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1.  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
2.  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
3.  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
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 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
6.  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
7.  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
8.  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
9.  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
10.  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)
11.  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
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
13.  Dramatic escalation in metabolic syndrome and cardiovascular risk in a Chinese population experiencing rapid economic development 
BMC Public Health  2014;14(1):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
14.  Impact of 4 different definitions used for the assessment of the prevalence of the Metabolic Syndrome in primary healthcare:The German Metabolic and Cardiovascular Risk Project (GEMCAS) 
The metabolic syndrome (MetSyn) places individuals at increased risk for type 2 diabetes and cardiovascular disease. Prevalence rates of the population of the MetSyn are still scarce. Moreover, the impact of different definitions of the MetSyn on the prevalence is unclear. Aim here is to assess the prevalence of the MetSyn in primary health care and to investigate the impact of four different definitions of the MetSyn on the determined prevalence with regard to age, gender and socio-economic status.
The German-wide cross-sectional study was conducted during two weeks in October 2005 in 1.511 randomly selected general practices. Blood samples were analyzed, blood pressure and waist circumference assessed, data on lifestyle, medication, chronic disorders, and socio-demographic characteristics collected. MetSyn prevalence was estimated according to the definitions of NCEP ATP III (2001), AHA/NHLBI (2004, 2005), and IDF (2005). Descriptive statistics and prevalence rate ratios using the PROG GENMOD procedure, were calculated. Cohen's kappa was used as measure for interreliability between the different prevalence estimates.
Data of 35,869 patients (age range: 18–99, women 61.1%) were included. The prevalence was lowest using the NCEP ATP III- (all: 19.8%, men 22.7%, women: 18.0%), highest according to the IDF-definition (32.7%, 40.3%, 28.0%). The increase in prevalence with recent definitions was more pronounced for men than for women, and was particularly high for men and women aged 60–79 years. The IDF-definition resulted in a higher prevalence especially in those with the highest educational status. Agreement (kappa) between the NCEP ATP III- and IDF-definition was 0.68 (men 0.61, women 0.74), between the updated the AHA/NHLBI- (2005) and IDF-definition 0.85 (men 0.79, women 0.89).
The prevalence of metabolic syndrome is associated with age, gender, and educational status and increases considerably with each newly published definition. Our data highlight the need for a better evidence regarding thresholds of the components of the metabolic syndrome, especially with regard to the IDF-definition – according to which in some populations a majority of subjects are diagnosed with the metabolic syndrome.
PMCID: PMC2031874  PMID: 17822558
Obesity (Silver Spring, Md.)  2013;21(1):203-209.
There is recent interest in characterizing the subset of obese individuals who have healthy metabolic profiles yet only two studies have examined this group prospectively but not in racially diverse populations. We analyzed factors associated with the prevalence and incidence of metabolic syndrome (MetSyn) among individuals grouped by body mass index (BMI) categories in a multi-center, community-based cohort of 14,663 African-American and white men and women aged 45-64 years at recruitment in 1987-1989, the Atherosclerosis Risk in Communities study. Logistic and proportional hazards regression were utilized to estimate odds ratios (OR) for the prevalence and hazard ratios (HR) for incidence of MetSyn with 95% confidence intervals (CI). At visit 1, MetSyn was positively associated with age, female gender, African-American race, and inversely related to education, associations being more pronounced among normal weight (NW) subjects. Among those without MetSyn at visit 1, obese (OB) subjects were more likely to develop MetSyn compared with NW [HR (95% CI): 4.53 (4.09-5.01)]. Several factors were associated with incident MetSyn among NW, including older age [per year: 1.05 (1.03-1.06)], female gender [vs. male: 1.29 (1.10-1.52)], heavy alcohol intake [vs. never: 0.75 (0.59-0.94)] and physical activity [tertile 3 vs. tertile 1: 0.71 (0.58-0.86)] but not OB. Weight gain (>5%) was also more highly associated with MetSyn in NW [1.61 (1.28-2.02)] compared with OB [1.01 (0.85-1.20)]. We conclude that lifestyle factors may play a stronger role in development of MetSyn in NW individuals compared with OB and that metabolically healthy obesity may not be a stable condition.
PMCID: PMC4170589  PMID: 23505187
metabolic syndrome; obesity
16.  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
17.  Relationships of low serum vitamin D3 with anthropometry and markers of the metabolic syndrome and diabetes in overweight and obesity 
Nutrition Journal  2008;7:4.
Low serum 25 hydroxyvitamin D3 (vitamin D3) is known to perturb cellular function in many tissues, including the endocrine pancreas, which are involved in obesity and type II diabetes mellitus (TIIDM). Vitamin D3 insufficiency has been linked to obesity, whether obesity is assessed by body mass index (BMI) or waist circumference (waist). Central obesity, using waist as the surrogate, is associated with the metabolic syndrome (MetSyn), insulin resistance, TIIDM and atherosclerotic cardiovascular disease (CVD). We tested how vitamin D3 was related to measures of fat mass, MetSyn markers, haemoglobin A1c (HbA1c) and MetSyn in a cross-sectional sample of 250 overweight and obese adults of different ethnicities. There were modest inverse associations of vitamin D3 with body weight (weight) (r = -0.21, p = 0.0009), BMI (r = -0.18, p = 0.005), waist (r = -0.14, p = 0.03), [but not body fat % (r = -0.08, p = 0.24)], and HbA1c (r = -0.16, p = 0.01). Multivariable regression carried out separately for BMI and waist showed a decrease of 0.74 nmol/L (p = 0.002) in vitamin D3 per 1 kg/m2 increase in BMI and a decrease of 0.29 nmol/L (p = 0.01) per 1 cm increase in waist, with each explaining approximately 3% of the variation in vitamin D3 over and above gender, age, ethnicity and season.
The similar relationships of BMI and waist with vitamin D3 may have been due to associations between BMI and waist, or coincidental, where different mechanisms relating hypovitaminosis D3 to obesity occur concurrently. Previously reviewed mechanisms include that 1) low vitamin D3, may impair insulin action, glucose metabolism and various other metabolic processes in adipose and lean tissue 2) fat soluble-vitamin D3 is sequestered in the large adipose compartment, and low in serum, 3) obese people may be sensitive about their body shape, minimising their skin exposure to view and sunlight (not tested). We showed evidence for the first theory but no evidence to support the second.
In the current study, serum vitamin D3 was inversely related to weight, BMI and markers of TIIDM (large waist, raised HbA1c) but not to adipose mass nor to MetSyn per se.
PMCID: PMC2265738  PMID: 18226257
18.  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
19.  Impaired hypoxic cerebral vasodilation in younger adults with metabolic syndrome 
Metabolic syndrome (MetSyn) increases the risk of cerebrovascular disease and stroke; however, its impact on human cerebral circulation remains unclear. Reduced cerebral dilation is also associated with an increased risk of stroke and may occur in MetSyn adults. We hypothesised that MetSyn adults would exhibit reduced cerebral vasodilation to hypoxia and hypercapnia. Middle cerebral artery velocity (MCAv) was insonated with Doppler ultrasound in younger (approximately 35 years) MetSyn and healthy adults. We measured mean arterial blood pressure (MABP), arterial oxygen saturation (SpO2) and end tidal carbon dioxide (PetCO2). Cerebrovascular conductance index (CVCi) was calculated as MCAv*100/MABP. Cerebral vasodilation (ΔCVCi) to hypoxia (SpO2 = 90% and 80%) and hypercapnia (+10 mm Hg PetCO2) was assessed. Baseline MCAv was similar, while adults with MetSyn had lower baseline CVCi. MetSyn adults demonstrated markedly reduced ΔCVCi compared to healthy adults in response to hypoxia (90% SpO2: 1±2 vs 6±2; 80% SpO2: 5±2 vs 15±3 cm/s/mmHg, p<0.05). Both groups demonstrated similar ΔCVCi to hypercapnia (18±2 vs 20±2 cm/s/mmHg). These data are the first to demonstrate that younger MetSyn adults have impaired hypoxia-mediated cerebral vasodilation prior to clinically overt cerebrovascular disease. These findings provide novel insight into cerebrovascular disease onset in MetSyn adults.
PMCID: PMC3899935  PMID: 22752659
Cerebral blood flow; transcranial Doppler; risk factors
20.  Atypical Protein Kinase C in Cardiometabolic Abnormalities 
Current opinion in lipidology  2012;23(3):175-181.
Review aberrations of insulin signaling to atypical protein kinase C (aPKC) in muscle and liver that generate cardiovascular risk factors, including, obesity, hypertriglyceridemia, hypercholesterolemia, insulin resistance and glucose intolerance in type 2 diabetes mellitus (T2DM), and obesity-associated metabolic syndrome (MetSyn).
Recent Findings
aPKC and/or Akt mediate insulin effects on glucose transport in muscle, and synthesis of lipids, cytokines and glucose in liver. In T2DM, whereas Akt and aPKC activation are diminished in muscle, and hepatic Akt activation is diminished, hepatic aPKC activation is conserved. Imbalance between muscle and hepatic aPKC activation (and expression of PKC-ι in humans) by insulin results from differential downregulation of insulin receptor substrates that control phosphatidylinositol 3-kinase. Conserved activation of hepatic aPKC in hyperinsulinemic states of T2DM, obesity and MetSyn is problematic as excessive activation of aPKC-dependent lipogenic, gluconeogenic and proinflammatory pathways increases cardiovascular risk factors. Indeed, selective inhibition of hepatic aPKC by adenoviral-mediated expression of kinase-inactive aPKC, or newly-developed small-molecule biochemicals, dramatically improves abdominal obesity, hepatosteatosis, hypertriglyceridemia, hypercholesterolemia, insulin resistance and glucose intolerance in murine models of obesity and T2DM.
Hepatic aPKC is a unifying target for treating multiple clinical abnormalities that increase cardiovascular risk in insulin-resistant states of obesity, MetSyn and T2DM.
PMCID: PMC3519242  PMID: 22449812
Atypical Protein Kinase C; Obesity; Metabolic Syndrome; Type 2 Diabetes Mellitus; Insulin Signaling in Liver and Muscle
21.  Metabolic Syndrome and Breast Cancer Risk: Is There a Role for Metformin? 
Current Breast Cancer Reports  2011;3(3):142-150.
Obesity is one of the most important known preventable causes of cancer, accounting for up to 20% of cancer deaths in women. Obese women have increased risk of dying from breast cancer as well as an increased risk of distant metastasis. Metabolic Syndrome (MetSyn) is a group of metabolic conditions that include 1) abdominal obesity, 2) atherogenic dyslipidemia, 3) elevated blood pressure, and 4) insulin resistance. MetSyn is known to promote the development of cardiovascular disease and diabetes and may be associated with increased breast cancer risk. Emerging evidence supports an association between mammary adipocytes and their secreted adipocytokines and breast cancer initiation and progression. Metformin (1,1-dimethylbiguanide hydrochloride) is a drug used to treat type 2 diabetes and MetSyn. We review the potential association between MetSyn in promoting breast cancer and emerging evidence for the use of metformin in cancer prevention.
PMCID: PMC3155025  PMID: 21949568
Metabolic syndrome; Breast cancer risk; Adipose tissue; Metformin
22.  Prevalence of cardiovascular risk factors and the metabolic syndrome in middle-aged men and women in Gothenburg, Sweden 
BMC Public Health  2008;8:403.
Random samples of 50-year-old men living in Gothenburg have been examined every 10th year since 1963 with a focus on cardiovascular risk factors. The aims of the study were to acquire up-to-date information about risk factors in the fifth cohort of 50-year-old men and women, to re-examine those who were 50 years of age in 1993, and to analyse the prevalence of the metabolic syndrome (MetSyn) using different definitions.
A random sample of men and women born in 1953 were examined in 2003–2004 for cardiovascular risk factors. Men born in 1943 and that participated in the examination in 1993 were also invited. Descriptive statistics were calculated.
The participation rate among men and women born in 1953 was 60 and 67% respectively. Among men born in 1943, the participation rate was 87%. The prevalence of obesity was from 15 to 17% (body mass index, BMI ≥ 30) in the three samples. The prevalence of known diabetes was 4% among the 50-year-old men and 6% among the 60-year-old men, and 2% among the women. Increased fasting plasma glucose varied substantially from 4 to 33% depending on cut-off level and gender. Mean cholesterol was 5.4 to 5.5 mmol/l. Smoking was more common among women aged 50 (26%) than among men aged 50 (22%) and 60 years (15%). The prevalence of the MetSyn varied with the definition used: from 10 to 15.8% among the women, from 16.1 to 26% among 50-year-old men, and from 19.9 to 35% among the 60-year-old men. Only 5% of the men and women had no risk factors.
This study provides up-to-date information about the prevalence of cardiovascular risk factors and the MetSyn in middle-aged Swedish men and women. Different definitions of the MetSyn create confusion regarding which definition to use.
PMCID: PMC2621201  PMID: 19063738
23.  Drugs are not Enough: Metabolic Syndrome—A Call for Intensive Therapeutic Lifestyle Change 
Whether intensive pharmacologic cardiovascular risk factor management reduces metabolic syndrome (MetSyn) prevalence is unknown. We compared the number of secondary prevention medications and ATP III defined MetSyn prevalence in coronary artery disease (CAD) patients entering cardiac rehabilitation from 1996-2001 (period 1, n=516) with those entering from 2002-2006 (period 2, n=609). Age, gender, and ethnicity were similar in both periods. From period 1 to period 2, participants took more secondary prevention medications (2.8+/-1.3 vs. 3.5+/-1.0, p<0.001). Prevalence of low HDL-cholesterol (66% vs. 66%), diabetes (37% vs. 38%), and hypertension (81% vs. 81%) were unchanged. The prevalence of hypertriglyceridemia decreased (48% vs. 36%, p<0.001), but the proportion meeting criteria for elevated waist circumference increased (51% vs. 58%, p<0.05), resulting in no change in overall MetSyn prevalence (60% vs. 59%, p=ns). More emphasis on therapeutic lifestyle change, in addition to intensive pharmacologic therapy, is needed to reduce MetSyn prevalence in CAD patients.
PMCID: PMC2774888  PMID: 19245512
24.  LDL cholesterol estimation in patients with the metabolic syndrome 
The Friedewald formula (LDL-F) for the estimation of low-density lipoprotein (LDL) cholesterol concentrations is the most often used formula in clinical trials and clinical practice. However, much concern has been raised as to whether this formula is applicable in all patient populations such as the presence of chylomicronaemia and/or hypertriglyceridaemia. The aim of the present study was to evaluate various LDL cholesterol calculation formulas as well as LDL cholesterol levels provided by the Lipoprint LDL System (LDL-L) in patients with the metabolic syndrome (MetSyn).
LDL-F showed significant differences from other formulas in the total cohort, as well as in MetSyn individuals. This was not the case in nonMetSyn subjects, where LDL-F did not differ with other formulas, with the exception of one formula (LDL by Planella, LDL-P). The bias between LDL-F and other LDL estimation formulas were significantly higher in MetSyn subjects compared to nonMetSyn individuals, except for LDL-L which produced similar bias with LDL-F in both study groups.
LDL-F seems to exhibit some limitations as far as the calculation of LDL-C levels in patients with the MetSyn is concerned. LDL-L might be more accurate in MetSyn subjects, but so far its use is limited for the estimation of small, dense LDL (sdLDL) cholesterol levels and mean LDL particle size for research purposes only.
PMCID: PMC1550231  PMID: 16600020
25.  Metabolic Syndrome in Obese Men and Women with Binge Eating Disorder: Developmental Trajectories of Eating and Weight-Related Behaviors 
Comprehensive psychiatry  2012;53(7):1021-1027.
The metabolic syndrome (MetSyn), characterized by vascular symptoms, is strongly correlated with obesity, weight-related medical diseases and mortality, and has increased commensurately with secular increases in obesity in the U.S. Little is known about the distribution of MetSynin obese patients with binge eating disorder (BED) or its associations with different developmental trajectories of dieting, binge eating, and obesity problems. Further, inconsistencies in the limited data necessitate elucidation. This study examined the frequency and correlates of MetSyn in a consecutive series of 148 treatment-seeking obese men and women with BED assessed with structured clinical interviews. Almost half of the participants met criteria for MetSyn. Participants with MetSyn did not differ from those without MetSyn on demographic variables or disordered eating psychopathology. However, our findings suggest that MetSyn is associated with a distinct developmental trajectory, specifically a later age at BED onset and shorter BED duration. Although the findings from this study shed some light on MetSyn and its associations with developmental trajectories of eating and weight-related behaviors, notable inconsistencies characterize the limited literature. Prospective studies are needed to examine causal connections in the development of the MetSyn in relation to disordered eating in addition to excess weight.
PMCID: PMC3394907  PMID: 22483368

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