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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.  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
3.  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
4.  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
5.  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
6.  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
7.  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
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.  Maternal ethnicity and risk of neural tube defects: a population-based study 
Maternal body mass and the presence of diabetes mellitus are probable risk factors for neural tube defects (NTDs). The association between maternal ethnicity and the risk of NTDs remains poorly understood, however.
We performed a retrospective population-based study and included all women in Ontario who underwent antenatal maternal screening (MSS) at 15 to 20 weeks' gestation between 1994 and late 2000. Self-declared maternal date of birth, ethnicity and weight and the presence of pregestational diabetes mellitus were recorded in a standardized fashion on the MSS requisition sheet. NTDs were detected antenatally by ultrasonography or fetal autopsy and postnatally by considering all live and stillborn affected infants beyond 20 weeks' gestation. The risk of open NTD was evaluated across the 5 broad ethnic groups used for MSS, with white ethnicity as the referent.
Compared with white women (n = 290 799), women of First Nations origin (n = 1551) were at increased associated risk of an NTD-affected pregnancy (adjusted odds ratio [OR] 5.2, 95% confidence interval [CI] 2.1–12.9). Women of other ethnic origins were not at increased associated risk compared with white women (women of Asian origin [n = 75 590]: adjusted OR 0.9, 95% CI 0.6–1.3; black women [n = 25 966]: adjusted OR 0.6, 95% CI 0.3–1.1; women of “other” ethnic origin [n = 10 009]: adjusted OR 0.1, 95% CI 0.02–0.9).
The associated risk of NTD-affected pregnancies was higher among women of First Nations origin than among women of other ethnic origins. The mechanisms for this discrepancy should be explored.
PMCID: PMC509047  PMID: 15313993
10.  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
11.  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
12.  Cross-Sectional Validation of Diabetes Risk Scores for Predicting Diabetes, Metabolic Syndrome, and Chronic Kidney Disease in Taiwanese 
Diabetes Care  2009;32(12):2294-2296.
To validate the performance of current diabetes risk scores (DRSs) based on simple clinical information in detecting type 2 diabetes, metabolic syndrome (MetSyn), and chronic kidney disease (CKD).
The performance of 10 DRSs was evaluated in a cross-sectional population screening of 2,759 Taiwanese subjects.
All DRSs significantly correlated with measures of insulin resistance, estimated glomerular filtration rate, and urine albumin excretion. The prevalence of screening-detected diabetes (SDM), MetSyn, and CKD increased with higher DRSs. For prediction of SDM, the Cambridge DRS by Griffin et al. and the Finnish DRS outperformed other DRSs in terms of discriminative power and model fit. For prediction of MetSyn and CKD, the Atherosclerosis Risk in Community Study score by Schmidt et al. outperformed other DRSs.
Risk scores based on simple clinical information are useful to identify individuals at high risk for diabetes, MetSyn, and CKD in different ethnic populations.
PMCID: PMC2782993  PMID: 19755627
13.  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
14.  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
15.  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
16.  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
17.  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
18.  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
19.  The association of lipoprotein lipase PvuII polymorphism and niacin intake in the prevalence of metabolic syndrome: a KMSRI-Seoul study 
Genes & Nutrition  2011;7(2):331-341.
Lipoprotein lipase (LPL) polymorphism correlated with LPL activity is associated with plasma lipid and lipoprotein levels. We aimed to investigate the frequency of LPL PvuII polymorphism and effects of LPL PvuII polymorphism and niacin intake on the prevalence of metabolic syndrome (MetSyn) in Koreans. Lifestyle questionnaires, anthropometry, and dietary records were completed, and LPL PvuII polymorphism, LPL mass, and lipid profiles were determined in 548 Koreans (MetSyn: 278, Non-MetSyn: 270). The MetSyn group showed a significantly lower frequency of P1P1 (wild type) and a higher frequency of P1P2 (hetero type) than the non-MetSyn group. The P2P2 (mutant type) group significantly showed lower levels of HDLc and LPL mass and a higher level of TG than the P1P1 group. As niacin intake increased, LPL mass decreased in the P2P2 group (r2 = 0.07). In particular, the lowest niacin intake group (≤14.82 mg/day) increased more than 3 times with regard to a higher risk of MetSyn than the others in the P2P2 mutant groups. However, the MetSyn risk declined 74% at the optimal levels of niacin intake (14.83–17.80 mg/day) in the P2P2 group compared to those of the P1 allele group. The findings indicate that optimal levels of niacin intake effectively decreased Korean MetSyn prevalence in the P2P2 mutant group.
PMCID: PMC3316739  PMID: 22038562
LPL mass; LPL PvuII gene polymorphism; Metabolic syndrome; Niacin; Recommended intake
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
21.  Metabolic syndrome: from epidemiology to systems biology 
Nature reviews. Genetics  2008;9(11):819-830.
Metabolic syndrome (MetSyn) is a group of metabolic conditions that occur together and promote the development of cardiovascular disease (CVD) and diabetes. Recent genome-wide association studies have identified several novel susceptibility genes for MetSyn traits, and studies in rodent models have provided important molecular insights. However, as yet, only a small fraction of the genetic component is known. Systems-based approaches that integrate genomic, molecular and physiological data are complementing traditional genetic and biochemical approaches to more fully address the complexity of MetSyn.
PMCID: PMC2829312  PMID: 18852695
22.  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
23.  Increased Toll-Like Receptor (TLR) mRNA Expression in Monocytes is a Feature of Metabolic Syndrome in Adolescents 
Pediatric obesity  2012;8(1):e19-e23.
The aim of this pilot study was to assess the correlation between activation of the innate immune system and metabolic syndrome (MetSyn), independent of BMI, in a young population. We quantitatively measured both systemic pro-inflammatory cytokines and gene expression of Toll-like receptors and downstream cytokines in circulating monocytes obtained from nine adolescents with metabolic syndrome (Overwt-MetSyn) and 8 BMI-matched controls (Overwt-Healthy). The Overwt-MetSyn group demonstrated a significant elevation in expression of TLR2, TLR4, TNFα and IL6 in peripheral monocytes, and increased circulating levels of TNFα and IL6 when compared to the Overwt-Healthy group. TLR2 (r = 0.78, P < 0.001), TLR4 (r = 0.57, P < 0.01) and TNFα (r=0.61, P < 0.01) gene expression positively correlated with serum levels of TNFα. Our study suggests that activation of the innate immune pathway via TLRs may be partially responsible for the increased systemic inflammation seen in adolescents with MetSyn.
PMCID: PMC3546604  PMID: 22991262
innate immunity; adolescents; monocytes; inflammation; obesity; metabolic syndrome
24.  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
25.  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

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