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1.  Metabolic Syndrome with Hyperglycemia and the Risk of Ischemic Stroke 
Yonsei Medical Journal  2013;54(2):283-287.
The association of ischemic stroke and metabolic syndrome (MetSyn) with or without diabetes mellitus (DM) is not clear. The present study aimed to identify the impact of diabetes or hyperglycemia on the risk of MetSyn-associated ischemic stroke.
Materials and Methods
This study comprised an Asian population of 576 patients with acute nonembolic cerebral infarction and 500 controls. MetSyn was defined according to the criteria of the International Diabetes Federation. MetSyn patients were further subgrouped according to their glucose levels: MetSyn with DM, MetSyn with impaired fasting glucose (IFG) and MetSyn with normal glucose tolerance (NGT). The impact of MetSyn on cerebral infarction was then evaluated.
At baseline, the prevalence of MetSyn in patients with cerebral infarction was higher than that of the controls (57.29% vs. 10.00%, p<0.01). In the stroke group, the prevalences of MetSyn with DM, IFG, and NGT were 25.69%, 8.85% and 22.74%, respectively, all of which were higher than that of the controls (all p-values <0.05). By multiple logistic regression analysis, we discovered that MetSyn was associated with an increased risk of cerebral infarction (odds ratio: 5.73, p<0.01). After adjustment for all the components of MetSyn, the odds ratios of MetSyn with DM, IFG, and NGT were 5.70, 2.24 and 2.19 (all p-values <0.05), respectively.
In Asian population, patients with MetSyn accompanied by T2DM are at the greatest risk for acute non-embolic stroke. Additionally, IFG was not observed to be associated with an increased risk for MetSyn-related ischemic stroke.
PMCID: PMC3575989  PMID: 23364957
Metabolic syndrome; cerebral infarction; hyperglycemia; diabetes
2.  Weight Loss and Low-Intensity Exercise for the Treatment of Metabolic Syndrome in Obese Postmenopausal Women 
The prevalence of the metabolic syndrome (MetSyn) approaches 50% in postmenopausal women. This study examines the efficacy of lifestyle modification for the treatment of MetSyn and its associated risk for cardiovascular disease and diabetes in this population.
This prospective controlled study examines the effects of a 6-month weight loss and low-intensity exercise program (WL+LEX) on body composition (dual-energy X-ray absorptiometry and abdominal computed tomography scans), fasting glucose and lipid levels, cytokines, and blood pressure in postmenopausal women with and without MetSyn.
WL+LEX reduced body weight (MetSyn: −5% vs non-MetSyn: −7%) and fat mass (−11% vs −15%) and increased VO2max (+2% vs +3%) in both MetSyn (N = 35) and non-MetSyn (N = 41) groups. Constituents of MetSyn decreased comparably in both groups. Fifteen (45%) MetSyn participants responded (R) by converting to non-MetSyn, 18 remained MetSyn (NR), and 2 had missing data. Reduction in fat mass (−15% vs −8%, p = .02) was greater in R than NR, but there were no between-group differences in changes in VO2max, cytokines, or other variables. The decrease in the number of MetSyn criteria was greater in R than in NR (−27 vs −13, p < .0001) due to decreases in blood pressure (p < .01), glucose (p = .02), and with a trend for triglyceride (p = .07). Reductions in fat mass best predicted resolution of MetSyn (p = .04).
Women who lose more fat are more likely to lower blood pressure, glucose, and triglyceride levels to resolve MetSyn. Thus, a WL+LEX program effectively treats postmenopausal women with MetSyn.
PMCID: PMC3156630  PMID: 21653990
Exercise; Dieting; Metabolic syndrome; Inflammation
3.  Association of vitamin D and vitamin D receptor gene polymorphisms with chronic inflammation, insulin resistance and metabolic syndrome components in type 2 diabetic Egyptian patients 
Meta Gene  2014;2:540-556.
To date the published data concerning the possible interplay between vitamin D (VitD) and Vit D receptor (VDR) gene polymorphism with the immune/inflammatory mediators in type 2 diabetes mellitus (DM) is insufficient. Some of the immune non-classical actions of vitamin D may point to its role in the pathogenesis of type 2 DM through down-regulation of cytokines (IL-6). Although there is evidence to support a relationship among vitamin D status, chronic inflammation and insulin resistance, the underlying mechanism requires further exploration. We aimed to investigate the role of vitamin D in chronic inflammation and insulin resistance in type 2 DM. Moreover, to examine the association of VDR gene polymorphisms [VDR 2228570 C > T (FokI); VDR 1544410 A > G (BsmI)] with the components of metabolic syndrome (MetSyn) in type 2 diabetic Egyptian patients .
Subjects and methods
A total of 190 subjects were enrolled in this study, 60 controls and 130 type 2 diabetic patients (Group II). Group II was subdivided into 63 patients without MetSyn (subgroup IIa) and 67 patients with MetSyn (subgroup IIb). Genetic analysis for VDR gene polymorphisms was done in all subjects. VitD and IL-6 plasma levels were estimated.
The TT genotype for the VDR FokI was significantly more frequent in subgroup IIb than in subgroup IIa and controls (X2 = 6.83, P = 0.03 and X2 = 16.592, P = 0.000) respectively. The T allele was more frequent in the MetSyn group as compared to diabetics without MetSyn (p = 0.001), odds ratio (OR) and 95% CI for the T allele of C > T (FokI) = 2.30 (1.37–3.86). We did not detect any significant difference in VDR BsmI genotypes between patients and control groups (P = 0.947). FokI VDR was significantly associated with the lipid profile parameters, VitD and IL-6 plasma levels in subgroup IIa and associated with HOMA-IR, insulin, VitD, IL-6 levels, waist circumference (WC) and body mass index (BMI) in subgroup IIb while BsmI VDR variant was associated only with VitD values in both subgroups.
The present study suggests an interaction between VDR polymorphisms and important components of MetSyn, VitD and pro-inflammatory cytokines (IL-6). FokI VDR polymorphisms may be linked to mild inflammation and insulin resistance and might represent a genetic determinant for developing MetSyn in type 2 diabetic Egyptian patients. The challenge is determining the mechanisms of VitD action for recommendation of VitD supplementation that reduces the risks of MetSyn, insulin resistance and progression to type 2 diabetes.
PMCID: PMC4287888  PMID: 25606437
VitD, Vitamin D; DM, diabetes mellitus; VDR, Vit D receptor; MetSyn, metabolic syndrome; HOMA, Homeostasis of Metabolic Assessment; WC, waist circumference; OR, odds ratio; BMI, body mass index; IL-6, interleukin -6; SOCS, suppressors of cytokine signaling; IRS, insulin receptor substrates; CRP, C-reactive protein; FBG, fasting blood glucose; SBP, systolic blood pressure; DBP, diastolic blood pressure; HbA1c, glycated hemoglobin; FPI, fasting plasma insulin; TC, total cholesterol; TG, triglyceride; HDL-C, high density lipoprotein cholesterol; LDL-C, low density lipoprotein cholesterol; HPLC, High performance liquid chromatography; SD, standard deviation; X2, Chi-square; CI, confidence intervals; PGs, pro-inflammatory prostaglandins; NHANES III, National Health and Examination Survey; PTH, parathyroid hormone; Insulin resistance; Type 2 diabetes mellitus (DM); Metabolic syndrome; Vitamin D; Vitamin D Receptor gene; Polymorphisms; Pro-inflammatory cytokines; Interleukin-6 (IL-6)
4.  Low HDL-Cholesterol with Normal Triglyceride Levels is the Most Common Lipid Pattern in West Africans and African Americans with Metabolic Syndrome: Implications for Cardiovascular Disease Prevention 
CVD prevention and control  2010;5(3):75-80.
Although designed to predict cardiovascular disease and type 2 diabetes mellitus, the Metabolic Syndrome (MetSyn) under-predicts these conditions in African-Americans (AA). Failure of MetSyn in AA is often attributed to their relative absence of hypertriglyceridemia. It is unknown if the African experience with MetSyn will be similar or different to that in AA. Focusing on the lipid profile, our goal was to determine in West Africans (WA) and AA the pattern of variables that leads to the diagnosis of the MetSyn.
Cross-sectional analysis of 1296 subjects (364 WA, 44% male, 932 AA, 46% male). WA were from urban centers in Nigeria and Ghana and enrolled in the Africa America Diabetes Mellitus Study. AA lived in Washington, DC and participated in the Howard University Family Study.
The prevalence of MetSyn was different in WA women and men: 42% vs.19%, P<0.001, and in AA women and men: 25% vs.17%, P<0.01. The three variables that most often led to the diagnosis of MetSyn in WA and AA were: low HDL-C, central obesity and hypertension. Less than 40% of AA and less than 25% of WA with the MetSyn had hypertriglyceridemia.
Elevated triglyceride levels were uncommon in both WA and AA with MetSyn. As the relative absence of hypertriglyceridemia is associated with a lack of efficacy of MetSyn in AA, caution is warranted in diagnosing MetSyn in WA, the ancestral population of AA. Prospective studies are necessary to determine if an ethnic-specific reformulation of the MetSyn scoring system for lipids might optimize risk identification in black populations.
PMCID: PMC2989612  PMID: 21113431
5.  Metabolic Syndrome: Do clinical criteria identify similar individuals among overweight premenopausal women? 
The purpose of this analysis was to determine to what extent the clinical criteria for metabolic syndrome (MetSyn) proposed by the World Health Organization (WHO), the European Group for Study of Insulin Resistance (EGIR), the National Cholesterol Education Program Adult Treatment Panel III (ATP III), the International Diabetes Foundation (IDF), triglyceride/HDL-cholesterol (TG/HDL-C) ratio ≥ 3.0, and enlarged waist circumference (≥ 88 cm) and elevated TG (≥ 129 mg/dL) (EWET) identified similar or different overweight women. Secondarily, to examine the effect of 7% weight reduction on MetSyn status. MetSyn was determined among 256 pre-menopausal women (age = 41±6 yrs, BMI = 32±4 kg/m²) participating in a dietary weight loss clinical trial based on the clinical criteria proposed by WHO, EGIR, ATP III, and IDF. The prevalence of TG/HDL-C ratio ≥ 3.0 and EWET were determined and compared to MetSyn status. Based on the clinical criteria, 16.1% (EGIR), 20.7% (WHO), 31.0% (ATP III), and 31.8% (IDF) of participants met the criteria for MetSyn; 30.3% and 31.8% had TG/HDL-C ≥ 3.0 and EWET, respectively. Between 77% – 99% of participants were similarly classified across the clinical criteria. The highest and lowest agreements were between ATP III and IDF (kappa = 0.98; 95% CI 0.96 – 1.0) and WHO and IDF (kappa = 0.39; 95% CI 0.26 – 0.51), respectively. TG/HDL-C ratio ≥ 3.0 and EWET moderately agreed with all four clinical criteria for MetSyn (kappa range 0.36 – 0.59). Among those diagnosed with MetSyn at baseline, 64.0% – 75.0% of the participants who lost ≥ 7% and 25.8% – 55.6% of participants who lost < 7% of their baseline body weight in six months no longer met the various clinical criteria for MetSyn, TG/HDL-C ≥ 3.0, or EWET. Our findings indicate that MetSyn varies substantially between clinical criteria, which raise questions about the clinical utility of these criteria. Regardless of MetSyn clinical criteria, ≥ 7% reduction in body weigh has a beneficial impact on variables used to define MetSyn.
PMCID: PMC2254306  PMID: 18078858
6.  Lipoprotein Particles, Insulin, Adiponectin, C-Reactive Protein and Risk of Coronary Heart Disease among Men with Metabolic Syndrome 
Atherosclerosis  2006;195(1):122-128.
We tested the hypotheses whether nuclear magnetic resonance (NMR) determined lipoprotein particles, insulin and adiponectin, and C-reactive protein (CRP) and white blood cell (WBC) count as markers of inflammation predicted risk of coronary heart disease (CHD) death among 428 men age 35–57 years with metabolic syndrome (MetSyn) in a matched case control study within the Multiple Risk Factor Intervention Trial.
Blood samples collected at entry into the study and stored at −60° C were obtained from central storage for blood analyte analysis. 214 men with MetSyn who died of CHD were matched with 214 men with MetSyn who did not die of CHD during 18 years of follow-up. Cases were matched to controls on age, study group, number of factors present in the MetSyn, and presence or absence of a non-fatal CVD event during the trial. Mortality follow up was determined using the National Death Index.
Higher levels of high density lipoprotein particles (HDL-P), especially medium-sized HDL-P, [hazard ratio (95% confidence interval) 0.45 (0.25–0.83, p<0.01), quartile 1 as compared to quartile 4], were associated with lower risk of CHD death. Low density lipoprotein (LDL) particles were not associated with increased risk of CHD. Elevated LDL cholesterol (LDL-C), smoking and WBC count were, but levels of adiponectin, insulin and CRP were not significantly related to CHD death. In multivariate models adjusting for smoking and LDL-C, medium HDL-P and WBC count remained independent predictors of CHD death.
Number of HDL particles, especially medium-sized HDL particles and WBC count were independent predictors of CHD death among men with MetSyn.
PMCID: PMC2098784  PMID: 17011566
Lipoproteins; metabolic syndrome; coronary heart disease; white blood cell count; C-reactive protein
7.  Variations in Prevalent Cardiovascular Disease and Future Risk by Metabolic Syndrome Classification in the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study 
American heart journal  2010;159(3):385-391.
The International Diabetes Federation (IDF) and Adult Treatment Panel (ATP) III define metabolic syndrome (MetSyn) differently, with unclear implications for cardiovascular disease (CVD) risk.
We examined 22,719 participants in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. We classified participants as: no MetSyn, MetSyn by ATP-III and IDF criteria, MetSyn by ATP-only, or MetSyn by IDF-only. To assess current CVD, we determined the odds of self-reported CVD by MetSyn category using multivariable logistic regression, controlling for socio-demographic and behavioral factors. To estimate future coronary heart disease (CHD) risk, we calculated Framingham risk scores (FRS).
Overall, 10,785 individuals (47%) had MetSyn. Of these, 79% had MetSyn by both definitions, 6% by ATP-only, and 14% by IDF-only. Compared to those without MetSyn, ATP-only individuals had the highest odds of current CVD and of having a FRS >20%. Also compared to those without MetSyn, IDF-only individuals had 43% higher odds of current CVD and two-fold increased odds of having a FRS >20%.
Consistent with previous reports, ATP-III MetSyn criteria identified individuals with increased odds of CVD and elevated future CHD risk. However, the IDF definition identified a clinically important number of additional individuals at excess CVD risk.
PMCID: PMC2841510  PMID: 20211299
8.  A healthy dietary pattern consisting of a variety of food choices is inversely associated with the development of metabolic syndrome 
Nutrition Research and Practice  2013;7(3):233-241.
There are limited data on healthy dietary patterns protective against metabolic syndrome (MetSyn) development. We identified dietary patterns among middle-aged and older adults and investigated the associations with the incidence of MetSyn. A population-based prospective cohort study included 5,251 male and female Koreans aged 40-69 years. At baseline, all individuals were free of MetSyn, other major metabolic diseases, and known cardiovascular disease or cancer. Cases of MetSyn were ascertained over a 6-year of follow-up. Dietary patterns and their factor scores were generated by factor analysis using the data of a food frequency questionnaire. We performed pooled logistic regression analysis to estimate multivariable-adjusted relative risk (RR) and 95% confidence interval (CI) for associations between factor scores and MetSyn risk. Two dietary patterns were identified; (1) a healthy dietary pattern, which included a variety of foods such as fish, seafood, vegetables, seaweed, protein foods, fruits, dairy products, and grains; and (2) an unhealthy dietary pattern, which included a limited number of food items. After controlling for confounding factors, factor scores for the healthy dietary pattern were inversely associated with MetSyn risk (P-value for trend < 0.05) while those for the unhealthy dietary pattern had no association. Individuals in the top quintile of the healthy diet scores showed a multivariable-adjusted RR [95% CI] of 0.76 [0.60-0.97] for MetSyn risk compared with those in the bottom quintile. The beneficial effects were derived from inverse associations with abdominal obesity, low HDL-cholesterol levels, and high fasting glucose levels. Our findings suggest that a variety of healthy food choices is recommended to prevent MetSyn.
PMCID: PMC3679333  PMID: 23766885
Dietary pattern; food choices; metabolic syndrome incidence; prospective study
9.  Metabolic syndrome and risk of venous thromboembolism: Longitudinal Investigation of Thromboembolism Etiology (LITE) 
In a recent case-control study, the odds of metabolic syndrome (MetSyn) among deep vein thrombosis cases was almost twice the odds as among controls. We tested the hypothesis that the incidence of non-cancer-related venous thromboembolism (VTE) is higher among adults with MetSyn and further, that associations are stronger for idiopathic than secondary VTE.
20,374 middle-aged and elderly adults were followed for over 12 years for incident VTE in the Longitudinal Study of Thromboembolism Etiology (LITE). All hospitalizations were identified and VTEs validated by chart review. Baseline MetSyn was defined usingATP III guidelines including ≥3 of abdominal obesity, elevated blood pressure, low HDL-cholesterol, high triglycerides, and high glucose. Because sex modified the relation between MetSyn and VTE (pinteraction=0.001), proportional hazards regression analyses were stratified by sex to assess the associations of MetSyn and its components with risk of incident non-cancer related VTE, adjusting for potential confounders.
Incident VTE (n=358) included 196 idiopathic events. Baseline MetSyn was associated with risk of total VTE (Hazard Ratio (HR) 1.84; 95%CI 1.30, 2.59) and idiopathic VTE (HR 1.59, 95% CI 1.02, 2.47) among men, but not women. The association was largely attributable to abdominal obesity (HR of VTE = 2.10, 95% CI 1.51, 2.93 in men and 1.70, 95% CI 1.24, 2.34 in women), with no additional contribution by the other MetSyn components.
Although abdominal obesity was associated with increased risk of VTE in both men and women, MetSyn and its other components do not seem important in VTE etiology.
PMCID: PMC2810102  PMID: 19175496
Arterial Stiffness, an intermediate pre-clinical marker of atherosclerosis, has been associated with an increased risk of stroke and cardiovascular disease (CVD). The metabolic syndrome and its components are established CVD risk factors and may also increase arterial stiffness, but data on this potential relationship is limited. The goal of this study was to determine the association between the metabolic syndrome (MetSyn) and carotid artery stiffness (STIFF) in an elderly multi-ethnic cohort.
STIFF was assessed by carotid ultrasound as part of the Northern Manhattan Study (NOMAS), a prospective population-based cohort of stroke-free individuals. STIFF was calculated as [ln(systolicBP/diastolicBP)/Strain], where Strain was [(Systolic Diameter Diastolic Diameter)/Diastolic Diameter]. MetSyn was defined by the National Cholesterol Education Program: Adult Treatment Panel III (NCEP ATP III) criteria. LogSTIFF was analyzed as the dependent variable in linear regression models, adjusting for demographics, education, current smoking, presence of carotid plaque and intima-media thickness.
STIFF was analyzed in 1133 NOMAS subjects (mean age 65±9 years; 61% women; 58% Hispanic, 22% Black, 20% White). The prevalence of MetSyn was 49%. The mean LogSTIFF was 2.01±0.61 among those with and 1.90±0.59 among those without MetSyn (p=0.003). MetSyn was significantly associated with increased logSTIFF in the final adjusted model (parameter estimate β=0.100, p=0.01). Among individual MetSyn components, waist circumference and elevated blood pressure were most significantly associated with a mean increase in logSTIFF (p<0.01).
MetSyn is significantly associated with increased carotid artery stiffness in a multiethnic population. Increased carotid artery stiffness may, in part, explain a high risk of stroke among individuals with the metabolic syndrome.
PMCID: PMC2980500  PMID: 20536608
metabolic syndrome; arterial stiffness; atherosclerosis; elderly; race-ethnicity
11.  Dramatic escalation in metabolic syndrome and cardiovascular risk in a Chinese population experiencing rapid economic development 
BMC Public Health  2014;14:983.
Metabolic syndrome (MetSyn) increases the incidence of cardiovascular disease. Information on changes in prevalence of MetSyn in developing countries is limited. This study aims to compare MetSyn prevalence and its associated vascular risk over the period between 2002 and 2010 in a population which has had the world’s fastest economic development over the past three decades.
Two health surveys were conducted by using the multistage cluster random sampling method in a Chinese population of 85 million in southern China. The participants received a full medical check-up, including measurement of blood pressure (BP), obesity indices, fasting lipids and glucose levels. Data describing socio-economic status and lifestyle factors were also collected through interview. Metabolic syndrome was defined in accordance with the International Diabetes Federation criteria.
A total of 3,561 participants from Survey 2010 were included in the data analysis. Women had a significantly higher prevalence of MetSyn than men. Comparison between the two surveys shows that age-standardized prevalence of MetSyn increased fourfold (from 5.4% in 2002 to 21.3% in 2010) in those ≧ 20 years. Among the MetSyn components, prevalence of hyperglycaemia has increased most (from 9.1% to 53.1%). The age-standardized prevalence of central obesity, hypertension, hypertriglyceridaemia and low HDL-cholesterol increased from 13.5% to 25.4%, from 23.6% to 40.8%, from 12.1% to 17.4% and from 32.1% to 71.1%, respectively. Differences between rural and urban residents in the prevalence in MetSyn and its components narrowed in 2010.
Cardiovascular risk escalated dramatically in this population between 2002 and 2010. The escalation may relate to the rapid economic development, which led to accelerating changes in nutrition, lifestyle, and socio-economic status. Our findings suggest that health transition in rapidly developing second- and third-world countries may be much faster than what has been observed in Western countries.
PMCID: PMC4247017  PMID: 25240739
Metabolic syndrome; Cardiovascular risk; Trend; Economic development; Chinese
12.  Association of Cigarette Smoking and Metabolic Syndrome in a Puerto Rican Adult Population 
Metabolic syndrome (MetSyn) is related to an increased risk for type 2 diabetes and cardiovascular disease. Smokers are at greater risk than nonsmokers of becoming insulin resistant and to develop cardiovascular disease. This study aimed to explore the association between cigarette smoking, MetSyn and its components among Puerto Rican adults.
A representative sample of 856 persons aged 21–79 years from the San Juan Metropolitan area participated in this study. Demographic and lifestyle characteristics, including smoking habits, were gathered from a self-reported questionnaire. MetSyn was defined according to the revised NCEP-ATP III criteria and measured using biochemical measurements and anthropometric indices. Logistic regression models were used to estimate prevalence odds ratios (POR) and its 95% confidence intervals (CI).
MetSyn was significantly (p<0.001) more prevalent in former smokers (48.4%) as compared to current (42.7%) and never smokers (40.0%). However, after adjusting for possible confounders, current smokers who used more than 20 cigarettes per day were 2.24 (95% CI= 1.00–4.99) times more likely to have MetSyn as compared to never smokers. Heavy smokers were also more likely to have high triglyceride levels (POR=2.22, 95% CI=1.12–4.38) and low HDL-cholesterol levels (POR=2.49, 95% CI= 1.28–4.86) as compared to never smokers.
This study supports previous reports of an increased risk of MetSyn among current smokers, particularly those with a heavier consumption. Tobacco control strategies, such as preventing smoking initiation and disseminating evidence-based cessation programs, are necessary to reduce the burden of MetSyn in Puerto Rico.
PMCID: PMC3502663  PMID: 22729380
Metabolic syndrome; Smoking; Puerto Rico; Hispanics
13.  Association of Cigarette Smoking and Metabolic Syndrome in a Puerto Rican Adult Population 
Metabolic syndrome (MetSyn) is related to an increased risk for type 2 diabetes and cardiovascular disease. Smokers are at greater risk than nonsmokers of becoming insulin resistant and to develop cardiovascular disease. This study aimed to explore the association between cigarette smoking, MetSyn, and its components among Puerto Rican adults.
A representative sample of 856 persons aged 21–79 years from the San Juan Metropolitan area participated in this study. Demographic and lifestyle characteristics, including smoking habits, were gathered from a self-reported questionnaire. MetSyn was defined according to the revised NCEP-ATP III criteria and measured using biochemical measurements and anthropometric indices. Logistic regression models were used to estimate prevalence odds ratios (POR) and its 95% confidence intervals (CI).
MetSyn was significantly (P < 0.001) more prevalent in former smokers (48.4%) as compared to current (42.7%) and never smokers (40.0%). However, after adjusting for possible confounders, current smokers who used more than 20 cigarettes per day were 2.24 (95% CI = 1.00–4.99) times more likely to have MetSyn as compared to never smokers. Heavy smokers were also more likely to have high triglyceride levels (POR = 2.22, 95% CI = 1.12–4.38) and low HDL-cholesterol levels (POR = 2.49, 95% CI = 1.28–4.86) as compared to never smokers.
This study supports previous reports of an increased risk of MetSyn among current smokers, particularly those with a heavier consumption. Tobacco control strategies, such as preventing smoking initiation and disseminating evidence-based cessation programs, are necessary to reduce the burden of MetSyn in Puerto Rico.
PMCID: PMC4124562  PMID: 25104996
Metabolic syndrome; Puerto Rico; smoking
14.  Defining genetic determinants of the Metabolic Syndrome in the Framingham Heart Study using association and structural equation modeling methods 
BMC Proceedings  2009;3(Suppl 7):S50.
The Metabolic Syndrome (MetSyn), which is a clustering of traits including insulin resistance, obesity, hypertension and dyslipidemia, is estimated to have a substantial genetic component, yet few specific genetic targets have been identified. Factor analysis, a sub-type of structural equation modeling (SEM), has been used to model the complex relationships in MetSyn. Therefore, we aimed to define the genetic determinants of MetSyn in the Framingham Heart Study (Offspring Cohort, Exam 7) using the Affymetrix 50 k Human Gene Panel and three different approaches: 1) an association-based "one-SNP-at-a-time" analysis with MetSyn as a binary trait using the World Health Organization criteria; 2) an association-based "one-SNP-at-a-time" analysis with MetSyn as a continuous trait using second-order factor scores derived from four first-order factors; and, 3) a multivariate SEM analysis with MetSyn as a continuous, second-order factor modeled with multiple putative genes, which were represented by latent constructs defined using multiple SNPs in each gene. Results were similar between approaches in that CSMD1 SNPs were associated with MetSyn in Approaches 1 and 2; however, the effects of CSMD1 diminished in Approach 3 when modeled simultaneously with six other genes, most notably CETP and STARD13, which were strongly associated with the Lipids and MetSyn factors, respectively. We conclude that modeling multiple genes as latent constructs on first-order trait factors, most proximal to the gene's function with limited paths directly from genes to the second-order MetSyn factor, using SEM is the most viable approach toward understanding overall gene variation effects in the presence of multiple putative SNPs.
PMCID: PMC2795950  PMID: 20018043
15.  Metabolic Syndrome, Strain, and Reduced Myocardial Function: Multi-Ethnic Study of Atherosclerosis 
Arquivos Brasileiros de Cardiologia  2014;102(4):327-335.
Subclinical cardiovascular disease is prevalent in patients with Metabolic Syndrome (MetSyn). Left ventricular (LV) circumferential strain (εCC) and longitudinal strain (εLL), assessed by Speckle Tracking Echocardiography (STE), are indices of systolic function: shortening is indicated by negative strain, and thus, the more negative the strain, the better the LV systolic function. They have been used to demonstrate subclinical ventricular dysfunction in several clinical disorders.
We hypothesized that MetSyn is associated with impaired myocardial function, as assessed by STE.
We analyzed Multi-Ethnic Study of Atherosclerosis (MESA) participants who underwent STE and were evaluated for all MetSyn components.
Among the 133 participants included [women: 63%; age: 65 ± 9 years (mean ± SD)], the prevalence of MetSyn was 31% (41/133). Individuals with MetSyn had lower εCC and lower εLL than those without MetSyn (-16.3% ± 3.5% vs. -18.4% ± 3.7%, p < 0.01; and -12.1% ± 2.5% vs. -13.9% ± 2.3%, p < 0.01, respectively). The LV ejection fraction (LVEF) was similar in both groups (p = 0.09). In multivariate analysis, MetSyn was associated with less circumferential myocardial shortening as indicated by less negative εCC (B = 2.1%, 95%CI:0.6 3.5, p < 0.01) even after adjusting for age, ethnicity, LV mass, and LVEF). Likewise, presence of MetSyn (B = 1.3%, 95%CI:0.3 2.2, p < 0.01) and LV mass (B = 0.02%, 95% CI: 0.01-0.03, p = 0.02) were significantly associated with less longitudinal myocardial shortening as indicated by less negative εLL after adjustment for ethnicity, LVEF, and creatinine.
Left ventricular εCC and εLL, markers of subclinical cardiovascular disease, are impaired in asymptomatic individuals with MetSyn and no history of myocardial infarction, heart failure, and/or LVEF < 50%.
PMCID: PMC4028951  PMID: 24844874
Atherosclerosis; Metabolic X Syndrome; Diabetes Mellitus / mortality; Ventricular Dysfunction / physiopathology; Ethnic Group
16.  Relationship between Vitamin D Receptor gene polymorphisms and the components of metabolic syndrome 
Nutrition Journal  2013;12:96.
The Vitamin D Receptor gene (VDR) is expressed in many tissues and modulates the expression of several other genes. The purpose of this study was to investigate the association between metabolic syndrome (MetSyn) with the presence of VDR 2228570 C > T and VDR 1544410 A > G polymorphisms in Brazilian adults.
Two hundred forty three (243) individuals were included in a cross-sectional study. MetSyn was classified using the criteria proposed by National Cholesterol Educational Program - Adult Treatment Panel III. Insulin resistance and β cell secretion were estimated by the mathematical models of HOMA IR and β, respectively. The VDR 2228570 C > T and VDR 1544410 A > G polymorphisms were detected by enzymatic digestion and confirmed by allele specific PCR or amplification of refractory mutation.
Individuals with MetSyn and heterozygosis for VDR 2228570 C > T have higher concentrations of iPTH and HOMA β than those without this polymorphism, and subjects with recessive homozygosis for the same polymorphisms presented higher insulin resistance than those with the heterozygous genotype. There is no association among VDR 1544410 A > G and components of MetSyn, HOMA IR and β, serum vitamin D (25(OH)D3) and intact parathormone (iPTH) levels in patients with MetSyn. A significant lower concentration of 25(OH)D3 was observed only in individuals without MetSyn in the VDR 1544410 A > G genotype. Additionally, individuals without MetSyn and heterozygosis for VDR 2228570 C > T presented higher concentration of triglycerides and lower HDL than those without this polymorphism.
Using two common VDR polymorphism data suggests they may influence insulin secretion, insulin resistance an serum HDL-cholesterol in our highly heterogeneous population. Whether VDR polymorphism may influence the severity of MetSyn component disorder, warrants examination in larger cohorts used for genome-wide association studies.
PMCID: PMC3726454  PMID: 23855914
Vitamin D; Vitamin D Receptor gene; Polymorphisms; Parathyroid hormone; Metabolic syndrome
17.  The Metabolic Syndrome and Behavioral Correlates in Obese Patients With Binge Eating Disorder 
Obesity (Silver Spring, Md.)  2008;17(3):481-486.
This study examined the frequency of the metabolic syndrome (MetSyn) and explored behavioral eating- and weight-related correlates in obese patients with binge eating disorder (BED). Ninety-three treatment-seeking obese BED patients (22 men and 71 women) with and without the MetSyn were compared on demographic features and a number of current and historical eating and weight variables. Sixty percent of the obese patients with BED met criteria for the MetSyn, with men and whites having significantly higher rates than women and African Americans, respectively. Patients with vs. without coexisting MetSyn did not differ significantly in self-reported frequency of binge eating or severity of eating disorder psychopathology. Multivariate hierarchical logistic regression analysis revealed that, after controlling for gender, ethnicity, and BMI, fewer episodes of weight cycling and regular meal skipping were significant predictors of the MetSyn. These findings suggest that lifestyle behaviors including weight loss attempts and regular meal consumption may be potential targets for prevention and/or treatment of the MetSyn in obese patients with BED.
PMCID: PMC2704920  PMID: 19219063
18.  Low levels of serum 25-hydroxyvitamin D and risk of metabolic syndrome in China 
Recent evidence indicates the potential role of vitamin D in the prevention of Metabolic syndrome (MetSyn). This is an analytical cross sectional study. A total of 3275 subjects were investigated. 25-hydroxyvitamin D(25[OH]D) was detected by electrochemiluminescence immunoassay (ECLIA) technology. Metabolic syndrome was defined according to the definition of International Diabetes Federation (IDF). Among the participants, the prevalence of the MetSyn was 6.0%. The prevalence of vitamin D deficiency and insufficiency was 50.1% and 25.0% respectively. Subjects with MetSyn presented with significantly lower 25(OH)Vit D serum levels compared with non-MetSyn group. The results shows that vitamin D deficiency is common in Chinese adults, and subjects with lower serum 25(OH)D have a higher risk of the MetSyn. The cut-off value of serum 25(OH)D that reflected MetSyn in Chinese adluts was 15.655 ng/mL.
PMCID: PMC4613012  PMID: 26550327
Vitamin D deficiency; metabolic syndrome; cardiovascular risk
19.  Metabolic Syndrome Does Not Detect Metabolic Risk in African Men Living in the U.S. 
Diabetes Care  2011;34(10):2297-2299.
Metabolic risk and metabolic syndrome (MetSyn) prevalence were compared in Africans who immigrated to the U.S. and African Americans. If MetSyn were an effective predictor of cardiometabolic risk, then the group with a worse metabolic risk profile would have a higher rate of MetSyn.
Cross-sectional analyses were performed on 95 men (39 Africans, 56 African Americans, age 38 ± 6 years [mean ± SD]). Glucose tolerance was determined by oral glucose tolerance test, visceral adipose tissue (VAT) was determined by computerized tomography, and MetSyn was determined by the presence of three of five factors: central obesity, hypertriglyceridemia, low levels of HDL cholesterol, hypertension, and fasting hyperglycemia.
MetSyn prevalence was similar in Africans and African Americans (10 vs. 13%, P = 0.74), but hypertension, glycemia (fasting and 2-h glucose), and VAT were higher in Africans.
African immigrants have a worse metabolic profile than African Americans but a similar prevalence of MetSyn. Therefore, MetSyn may underpredict metabolic risk in Africans.
PMCID: PMC3177749  PMID: 21873563
20.  Long-Term Impact of Caregiving and Metabolic Syndrome with Perceived Decline in Cognitive Function 8 Years Later: A Pilot Study Suggesting Important Avenues for Future Research 
The chronic stress of caregiving has been associated with increased risk for cognitive decline and dementia. One theoretical model suggests that a group of risk factors known as the metabolic syndrome MET_SYN (e.g. hypertension, poor glucose regulation, central obesity, and high triglyceride levels) that have demonstrated associations with both stress and cognitive decline, may mediate the association between caregiver stress and cognitive decline. It is also possible that caregiving may moderate the association between MET_SYN and cognitive decline. The present study examined these two potential models. The study sample consisted of 53 caregivers for a relative with dementia and 24 participants who did not have caregiving responsibilities at baseline. We examined associations among caregiving history (yes/no), self-reported decline in cognitive function (the AD8) at follow-up, and a MET_SYN factor comprised of increased systolic blood pressure (SBP), glycosylated hemoglobin concentration (HbA1c), waist circumference, and triglyceride levels at baseline when caregiving was assessed. MET_SYN was associated with AD8 (p = 0.010). Caregiving history was not directly associated with AD8 ratings, however, caregiving did moderate the association between MET_SYN and AD8 (p = 0.043) assessed 8 years later. In caregivers MET_SYN scores reflecting higher risk were associated with scores on the AD8 indicting decline, whereas, in controls MET_SYN was unrelated to AD8 assessment. Thus, it can be concluded that caregiver stress may increase the association between metabolic risk factors and decline in cognitive functioning up to 8 years later.
PMCID: PMC3952276  PMID: 24634805
Caregiving; Metabolic Syndrome; Cognitive Decline
21.  Neural control of blood flow during exercise in human metabolic syndrome 
Experimental physiology  2014;99(9):1191-1202.
α-Adrenergic-mediated vasoconstriction is greater during simulated exercise in animal models of metabolic syndrome (MetSyn) when compared with control animals. In an attempt to translate such findings to humans, we hypothesized that adults with MetSyn (n = 14, 35 ± 3 years old) would exhibit greater α-adrenergic responsiveness during exercise when compared with age-matched healthy control subjects (n = 16, 31 ± 3 years old). We measured muscle sympathetic nerve activity (MSNA; microneurography) and forearm blood flow (Doppler ultrasound) during dynamic forearm exercise (15% of maximal voluntary contraction). α-Adrenergic agonists (phenylephrine and clonidine) and an antagonist (phentolamine) were infused intra-arterially to assess α-adrenergic receptor responsiveness and restraint, respectively. Resting MSNA was ~35% higher in adults with MetSyn (P < 0.05), but did not change in either group with dynamic exercise. Clonidine-mediated vasoconstriction was greater in adults with MetSyn (P < 0.01). Group differences in vascular responses to phenylephrine and phentolamine were not detected (P > 0.05). Interestingly, exercise-mediated vasodilatation was greater in MetSyn (P < 0.05). Adults with MetSyn exhibit greater resting MSNA and clonidine-mediated vasoconstriction, yet preserved functional sympatholysis and higher exercise blood flow during low-intensity hand-grip exercise when compared with age-matched healthy control subjects. These results suggest that adults with MetSyn exhibit compensatory vascular control mechanisms capable of preserving blood flow responses to exercise in the face of augmented sympathetic adrenergic activity.
PMCID: PMC4162814  PMID: 24659613
22.  Association of High Sensitivity C-Reactive Protein with the Components of Metabolic Syndrome in Diabetic and Non-Diabetic Individuals 
Background and Objectives: High sensitivity C-reactive protein (hsCRP) has been associated with metabolic syndrome (MetS) and its components. Several studies have suggested hsCRP to be used as a marker for the primary prevention of cardiovascular diseases. So, we aimed to evaluate the association between hsCRP levels and the components of MetS in diabetic and non-diabetic population.
Materials and Methods: Type II diabetic patients (T2DM) (n= 121) and healthy controls (n= 121) were enrolled for the study. Anthropometric measurements were taken along with blood pressure from the arm. Ten ml of blood was collected after overnight fasting for the measurement of lipid profile, hsCRP, C-peptide and glucose levels. Insulin resistance (HOMA2-IR) was estimated by HOMA2 calculator utilizing glucose and C-peptide values. All participants were classified into two groups on the basis of the presence or absence of MetS. Data were analysed through SPSS 14 software.
Results: hsCRP, C-peptide and HOMA2-IR were significantly higher in T2DM subjects when compared with controls. As the number of the components of MetS increased, there was a linear increase in hsCRP levels in whole study population (p trend <.001), diabetic subjects (p trend <.001), as well as in controls (p trend <.001). HOMA2-IR and hsCRP levels were found to be better than LDL cholesterol and waist circumference for predicting the presence of MetS.
Conclusion: hsCRP was found to be better than LDL cholesterol and waist circumference for the prediction of MetS. Hence, hsCRP could be used as a defining marker of MetS in the near future.
PMCID: PMC4129304  PMID: 25120975
C-peptide; HOMA2 calculator; Insulin resistance
23.  Self-Reported Long Total Sleep Duration Is Associated With Metabolic Syndrome 
Diabetes Care  2011;34(10):2317-2319.
To examine the association between total sleep duration and the prevalence of metabolic syndrome (MetSyn) in older Chinese.
Cross-sectional analysis of baseline data from the Guangzhou Biobank Cohort Study (GBCS) was performed. Participants (n = 29,333) were aged ≥50 years. Risk of MetSyn and its components were identified for self-reported total sleep duration.
Participants reporting long (≥9 h) and short (<6 h) total sleep duration had increased odds ratio (OR) of 1.18 (95% CI 1.07–1.30) and 1.14 (1.05–1.24) for the presence of MetSyn, respectively. The relationship remained in long sleepers (OR 1.21 [1.10–1.34]) but diminished in short sleepers (0.97 [0.88–1.06]) after full adjustment.
Long sleep duration was associated with greater risk of MetSyn in older Chinese. Confirmation through longitudinal studies is needed. The mechanisms mediating the link between long sleep duration and MetSyn require further investigation.
PMCID: PMC3177714  PMID: 21873559
24.  Assessing the prevalence of the Metabolic Syndrome according to NCEP ATP III in Germany: feasibility and quality aspects of a two step approach in 1550 randomly selected primary health care practices 
Objective: Metabolic Syndrome (MetSyn) describes a cluster of metabolic disorders and is considered a risk factor for development of cardiovascular disease. Although a high prevalence is commonly assumed in Germany data about the degree of its occurrence in the population and in subgroups are still missing. The aim of this study was to assess the prevalence of the MetSyn according to the NCEP ATP-III (National Cholesterol Education Program Adult Treatment Panel III) criteria in persons aged ≥18 years attending a general practitioner in Germany. Here we describe in detail the methods used and the feasibility of determining the MetSyn in a primary health care setting.
Research design and methods: The German-wide cross-sectional study was performed during two weeks in October 2005. Blood samples were analyzed in a central laboratory. Waist circumference and blood pressure were assessed, data on smoking, life style, fasting status, socio-demographic characteristics and core information from non-participants collected. Quality control procedures included telephone-monitoring and random on-site visits. In order to achieve a maximal number of fasting blood samples with a minimal need for follow-up appointments a stepwise approach was developed. Basic descriptive statistics were calculated, the Taylor expansion method used to estimate standard errors needed for calculation of confidence intervals for clustered observations.
Results: In total, 1511 randomly selected general practices from 397 out of 438 German cities and administrative districts enrolled 35,869 patients (age range: 18-99, women 61.1%). More than 50,000 blood samples were taken. Fasting blood samples were available for 49% of the participants. Of the participating patients 99.3% returned questionnaires to the GP, only 12% were not filled out completely. The overall prevalence of the MetSyn (NCEP/ATP III 2001) was found to be 19.8%, with men showing higher prevalence rates than women (22.7% respective 18.0%).
Conclusions: This study was designed to provide data as robust as possible within the confines of an epidemiological study. Judging by the low degree of missing data and the high data quality, the feasibility for this kind of a research setting (short evaluation period, practitioners as data assessment sites) was found to be very good. The results will help to gain a more comprehensive insight into the prevalence of MetSyn for patients in primary health care in Germany.
PMCID: PMC2703219  PMID: 19675698
Metabolic Syndrome X; primary health care; cross-sectional study; prevalence study; family practice; Germany
25.  Diagnosis of the Metabolic Syndrome Is Associated With Disproportionately High Levels of High-Sensitivity C-Reactive Protein in Non–Hispanic Black Adolescents 
Diabetes Care  2011;34(3):734-740.
Whereas it is known that the metabolic syndrome (MetS) has a paradoxically lower prevalence in non–Hispanic black adolescents than in non–Hispanic whites or Hispanics, the relative severity of MetS by race/ethnicity is unknown. Inflammation, indicated by high-sensitivity C-reactive protein (hsCRP), is a key factor linking MetS to cardiovascular disease and type 2 diabetes. Our goal was to determine whether elevations of hsCRP vary by race/ethnicity among adolescents with MetS.
We used the National Health and Nutrition Examination Survey (1999–2008) and evaluated adolescents (age 12–19 years) using a pediatric/adolescent adaptation of the ATP III definition of MetS. We used linear regression to evaluate the interaction between MetS status and ethnicity with respect to hsCRP concentration.
For male and female adolescents, MetS was associated with elevated hsCRP levels compared with adolescents without MetS. However, the elevation in hsCRP between adolescents with and without MetS was greater in non–Hispanic blacks compared with that in non–Hispanic whites (P = 0.04) but not that in Hispanics (P = 0.18). hsCRP concentrations correlated with individual MetS components similarly among all ethnicities. In an evaluation of adolescents diagnosed with MetS, non–Hispanic blacks had higher BMI and more hypertension than other ethnicities but there were no other racial/ethnic differences in the features of MetS.
Non–Hispanic black adolescents have a greater differential in hsCRP between those with and those without MetS than the differential in non–Hispanic whites but not that in Hispanics. Therefore, even though MetS has a low prevalence in non–Hispanic blacks, MetS is a particularly good indicator of inflammation in non–Hispanic black adolescents.
PMCID: PMC3041218  PMID: 21285387

Results 1-25 (1999110)