk of MES by WHO definition (odds ratio, 2.8; 95% confidence interval, 1.6–4.8; P < 0.001) after adjustment for age.


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  		TABLE 1. Percentage of Chinese middle-aged men with the MES defined by the WHO, NCEP-ATP III, or IDF criteria

 
All subsequent analyses were performed using the WHO criteria for MES. Table 2Go compares the clinical, hormonal, and metabolic parameters between subjects categorized by FH or MES. The frequency of MES was higher among subjects who were current or ex-smokers. Among men with FH, those with MES were older, had higher serum level of hs-CRP but lower serum concentrations of IGF-I, SHBG, and total testosterone than those without MES. In men with MES, despite having similar BMI, waist circumference, waist-to-hip ratio, and HOMA-IR, those with FH were younger, had lower serum levels of HDL-C (P = 0.005) and SHBG (P = 0.033) but higher levels of WCC (P = 0.021) and hs-CRP (P = 0.003) than those without FH.


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  		TABLE 2. Clinical, metabolic, and hormonal parameters of 307 Chinese middle-aged men with or without MES defined according to the WHO criteria

 
Among men with FH, 35% of the variance of MES was explained by log-transformed serum concentrations of total testosterone (odds ratio [95% confidence interval]: 0.09 [0.02–0.36]; P = 0.001), IGF-I (0.33 [0.12–0.88]; P = 0.026), hs-CRP (2.07 [1.41–3.04]; P < 0.001), and smoking history (ex and current) (2.94 [1.39–6.20]; P = 0.005) on logistic regression analysis. In contrast, only smoking history (4.92 [1.85–13.03]; P = 0.001) and total testosterone (0.23 [0.05–0.95]; P = 0.04) were independent predictors of MES in subjects without FH, explaining 14% of the variance. Applying the NCEP-ATP III definition for MES, 27% of the variance of MES in subjects with FH was explained by age (1.04 [1.00–1.10]; P = 0.045), hs-CRP (1.96 [1.35–2.83]; P < 0.001) and total testosterone (0.11 [0.03–0.40]; P = 0.001).

Table 3Go lists the frequency of MES according to tertiles of total testosterone, IGF-I, and hs-CRP among subjects with FH. The highest frequency of MES was observed in subjects who were in the lowest tertiles of IGF-I and testosterone (Fig. 1AGo) and in subjects who were in the top tertile of hs-CRP and the lowest tertile of total testosterone (Fig. 1BGo). Using the lowest tertiles of serum concentrations of total testosterone and IGF-I and the highest tertile of serum level of hs-CRP as risk factors, the association between different combinations of risk factors and the frequency of MES was examined by logistic regression analysis. After adjustment for age and smoking history, subjects with all three risk factors had a 13-fold increase in risk association with MES compared with those who did not have these hormonal and inflammatory risk factors (Table 4Go). There were disproportionate increases in odds ratios of up to 4-fold among individuals who had two risk factors compared with those who had only a single risk factor.


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  		TABLE 3. Percentages of 179 Chinese middle-aged men with MES (WHO definition) and FH

 


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  		FIG. 1. A, Interaction between total testosterone (tertiles) and IGF-I (tertiles) on the frequency of MES (WHO criteria) in 179 subjects with FH. B, Interaction between total testosterone (tertiles) and hs-CRP (tertiles) on the frequency of MES (WHO criteria) in 179 subjects with a family history of diabetes

 

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  		TABLE 4. Odds ratios and 95% confidence interval of different combinations of risk factors (lowest tertile of total testosterone, lowest tertile of IGF-I and highest tertile of hs-CRP) for the association of MES (WHO criteria) in 179 subjects with FH

 

   Discussion
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
References
 
In this cohort of Hong Kong Chinese middle-aged men, we observed high rates of MES ranging from 20 to 30% depending on the criteria used. Obesity was the commonest component, followed by dyslipidemia. Despite the predefined nature of our study population using either FH or working age as inclusion criteria, the frequency of MES in these Chinese middle-aged men was comparable to that reported in community-based studies conducted in the mid 1990s in Singapore (16) and Hong Kong (17).

In agreement with other reports, subjects with MES in our study had clinical evidence of inflammation with elevated levels of hs-CRP and WCC (18). Of note, in this study, subjects with MES were more likely to be current or ex-smokers. The independent effect of smoking on MES has been reported in several studies (19, 20), although the nature of this association remains to be clarified. Although smoking and obesity may share similar lifestyle-related or personality factors, the elevation in WCC and hs-CRP level may be partly explained by the activating effects of smoking on our innate immune system. Furthermore, smoking can have direct adverse effects on the vasculature (21) and pancreatic ß-cell function leading to hypertension and glucose intolerance (22).

In support of the important role of FH in the development of MES (7), subjects with FH in this study had a higher frequency of MES than those without FH, analyzed either by WHO or NCEP-ATP III criteria. Furthermore, on multivariate analysis, smoking, hs-CRP, total testosterone, and IGF-I explained 35% of the variance of MES in men with FH. By contrast, only smoking and total testosterone were explanatory variables for MES in men without FH (14%). Although hs-CRP and other inflammatory cytokines can be released from adipocytes, the association between hs-CRP and MES was independent of obesity on logistic regression. These findings suggest that other causes such as low-grade infections might play a role in development of MES. There is now clinical and experimental evidence suggesting that low-grade chronic inflammation with hepatitis C (23) or Helicobacter pylori (24) may induce endothelial dysfunction and insulin resistance (25), thus providing the pathogenic basis for their associations with MES. It is plausible that low-grade inflammation due to shared environment may contribute to the high rates of MES and inflammatory state among subjects with FH, although such a hypothesis requires further testing.

We also observed that the association between low testosterone and MES was independent of FH while that between low IGF-I and MES was found only in men with FH. While the nature of these findings requires further elucidation, they lend support to the possible role of hormonal dysregulation in the pathogenesis of MES. In this respect, low dose GH (26) and testosterone therapy (27) have been shown to improve body composition and metabolic profile in subjects with low normal levels of these parameters. Besides, low level of testosterone has been shown to be associated with increased fat mass, reduced lean body mass (28, 29) and increased visceral fat area on magnetic resonance imaging (30). These changes in body composition are typical among subjects with insulin resistance and MES (31). In a cross-sectional study involving 1896 Caucasian men, low serum testosterone and low SHBG levels were associated with MES independent of BMI (18). Importantly, both of these parameters were predictive of development of MES and diabetes in middle-aged men in a prospective study (32).

Taken together, these results suggest that different factors are contributing to the development of MES in middle-aged men with or without FH. Apart from central obesity or insulin resistance, low-grade inflammation and hormonal disturbances may also be linked with MES, especially among subjects with FH. The underlying mechanisms of these associations are beyond the scope of the present study, although the clustering of these multiple risk factors is most likely to be attributed to a combination of shared environment and genetic factors (33).

There are several limitations in this study. First, more subjects with FH were included compared with subjects without FH. Hence, the association between hs-CRP and IGF-I levels with MES may be underestimated in the latter group. Second, control subjects were not systemically matched for age and central obesity because they were recruited consecutively from a community health screening program. Nevertheless, given the similar rates of MES between our cohort and that reported in community-based studies in several Asian populations including Hong Kong Chinese (6, 16, 17), major bias was not likely. Third, although subjects with FH were younger than those without FH, these factors have been adjusted in our comparisons, which did not attenuate the significance of our findings. The aim of this study was to test the hypothesis regarding the association of hormonal and chronic inflammatory parameters and their interactions with FH on MES. Therefore, our findings cannot be fully generalized. Of note, by including an indirect marker of insulin resistance and albuminuria, we found that the WHO criteria for MES were considerably more informative than NCEP-ATP III in our subsequent analysis. Using the new IDF world definition of MES, the percentage of subjects with MES in our cohort was reduced from 32.6 to 20.2%. In the IDF definition of MES, central obesity is a prerequisite of MES. Hence, subjects with all other components apart from central obesity will be excluded. Prospective studies are required to determine the validity of the new IDF definition in identifying subjects at high risk of developing type 2 diabetes and/or cardiovascular disease. Lastly, due to the complex effects of SHBG on circulating levels of testosterone, different formulae and methodologies have been developed to determine the bioavailable and free testosterone levels. However, these derivations or methods were either problematic or laborious. Hence, total testosterone remains a widely acceptable measurement in the evaluation of androgen deficiency in males in both clinical practice and research settings (34).

In conclusion, both low total testosterone and smoking were associated with MES in Chinese middle-aged men. Low IGF-I and elevated hs-CRP levels were also associated with MES in subjects with FH. Our findings lend support to a possible hormonal basis for the association of aging, FH, and MES in individuals who are at high risk of developing diabetes.


   Acknowledgments
 
We thank our research nurses, Delanda Wong, Yee-Mui Lee, and Cherry Chiu, for their assistance in recruiting and phenotyping these volunteers. We thank Patty Tse, Vincent Lam, and Stanley Ho of the Lee Hysan Research Laboratory for their technical support. We are grateful to the family members and volunteers for their participation in this study.


   Footnotes
 
This project was supported by educational grants from Organon, Research Grant Committee (Project code 2040980), and the Hong Kong Foundation for Research and Development in Diabetes of the Chinese University of Hong Kong.

First Published Online September 27, 2005

Abbreviations: ACR, Albumin:creatinine ratio; BMI, body mass index; BP, blood pressure; FH, a family history of diabetes; HDL-C, high-density lipoprotein-cholesterol; HOMA-IR, homeostasis model assessment-insulin resistance index; hs-CRP, high-sensitive C-reactive protein; MES, metabolic syndrome; PG, plasma glucose; TG, triglyceride; WCC, white blood cell count.

Received February 3, 2005.

Accepted September 15, 2005.


   References
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
 References
 

  1. Chan JCN, Ng MCY, Critchley JAJH, Lee SC, Cockram CS 2001 Diabetes mellitus: a special medical challenge from a Chinese perspective. Diabetes Res Clin Pract 54:S19–S27
  2. Lam TH, Liu LJ, Janus ED, Lam KS, Hedley AJ, Hong Kong Cardiovascular Risk Factor Prevalence Study Steering Committee 2000 Fibrinogen, other cardiovascular risk factors and diabetes mellitus in Hong Kong Chinese: a community with high prevalence of type 2 diabetes mellitus and impaired glucose tolerance. Diabet Med 17:798–806[CrossRef][Medline]
  3. Ko GT, Chan JC, Tsang LW, Yeung VT, Chow CC, Cockram CS 2000 Outcomes of screening for glucose intolerance in high risk Hong Kong Chinese. Diabetes Care 23:1290–1294[Abstract/Free Full Text]
  4. Zimmet P, Alberti KG, Shaw J 2001 Global and societal implications of the diabetes epidemic. Nature 414:782–787[CrossRef][Medline]
  5. Björntorp P 1991 Metabolic implications of body fat distribution. Diabetes Care 14:1132–1143[Abstract]
  6. Chan JC, Cheung JC, Lau EM, Wooa J, Chan AY, Swaminathan R, Cockrama CS 1996 The metabolic syndrome in Hong Kong Chinese—the inter-relationships amongst its components analysed by structural equation modeling. Diabetes Care 19:953–959[Abstract]
  7. Ng MC, So WY, Cox NJ, Lam VK, Cockram CS, Critchley JA, Bell GI, Chan JC 2004 Genome wide scan for type 2 diabetes loci in Hong Kong Chinese and confirmation of a susceptibility locus on chromosome 1q21–q25. Diabetes 53:1609–1613[Abstract/Free Full Text]
  8. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC 1985 Homeostasis model assessment: insulin resistance and ß-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419[CrossRef][Medline]
  9. Friedewald WT, Levy RI, and Fredrickson DS 1972 Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 18:499–502[Abstract]
  10. WHO Expert Consultation 2004 Appropriate body mass index for Asian populations and its implications for policy and intervention strategies. Lancet 363:157–163[CrossRef][Medline]
  11. WHO/IASO/IOTF 2000 The Asia-Pacific perspective: redefining obesity and its treatment. World Health Organization, Western Pacific Region
  12. Alberti KG, Zimmet PZ 1998 Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med 15:539–553[CrossRef][Medline]
  13. Laaksonen DE, Lakka HM, Niskanen LK, Kaplan GA, Salonen JT, Lakka TA 2002 Metabolic syndrome and development of diabetes mellitus: application and validation of recently suggested definitions of the metabolic syndrome in a prospective cohort study. Am J Epidemiol 156:1070–1077[Abstract/Free Full Text]
  14. Balkau B, Charles MA 1999 Comment on the provisional report from the WHO consultation. European Group for the Study of Insulin Resistance (EGIR). Diabet Med 16:442–443[CrossRef][Medline]
  15. 2002 Third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). Final report. Circulation 106:3143–3421
  16. Tan CE, Ma S, Wai D, Chew SK, Tai ES 2004 Can we apply the National Cholesterol Education Program Adult Treatment Panel Definition of the Metabolic Syndrome to Asians. Diabetes Care 27:1182–1186[Abstract/Free Full Text]
  17. Thomas G, Ho S, Janus E, Lam K, Hedley A, Lam T, Hong Kong Cardiovascular Risk Factor Prevalence Study Steering Committee 2005 The U.S. National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) prevalence of the metabolic syndrome in a Chinese population. Diabetes Res Clin Pract 67:251–257[CrossRef][Medline]
  18. Laaksonen DE, Niskanen L, Punnonen K, Nyyssonen K, Tuomainen TP, Salonen R, Rauramaa R, Salonen JT 2003 Sex hormones, inflammation and the metabolic syndrome: a population-based study. Eur J Endocrinol 149:601–608[Abstract]
  19. Phillips G, Jing T, Heymsfield S 2003 Relationships in men of sex hormones, insulin, adiposity, and risk factors for myocardial infarction. Metabolism 52:784–790[CrossRef][Medline]
  20. Svartberg J, Midtby M, Bonaa KH, Sundsfjord J, Joakimsen RM, Jorde R 2003 The association of age, lifestyle factors and chronic disease with testosterone in men: the Tromso study. Eur J Endocrinol 149:145–152[Abstract]
  21. Noma K, Higashi Y, Jitsuiki D, Hara K, Kimura M, Nakagawa K, Goto C, Oshima T, Yoshizumi M, Chayama K 2003 Smoking activates rho-kinase in smooth muscle cells of forearm vasculature in humans. Hypertension 41:1102–1105[Abstract/Free Full Text]
  22. Ko GT, Chan JC, Tsang LW, Critchley JA, Cockram CS 2000 Smoking and diabetes in Chinese men. Postgrad Med J 77:240–243
  23. Mehta SH, Brancati FL, Strathdee SA, Pankow JS, Netski D, Coresh J, Szklo M, Thomas DL 2003 Hepatitis C virus infection and incident type 2 diabetes. Hepatology 38:50–56[CrossRef][Medline]
  24. Quadri R, Rossi C, Catalfamo E, Masoero G, Lombardo L, Della Monica P, Rovera L, Pera A, Cavello Perin P 2000 Helicobacter pylori infection in type 2 diabetic patients. Nutr Metab Cardiovasc Dis 10:263–266[Medline]
  25. Mendall MA 1998 Inflammatory responses and coronary heart disease: the dirty chicken hypothesis of cardiovascular risk factors. BMJ 316:953–954[Free Full Text]
  26. Johannsson G, Marin P, Lonn L, Ottosson M, Stenlof K, Bjorntorp P, Sjostrom L, Bengtsson BA 1997 Growth hormone treatment of abdominally obese men reduces abdominal fat mass, improves glucose and lipoprotein metabolism, and reduces diastolic blood pressure. J Clin Endocrinol Metab 82:727–734[Abstract/Free Full Text]
  27. Boyanov MA, Boneva Z, Christov VG 2003 Testosterone supplementation in men with type 2 diabetes, visceral obesity and partial androgen deficiency. Aging Male 6:1–7[Medline]
  28. Tsai EC, Boyko EJ, Leonetti DL, Fujimoto WY 2000 Low serum testosterone level as a predictor of increased visceral fat in Japanese-American men. Int J Obes Relat Metab Disord 24:485–491[CrossRef][Medline]
  29. Vermeulen A, Goemaere S, Kaufman JM 1999 Testosterone, body composition and aging. J Endocrinol Invest 22(5 Suppl):110–116
  30. Seidell JC, Bjorntorp P, Sjostrom L, Kvist H, Sannerstedt R 1990 Visceral fat accumulation in men is positively associated with insulin, glucose and C peptide levels but negatively with testosterone levels. Metabolism 39:897–901[CrossRef][Medline]
  31. Haffner SM 2000 Sex hormones, obesity, fat distribution, type 2 diabetes and insulin resistance: epidemiological and clinical correlation. Int J Obes Relat Metab Disord 24:S56–S58
  32. Laaksonen DE, Niskanen L, Punnonen K, Nyyssonen K, Tuomainen TP, Valkonen VP, Salonen R, Salonen JT 2004 Testosterone and sex hormone-binding globulin predict the metabolic syndrome and diabetes in middle-aged men. Diabetes Care 27:1036–1041[Abstract/Free Full Text]
  33. Hong Y, Pedersen NL, Brismar K, de Faire U 1997 Genetic and environmental architecture of the features of the insulin resistance syndrome. Am J Hum Genet 60:143–152[Medline]
  34. Wang C, Catlin DH, Demers LM, Starcevic B, Swerdloff RS 2004 Measurement of total serum testosterone in adult men: comparison of current laboratory methods versus liquid chromatography tandem mass spectrometry. J Clin Endocrinol Metab 89:534–543[Abstract/Free Full Text]




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Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals