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1.  Testosterone replacement therapy among elderly males: the Testim Registry in the US (TRiUS) 
Background:
Testosterone levels naturally decline with age in men, often resulting in testosterone deficiency (hypogonadism). However, few studies have examined hypogonadal characteristics and treatment in older (≥65 years) men.
Objective:
To compare data at baseline and after 12 months of testosterone replacement therapy (TRT) in hypogonadal men ≥65 vs <65 years old. Data for participants 65–74 vs ≥75 years old were also compared.
Methods:
Data were from TRiUS (Testim Registry in the United States), which enrolled 849 hypogonadal men treated with Testim® 1% (50–100 mg testosterone gel/day) for the first time. Anthropometric, laboratory, and clinical measures were taken at baseline and 12 months, including primary outcomes of total testosterone (TT), free testosterone (FT), and prostate-specific antigen (PSA) levels. Comparisons of parameters were made using Fisher’s exact test or analysis of variance. Nonparametric Spearman’s ρ and first-order partial correlation coefficients adjusted for the effect of age were used to examine bivariate correlations among parameters.
Results:
Of the registry participants at baseline with available age information, 16% (133/845) were ≥65 years old. They were similar to men <65 years old in the duration of hypogonad-ism prior to enrollment (∼1 year), TT and FT levels at baseline, TT and FT levels at 12-month follow-up, and in reported compliance with treatment. Older patients were more likely to receive lower doses of TRT. PSA levels did not statistically differ between groups after 12 months of TRT (2.18 ± 2.18 ng/mL for ≥65 vs 1.14 ± 0.84 ng/mL for <65 years old, P = 0.1). Baseline values for the >75-year-old subcohort were not significantly different from subcohorts aged 65–74 years and <65 years.
Conclusion:
Hypogonadal men ≥65 years old showed significant benefit from TRT over 12 months, similar to that found for hypogonadal men <65 years old. TRT was well tolerated in older patients, successfully increased testosterone level regardless of age, and did not significantly increase PSA levels in older men.
doi:10.2147/CIA.S32036
PMCID: PMC3430096  PMID: 22956867
male hypogonadism; elderly; testosterone replacement therapy; testosterone gel; TRiUS registry; Testim
2.  Metabolic syndrome and gallstone disease 
AIM: To investigate the association between metabolic syndrome (MetS) and the development of gallstone disease (GSD).
METHODS: A cross-sectional study was conducted in 7570 subjects (4978 men aged 45.0 ± 8.8 years, and 2592 women aged 45.3 ± 9.5 years) enrolled from the physical check-up center of the hospital. The subjects included 918 patients with gallstones (653 men and 265 women) and 6652 healthy controls (4325 men and 2327 women) without gallstones. Body mass index (BMI), waist circumference, blood pressure, fasting plasma glucose (FPG) and serum lipids and lipoproteins levels were measured. Colorimetric method was used to measure cholesterol, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). Dextrose oxidizing enzyme method was used to measure FPG. Subjects were asked to complete a questionnaire that enquired about the information on demographic data, age, gender, histories of diabetes mellitus, hypertension, and chronic liver disease and so on. Metabolic syndrome was diagnosed according to the Adult Treatment Panel III (ATP III) criteria. Gallstones were defined by the presence of strong intraluminal echoes that were gravity-dependent or attenuated ultrasound transmission.
RESULTS: Among the 7570 subjects, the prevalence of the gallstone disease was 12.1% (13.1% in men and 10.2% in women). BMI, waist circumference, systolic blood pressure, diastolic blood pressure, fasting blood glucose and serum triglyceride (TG) in cases group were higher than in controls, while serum high-density lipid was lower than in controls. There were significant differences in the waist circumference, blood pressure, FPG and TG between cases and controls. In an age-adjusted logistic regression model, metabolic syndrome was associated with gallstone disease. The age-adjusted odds ratio of MetS for GSD in men was 1.29 [95% confidence interval (CI), 1.09-1.52; P = 0.0030], and 1.68 (95% CI, 1.26-2.25; P = 0.0004) in women; the overall age-adjusted odds ratio of MetS for GSD was 1.42 (95% CI, 1.23-1.64; P < 0.0001). The men with more metabolic disorders had a higher prevalence of gallstone disease, the trend had statistical significance (P < 0.0001). The presence of 5 components of the MetS increased the risk of gallstone disease by 3.4 times (P < 0.0001). The prevalence of GSD in women who had 5 components of MetS was 5 times higher than in those without MetS component. The more the components of MetS, the higher the prevalence of GSD (P < 0.0001). The presence of 5 components of the MetS increased the risk of gallstone disease by 4.0 times.
CONCLUSION: GSD appears to be strongly associated with MetS, and the more the components of MetS, the higher the prevalence of GSD.
doi:10.3748/wjg.v18.i31.4215
PMCID: PMC3422804  PMID: 22919256
Gallstone disease; Obesity; Hypertension; Dyslipidemia; Metabolic syndrome
3.  Prediction of Metabolic Syndrome by Low Serum Testosterone Levels in Men 
Diabetes  2009;58(9):2027-2031.
OBJECTIVE
The aim of this analysis was to assess the prospective association of serum testosterone and dehydroepiandrosterone sulfate (DHEAS) levels with incident metabolic syndrome (MetS) in men.
RESEARCH DESIGN AND METHODS
Data were obtained from the Study of Health in Pomerania (SHIP), a population-based prospective cohort of adults aged 20–79 years. Analyses were conducted in 1,004 men without baseline MetS defined by National Cholesterol Education Program Adult Treatment Panel III guidelines. Testosterone and DHEAS were categorized by age-specific quartiles and Poisson regression models with relative risks (RRs) and 95% CIs were estimated.
RESULTS
After a median follow-up time of 5.0 years, 480 men (47.8%) developed MetS. Testosterone levels decreased with increasing number of MetS components. Testosterone in the lowest quartile predicted MetS (RR 1.38 [95% CI 1.13–1.69]), particularly among men aged 20–39 years (2.06 [1.29–3.29]), even after adjustment for age, smoking, alcohol consumption, physical activity, waist circumference, self-related health, and time of blood sampling. DHEAS levels were not related to incident MetS (0.99 [0.83–1.19]).
CONCLUSIONS
Low testosterone but not DHEAS predicts development of MetS in a population-based cohort of 1,004 men aged 20–79 years. Especially in young men aged 20–39 years, results suggest low testosterone as a strong predictor for incident MetS. Assessment of testosterone in young and middle-age men may allow early interventions in the general population.
doi:10.2337/db09-0031
PMCID: PMC2731522  PMID: 19581420
4.  Associations between smoking, components of metabolic syndrome and lipoprotein particle size 
BMC Medicine  2013;11:195.
Background
The clustering of metabolic and cardiovascular risk factors is known as metabolic syndrome (MetS). The risk of having MetS is strongly associated with increased adiposity and can be further modified by smoking behavior. Apolipoproteins (apo) associated with low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein-cholesterol (HDL-C) may be altered in MetS. This study aimed to examine the association between smoking and the following parameters: MetS and its components, levels of apolipoproteins and estimated lipoprotein particle size, separately for men and women, and in different body mass index (BMI) classes.
Methods
We included 24,389 men and 35,078 women aged between 18 and 80 years who participated in the LifeLines Cohort Study between December 2006 and January 2012; 5,685 men and 6,989 women were current smokers. Participants were categorized into three different body mass index (BMI) classes (BMI <25; BMI 25 to 30; BMI ≥30 kg/m2). MetS was defined according to the National Cholesterol Education Program’s Adult Treatment Panel III (NCEP:ATPIII) criteria. Blood pressure, anthropometric and lipid measurements were rigorously standardized, and the large sample size enabled a powerful estimate of quantitative changes. The association between smoking and the individual MetS components, and apoA1 and apoB, was tested with linear regression. Logistic regression was used to examine the effect of smoking and daily tobacco smoked on risk of having MetS. All models were age adjusted and stratified by sex and BMI class.
Results
Prevalence of MetS increased with higher BMI levels. A total of 64% of obese men and 42% of obese women had MetS. Current smoking was associated with a higher risk of MetS in both sexes and all BMI classes (odds ratio 1.7 to 2.4 for men, 1.8 to 2.3 for women, all P values <0.001). Current smokers had lower levels of HDL cholesterol and apoA1, higher levels of triglycerides and apoB, and higher waist circumference than non-smokers (all P <0.001). Smoking had no consistent association with blood pressure or fasting blood glucose. In all BMI classes, we found a dose-dependent association of daily tobacco consumption with MetS prevalence as well as with lower levels of HDL cholesterol, higher triglyceride levels and lower ratios of HDL cholesterol/apoA1 and, only in those with BMI <30, LDL cholesterol/apoB (all P <0.001).
Conclusions
Smoking is associated with an increased prevalence of MetS, independent of sex and BMI class. This increased risk is mainly related to lower HDL cholesterol, and higher triglycerides and waist circumference. In addition, smoking was associated with unfavorable changes in apoA1 and apoB, and in lipoprotein particle size.
Please see related commentary: http://www.biomedcentral.com/1741-7015/11/196.
doi:10.1186/1741-7015-11-195
PMCID: PMC3766075  PMID: 24228807
Metabolic syndrome; Smoking; HDL; Cholesterol; Apolipoproteins; Triglycerides; Obesity; Cross-sectional; BMI classes
5.  Relationship between blood peroxidases activity and visfatin levels in metabolic syndrome patients 
ARYA Atherosclerosis  2014;10(4):218-226.
BACKGROUND
The observed relationships between visfatin, peroxidases activity, and metabolic syndrome (MetS) are inconsistent; therefore, this study was undertaken to understand these relationships.
METHODS
This cross-sectional study was conducted as a part of the Isfahan Healthy Heart Program, Iran. A blood sample of 90 MetS and non-MetS patients were used to estimate total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C), triglycerides (TGs), fasting blood glucose (FBG), waist circumference (WC), systolic blood pressure (SBP) and diastolic blood pressure (DBP), visfatin and peroxidases activity. Data analysis for MetS group was carried out in two ways. (1) MetS with three components and with > 3 components. (2) MetS with hyperglycemia and without hyperglycemia.
RESULTS
SBP, DBP, WC, FBG, TC, TG, LDL-C, and were higher and HDL-C levels was lower in MetS patients. There was a significant correlation between visfatin levels and peroxidases activity in MetS patients with three components. Levels of visfatin were significantly higher in male as compared to female subjects in the MetS with three components group. There was a significant decrease in peroxidases activity in > 45 years old subjects in the MetS with > 3 components group. A significant correlation was observed between serum visfatin levels and FBG in the MetS without hyperglycemia group.
CONCLUSION
Peroxidases activities in MetS patients can be related to visfatin levels. Gender influences on peroxidases activity probably and was lower in female patients with MetS. Hyperglycemia does not influence peroxidases activities and visfatin levels.
PMCID: PMC4173313  PMID: 25258638
Peroxidase; Metabolic Syndrome; Visfatin
6.  Lower levels sex hormone-binding globulin independently associated with metabolic syndrome in pre-elderly and elderly men in China 
Objective
To examine the relationship between sex hormone–binding globulin (SHBG) and the metabolic syndrome (MetS) in pre-elderly and elderly men in China.
Methods
A cross-sectional study was done among 437 men, aged 45 to 94 years old. Early morning fasting sera were assayed for total testosterone (TT), SHBG and other biochemical markers. Free testosterone (FT) was calculated.
Results
The SHBG level of the MetS group was significantly lower than those without MetS 35.70 (25.18, 47.10) nmol/L vs. 41.90 (31.80, 55.20) nmol/L; P < 0.001). As the number of MetS components increases, SHBG and TT levels became lower. SHBG correlated with age, as did TT and most of metabolic components. Body mass index (BMI), high density lipoprotein-cholesterol (HDL-C), triglyceride (TG), and TT remained independently associated with SHBG by multivariate regression analysis. In a logistic regression taking MetS as the dependent variable, SHBG (95% confidence interval (95% CI): 0.975−0.994, P = 0.018) and homeostasis model assessment for insulin resistance (HOMA-IR) (95%CI: 1.535−2.647, P < 0.001) were included in the final model.
Conclusions
Lower SHBG is independently associated with MetS among pre-elderly and elderly men. SHBG may be an independent predictor of MetS, but the mechanism of how SHBG is involved in MetS requires further studied.
doi:10.3969/j.issn.1671-5411.2013.01.006
PMCID: PMC3627720  PMID: 23610571
Sex hormone–binding globulin; Metabolic Syndrome; Testosterone; Males
7.  Association between Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and Components of Metabolic Syndrome in Young Chinese Men 
Background:
To investigate the prevalence of metabolic syndrome (MetS) in young Chinese population and assess the association between HOMA-IR and different components of MetS in young Chinese men.
Methods:
Overall 5576 young Chinese subjects (age range [19–44 yr], 3636 men) were enrolled in, who visited our Health Care Center for a related health checkup from March to December 2008. The international diabetes federation (IDF) definition for MetS was used. The SPSS statistical package, version 11.5 was used for the statistical analysis.
Results:
The prevalence of MetS was 21.81% in young men and 5.62% in young women. According to suffering from different numbers of MetS components, the male subjects were divided into four groups. Numbers of MetS components were more and HOMA-IR values were significantly higher. In this male population, the quartile of HOMA-IR was higher, values of triglyceride (TG), fasting plasma glucose (FBG), systolic blood pressure(SBP), diastolic blood pressure(DBP) and waist circumference (WC) were all significantly higher, as well as high density lipoprotein cholesterol (HDL-C) value was significantly lower (P= 0.000). In Spearman’s correlation analysis, HOMA-IR was positively correlated with TG, FBG, SBP, DBP and WC, and negatively correlated with HDL-C (r= 0.460, 0.464, 0.362, 0.346, 0.586, −0.357, respectively, all P value= 0.000).
Conclusion:
The prevalence of MetS in these young Chinese men was obviously high. Insulin resistance played an important role in occurrence and development of MetS. Waist circumference was the best correlation with HOMA-IR among all components of MetS.
PMCID: PMC3481778  PMID: 23113066
Homeostasis model assessment; Insulin resistance; Metabolic syndrome; Young men
8.  Weight change and incident metabolic syndrome in Iranian men and women; a 3 year follow-up study 
BMC Public Health  2009;9:138.
Background
Although the association of weight gain and developing metabolic syndrome (MetS) has been reported in the Western and Asian populations, data on the gender-stratified effects of weight change (including weight loss) on incident MetS and its components in the Middle East Caucasians is still scarce.
Methods
A total of 1431 men and 2036 women aged ≥ 20 years with BMI > 18.5 kg/m2 were followed over 3 years. Multivariate logistic regression analysis was used to estimate the relative risk (RR) of MetS and its components (the Adult Treatment Panel III definition) associated with gender-stratified quintiles of percent weight change. Subjects with MetS at baseline were excluded for analyzing the RR of MetS.
Results
There was 20.4% (95% CI, 19.6–21.2) age-adjusted incident MetS (18.4% male vs. 23.1% women). In men, mild weight gain (WG) predicted high waist circumference (WC) and high triglyceride; moderate WG predicted MetS (RR 2.5, 95% CI 1.4–4.3), high WC and high blood pressure (BP); large WG predicted MetS (RR 3.2, 95% CI 1.8–5.7) and its components, except for high fasting plasma glucose. In women, mild WG predicted MetS (RR 2.5, 95% CI 1.4–4.3), high WC and high BP; moderate WG predicted Mets (RR 4.6, 95% CI 2.7–8.0), high WC and high triglyceride; large WG predicted MetS (RR 6.6, 95% CI 3.8–11.3) and its components except for low HDL-cholesterol. Mild weight loss had protective effect on high WC in both genders and MetS in men (RR 0.5, 95% CI 0.26–0.97, P = 0.04).
Conclusion
Weight change showed different effects on MetS in men and women. In women, mild WG predicted MetS; however, mild weight loss was protective against MetS in men and high WC in both genders.
doi:10.1186/1471-2458-9-138
PMCID: PMC2696430  PMID: 19435528
9.  Sex based levels of C-reactive protein and white blood cell count in subjects with metabolic syndrome: Isfahan Healthy Heart Program 
Background:
C-reactive protein (CRP) and white blood cell (WBC) are proinflammatory markers. They are major pathophysiological for the development of metabolic syndrome (MetS). This study aimed to address the independent associations between MetS and WBC counts and serum CRP levels and evaluation of their magnitude in relation to the MetS, based on the sex in the Iranian adults.
Materials and Methods:
In this cross-sectional study, subjects who met the MetS criteria, based on the Adult Treatment Panel III were selected from the Isfahan Healthy Heart Program database. A questionnaire containing the demographic data, weight, height, waist, and hip circumference of the respondents was completed for each person. Blood pressure was measured and the anthropometric measurements were done, and fasting blood samples were taken for 2 h postload plasma glucose (2 hpp). Serum [total, high-density lipoprotein (HDL), and low-density lipoprotein] levels of cholesterol, triglyceride, and CRP as well as WBC counts were determined. The univariate analyses were carried out to assess the relation between the CRP levels, WBC counts with the MetS in both sexes the.
Results:
In men with the abdominal obesity, the higher levels of WBC count, high serum triglyceride and blood glucose levels, a low serum HDL level, and raised systolic and diastolic blood pressure were observed. However, the higher serum CRP levels were only observed in those with the low serum HDL-cholesterol levels. The mean values of the WBC counts were statistically different between the men with and without MetS, but the mean values of the CRP levels were similar between the two groups. In women, the mean values of WBC count and CRP levels were statistically different in the subjects with and without a MetS components (except for the low serum HDL levels and high diastolic blood pressure for the WBC measures and abdominal obesity for the CRP measures) and for those with and without MetS. The age and smoking adjusted changes in the CRP levels and WBC counts correlated with the number of Mets components in the women.
Conclusion:
The findings of this study suggest substantial implications for the prevention and management of the MetS and atherosclerotic diseases, as these involve the suppression of inflammatory conditions rather than the incitement of anti-inflammatory conditions.
PMCID: PMC3818614  PMID: 24250693
C-reactive protein level; metabolic syndrome; white blood cell count
10.  The Relationship between Metabolic Syndrome and Childhood Maternal Education Level, Job Status Findings from the Korean National Health and Nutrition Examination, 2007-2009 
Korean Journal of Family Medicine  2014;35(4):207-215.
Background
Childhood socioeconomic status (SES) is known to affect cardio-metabolic disease risk. However, the relationship between childhood SES and metabolic syndrome (MetS) remains uncertain. Therefore, we investigated the relationship between childhood SES, as measured by maternal education and occupational status and adult-onset MetS in the Korean population.
Methods
We examined the association between childhood SES, as measured by maternal education level and occupational status during an individual's childhood, and MetS in Korean adults aged 20 to 79 years who participated in the 2007-2009 Korean National Health Examination and Nutrition Survey. The components of MetS, including waist circumference, fasting glucose, lipid profiles, and blood pressure, were measured. Adjusted odds ratios (ORs) for MetS were calculated using multiple logistic regression models.
Results
Significant differences in the association between maternal education level, occupational status, and MetS were found between males and females. In females, the adjusted MetS OR for the highest maternal education quartile relative to the lowest quartile was 0.46 (0.21-0.99). Similarly, in females, the adjusted OR for individuals whose mothers worked when they were children relative to those whose mothers did not work was 1.23 (1.04-1.44). In males, no significant associations between maternal education, maternal occupational status, and MetS were found.
Conclusion
We found independent, positive associations between maternal education and occupational status and MetS in Korean females. These findings suggest that public health education targeting MetS prevention should be considered, especially among children with less opportunity for maternal support.
doi:10.4082/kjfm.2014.35.4.207
PMCID: PMC4129248  PMID: 25120892
Childhood Socioeconomic Status; Metabolic Syndrome
11.  Metabolic effects of testosterone replacement therapy on hypogonadal men with type 2 diabetes mellitus: A systematic review and meta-analysis of randomized controlled trials 
Asian Journal of Andrology  2013;16(1):146-152.
This systematic review was aimed at assessing the metabolic effects of testosterone replacement therapy (TRT) on hypogonadal men with type 2 diabetes mellitus (T2DM). A literature search was performed using the Cochrane Library, EMBASE and PubMed. Only randomized controlled trials (RCTs) were included in the meta-analysis. Two reviewers retrieved articles and evaluated the study quality using an appropriate scoring method. Outcomes including glucose metabolism, lipid parameters, body fat and blood pressure were pooled using a random effects model and tested for heterogeneity. We used the Cochrane Collaboration's Review Manager 5.2 software for statistical analysis. Five RCTs including 351 participants with a mean follow-up time of 6.5-months were identified that strictly met our eligibility criteria. A meta-analysis of the extractable data showed that testosterone reduced fasting plasma glucose levels (mean difference (MD): −1.10; 95% confidence interval (CI) (−1.88, −0.31)), fasting serum insulin levels (MD: −2.73; 95% CI (−3.62, −1.84)), HbA1c % (MD: −0.87; 95% CI (−1.32, −0.42)) and triglyceride levels (MD: −0.35; 95% CI (−0.62, −0.07)). The testosterone and control groups demonstrated no significant difference for other outcomes. In conclusion, we found that TRT can improve glycemic control and decrease triglyceride levels of hypogonadal men with T2DM. Considering the limited number of participants and the confounding factors in our systematic review; additional large, well-designed RCTs are needed to address the metabolic effects of TRT and its long-term influence on hypogonadal men with T2DM.
doi:10.4103/1008-682X.122346
PMCID: PMC3901874  PMID: 24369149
humans; hypogonadism; male; testosterone; type 2 diabetes mellitus
12.  LINE-1 methylation in visceral adipose tissue of severely obese individuals is associated with metabolic syndrome status and related phenotypes 
Clinical Epigenetics  2012;4(1):10.
Background
Epigenetic mechanisms may be involved in the regulation of genes found to be differentially expressed in the visceral adipose tissue (VAT) of severely obese subjects with (MetS+) versus without (MetS-) metabolic syndrome (MetS). Long interspersed nuclear element 1 (LINE-1) elements DNA methylation levels (%meth) in blood, a marker of global DNA methylation, have recently been associated with fasting glucose, blood lipids, heart diseases and stroke.
Aim
To test whether LINE-1%meth levels in VAT are associated with MetS phenotypes and whether they can predict MetS risk in severely obese individuals.
Methods
DNA was extracted from VAT of 34 men (MetS-: n = 14, MetS+: n = 20) and 152 premenopausal women (MetS-: n = 84; MetS+: n = 68) undergoing biliopancreatic diversion for the treatment of obesity. LINE-1%meth levels were assessed by pyrosequencing of sodium bisulfite-treated DNA.
Results
The mean LINE-1%meth in VAT was of 75.8% (SD = 3.0%). Multiple linear regression analyses revealed that LINE-1%meth was negatively associated with fasting glucose levels (β = -0.04; P = 0.03), diastolic blood pressure (β =  -0.65; P = 0.03) and MetS status (β = -0.04; P = 0.004) after adjustments for the effects of age, sex, waist circumference (except for MetS status) and smoking. While dividing subjects into quartiles based on their LINE-1%meth (Q1 to Q4: lower %meth to higher %meth levels), greater risk were observed in the first (Q1: odds ratio (OR) = 4.37, P = 0.004) and the second (Q2: OR = 4.76, P = 0.002) quartiles compared to Q4 (1.00) when adjusting for age, sex and smoking.
Conclusions
These results suggest that lower global DNA methylation, assessed by LINE-1 repetitive elements methylation analysis, would be associated with a greater risk for MetS in the presence of obesity.
doi:10.1186/1868-7083-4-10
PMCID: PMC3464682  PMID: 22748066
Blood pressure; Epigenetics; Fasting glucose; Global DNA methylation; LINE-1; Metabolic syndrome; Severe obesity; Visceral adipose tissue
13.  Testosterone Replacement in Hypogonadal Men With Type 2 Diabetes and/or Metabolic Syndrome (the TIMES2 Study) 
Diabetes Care  2011;34(4):828-837.
OBJECTIVE
This study evaluated the effects of testosterone replacement therapy (TRT) on insulin resistance, cardiovascular risk factors, and symptoms in hypogonadal men with type 2 diabetes and/or metabolic syndrome (MetS).
RESEARCH DESIGN AND METHODS
The efficacy, safety, and tolerability of a novel transdermal 2% testosterone gel was evaluated over 12 months in 220 hypogonadal men with type 2 diabetes and/or MetS in a multicenter, prospective, randomized, double-blind, placebo-controlled study. The primary outcome was mean change from baseline in homeostasis model assessment of insulin resistance (HOMA-IR). Secondary outcomes were measures of body composition, glycemic control, lipids, and sexual function. Efficacy results focused primarily on months 0−6 (phase 1; no changes in medication allowed). Medication changes were allowed in phase 2 (months 6−12).
RESULTS
TRT reduced HOMA-IR in the overall population by 15.2% at 6 months (P = 0.018) and 16.4% at 12 months (P = 0.006). In type 2 diabetic patients, glycemic control was significantly better in the TRT group than the placebo group at month 9 (HbA1c: treatment difference, −0.446%; P = 0.035). Improvements in total and LDL cholesterol, lipoprotein a (Lpa), body composition, libido, and sexual function occurred in selected patient groups. There were no significant differences between groups in the frequencies of adverse events (AEs) or serious AEs. The majority of AEs (>95%) were mild or moderate.
CONCLUSIONS
Over a 6-month period, transdermal TRT was associated with beneficial effects on insulin resistance, total and LDL-cholesterol, Lpa, and sexual health in hypogonadal men with type 2 diabetes and/or MetS.
doi:10.2337/dc10-1233
PMCID: PMC3064036  PMID: 21386088
14.  Metabolic Syndrome Derived from Principal Component Analysis and Incident Cardiovascular Events: The Multi Ethnic Study of Atherosclerosis (MESA) and Health, Aging, and Body Composition (Health ABC) 
Background. The NCEP metabolic syndrome (MetS) is a combination of dichotomized interrelated risk factors from predominantly Caucasian populations. We propose a continuous MetS score based on principal component analysis (PCA) of the same risk factors in a multiethnic cohort and compare prediction of incident CVD events with NCEP MetS definition. Additionally, we replicated these analyses in the Health, Aging, and Body composition (Health ABC) study cohort. Methods and Results. We performed PCA of the MetS elements (waist circumference, HDL, TG, fasting blood glucose, SBP, and DBP) in 2610 Caucasian Americans, 801 Chinese Americans, 1875 African Americans, and 1494 Hispanic Americans in the multiethnic study of atherosclerosis (MESA) cohort. We selected the first principal component as a continuous MetS score (MetS-PC). Cox proportional hazards models were used to examine the association between MetS-PC and 5.5 years of CVD events (n = 377) adjusting for age, gender, race, smoking and LDL-C, overall and by ethnicity. To facilitate comparison of MetS-PC with the binary NCEP definition, a MetS-PC cut point was chosen to yield the same 37% prevalence of MetS as the NCEP definition (37%) in the MESA cohort. Hazard ratio (HR) for CVD events were estimated using the NCEP and Mets-PC-derived binary definitions. In Cox proportional models, the HR (95% CI) for CVD events for 1-SD (standard deviation) of MetS-PC was 1.71 (1.54–1.90) (P < 0.0001) overall after adjusting for potential confounders, and for each ethnicity, HRs were: Caucasian, 1.64 (1.39–1.94), Chinese, 1.39 (1.06–1.83), African, 1.67 (1.37–2.02), and Hispanic, 2.10 (1.66-2.65). Finally, when binary definitions were compared, HR for CVD events was 2.34 (1.91–2.87) for MetS-PC versus 1.79 (1.46–2.20) for NCEP MetS. In the Health ABC cohort, in a fully adjusted model, MetS-PC per 1-SD (Health ABC) remained associated with CVD events (HR = 1.21, 95%CI 1.12–1.32) overall, and for each ethnicity, Caucasian (HR = 1.24, 95%CI 1.12–1.39) and African Americans (HR = 1.16, 95%CI 1.01–1.32). Finally, when using a binary definition of MetS-PC (cut point 0.505) designed to match the NCEP definition in terms of prevalence in the Health ABC cohort (35%), the fully adjusted HR for CVD events was 1.39, 95%CI 1.17–1.64 compared with 1.46, 95%CI 1.23–1.72 using the NCEP definition. Conclusion. MetS-PC is a continuous measure of metabolic syndrome and was a better predictor of CVD events overall and in individual ethnicities. Additionally, a binary MetS-PC definition was better than the NCEP MetS definition in predicting incident CVD events in the MESA cohort, but this superiority was not evident in the Health ABC cohort.
doi:10.1155/2012/919425
PMCID: PMC3318892  PMID: 22536533
15.  Prediction of metabolic syndrome in women with polycystic ovary syndrome 
Objective
To identify biochemical factors that serve as predictors for the metabolic syndrome (MetS) in patients with polycystic ovary syndrome (PCOS) and to investigate the value of adipocytokines in the prediction of metabolic syndrome.
Material and Methods
A total of 91 pre-menopausal women with PCOS diagnosed according to the Rotterdam consensus criteria were recruited as study subjects. Waist circumference, blood pressure, body mass index (BMI), fasting glucose, serum lipids, insulin, FSH, LH, E2, total testosteron, homeostatic model assessment–insulin resistance (HOMA-IR), serum leptin and adiponectin levels were evaluated for all patients.
Results
Of the 91 women with PCOS, 15 patients met the criteria for MetS. Body weight, BMI, waist circumference, systolic blood pressure, diastolic blood pressure, fasting glucose, total cholesterol, triglyceride, and VLDL concentrations were significantly higher and HDL was significantly lower in women with PCOS+MetS compared with those with PCOS only. However, the level of LDL, FSH, LH, E2 and total testesterone was not significantly different between these two groups. Women with PCOS+MetS had significantly higher levels of leptin and HOMA-IR, and significantly lower levels of adiponectin compared to the women with PCOS only. In the multiple logistic regression model, the association between HOMA-IR and leptin, and MetS remained statistically significant (p=0.001 and 0.018), while the association between adiponectin and MetS was no longer statistically significant.
Conclusion
Aside from the biochemical markers such as glucose, cholesterol and triglyceride, adipose tissue factors and insulin resistance are valuable parameters in the prediction of MetS in patients with PCOS.
doi:10.5152/jtgga.2012.24
PMCID: PMC3939237  PMID: 24592034
Metabolic syndrome; polycystic ovary syndrome; leptin; adiponectin; HOMA-IR
16.  Adiponectin in eutrophic and obese children as a biomarker to predict metabolic syndrome and each of its components 
BMC Public Health  2013;13:88.
Background
Obesity is associated with the rise of noncommunicable diseases worldwide. The pathophysiology behind this disease involves the increase of adipose tissue, being inversely related to adiponectin, but directly related to insulin resistance and metabolic syndrome (MetS). Therefore, this study aimed to determine the relationship between adiponectin levels with each component of MetS in eutrophic and obese Mexican children.
Methods
A cross sectional study was conducted in 190 school-age children classified as obese and 196 classified as eutrophic. Adiponectin, glucose, insulin, high density lipoprotein cholesterol (HDL-C) and triglycerides were determined from a fasting blood sample. Height, weight, waist circumference, systolic and diastolic blood pressures (BP) were measured; MetS was evaluated with the IDF definition. The study groups were divided according to tertiles of adiponectin, using the higher concentration as a reference. Linear regression analysis was used to assess the association between adiponectin and components of the MetS. Finally, stepwise forward multiple logistic regression analysis controlling for age, gender, basal HOMA-IR values and BMI was performed to determine the odds ratio of developing MetS according to adiponectin tertiles.
Results
Anthropometric and metabolic measurements were statistically different between eutrophic and obese children with and without MetS (P <0.001). The prevalence of MetS in obese populations was 13%. Adiponectin concentrations were 15.5 ± 6.1, 12.0 ± 4.8, 12.4 ± 4.9 and 9.4 ± 2.8 μg/mL for eutrophic and obese subjects, obese without MetS, and obese with MetS, respectively (P <0.001). Obese children with low values of adiponectin exhibited a higher frequency of MetS components: abdominal obesity, 49%; high systolic BP, 3%; high diastolic BP, 2%; impaired fasting glucose, 17%; hypertriglyceridemia, 31%; and low HDL-C values, 42%. Adjusted odds ratio of presenting MetS according to adiponectin categories was 10.9 (95% CI 2.05; 48.16) when the first tertile was compared with the third.
Conclusion
In this sample of eutrophic and obese Mexican children we found that adiponectin concentrations and MetS components have an inversely proportional relationship, which supports the idea that this hormone could be a biomarker for identifying individuals with risk of developing MetS.
doi:10.1186/1471-2458-13-88
PMCID: PMC3570482  PMID: 23363707
Obesity; Adiponectin; Child; Insulin resistance; Metabolic syndrome; Biomarker
17.  Effects of lifestyle modification on metabolic syndrome: a systematic review and meta-analysis 
BMC Medicine  2012;10:138.
Background
To evaluate the effect of lifestyle modifications on metabolic syndrome (MetS) as assessed by its resolution and improved values for its components.
Methods
This was a systematic review and meta-analysis. Searches were performed of MEDLINE and the Cochrane Database from January 1966 to October 2011 to identify randomized controlled trials (RCTs) related to the study objective. The included studies were RCTs restricted to the English language, with a follow-up period of 6 months or more, which reported overall resolution of MetS or values of MetS components (fasting blood glucose, waist circumference, high-density lipoprotein (HDL), triglycerides, and systolic and diastolic blood pressure (SBP, DBP)). Two investigators independently assessed study eligibility. The effect sizes were the relative proportion of patients with resolved MetS and mean differences in MetS component values from baseline to 1-year follow-up in a lifestyle-modification intervention (LMI) group versus a control (conventional lifestyle education or no treatment) group. Meta-analyses were conducted using a random-effects model.
Results
Eleven interventions in eight RCTs were used for the meta-analyses. The relative proportion of patients with resolved MetS in the intervention group was approximately 2.0 (95% CI 1.5 to 2.7) times greater in the intervention group compared with the control group (7 interventions, n = 2.839). LMI (5 interventions, n = 748) significantly reduced mean values for SBP by -6.4 mmHg (95% CI -9.7 to -3.2), DBP by -3.3 mmHg (95% CI -5.2 to -1.4), triglycerides by -12.0 mg/dl (95% CI -22.2 to -1.7), waist circumference by -2.7 cm (95% CI -4.6 to -0.9), and fasting blood glucose by -11.5 mg/dl (95% CI -22.4 to -0.6) (5 interventions), but reductions were not significant for HDL (1.3 mg/dl; 95% CI -0.6 to 3.1).
Conclusions
The LMI was effective in resolving MetS and reducing the severity of related abnormalities (fasting blood glucose, waist circumference, SBP and DBP, and triglycerides) in subjects with MetS.
doi:10.1186/1741-7015-10-138
PMCID: PMC3523078  PMID: 23151238
Systematic review; meta-analysis; randomized controlled trial; metabolic syndrome; lifestyle modification
18.  Hormonal Modulation in Aging Patients with Erectile Dysfunction and Metabolic Syndrome 
Erectile dysfunction (ED), metabolic syndrome (MetS), and hypogonadism are closely related, often coexisting in the aging male. Obesity was shown to raise the risk of ED and hypogonadism, as well as other endocrinological disturbances with impact on erectile function. We selected 179 patients referred for ED to our andrology unit, aiming to evaluate gonadotropins and estradiol interplay in context of ED, MetS, and hypogonadism. Patients were stratified into groups in accordance with the presence (or not) of MetS and/or hypogonadism. Noticeable differences in total testosterone (TT) and free testosterone (FT) levels were found between patients with and without MetS. Men with MetS evidenced lower TT circulating levels with an increasing number of MetS parameters, for which hypertriglyceridemia and waist circumference strongly contributed. Regarding the hypothalamic-pituitary-gonadal axis, patients with hypogonadism did not exhibit raised LH levels. Interestingly, among those with higher LH levels, estradiol values were also increased. Possible explanations for this unexpected profile of estradiol may be the age-related adiposity, other estrogen-raising pathways, or even unknown mechanisms. Estradiol is possibly a molecule with further interactions beyond the currently described. Our results further enlighten this still unclear multidisciplinary and complex subject, raising new investigational opportunities.
doi:10.1155/2013/107869
PMCID: PMC3888699  PMID: 24459467
19.  Long-term testosterone therapy in hypogonadal men ameliorates elements of the metabolic syndrome: an observational, long-term registry study 
Aim
The goal of this study was to determine if long-term testosterone (T) therapy in men with hypogonadism, henceforth referred to as testosterone deficiency (TD), ameliorates or improves metabolic syndrome (MetS) components.
Methods
We performed a cumulative registry study of 255 men, aged between 33 and 69 years (mean 58.02 ± 6.30) with subnormal plasma total T levels (mean: 9.93 ± 1.38; range: 5.89–12.13 nmol/l) as well as at least mild symptoms of TD assessed by the Aging Males' symptoms scale. All men received treatment with parenteral T undecanoate 1000 mg (Nebido®, Bayer Pharma, Berlin, Germany), administered at baseline and 6 weeks and thereafter every 12 weeks for up to 60 months. Lipids, glucose, liver enzymes and haemoglobin A1c analyses were carried out in a commercial laboratory. Anthropometric measurements were also made throughout the study period.
Results
Testosterone therapy restored physiological T levels and resulted in reductions in total cholesterol (TC) [7.29 ± 1.03 to 4.87 ± 0.29 mmol/l (281.58 ± 39.8 to 188.12 ± 11.31 mg/dl)], low-density lipoprotein cholesterol [4.24 ± 1.07 to 2.84 ± 0.92 mmol/l (163.79 ± 41.44 to 109.84 ± 35.41 mg/dl)], triglycerides [3.14 ± 0.58 to 2.16 ± 0.13 mmol/l (276.16 ± 51.32 to 189.78 ± 11.33 mg/dl)] and increased high-density lipoprotein levels [1.45 ± 0.46 to 1.52 ± 0.45 mmol/l (56.17 ± 17.79 to 58.85 ± 17.51 mg/dl)] (p < 0.0001 for all). There were marked reductions in systolic and diastolic blood pressure, blood glucose, haemoglobin A1c, C-reactive protein (6.29 ± 7.96 to 1.03 ± 1.87 U/l), alanine aminotransferase and aspartate aminotransferase (p < 0.0001 for all).
Conclusions
Long-term T therapy, at physiological levels, ameliorates MetS components. These findings strongly suggest that T therapy in hypogonadal men may prove useful in reducing the risk of cardiometabolic diseases.
doi:10.1111/ijcp.12319
PMCID: PMC4282282  PMID: 24127736
20.  White Blood Cell Counts as Risk Markers of Developing Metabolic Syndrome and Its Components in the Predimed Study 
PLoS ONE  2013;8(3):e58354.
Background
The Metabolic Syndrome (MetS) is a cluster of metabolic abnormalities that includes hyperglucemia, hypertension, dyslipidemia and central obesity, conferring an increased risk of cardiovascular disease. The white blood cell (WBC) count has been proposed as a marker for predicting cardiovascular risk. However, few prospective studies have evaluated the relationship between WBC subtypes and risk of MetS.
Methods
Participants were recruited from seven PREDIMED study centers. Both a baseline cross-sectional (n = 4,377) and a prospective assessment (n = 1,637) were performed. Participants with MetS at baseline were excluded from the longitudinal analysis. The median follow-up was 3.9 years. Anthropometric measurements, blood pressure, fasting glucose, lipid profile and WBC counts were assessed at baseline and yearly during the follow-up. Participants were categorized by baseline WBC and its subtype count quartiles. Adjusted logistic regression models were fitted to assess the risk of MetS and its components.
Results
Of the 4,377 participants, 62.6% had MetS at baseline. Compared to the participants in the lowest baseline sex-adjusted quartile of WBC counts, those in the upper quartile showed an increased risk of having MetS (OR, 2.47; 95%CI, 2.03–2.99; P-trend<0.001). This association was also observed for all WBC subtypes, except for basophils. Compared to participants in the lowest quartile, those in the top quartile of leukocyte, neutrophil and lymphocyte count had an increased risk of MetS incidence. Leukocyte and neutrophil count were found to be strongly associated with the MetS components hypertriglyceridemia and low HDL-cholesterol. Likewise, lymphocyte counts were found to be associated with the incidence of the MetS components low HDL-cholesterol and high fasting glucose. An increase in the total WBC during the follow-up was also associated with an increased risk of MetS.
Conclusions
Total WBC counts, and some subtypes, were positively associated with MetS as well as hypertriglyceridemia, low HDL-cholesterol and high fasting glucose, all components of MetS.
Trial registration
Controlled-Trials.comISRCTN35739639.
doi:10.1371/journal.pone.0058354
PMCID: PMC3602299  PMID: 23526980
21.  Serum uric acid level and its association with metabolic syndrome and carotid atherosclerosis in patients with type 2 diabetes 
Objective
We aimed to investigate whether elevated serum uric acid concentrations are associated with higher risk of metabolic syndrome (MetS) and carotid atherosclerosis in patients with type 2 diabetes.
Methods
We conducted a population-based cross-sectional survey in Shanghai, with a total of 395 men and 631 women age 41 to 92 years. The carotid artery intima-media thickness (IMT) and carotid atherosclerotic plaques (PLQ) were measured by B-mode ultrasound. MetS was defined according to the updated National Cholesterol Education Program Adult Treatment Panel III criteria for Asian Americans.
Results
Uric acid levels were negatively associated with duration of diabetes, fasting plasma glucose, glycohemoglobin, eGFR, HDL-cholesterol (all P < 0.001) and positively with BMI, CRP, waist circumference, triglycerides, systolic blood pressure, ACR, HOMA-IR and IMT (all P < 0.05). In the highest quartile of uric acid levels, the risks were substantially higher for MetS [odds ratio 3.97, (95% confidence interval 2.58-6.13)] (P < 0.001 for trend) and PLQ [odds ratio 2.71 (95% confidence interval 1.62-4.47)] (p = 0.013 for trend) compared with that in the lowest quartile of uric acid levels after multiple adjustment. These associations remained significant after further adjustment for potential confounders.
Conclusions
Serum uric acid level is associated with MetS and is an independent risk factor for carotid atherosclerosis in patients with type 2 diabetes.
doi:10.1186/1475-2840-10-72
PMCID: PMC3163178  PMID: 21816063
uric acid; metabolic syndrome; intima-media thickness; atherosclerosis
22.  Supplementary use of HbA1c as hyperglycemic criterion to detect metabolic syndrome 
Background
Metabolic syndrome (MetS) refers to a cluster of cardiovascular risk factors including hyperglycemia, dyslipidemia, abdominal obesity and hypertension. An effective detection of MetS not only reflects the prediction risk of diabetes mellitus and cardiovascular diseases but also helps to plan for management strategy which could reduce the healthcare burden of the society. This study aimed to compare the use of hemoglobin A1c (HbA1c) to fasting plasma glucose (FPG) as the hyperglycemic component in MetS diagnosis.
Methods
Waist circumference, blood pressure, blood triglyceride, high-density lipoprotein (HDL)-cholesterol, FPG, and HbA1c were examined in 120 Hong Kong Chinese adults with MetS and 120 without MetS. After reviewing the subject basal characteristics, 11 of them were found with undiagnosed diabetes (FPG ≧7.0 mmol/L) and were excluded for further analysis.
Results
The most prevalent MetS components among the included subjects were elevated systolic blood pressure and central obesity. Significant correlation relationships existed between FPG and HbA1c in both subject pools diagnosed with and without MetS (p < 0.001). The diagnostic rate of MetS using HbA1c was compared to FPG by the receiver operating characteristics (ROC) analysis which suggested an area under curve of 0.807 (95% CI: 0.727 to 0.887). The agreement was 90.7% in MetS-positive group with increased FPG as one of the criterion co-existed with elevated HbA1c. If including HbA1c as an additional criterion to FPG in the MetS diagnosis, 30 more participants in MetS-negative group would be MetS-positive leading to an increase in detection rate. Furthermore, 47 subjects (38 from MetS-positive group and 9 from MetS-negative group) were found having HbA1c ≧6.5%, who would have been diagnosed with diabetes based on the diagnostic criteria implemented by the Expert Group in 2009.
Conclusion
These findings suggest that HbA1c enhances the detection of hyperglycemia for the diagnosis of MetS.
doi:10.1186/1758-5996-6-119
PMCID: PMC4232661  PMID: 25400701
23.  Testosterone and metabolic syndrome: The link 
Metabolic syndrome (MetS) or “Syndrome X” which is a constellation of insulin resistance, hyperglycemia, hypertension, low high-density lipoprotein cholesterol (HDL-C), and increased very-low-density lipoprotein (VLDL) and triglyceride (TG) levels. It is one of the main threats for public health in the 21st century with its associated risk of cardiovascular disease. This condition affects a major chunk of mankind. International Diabetes Federation (IDF) estimated that around 20-25% of the adult population of the world has MetS. Several definitions have been put forward by different expert bodies leading to confusion. To overcome this, joint new statement of many expert group have been issued. Serum testosterone (T) has been shown to be associated with MetS. Several studies have shown a higher prevalence of MetS in subjects with low testosterone. There are also several studies showing a significant difference in serum T between those with MetS and those without. Serum T has also been shown to be associated with components of MetS and testosterone replacement therapy (TRT) improves various metabolic and anthropometric parameters in MetS. Patients with androgen deprivation for treatment of various cancers have also been reported to have higher prevalence of MetS. But the evidence of association is not sufficient evidence for the causation of MetS by low testosterone and long-term studies are needed to confirm whether T deficiency is the cause or is a feature of MetS.
doi:10.4103/2230-8210.94248
PMCID: PMC3354945  PMID: 22701831
Androgen deprivation; insulin resistance; metabolic syndrome; testosterone; testosterone replacement therapy
24.  Age- and Gender Dependent Association between Components of Metabolic Syndrome and Subclinical Arterial Stiffness in a Chinese Population 
Background: The aim of this study was to estimate the relationship between arterial stiffness and components of metabolic syndrome (MetS) in different age- and gender groups.
Methods: A total of 12,900 Chinese adults aged 20-79 years were recruited and stratified on the basis of gender and age. All participants underwent the measurement of waist circumference, blood pressure (BP), brachial-ankle pulse wave velocity (baPWV; an indicator of arterial stiffness), and blood chemistry. Multiple linear regression analysis was performed to evaluate the relationship between baPWV and above variables, to determine the relative influence of each component of MetS on baPWV.
Results: The prevalence of metabolic disorders except for low high-density lipoprotein cholesterol (HDL-C) was much higher in men than in women. All participants with MetS or any component of MetS except for low HDL-C had higher baPWV. BP was positively correlated with baPWV in all groups, while HDL-C was not correlated with baPWV in any groups. In addition, fasting glucose was related to baPWV in middle-aged adults and the elderly. Waist circumference had a positive association with baPWV in middle-aged adults and young men, triglyceride levels showed a significant correlation with baPWV in middle-aged women and young men. Of the MetS components, elevated BP was the strongest predictor of baPWV.
Conclusion: The prevalence of metabolic disorders and the association between baPWV and metabolic variables are dependent on age and gender. Different components of MetS exert distinct impacts on the baPWV in different age- and gender groups, with BP being the strongest predictor. It is suggested that age and gender should be taken into accounted in the management of MetS aiming to reduce subsequent complications.
doi:10.7150/ijms.4752
PMCID: PMC3477683  PMID: 23091411
Gender difference; Metabolic syndrome; Brachial-ankle pulse wave velocity; Subclinical arterial stiffness.
25.  Associations of Amylin with Inflammatory Markers and Metabolic Syndrome in Apparently Healthy Chinese 
PLoS ONE  2011;6(9):e24815.
Background
Cellular and animal studies implicate multiple roles of amylin in regulating insulin action, glucose and lipid metabolisms. However, the role of amylin in obesity related metabolic disorders has not been thoroughly investigated in humans. Therefore, we aimed to evaluate the distribution of circulating amylin and its association with metabolic syndrome (MetS) and explore if this association is influenced by obesity, inflammatory markers or insulin resistance in apparently healthy Chinese.
Methods
A population-based sample of 1,011 Chinese men and women aged 35–54 years was employed to measure plasma amylin, inflammatory markers (C-reactive protein [CRP] and interleukin-6 [IL-6]), insulin, glucose and lipid profiles. MetS was defined according to the updated National Cholesterol Education Program Adult Treatment Panel III criteria for Asian-Americans.
Results
Plasma amylin concentrations were higher in overweight/obese participants than normal-weight counterparts (P<0.001) without sex difference. Circulating amylin was positively associated with CRP, IL-6, BMI, waist circumference, blood pressure, fasting glucose, insulin, amylin/insulin ratio, HOMA-IR, LDL cholesterol and triglycerides, while negatively associated with HDL cholesterol (all P<0.001). After multiple adjustments, the risk of MetS was significantly higher (odds ratio 3.71; 95% confidence interval: 2.53 to 5.46) comparing the highest with the lowest amylin quartile. The association remained significant even further controlling for BMI, inflammatory markers, insulin or HOMA-IR.
Conclusions
Our study suggests that amylin is strongly associated with inflammatory markers and MetS. The amylin-MetS association is independent of established risk factors of MetS, including obesity, inflammatory markers and insulin resistance. The causal role of hyperamylinemia in the development of MetS needs to be confirmed prospectively.
doi:10.1371/journal.pone.0024815
PMCID: PMC3174205  PMID: 21935471

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