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1.  Association of Biomarkers of Inflammation with Dyslipidemia and Its Components among Mongolians in China 
PLoS ONE  2014;9(2):e89023.
Objective
This study aims to examine the association between inflammatory biomarkers and dyslipidemia and its components among Mongolians in China.
Methods
Data were obtained from 2544 Mongolians via standard questionnaires and blood samples in Inner Mongolia, China. High sensitivity C-reactive protein (hsCRP), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble E-selectin (sE-selectin) as well as blood lipids were examined.
Results
Individuals with dyslipidemia had higher levels of hsCRP, sICAM-1 and sE-selectin than those without dyslipidemia (all P values<0.001). Compared to the lowest quartile of inflammatory biomarkers, individuals with the highest quartile were more likely to have dyslipidemia (odds ratio, 95% confidence interval: 3.215, 2.551–4.116 for hsCRP; 1.575, 1.253–1.980 for sICAM-1; 1.495, 1.193–1.873 for sE-selectin). Moreover, hsCRP was associated with all the components of dyslipidemia, whereas, sICAM-1 was not related to high density lipoprotein cholesterol (HDL-c) or triglycerides (TAG). Additionally, sE-selectin was just associated with TAG.
Conclusion
Our study indicated that elevated plasma levels of hsCRP, sICAM-1 and sE-selectin were positively and significantly associated with increased risk of dyslipidemia among Mongolians. However, the associations were not identical for different inflammatory biomarkers with the components of dyslipidemia.
doi:10.1371/journal.pone.0089023
PMCID: PMC3928392  PMID: 24558466
2.  Association of Endothelial and Oxidative Stress with Metabolic Syndrome and Subclinical Atherosclerosis: Multi-Ethnic Study of Atherosclerosis 
Objectives
A cluster of metabolic abnormalities termed metabolic syndrome (MetS) is associated with vascular endothelial dysfunction and oxidative internal milieu. We examined whether the association of MetS with subclinical atherosclerosis is explained by biomarkers of endothelial damage and oxidative stress.
Methods
MESA is a population based study of 45-84 year old individuals of four US ethnicities without clinical cardiovascular disease. A random sample of 997 MESA participants had data on the following biomarkers: von Willebrand Factor, soluble intercellular adhesion molecule-1 (sICAM1), CD40 ligand, soluble thrombomodulin, E-selectin, and oxidized LDL (oxLDL). We examined whether the associations of MetS with B-mode ultrasound-defined common and internal carotid intimal medial thickness (IMT) and coronary artery calcium (CAC) measured using computerized tomography were explained by the biomarkers using multiple regression methods.
Results
MetS was associated with higher levels of each of the biomarkers (p<0.001, CD40L suggestive association p=0.004), with greater IMT (p<0.001), and with greater extent of CAC in those in whom CAC was detectable (p=0.01). The association of MetS with measures of subclinical atherosclerosis remained unchanged after adjustment for the biomarkers. After adjusting for MetS, oxLDL was suggestively associated with greater prevalence of detectable CAC (p=0.005) and thicker internal carotid IMT (p=0.002), while sICAM-1was significantly associated with greater prevalence of detectable CAC (p=0.001).
Conclusions
The association of MetS with subclinical atherosclerosis was independent of its association with biomarkers of endothelial damage and oxidative stress, suggesting that metabolic abnormalities and oxidative endothelial damage may lead to atherosclerotic disease through distinct mechanisms.
doi:10.1038/ejcn.2011.47
PMCID: PMC3130805  PMID: 21505504
Metabolic syndrome; biomarkers; coronary artery atherosclerosis; carotid arteries
3.  Association between Childhood Obesity and Metabolic Syndrome: Evidence from a Large Sample of Chinese Children and Adolescents 
PLoS ONE  2012;7(10):e47380.
Data about metabolic syndrome (MetS) in children is limited in China. We aimed to assess the prevalence of MetS related components, and their association with obesity. Data were collected as part of a representative study on MetS among 19593 children, aged 6–18 years old in Beijing. General obesity was assessed by body mass index (BMI) and central obesity by waist circumference. Finger capillary blood tests were used to assess triglyceride (TG), total cholesterol (TC) and impaired fasting glucose (IFG). Vein blood samples were collected from a subsample of 3814 children aged 10–18 years to classify MetS. MetS was defined according to the International Diabetes Federation 2007 definition. The associations between MetS related components and the degree and type of obesity were tested using logistic regression models. The prevalence of overweight, obesity, high blood pressure, elevated TG, TC and IFG were13.6%, 5.8%, 8.5%, 8.8%, 1.2% and 2.5%, respectively. Compared with normal weight children, overweight and obese children were more likely to have other MetS related components. In the subsample of 3814 children aged 10–18 years, the prevalence of MetS was much higher in obese subjects than in their normal weight counterparts (27.6% vs. 0.2%). Children with both general and central obesity had the highest prevalence of MetS. Compared with normal weight children, overweight and obese children were more likely to have MetS (overweight: OR = 67.33, 95%CI = 21.32–212.61; obesity: OR = 249.99, 95% CI = 79.51–785.98). Prevalence of MetS related components has reached high level among Beijing children who were overweight or obese. The association between metabolic disorders and obesity was strong.
doi:10.1371/journal.pone.0047380
PMCID: PMC3474816  PMID: 23082159
4.  Association between metabolic syndrome and sexual dysfunction among men with clinically diagnosed diabetes 
Background
The worldwide epidemic of diabetes and obesity has resulted in a rapid upsurge in the prevalence of metabolic syndrome (MetS). MetS makes the individual liable to endothelial dysfunction which can initiate sexual dysfunction (SD). This study assessed the association between MetS and SD among clinically diagnosed diabetic subjects in Tema, Greater Accra Region of Ghana.
Method
Sexual functioning was assessed using Golombok Rust Inventory of Sexual Satisfaction in 300 consecutive diabetic men visiting the diabetic clinic of Tema General Hospital between November, 2010 and March, 2011. Anthropometric data including waist and hip circumference as well as blood pressure were measured. The levels of fasting blood glucose and serum lipid profile were assessed. All the men had a steady heterosexual relationship for at least 2 years before enrolment in the study.
Results
The response rate was 91.3% out of the 300 subjects recruited for the study. Those with SD were significantly older and had diabetes for a longer period as compared to those without SD. The prevalence of MetS as defined by the various criteria was 78.8%, 43.4% and 51.8% for WHO, NCEP ATP III and IDF respectively. Central obesity (p = 0.0482) and raised blood pressure (p = 0.0309) are the significant MetS components when the studied population was stratified according to sexual functioning. Generally, SD as well as its sub-scales correlate positively with age, blood pressure, duration of diabetes and MetS score. Whereas TC and LDL-c correlated positively with non-communication, TG correlates positively with avoidance and infrequency.
Conclusion
SD and its sub-scales have a direct relationship with duration of diabetes, blood pressure and MetS score from this study. Central obesity and raised blood pressure seem to be the link between MetS and SD among this clinically diagnosed diabetic subjects.
doi:10.1186/1758-5996-5-42
PMCID: PMC3733639  PMID: 23895401
5.  Biomarkers of Vascular Dysfunction in Children Infected with Human Immunodeficiency Virus-1 
Background
We compared biomarkers of vascular dysfunction among HIV-infected children to a demographically-similar group of uninfected children and determined factors associated with these biomarkers.
Methods and Results
We measured several biomarkers of vascular dysfunction: C-Reactive Protein (CRP), interleukin-6 (IL-6), and monocyte chemoattractant protein -1 (MCP1) [inflammation]; fibrinogen and P-selectin [coagulant dysfunction]; soluble intracellular cell adhesion molecule-1 (sICAM), soluble vascular cell adhesion molecule-1 (sVCAM), and E-selectin [endothelial dysfunction]; and leptin [metabolic dysfunction]. Anthropometry, body composition, CD4%, HIV viral load, and antiretroviral therapy were recorded. Mean age was 14.8y [106 HIV-infected children] and 12.3y [55 control children]. Sex and body mass index Z-scores were similar. Infected children had higher sICAM, sVCAM, MCP1, IL-6, and fibrinogen levels. E-selectin (p=0.07), and CRP (p=0.08) trended to be greater in the HIV group, yet leptin, and P-selectin were similar. In multivariable analyses in the HIV-infected children alone, each 1-standard-deviation increase in waist:hip ratio was associated with increases in sICAM (17%), MCP1 (19%), IL6 (18%), and CRP (59%). CD4% was inversely associated with sVCAM, MCP1, IL6, fibrinogen, and CRP.
Conclusion
HIV-infected children have higher levels of biomarkers of vascular dysfunction than healthy children. Risk factors associated with these biomarkers include higher waist:hip ratios and HIV disease severity.
doi:10.1097/QAI.0b013e3181e222c9
PMCID: PMC2943965  PMID: 20531209
Children; HIV/AIDS; vascular dysfunction; cardiovascular risk factors; biomarkers
6.  Metabolic Abnormalities and Viral Replication is Associated with Biomarkers of Vascular Dysfunction in HIV-Infected Children 
HIV Medicine  2011;13(5):264-275.
Objectives
Human immunodeficiency virus (HIV)-infected children may be at risk for premature cardiovascular disease. We compared levels of biomarkers of vascular dysfunction among HIV-infected children with and without hyperlipidemia to HIV-exposed, uninfected children (HEU) enrolled in the Pediatric HIV/AIDS Cohort Study (PHACS), and determined factors associated with these biomarkers.
Design
Prospective cohort study
Methods
Biomarkers of inflammation (C-reactive protein (CRP), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP1)); coagulant dysfunction (fibrinogen and P-selectin); endothelial dysfunction (soluble intracellular cell adhesion molecule-1 (sICAM), soluble vascular cell adhesion molecule-1 (sVCAM), and E-selectin); and metabolic dysfunction (adiponectin) were measured in 226 HIV-infected and 140 HEU children. Anthropometry, body composition, lipids, glucose, insulin, HIV disease severity, and antiretroviral therapy were recorded.
Results
The median ages were 12.3 y (HIV-infected) and 10.1 y (HEU). Body mass index (BMI) Z-scores, waist and hip circumference, and percent body fat were lower among HIV-infected. Total and non-HDL cholesterol and triglycerides were higher in HIV-infected children. HIV-infected children had higher MCP-1, fibrinogen, sICAM, and sVCAM levels. In multivariable analyses in the HIV-infected children alone, BMI z-score was associated with higher CRP and fibrinogen, but lower MCP-1 and sVCAM. Unfavorable lipid profiles were positively associated with IL6, MCP1, fibrinogen, and P- and E-selectin, whereas increased HIV viral load was associated with markers of inflammation (MCP1 and CRP) and endothelial dysfunction (sICAM and sVCAM).
Conclusions
HIV-infected children have higher levels of biomarkers of vascular dysfunction than do HEU children. Risk factors associated with higher biomarkers include unfavorable lipid levels and active HIV replication.
doi:10.1111/j.1468-1293.2011.00970.x
PMCID: PMC3297698  PMID: 22136114
Children; HIV/AIDS; vascular dysfunction; cardiovascular risk factors; biomarkers
7.  Acute and long term effects of grape and pomegranate juice consumption on endothelial dysfunction in pediatric metabolic syndrome 
BACKGROUND:
This study aimed to determine the short- and long-term effects of consumption of grape and pomegranate juices on markers of endothelial function and inflammation in adolescents with metabolic syndrome (MetS).
METHODS:
In a non-pharmacologic randomized controlled trial, 30 individuals were randomly assigned to two groups of drinking natural grape or pomegranate juice for 1 month. Measurements of inflammatory factors [Hs-CRP, sE-selectin, sICAM-1, sVCAM, and interleukin 6 (IL-6)] and flow-mediated dilation (FMD) were made at baseline, 4 hours after first juice consumption and after one month of juice consumption.
RESULTS:
The percent changes of FMD were significant in both groups in the short- and long-term. Hs-CRP had a nonsignificant decrease. sE selectin had a significant decrease after 4 hours in total and in the pomegranate juice group, followed by a significant decrease after 1 month in both groups. After 4 hours, sICAM-1 significantly decreased in the pomegranate juice group, and after 1 month it decreased in total and pomegranate juice group. Interleulkin-6 (IL-6) had a significant constant decrease at 4-hour and 1-month measurements after drinking pomegranate juice, and in both groups after 1 month. Significant negative correlations of changes in sICAM-1 and sE-selectin with changes in FMD were found in both periods of follow-up; and at 1 month for IL-6.
CONCLUSIONS:
Decline in inflammation was associated with improvement in FMD without changes in conventional risk factors. Daily consumption of natural antioxidants may improve endothelial function in adolescents with MetS.
PMCID: PMC3214329  PMID: 22091240
Endothelium function; metabolic syndrome; antioxidants; inflammation; adolescents
8.  Diagnosis of the Metabolic Syndrome Is Associated With Disproportionately High Levels of High-Sensitivity C-Reactive Protein in Non–Hispanic Black Adolescents 
Diabetes Care  2011;34(3):734-740.
OBJECTIVE
Whereas it is known that the metabolic syndrome (MetS) has a paradoxically lower prevalence in non–Hispanic black adolescents than in non–Hispanic whites or Hispanics, the relative severity of MetS by race/ethnicity is unknown. Inflammation, indicated by high-sensitivity C-reactive protein (hsCRP), is a key factor linking MetS to cardiovascular disease and type 2 diabetes. Our goal was to determine whether elevations of hsCRP vary by race/ethnicity among adolescents with MetS.
RESEARCH DESIGN AND METHODS
We used the National Health and Nutrition Examination Survey (1999–2008) and evaluated adolescents (age 12–19 years) using a pediatric/adolescent adaptation of the ATP III definition of MetS. We used linear regression to evaluate the interaction between MetS status and ethnicity with respect to hsCRP concentration.
RESULTS
For male and female adolescents, MetS was associated with elevated hsCRP levels compared with adolescents without MetS. However, the elevation in hsCRP between adolescents with and without MetS was greater in non–Hispanic blacks compared with that in non–Hispanic whites (P = 0.04) but not that in Hispanics (P = 0.18). hsCRP concentrations correlated with individual MetS components similarly among all ethnicities. In an evaluation of adolescents diagnosed with MetS, non–Hispanic blacks had higher BMI and more hypertension than other ethnicities but there were no other racial/ethnic differences in the features of MetS.
CONCLUSIONS
Non–Hispanic black adolescents have a greater differential in hsCRP between those with and those without MetS than the differential in non–Hispanic whites but not that in Hispanics. Therefore, even though MetS has a low prevalence in non–Hispanic blacks, MetS is a particularly good indicator of inflammation in non–Hispanic black adolescents.
doi:10.2337/dc10-1877
PMCID: PMC3041218  PMID: 21285387
9.  High-Density Lipoprotein Particles and Markers of Inflammation and Thrombotic Activity in Patients with Untreated HIV Infection 
The Journal of infectious diseases  2010;201(2):285-292.
Background
Untreated HIV infection is associated with changes in blood lipids, inflammation, thrombotic activity, and increased risk for CVD.
Methods
We studied high-density lipoprotein particle (HDLp) concentrations and inflammatory (hsCRP, IL-6), endothelial activation (E-selectin, sICAM-1) and thrombotic (fibrinogen and D-dimer) biomarkers in 32 untreated HIV-infected and 29 uninfected persons. Differences in blood lipids and biomarkers by HIV status were examined before and after adjustment for: age, gender, race/ethnicity, smoking status, BMI, and hepatitis C.
Results
HIV-infected, versus uninfected, participants had lower HDLc (−26%) and total (−21%), large (−50%)and small HDLp (−20%; p≤0.01 for all), but not medium HDLp. A trend was present for higher total cholesterol (p=0.15) and triglycerides (p=0.11) with HIV infection. Levels of IL-6, sICAM-1 and D-dimer were 65–70% higher in HIV-infected participants (p≤0.02 for all). Covariate adjustment did not diminish these associations. For HIV-infected participants, total and small HDLp (respectively) tended to correlate inversely with levels of IL-6 (p=0.08 and p=0.02), sICAM-1 (p<0.01 for both) and D-dimer (p=0.03 and p<0.01).
Conclusions
Persons with untreated HIV infection have lower HDLp, primarily large and small HDLp, and higher IL-6, sICAM-1, and D-dimer levels, and the relationship of these markers with risk for HIV-mediated atherosclerotic risk requires further study.
doi:10.1086/649560
PMCID: PMC2798007  PMID: 19954384
HIV-infection; inflammation; thrombosis; endothelial dysfunction; lipoprotein particles; HDL; cardiovascular disease
10.  Inflammation Markers are Associated with Cardiovascular Diseases Risk in Adolescents: The Young Hearts Project 2000 
The Journal of Adolescent Health  2010;47(4):346-351.
Purpose
The traditional approach for identifying subjects at risk from cardiovascular diseases (CVD) is to determine the extent of clustering of biological risk factors adjusted for lifestyle. Recently, markers of endothelial dysfunction and low grade inflammation, including high sensitivity C-reactive protein (hsCRP), soluble intercellular adhesion molecules (sICAM), and soluble vascular adhesion molecules (sVCAM), have been included in the detection for high risk individuals. However, the relationship of these novel biomarkers with CVD risk in adolescents remains unclear. The purpose of this study, therefore, was to establish the association of hsCRP, sICAM, and sVCAM with CVD risk in an adolescent population.
Methods
Data from the Young Hearts 2000 cross-sectional cohort study, carried out in 1999–2001, were used. From a total of 2,017 male and female participants, 95 obese subjects were identified and matched according to age, sex, and cigarette smoking, with 95 overweight and 95 normal-weight adolescents. Clustered CVD risk was computed using a sum of Z-scores of biological risk factors. The relationship was described using multiple linear regression analyses.
Results
hsCRP, sICAM, and sVCAM showed significant associations with CVD risk. hsCRP and sICAM had a positive relation with CVD risk, whereas sVCAM showed an inverse relationship. In this study, lifestyle factors showed no relation with CVD risk.
Conclusion
The results fit the hypothesized role of low grade inflammation and endothelial dysfunction in CVD risk in asymptomatic adolescents. The inverse relationship of VCAM, however, is hard to explain and indicates the complex mechanisms underlying CVD. Further research is needed to draw firm conclusions on the biomarkers used.
doi:10.1016/j.jadohealth.2010.04.008
PMCID: PMC2958312  PMID: 20864003
Cardiovascular diseases; Adolescence; hsCRP; sICAM; sVCAM
11.  Metabolic Syndrome among Emirati Adolescents: A School-Based Study 
PLoS ONE  2013;8(2):e56159.
Objectives
Population-based data on metabolic syndrome (MetS) among children is lacking in the United Arab Emirates which has among the highest rates of diabetes in the world. In this study we determined the prevalence of MetS and its correlates in a sample of adolescents.
Materials and Methods
A cross-sectional school-based study was conducted on 1,018 adolescents (48.4% girls) aged 12–18 years from Al Ain Abu Dhabi Emirates. A self-administered questionnaire was used to assess socio-demographic characteristics, physical activity and dietary habits. Blood pressure, height, weight, waist circumference, fasting glucose, HDL-cholesterol and triglycerides were measured. MetS was defined using the International Diabetes Federation (IDF) criteria.
Results
The prevalence of metabolic syndrome was 13%. Boys compared to girls were more likely to have MetS (21% vs. 4%, odds ratio [OR]: 6.57, 95%CI: 4.01 to 10.75). The prevalence of MetS increased with increase in body mass index and reached 59 percent in obese boys. After multivariable adjustment boys who were overweight (adjusted OR: 2.72 [1.37 to 5.35]), or obese (AOR: 12.70 [7.31 to 22.05]), or spent two or more than two hours on screen in a day (AOR: 1.65 [1.01 to 2.69) were more likely to have MetS. Girls who were overweight (AOR: 4.23 [1.32 to 13.62]) or obese (AOR: 8.32 [2.73 to 25.32]) were more likely to have MetS.
Conclusions
The prevalence of MetS is high among UAE boys. Population-based strategies are needed to address the high burden of metabolic syndrome targeted at the identified risk factors.
doi:10.1371/journal.pone.0056159
PMCID: PMC3572014  PMID: 23418529
12.  Relations of Dietary Magnesium Intake to Biomarkers of Inflammation and Endothelial Dysfunction in an Ethnically Diverse Cohort of Postmenopausal Women 
Diabetes Care  2009;33(2):304-310.
OBJECTIVE
Although magnesium may favorably affect metabolic outcomes, few studies have investigated the role of magnesium intake in systemic inflammation and endothelial dysfunction in humans.
RESEARCH DESIGN AND METHODS
Among 3,713 postmenopausal women aged 50–79 years in the Women's Health Initiative Observational Study and free of cardiovascular disease, cancer, and diabetes at baseline, we measured plasma concentrations of high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), turnor necrosis factor-α receptor 2 (TNF-α-R2), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and E-selectin. Magnesium intake was assessed using a semiquantitative food frequency questionnaire.
RESULTS
After adjustment for age, ethnicity, clinical center, time of blood draw, smoking, alcohol, physical activity, energy intake, BMI, and diabetes status, magnesium intake was inversely associated with hs-CRP (P for linear trend = 0.003), IL-6 (P < 0.0001), TNF-α-R2 (P = 0.0006), and sVCAM-1 (P = 0.06). Similar findings remained after further adjustment for dietary fiber, fruit, vegetables, folate, and saturated and trans fat intake. Multivariable-adjusted geometric means across increasing quintiles of magnesium intake were 3.08, 2.63, 2.31, 2.53, and 2.16 mg/l for hs-CRP (P = 0.005); 2.91, 2.63, 2.45, 2.27, and 2.26 pg/ml for IL-6 (P = 0.0005); and 707, 681, 673, 671, and 656 ng/ml for sVCAM-1 (P = 0.04). An increase of 100 mg/day magnesium was inversely associated with hs-CRP (−0.23 mg/l ± 0.07; P = 0.002), IL-6 (−0.14 ± 0.05 pg/ml; P = 0.004), TNF-α-R2 (−0.04 ± 0.02 pg/ml; P = 0.06), and sVCAM-1 (−0.04 ± 0.02 ng/ml; P = 0.07). No significant ethnic differences were observed.
CONCLUSIONS
High magnesium intake is associated with lower concentrations of certain markers of systemic inflammation and endothelial dysfunction in postmenopausal women.
doi:10.2337/dc09-1402
PMCID: PMC2809271  PMID: 19903755
13.  Impact of HbA1c criterion on the definition of glycemic component of the metabolic syndrome: the China health and nutrition survey 2009 
BMC Public Health  2013;13:1045.
Background
In 2009, a unified definition of metabolic syndrome (MetS) was proposed, of which, the glycemic component is defined on the basis of fasting plasma glucose (FPG) level. Recently, the American Diabetes Association (ADA) recommended the use of glycated hemoglobin (HbA1c) as an alternative to FPG to define prediabetes. Hence, we aim to compare the performance of HbA1c and FPG in the definition of glycemic component of the MetS among Chinese adults.
Methods
We conducted a cross-sectional analysis of 7641 Chinese participants aged ≥18 years using data from the China Health and Nutrition Survey 2009. MetS was defined according to the consensus criteria in 2009. We compared the use of HbA1c versus FPG in the definition of the glycemic component of MetS. Increased HbA1c value was defined following the criterion of HbA1c cut-off point of ≥5.7% recommended by the ADA.
Results
Overall, 1136 (14.9%) had MetS according to FPG ≥ 5.6 mmol/l, and 1640 (21.5%) had MetS according to HbA1c ≥ 5.7%. Compared with individuals with FPG-based diagnosis of MetS, individuals with HbA1c-based diagnosis of MetS were older, had higher levels of LDL-C, magnesium, and transferrin, and lower levels of uric acid. Of those found to have MetS according to either FPG or HbA1c (n = 2008), overlap between HbA1c- and FPG-based diagnosis of MetS was limited (n = 768, 38.2%). The overlap index regarding MetS diagnosed by FPG or HbA1c persisted low in each evaluated subgroup (≤ 50.0%).
Conclusions
We note limited overlap and poor agreement between FPG- and HbA1c-based diagnosis of MetS. Screening MetS through introduction of HbA1c in addition to FPG could contribute to identification of more people with MetS.
doi:10.1186/1471-2458-13-1045
PMCID: PMC3924337  PMID: 24188743
Fasting plasma glucose; HbA1c; Metabolic syndrome; CVD risk factors
14.  Clustering of metabolic syndrome components in a Middle Eastern diabetic and non-diabetic population 
Background
Metabolic syndrome (MetS) encompasses a cluster of coronary heart disease and diabetes mellitus risk factors. In this study, we aimed to elucidate the factors underlying the clustering of MetS components in diabetic and non-diabetic individuals.
Methods
Factor analysis was performed on 2978 (1652 non-diabetic and 1326 diabetic) participants. Entering waist circumference, homeostasis model assessment of insulin resistance (HOMA-IR), triglycerides, high-density lipoprotein-cholesterol (HDL-C) and systolic blood pressure (SBP), we performed exploratory factor analysis in diabetic and non-diabetic individuals separately. The analysis was repeated after replacing triglycerides and HDL-C with triglycerides to HDL-C ratio (triglycerides/HDL-C). MetS was defined by either adult treatment panel III (ATPIII), international diabetes federation (IDF) criteria, or by the modified form of IDF using waist circumference cut-off points for Iranian population.
Results
The selection of triglycerides and HDL-C as two distinct variables led to identifying two factors explaining 61.3% and 55.4% of the total variance in non-diabetic and diabetic participants, respectively. In both diabetic and non-diabetic subjects, waist circumference, HOMA-IR and SBP loaded on factor 1. Factor 2 was mainly determined by triglycerides and HDL-C. Factor 1 and 2 were directly and inversely associated with MetS, respectively. When triglycerides and HDL-C were replaced by triglycerides/HDL-C, one factor was extracted, which explained 47.6% and 38.8% of the total variance in non-diabetic and diabetic participants, respectively.
Conclusion
This study confirms that in both diabetic and non-diabetic participants the concept of a single underlying factor representing MetS is plausible.
doi:10.1186/1758-5996-2-36
PMCID: PMC2897775  PMID: 20529329
15.  Obesity Index That Better Predict Metabolic Syndrome: Body Mass Index, Waist Circumference, Waist Hip Ratio, or Waist Height Ratio 
Journal of Obesity  2013;2013:269038.
Aim. The aim was to compare body mass index (BMI), waist circumference (WC), waist hip ratio (WHR), and waist height ratio (WHtR) to identify the best predictor of metabolic syndrome (MetS) among Qatari adult population. Methods. A cross-sectional survey from April 2011 to December 2012. Data was collected from 1552 participants followed by blood sampling. MetS was defined according to Third Adult Treatment Panel (ATPIII) and International Diabetes Federation (IDF). Receiver operating characteristics (ROC) curve analysis was performed. Results. Among men, WC followed by WHR and WHtR yielded the highest area under the curve (AUC) (0.78; 95% CI 0.74–0.82 and 0.75; 95% CI 0.71–0.79, resp.). Among women, WC followed by WHtR yielded the highest AUC (0.81; 95% CI 0.78–0.85 & 0.79; 95% CI 0.76–0.83, resp.). Among men, WC at a cut-off 99.5 cm resulted in the highest Youden index with sensitivity 81.6% and 63.9% specificity. Among women, WC at a cut-off 91 cm resulted in the highest Youden index with the corresponding sensitivity and specificity of 86.5% and 64.7%, respectively. BMI had the lowest sensitivity and specificity in both genders. Conclusion. WC at cut-off 99.5 cm in men and 91 cm in women was the best predictor of MetS in Qatar.
doi:10.1155/2013/269038
PMCID: PMC3755383  PMID: 24000310
16.  CRP and Adiponectin and Its Oligomers in the Metabolic Syndrome 
The metabolic syndrome (MetS) confers an increased risk for diabetes and cardiovascular disease. Although high-sensitive C-reactive protein (hsCRP) concentrations are higher and adiponectin concentrations lower in MetS, there is no reliable biochemical measure that can capture its various features. We evaluated whether hsCRP, adiponectin, or the ratio of adiponectin or its oligomers, especially the high-molecular-weight (HMW) oligomer, to hsCRP predict MetS in 123 subjects with MetS compared with that in 91 healthy control subjects. MetS subjects had significantly higher hsCRP levels and lower total adiponectin and oligomer levels relative to control subjects (P < .0001). The HMW/total adiponectin and adiponectin/CRP ratios were significantly lower in MetS subjects than control subjects (P < .005). The odds ratio (OR) of MetS using the 75th percentile cutoff for CRP was 3.8 (95% confidence interval [CI], 2.1–6.8) and equivalent to low total adiponectin (OR, 2.5; 95% CI, 1.3–4.5), its oligomers, or the adiponectin/hsCRP ratio (OR, 2.6; 95% CI, 1.5, 4.8). Thus, measurements of CRP, adiponectin, or its oligomers provide robust biomarkers for predicting MetS.
doi:10.1309/RN84K51B2JJY1Y0B
PMCID: PMC2664630  PMID: 18426744
C-reactive protein; Adiponectin; Biomarker; Metabolic syndrome
17.  Evaluation of Adiposity-Related Biomarkers as Metabolic Syndrome Indicators 
Clinical Nutrition Research  2013;2(2):91-99.
Recent studies have suggested a relationship of the increased circulating adipokines and inflammatory cytokine, and the risk of metabolic syndrome (MetS). The objective of this study was to identify adiposity-related factors that reflect MetS in order to establish early intervention targets. We performed a cross-sectional study which included 108 MetS subjects and 91 controls. Blood adiponectin, leptin, vascular-, and intercellular adhension molecules (VCAM, ICAM), monocyte chemoattractant protein 1 (MCP1), high-sensitivity C-reactive protein (hsCRP), oxidized LDL (oxLDL), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were measured. The correlation analysis indicated that the MetS score (sum of the number of MetS risk factors) had an inverse relationship with adiponectin (p < 0.0001), and positive correlations with leptin (p < 0.05), ICAM (p < 0.01), MCP1 (p < 0.05), oxLDL (p < 0.05), TNF-α (p < 0.0001), IL-6 (p < 0.05) and hsCRP (p < 0.01). In multivariate logistic regression analyses, plasma triglyceride (TG) was independently associated with adiponectin, ICAM and TNF-α with the standardized β coefficients of -0.213, 0.197, and 0.193, respectively. Plasma HDL-cholesterol was independently associated with ICAM and hsCRP with the standardized β coefficients of -0.150 and -0.173. Adiponectin, TNF-α, and hsCRP were the most proximate markers reflecting MetS. Among MetS components, TG and HDL-cholesterol concentrations displayed the relationship with inflammatory markers measured in this study.
doi:10.7762/cnr.2013.2.2.91
PMCID: PMC3728468  PMID: 23908975
Metabolic syndrome; Adiposity; Adipokines; Inflammatory cytokines; Abdominal fat
18.  Relationship of Weekly Activity Minutes to Metabolic Syndrome in Prediabetes: The Healthy Living Partnerships to Prevent Diabetes 
Background
Physical inactivity contributes to metabolic syndrome (MetS) in overweight/obesity. However, little is known about this relationship in prediabetes.
Methods
The study purpose is to examine relationships between physical activity (PA) and MetS in prediabetes. The Healthy Living Partnerships to Prevent Diabetes tested a community translation of the Diabetes Prevention Program (DPP). Three hundred one overweight/obese prediabetics provided walking minutes/week (WM) and total activity minutes/week (AM) via the International Physical Activity Questionnaire. MetS was at least 3 of waist (men ≥ 102 cm, women ≥ 88 cm), triglycerides (≥150 mg·dl), blood pressure (≥130·85 mm Hg), glucose (≥100mg·dl), and HDL (men < 40mg·dl, women < 50mg·dl).
Results
The sample was 57.5% female, 26.7% nonwhite/Hispanic, 57.9 ± 9.5 years and had a body mass index (BMI) 32.7 ± 4 kg·m2. Sixty percent had MetS. Eighteen percent with MetS reported at least 150 AM compared with 29.8% of those without MetS. The odds of MetS was lower with greater AM (Ptrend = .041) and WM (Ptrend = .024). Odds of MetS with 0 WM were 2.08 (P = .046) and with no AM were 2.78 (P = .009) times those meeting goal. One hour additional WM led to 15 times lower MetS odds.
Conclusions
Meeting PA goals reduced MetS odds in this sample, which supported PA for prediabetes to prevent MetS.
PMCID: PMC3765007  PMID: 23036940
obesity; walking; physical activity
19.  Relationship Between Carotid Intima-Media Thickness with some Inflammatory Biomarkers, Ghrelin and Adiponectin in Iranians with and without Metabolic Syndrome in Isfahan Cohort Study 
ARYA Atherosclerosis  2010;6(2):56-61.
BACKGROUND
Recent studies have confirmed inflammatory factors and metabolic syndrome (MetS) as important cardiovascular disease (CVD) risk factors. Recently measurement of carotid intima-media thickness (IMT) has been used for evaluation of early atherosclerosis. This study was designed to assess the correlation between IMT with some inflammatory biomarkers, ghrelin and adiponectin in people with and without MetS in a cohort sample in Isfahan province.
METHODS
Among participants of Isfahan Cohort Study (ICS) by random sampling, 88 participants were selected and divided into case (with MetS) and control (without MetS) groups. A questionnaire including demographic data and CVD risk factors was completed for all of the participants. Physical examination and blood pressure, height, weight and waist circumference measurements were done for all subjects. Vascular echocardiography was done for evaluation of IMT of each carotid artery of both sides. Interlukin-6 (IL-6), interlukin-10 (IL-10), highly sensitive C-reactive protein (hs-CRP), ghrelin and adiponectin levels were measured using ELIZA method. Data were entered in SPSS15 software and analyzed by t-test, chi square, Pearson correlation and linear regression analyze.
RESULTS
The mean waist circumference, BMI, systolic blood pressure, diastolic blood pressure, hs-CRP and IMT of left carotid artery were significantly higher in participants with Mets. There was significant correlation between left carotid IMT and IL-6 level in all patients (P = 0.03). After adjustment for age and sex, significant relationship in groups with MetS was only reported between the left IMT and IL-6 (P = 0.02). There was no relation between IMT and other inflammatory markers in subjects with and without MetS.
CONCLUSION
Significant correlation between IL-6 and IMT was reported in patients with MetS. While no significant correlation between IL-10, adiponectin and ghrelin with IMT was observed in metabolic syndrome group.
PMCID: PMC3347812  PMID: 22577415
Intima-media thickness (IMT); Carotid artery; hs-CRP; Ghrelin; Adiponectin IL-6; IL-10
20.  Gamma-tocopherol supplementation alone and in combination with alpha-tocopherol alters biomarkers of oxidative stress and inflammation in subjects with metabolic syndrome 
Free radical biology & medicine  2007;44(6):1203-1208.
Metabolic syndrome (MetS) is associated with increased incidence of diabetes and cardiovascular disease (CVD). Prospective clinical trials with alpha-tocopherol (AT) have not yielded positive results. Because AT supplementation decreases circulating gamma-tocopherol (GT), we evaluated supplementation with GT (800 mg/day), AT (800 mg/day), the combination or placebo for 6 weeks alone AT and GT concentrations, biomarkers of oxidative stress, and inflammation in subjects with MetS (n=20/group). Plasma AT and GT levels increased following supplementation with AT alone or GT alone or in combination. AT supplementation significantly decreased GT levels. Urinary alpha- and gamma-CEHC, metabolites of the respective Ts, also increased correspondingly, i.e., alpha-CEHC with ATand gamma-CEHC with GT supplementation, compared to placebo. HsCRP levels significantly decreased in the combined AT+GT group. LPS-activated whole blood release of IL-1 and IL-6 did not change. There was a significant decrease in TNF with AT alone or in combination with GT. Plasma MDA/HNE and lipid peroxides were significantly decreased with AT, GT, or in combination. Nitrotyrosine levels were significantly decreased only with GT or GT+AT but not with AT compared to placebo. Thus, the combination of AT and GT supplementation appears to be superior to either supplementation alone on biomarkers of oxidative stress and inflammation and needs to be tested in prospective clinical trials to elucidate its utility in CVD prevention.
doi:10.1016/j.freeradbiomed.2007.12.018
PMCID: PMC2676174  PMID: 18191645
Antioxidant; Tocopherol; Inflammation; Oxidative stress; Nitrative stress
21.  Hantaviruses in Rodents and Humans, Inner Mongolia Autonomous Region, China 
Emerging Infectious Diseases  2009;15(6):885-891.
Vigilance is needed to prevent hemorrhagic fever renal syndrome caused by Hantaan and Seoul viruses in this region.
Surveys were carried out in 2003–2006 to better understand the epidemiology of hantaviruses in the Inner Mongolia Autonomous Region of China (Inner Mongolia). Hemorrhagic fever with renal syndrome (HFRS) was first reported in this region in 1955 and has been an important public health problem here since then. During 1955–2006, 8,309 persons with HFRS were reported in Inner Mongolia (average incidence rate 0.89/100,000), and 261 (3.14%) died. Before the 1990s, all HFRS cases occurred in northeastern Inner Mongolia. Subsequently, HFRS cases were registered in central (1995) and western (1999) Inner Mongolia. In this study, hantaviral antigens were identified in striped field mice (Apodemus agrarius) from northeastern Inner Mongolia and in Norway rats (Rattus norvegicus) from middle and western Inner Mongolia. Phylogenetic analysis of hantaviral genome sequences suggests that HFRS has been caused mainly by Hantaan virus in northeastern Inner Mongolia and by Seoul virus in central and western Inner Mongolia.
doi:10.3201/eid1506.081126
PMCID: PMC2727351  PMID: 19523286
Viruses; zoonoses; hemorrhagic fever with renal syndrome; hantavirus; Hantaan virus; Seoul virus; China; Mongolia; research
22.  The Prevalence and Characteristics of Metabolic Syndrome in Patients with Vertigo 
PLoS ONE  2013;8(12):e80176.
Objectives/Hypothesis
Metabolic syndrome (MetS) is a condition that increases the risk of coronary artery disease and cerebral infarction. We determined the prevalence of MetS in vertigo patients and clinically investigated the association between MetS and vertigo.
Study Design
Case-control study
Methods
The subjects were 333 patients, including 107 males and 226 females, who presented with vertigo as a primary symptom. MetS was diagnosed according to the International Diabetes Federation definition, which is based on waist circumference, blood serum levels, and blood pressure.
Results
MetS was detected in 53 (15.9%) of 333 vertigo patients, including 24 males (22.4%) and 29 females (12.8%); i.e., the frequency of MetS was significantly higher among the male patients than the female patients. The overall prevalence of MetS (15.9%) among vertigo patients did not differ from that observed among general adults in previous Japanese surveillance studies; however, MetS was significantly more common among the vertigo patients in males than general adult males. The prevalence of MetS was also examined in five types of vertigo, Concomitant MetS was noted in many males with vertebrobasilar insufficiency (VBI) and isolated vertigo of unknown etiology.
Conclusion
It was suggested that MetS is involved in the development of vertigo in males. MetS might be a risk factor for vascular vertigo such as VBI in males. The high frequency of MetS among males with vertigo of unknown etiology suggested that the pathogenesis of metabolic syndrome is involved in this type of isolated vertigo.
doi:10.1371/journal.pone.0080176
PMCID: PMC3848922  PMID: 24312461
23.  Metabolic Syndrome, Inflammation, and the Incident Heart Failure in the Elderly: the Cardiovascular Health Study 
Circulation. Heart failure  2008;1(4):242-248.
Background
Inflammation markers and MetS are associated with risk of CHF. We evaluated whether combining inflammation markers and metabolic syndrome (MetS) provided additive information for incident congestive heart failure (CHF), and if incorporating inflammation markers to the MetS definition added prognostic information.
Methods and Results
We studied 4017 men and women ≥ 65 years old, without baseline CHF or diabetes, participating in the Cardiovascular Health Study, an observational study with 12.2 years follow-up and 966 cases of incident CHF. Baseline “C-reactive protein (CRP)-MetS” or “interleukin-6 (IL-6)-MetS” were defined as presence of 3 out of 6 components, with elevated CRP (≥3 mg/L) or IL-6 (≥2.21 pg/mL) as a 6th component added to ATPIII criteria. Cox models adjusted for CHF risk factors and incident coronary disease, were used to calculate HRs for CHF. MetS and elevated inflammation markers were independently associated with CHF risk (HRs, 95 % CI: 1.32, 1.16–1.51 for MetS; 1.53, 1.34–1.75 for CRP; 1.37, 1.19–1.55 for IL-6). There was a 20% relative excess risk attributed to the combination of MetS and CRP (95% CI −44% to 88%). CRP-MetS and IL-6-MetS definitions reclassified 18% and 13%, respectively of participants as MetS. Both CRP-MetS and IL-6-MetS increased risk of CHF by 60% compared to those without MetS.
Conclusion
MetS and inflammation markers provided additive information on CHF risk in this elderly cohort. Inflammation-incorporated MetS definitions identified more participants with the same risk level as ATPIII MetS. Considering inflammation markers and MetS together may be useful in clinical and research settings.
doi:10.1161/CIRCHEARTFAILURE.108.785485
PMCID: PMC2762642  PMID: 19808298
heart failure; metabolism; inflammation
24.  A confirmatory factor analysis of the metabolic syndrome in adolescents: an examination of sex and racial/ethnic differences 
Objective
The metabolic syndrome (MetS) is a cluster of clinical indices that signals increased risk for cardiovascular disease and Type 2 diabetes. The diagnosis of MetS is typically based on cut-off points for various components, e.g. waist circumference and blood pressure. Because current MetS criteria result in racial/ethnic discrepancies, our goal was to use confirmatory factor analysis to delineate differential contributions to MetS by sub-group.
Research Design and Methods
Using 1999–2010 data from the National Health and Nutrition Examination Survey (NHANES), we performed a confirmatory factor analysis of a single MetS factor that allowed differential loadings across sex and race/ethnicity, resulting in a continuous MetS risk score that is sex and race/ethnicity-specific.
Results
Loadings to the MetS score differed by racial/ethnic and gender subgroup with respect to triglycerides and HDL-cholesterol. ROC-curve analysis revealed high area-under-the-curve concordance with MetS by traditional criteria (0.96), and with elevations in MetS-associated risk markers, including high-sensitivity C-reactive protein (0.71), uric acid (0.75) and fasting insulin (0.82). Using a cut off for this score derived from ROC-curve analysis, the MetS risk score exhibited increased sensitivity for predicting elevations in ≥2 of these risk markers as compared with traditional pediatric MetS criteria.
Conclusions
The equations from this sex- and race/ethnicity-specific analysis provide a clinically-accessible and interpretable continuous measure of MetS that can be used to identify children at higher risk for developing adult diseases related to MetS, who could then be targeted for intervention. These equations also provide a powerful new outcome for use in childhood obesity and MetS research.
doi:10.1186/1475-2840-11-128
PMCID: PMC3489601  PMID: 23062212
Metabolic syndrome; Factor analysis, Statistical; Insulin resistance; Pediatrics; Adolescents; Epidemiology; Clinical studies; Obesity; Risk factors
25.  Retinal Vascular Caliber, Cardiovascular Risk Factors, and Inflammation: The Multi-Ethnic Study of Atherosclerosis (MESA) 
Purpose
To describe the relationship of retinal arteriolar and venular caliber with cardiovascular risk factors, including inflammatory biomarkers, in a multiethnic population of whites, blacks, Hispanics, and Chinese.
Methods
A cross-sectional study comprising 5979 persons aged 45 to 84 years residing in six U.S. communities. Retinal vascular caliber was measured and summarized from digital retinal photographs. Standard cardiovascular risk factors, including biomarkers of inflammation (e.g., high-sensitivity C-reactive protein [hsCRP], interleukin [IL]-6, and plasma fibrinogen) and endothelial dysfunction (e.g., soluble intercellular adhesion molecule [sICAM]-1 [, plasminogen activator inhibitor [PAI]-1) were assessed.
Results
Mean retinal arteriolar caliber was 144.1 ± 14.4 (SD) μm, and venular caliber 214.0 ± 22.2 μm. In models controlling for age, gender, race-ethnicity, and center, smaller retinal arteriolar caliber was related to higher systolic and diastolic blood pressure, hypertension status, current alcohol consumption, greater body mass index, and higher levels of total homocysteine; larger retinal arteriolar caliber was related to diabetes, current cigarette smoking, and higher levels of plasma fibrin-ogen; and larger retinal venular caliber was related to diabetes, current cigarette smoking, greater body mass index and waist-hip ratio, higher levels of serum glucose, plasma triglyceride, plasma LDL-cholesterol, hsCRP, plasma fibrinogen, IL6, sICAM-1, and PAI-1 and lower levels of HDL-cholesterol. In multivariate analyses, blacks and Hispanics had larger retinal arteriolar and venular calibers than did whites and Chinese.
Conclusions
Retinal arteriolar and venular caliber is associated with a range of cardiovascular risk factors, including hypertension, diabetes, measures of obesity, and dyslipidemia. Venular caliber is also associated with systemic inflammation.
doi:10.1167/iovs.05-1539
PMCID: PMC2258139  PMID: 16723443

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