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1.  Metabolic syndrome and health-related quality of life in Iranian population 
To investigate the association between Metabolic syndrome (MetS) and Health related quality of life (QoL) in Iranian population.
We used data from the post-intervention phase of Isfahan Healthy Heart Program (IHHP), a community trial for cardiovascular disease (CVD) prevention and control. We recruited 9570 healthy adults, aged ≥ 19 years who were randomly selected using multistage random sampling method. World Health Organization QoL questionnaire (WHOQOL-BREF) which contains 26 items was used to assess QoL. It assesses four domains of QoL; Physical health, Psychological health, Social relationship and Environmental issues. MetS was defined based on ATP III criteria.
The mean age of participants was 38.8±15.6 years (mean ± SD) and the prevalence of MetS was 22.5%. From all participant 18.2% were illiterate and 13.2% had university educational level. Two way multivariate analyses of covariance (MANCOVA) test after adjusting age showed significant difference between women with and without Mets in regard to physical health and social relations domains, while none of QoL domains was different in men with Mets in comparison to men without it.
After adjusting the role of socio-demographic factors as components of QoL score, no association was observed between QoL domains and MetS in men, while only social relations and physical health scores were higher in women with Mets compared to those without Mets. Other variety of health-related QoL assessment tools or definitions of MetS may show different relationship in the Iranian socio-cultural context.
PMCID: PMC3214330  PMID: 22091241
Metabolic syndrome; Quality of life; General population
2.  Health-Related Quality of Life, Subjective Health Complaints, Psychological Distress and Coping in Pakistani Immigrant Women With and Without the Metabolic Syndrome 
The increasingly high number of immigrants from South-East Asia with The Metabolic Syndrome (MetS) is an important challenge for the public health sector. Impaired glucose is essential in MetS. The blood glucose concentration is not only governed by diet and physical activity, but also by psychological distress which could contribute to the development of MetS. The aim of this study is to describe health-related quality of life, subjective health complaints (SHC), psychological distress, and coping in Pakistani immigrant women, with and without MetS. As a part of an randomized controlled intervention study in Oslo, Norway, female Pakistani immigrants (n = 198) answered questionnaires regarding health related quality of life, SHC, psychological distress, and coping. Blood variables were determined and a standardized oral glucose tolerance test was performed. The participants had a high score on SHC and psychological distress. About 40% of the participants had MetS, and this group showed significantly lower general health, lower physical function, and more bodily pain, than those without MetS. Those with MetS also had more SHC, depressive symptoms, higher levels of somatisation, and scored significantly lower on the coping strategy of active problem solving. Pakistani immigrant women seem to have a high prevalence of SHC and psychological distress, especially those with MetS.
PMCID: PMC3132418  PMID: 21061066
Pakistani immigrant women; Immigration; Psychological distress; Coping; Metabolic syndrome
3.  Relationship between Metabolic Syndrome and Its Components with Psychological Distress 
Background. Metabolic syndrome (MetS) and psychological distress are hypothesized to have a bidirectional relationship. According to their high prevalence in most populations, appraisal of this theory would be of great clinical and research interest. Methods. Data were available as part of the Isfahan Healthy Heart Program (IHHP). A total of 9553 men and women aged ≥19 years from three counties in central Iran were selected. Measurements consisted of serologic tests, anthropometrics, and self-reported 12-item general health questionnaire. Logistic regression analysis was used to find the association between MetS, MetS components, and distress level. Results. The mean age of 9553 participants (50% male) was 38.7 ± 15.8 years. After adjusting for demographic factors, MetS (OR = 1.25, 95% CI: 1.01–1.37), central obesity (OR = 1.40, 95% CI: 1.15–1.49), and hypertension (OR = 1.55, 95% CI: 1.42–1.70) were associated with high distress level. However, after adding smoking status and low-density lipoprotein cholesterol to the adjustment factors, hypertension (OR = 1.79, 95% CI: 1.53–1.98) and central obesity (OR = 1.41, 95% CI: 1.17–1.55), but not the MetS, remained significantly associated with distress level. Conclusion. The presence of association between the MetS as well as its key components and high distress level signifies the importance of integrating psychological assessment and intervention in the standard management of MetS patients.
PMCID: PMC3941148  PMID: 24672543
4.  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.
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.
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.
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.
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
5.  Adherence to the Nordic Nutrition Recommendations in a Nordic population with metabolic syndrome: high salt consumption and low dietary fibre intake (The SYSDIET study) 
Food & Nutrition Research  2013;57:10.3402/fnr.v57i0.21391.
The Nordic countries collaborate in setting recommendations for intake of nutrients by publishing the Nordic Nutrition Recommendations (NNR). Studies exploring how well the Nordic population adheres to the NNR are limited and none are available for the metabolic syndrome (MetS) subgroup. Individuals with MetS are a large part of the adult Nordic population and their diet's nutritional quality is of great importance as it can affect the progression of MetS.
To evaluate nutritional intake in a cohort of Nordic adults with MetS or MetS risk factors and their adherence to the NNR.
A multi-centre study was carried out in six centres in four Nordic countries (SYSDIET CoE). Participants (n=175) were 30–65 years of age, with BMI 27–38 kg/m2 and had at least two criteria for MetS. The NNR was used to evaluate the baseline nutrient intake calculated from the participants’ 4-day food diaries using national nutrient databases.
Less than 20% of participants consumed ≤10 E% from saturated fat as recommended in the NNR. Recommended intake (RI) of polyunsaturated fat was met by approximately one-third of participants. Only 20% of men and 26% of women met the RI of dietary fibre. Intake below the defined lower intake level of 2.5 µg/day for vitamin D was observed in nearly 20% of participants. The daily median intake of salt was 8.8 g for men and 6.7 g for women.
Dietary quality of this Nordic population with Mets or MetS risk factors is unsatisfactory and characterised by high intakes of SFA and sodium and low intakes of PUFA and dietary fibre. Vitamin D intake was below RI level in a large part of the population. Authorities in the Nordic countries are encouraged to develop intervention programmes for high-risk groups.
PMCID: PMC3866840  PMID: 24358036
diet records; dietary fibre; guideline adherence; metabolic syndrome; multicenter study; sodium; dietary
6.  Metabolic syndrome and onset of depressive symptoms in the elderly: findings from the three-city study 
Diabetes Care  2011;34(4):904-909.
Given the increasing prevalence of both metabolic syndrome (MetS) and depressive symptoms during old age, we aimed to examine prospectively the association between MetS and onset of depressive symptoms according to different age-groups in a large general elderly population.
Research Design and Methods
Prospective cohort study of 4446 men and women aged 65 to 91 and free of depression or depressive symptoms at baseline (the Three-City study, France). MetS was defined using the NCEP-ATP III criteria. New onset of depressive symptoms (the Center for Epidemiologic Studies Depression Scale (CES-D) score≥16 and use of antidepressant treatment) was assessed at 2- and 4-year follow-ups.
After adjusting for a large range of potential confounders, we observed MetS to be associated with a 1.73-fold (95% CI: 1.02–2.95) odds for new-onset depressive symptoms in the youngest age group (65 to 70 at baseline), independently of cardiovascular diseases. No such association was seen in older age groups.
Our findings suggest that the link between MetS and depressive symptoms evidenced until now in middle-aged can be extended to older adults but not to the oldest ones. Further research is needed to examine if a better management of MetS prevents depressive symptoms in people aged 65 to 70.
PMCID: PMC3064049  PMID: 21346185
Depressive symptoms; metabolic syndrome; elderly; prospective study
7.  Prevalence of neck pain in subjects with metabolic syndrome - a cross-sectional population-based study 
Metabolic syndrome (MetS) is increasingly common. Obesity has been suggested to associate with neck pain but prevalence of neck pain in subjects with MetS has not been studied. Aim of this study was to analyse the association between MetS and neck pain.
The study population consisted of 1294 middle-aged subjects in Pieksämäki, Finland. A total of 399 males and 500 females participated (69%). The mean age of both males and females was 46 years. Clinical and biochemical measurements were taken. The participants filled out a standard questionnaire. Psychological distress was assessed with the 12-item General Health Questionnaire (GHQ-12). Neck pain was defined as neck pain perceived daily. MetS was defined using National Cholesterol Education Program (NCEP) criteria. Statistical comparisons between the groups were performed using a bootstrap-type t-test or Chi-Square test. Risk ratios of having neck pain were calculated using generalised linear models with age, smoking, alcohol use, exercise and GHQ-12 score as covariates.
The prevalence of MetS was 33% in males and 29% in females. Neck pain was present in 11% (N = 42) of males and 19% (N = 93) of females (P < 0.001). The prevalence of neck pain was 7.9% (95% CI, 4.9% to 12%) among male subjects without MetS and 16% (95% CI, 10% to 23%) among those with MetS. The respective proportions among females were 16% (95% CI, 12% to 20%) and 25% (95% CI, 18% to 33%). The multivariate analysis showed an increased risk of neck pain in males with MetS (RR 2.1, 95% CI, 1.2 to 3.7, P = 0.010) and in females with MetS (RR 1.5, 95% CI, 1.0 to 2.1, P = 0.040).
MetS was associated with neck pain. This association was stronger in males, but the prevalence of neck pain was higher in females. Prospective studies should explore the potential causal association between neck pain and MetS and the potential common background factors of neck pain and MetS.
PMCID: PMC2918543  PMID: 20670458
8.  Metabolic Syndrome and Onset of Depressive Symptoms in the Elderly 
Diabetes Care  2011;34(4):904-909.
Given the increasing prevalence of both metabolic syndrome (MetS) and depressive symptoms during old age, we aimed to examine prospectively the association between MetS and the onset of depressive symptoms according to different age-groups in a large, general elderly population.
This was a prospective cohort study of 4,446 men and women aged 65–91 years who were free of depression or depressive symptoms at baseline (the Three-City Study, France). MetS was defined using the National Cholesterol Education Program Adult Treatment Panel III criteria. New onset of depressive symptoms (the Center for Epidemiologic Studies Depression Scale score ≥16 and use of antidepressant treatment) was assessed at 2- and 4-year follow-ups.
After adjusting for a large range of potential confounders, we observed MetS to be associated with 1.73-fold (95% CI 1.02–2.95) odds for new-onset depressive symptoms in the youngest age-group (65–70 years at baseline), independently of cardiovascular diseases. No such association was seen in older age-groups.
Our findings suggest that the link between MetS and depressive symptoms evidenced until now in middle-aged people can be extended to older adults but not to the oldest ones. Additional research is needed to examine if a better management of MetS prevents depressive symptoms in people aged 65–70 years.
PMCID: PMC3064049  PMID: 21346185
9.  Sex based levels of C-reactive protein and white blood cell count in subjects with metabolic syndrome: Isfahan Healthy Heart Program 
C-reactive protein (CRP) and white blood cell (WBC) are proinflammatory markers. They are major pathophysiological for the development of metabolic syndrome (MetS). This study aimed to address the independent associations between MetS and WBC counts and serum CRP levels and evaluation of their magnitude in relation to the MetS, based on the sex in the Iranian adults.
Materials and Methods:
In this cross-sectional study, subjects who met the MetS criteria, based on the Adult Treatment Panel III were selected from the Isfahan Healthy Heart Program database. A questionnaire containing the demographic data, weight, height, waist, and hip circumference of the respondents was completed for each person. Blood pressure was measured and the anthropometric measurements were done, and fasting blood samples were taken for 2 h postload plasma glucose (2 hpp). Serum [total, high-density lipoprotein (HDL), and low-density lipoprotein] levels of cholesterol, triglyceride, and CRP as well as WBC counts were determined. The univariate analyses were carried out to assess the relation between the CRP levels, WBC counts with the MetS in both sexes the.
In men with the abdominal obesity, the higher levels of WBC count, high serum triglyceride and blood glucose levels, a low serum HDL level, and raised systolic and diastolic blood pressure were observed. However, the higher serum CRP levels were only observed in those with the low serum HDL-cholesterol levels. The mean values of the WBC counts were statistically different between the men with and without MetS, but the mean values of the CRP levels were similar between the two groups. In women, the mean values of WBC count and CRP levels were statistically different in the subjects with and without a MetS components (except for the low serum HDL levels and high diastolic blood pressure for the WBC measures and abdominal obesity for the CRP measures) and for those with and without MetS. The age and smoking adjusted changes in the CRP levels and WBC counts correlated with the number of Mets components in the women.
The findings of this study suggest substantial implications for the prevention and management of the MetS and atherosclerotic diseases, as these involve the suppression of inflammatory conditions rather than the incitement of anti-inflammatory conditions.
PMCID: PMC3818614  PMID: 24250693
C-reactive protein level; metabolic syndrome; white blood cell count
10.  Metabolic syndrome is associated with self-perceived depression 
To study the association between metabolic syndrome (MetS) and self-perceived depression.
A cross-sectional community-based study.
Semi-rural community of Lapinlahti in eastern Finland in 2005.
A total of 416 subjects in eight adult birth cohorts (55%) with complete Beck Depression Inventory (BDI-21) questionnaire data.
Main outcome measures
The values of the 21 BDI items and the BDI-21 total score with a cut-off point of 14/15 were used to study the association between MetS and depression. National Cholesterol Education Programme (NCEP) 2005 criteria were used for MetS classification.
The total BDI-21 score was significantly higher in the subjects with MetS than in the subjects without MetS (p=0.020). Men with MetS were significantly worse off than men without MetS in the BDI-21 items of irritability (p=0.008), work inhibition (p=0.008), fatigability (p=0.037), weight loss (p=0.045), and loss of libido (p=0.014), while women were only so on the item of loss of libido (p=0.007). In a logistic regression analysis using a BDI-21 cut-off point of 14/15 adjusted for age, marital status, vocational education, and working status, significant association was retained between perceived depression and elevated blood glucose among men (OR=1.697) and large waist circumference among women (OR=1.066).
Elevated plasma glucose in men and central obesity in women are associated with self-perceived depression. This co-occurrence deserves attention in clinical practice.
PMCID: PMC3406636  PMID: 18609254
Adult population; depression; family practice; fasting plasma glucose; metabolic syndrome; waist circumference
11.  Childhood Predictors of the Metabolic Syndrome in Middle-aged Adults: The Muscatine Study 
The Journal of pediatrics  2009;155(3):S5.e17-S5.e26.
To investigate the association between components of the metabolic syndrome (MetS) measured during childhood/adolescence, and adult MetS.
Study design
This investigation focused on members of the Muscatine Study Longitudinal Adult Cohort. Predictor variables were risk factor measurements obtained between 1970 and 1981 when Cohort members participated in school survey examinations. Risk factor measurements obtained between 1982 and 2008 when Cohort members participated in follow-up examinations as young and middle-aged adults were utilized for MetS classification.
33.0% (29.7% of 474 women; 37.0% of 384 men) of Cohort members were classified as having the MetS. The initial MetS classification occurred at ages ranging from 23 to 52 with a mean age of 37.2 years (SD = 7.4). Cohort members with the MetS had significantly higher body mass index (BMI), systolic blood pressure, and triglycerides (TRIG) at the time they participated in the school survey examinations (p < 0.0001). Estimated probabilities of remaining MetS free at age 35 for those whose school survey BMI and TRIG measurements were both < 50th vs. ≥ 75th percentile were strikingly different (0.94 vs. 0.42).
BMI is the strongest childhood predictor of adult MetS. Early identification of at-risk children may reduce the burden of atherosclerotic cardiovascular disease.
PMCID: PMC2739835  PMID: 19732563
12.  Adiponectin/leptin ratio and Metabolic Syndrome in a Mexican American population 
Adiponectin and leptin play critical roles in the development of Metabolic Syndrome (MetS). The study was designed to assess circulating levels of adiponectin and leptin in early diagnosis of Metabolic Syndrome (MetS).
This cross-sectional study was performed on 367 participants randomly selected from a well-characterized cohort of Mexican-Americans living at the US-Mexico border.
Significant differences in circulating levels of adiponectin and leptin were observed between males and females. The adiponectin/leptin ratio significantly correlated with MetS in this population. A receiver-operator characteristic (ROC) analysis demonstrated that adiponectin/leptin ratio is a valuable biomarker for the diagnosis of MetS
Our study supported the central role of adiponectin and leptin in MetS, and demonstrated that adiponectin/leptin ratio can be used as a highly sensitive and specific biomarker for MetS.
PMCID: PMC3256930  PMID: 21968271
adiponectin; computer-aided diagnosis; leptin; MetS; receiver operator characteristic
13.  Effects of a Physical Activity Program on Markers of Endothelial Dysfunction, Oxidative Stress, and Metabolic Status in Adolescents with Metabolic Syndrome 
ISRN Endocrinology  2012;2012:970629.
The metabolic syndrome (MetS) is a precursor of diabetes. Physical activity (PA) improves endothelial dysfunction and may benefit patients with MetS. Aims. To evaluate the effect of a physical activity (PA) program on markers of endothelial dysfunction and oxidative stress in adolescents with (MetS). Methods. We carried out a cohort study of 38 adolescents with and without MetS (18 females and 20 males). All participants completed a 3-month PA program. All variables of the MetS as well as markers of endothelial dysfunction and oxidative stress tests were evaluated. Results. Females with and without MetS showed significant differences for almost all components of the MetS, whereas males were significantly different in half of the components. After the PA program, components of the MetS were not different from baseline values except for HDL-C levels. Some baseline endothelial dysfunction markers were significantly different among adolescents with and without MetS; however, after the PA program, most of these markers significantly improved in subjects with and without MetS. Conclusion. PA improves the markers of endothelial dysfunction in adolescents with MetS although other changes in the components of the MetS were not observed. Perhaps the benefits of PA on all components of MetS would appear after a PA program with a longer duration.
PMCID: PMC3410314  PMID: 22888450
14.  Association of Serum Ferritin and the Development of Metabolic Syndrome in Middle-Aged Korean Men 
Diabetes Care  2012;35(12):2521-2526.
Elevated serum ferritin has been known to be associated with the prevalence of metabolic syndrome (MetS). However, there was no research to examine whether serum ferritin levels have been actually associated with the prospective development of MetS. Accordingly, we carried out a prospective study to evaluate the longitudinal effects of baseline serum ferritin levels on the development of MetS.
A MetS-free cohort of 18,022 healthy Korean men, who had participated in a medical health checkup program in 2005, was followed until 2010. MetS was defined according to the joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention. Cox proportional hazards models were performed.
During 45,919.3 person-years of follow-up, 2,127 incident cases of MetS developed between 2006 and 2010. After adjusting for multiple covariates, the hazard ratios (95% CI) for incident MetS comparing the second quintile to the fifth quintile of serum ferritin levels versus the first quintile were 1.19 (0.98–1.45), 1.17 (0.96–1.43), 1.36 (1.12–1.65), and 1.66 (1.38–2.01), respectively (P for trend <0.001). These associations were apparent in the clinically relevant subgroup analyses.
Elevated serum ferritin levels were independently associated with future development of MetS during the 5-year follow-up period.
PMCID: PMC3507565  PMID: 22933431
15.  Associations between smoking, components of metabolic syndrome and lipoprotein particle size 
BMC Medicine  2013;11:195.
The clustering of metabolic and cardiovascular risk factors is known as metabolic syndrome (MetS). The risk of having MetS is strongly associated with increased adiposity and can be further modified by smoking behavior. Apolipoproteins (apo) associated with low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein-cholesterol (HDL-C) may be altered in MetS. This study aimed to examine the association between smoking and the following parameters: MetS and its components, levels of apolipoproteins and estimated lipoprotein particle size, separately for men and women, and in different body mass index (BMI) classes.
We included 24,389 men and 35,078 women aged between 18 and 80 years who participated in the LifeLines Cohort Study between December 2006 and January 2012; 5,685 men and 6,989 women were current smokers. Participants were categorized into three different body mass index (BMI) classes (BMI <25; BMI 25 to 30; BMI ≥30 kg/m2). MetS was defined according to the National Cholesterol Education Program’s Adult Treatment Panel III (NCEP:ATPIII) criteria. Blood pressure, anthropometric and lipid measurements were rigorously standardized, and the large sample size enabled a powerful estimate of quantitative changes. The association between smoking and the individual MetS components, and apoA1 and apoB, was tested with linear regression. Logistic regression was used to examine the effect of smoking and daily tobacco smoked on risk of having MetS. All models were age adjusted and stratified by sex and BMI class.
Prevalence of MetS increased with higher BMI levels. A total of 64% of obese men and 42% of obese women had MetS. Current smoking was associated with a higher risk of MetS in both sexes and all BMI classes (odds ratio 1.7 to 2.4 for men, 1.8 to 2.3 for women, all P values <0.001). Current smokers had lower levels of HDL cholesterol and apoA1, higher levels of triglycerides and apoB, and higher waist circumference than non-smokers (all P <0.001). Smoking had no consistent association with blood pressure or fasting blood glucose. In all BMI classes, we found a dose-dependent association of daily tobacco consumption with MetS prevalence as well as with lower levels of HDL cholesterol, higher triglyceride levels and lower ratios of HDL cholesterol/apoA1 and, only in those with BMI <30, LDL cholesterol/apoB (all P <0.001).
Smoking is associated with an increased prevalence of MetS, independent of sex and BMI class. This increased risk is mainly related to lower HDL cholesterol, and higher triglycerides and waist circumference. In addition, smoking was associated with unfavorable changes in apoA1 and apoB, and in lipoprotein particle size.
Please see related commentary:
PMCID: PMC3766075  PMID: 24228807
Metabolic syndrome; Smoking; HDL; Cholesterol; Apolipoproteins; Triglycerides; Obesity; Cross-sectional; BMI classes
16.  The prevalence of metabolic syndrome and metabolically healthy obesity in Europe: a collaborative analysis of ten large cohort studies 
Not all obese subjects have an adverse metabolic profile predisposing them to developing type 2 diabetes or cardiovascular disease. The BioSHaRE-EU Healthy Obese Project aims to gain insights into the consequences of (healthy) obesity using data on risk factors and phenotypes across several large-scale cohort studies. Aim of this study was to describe the prevalence of obesity, metabolic syndrome (MetS) and metabolically healthy obesity (MHO) in ten participating studies.
Ten different cohorts in seven countries were combined, using data transformed into a harmonized format. All participants were of European origin, with age 18–80 years. They had participated in a clinical examination for anthropometric and blood pressure measurements. Blood samples had been drawn for analysis of lipids and glucose. Presence of MetS was assessed in those with obesity (BMI ≥ 30 kg/m2) based on the 2001 NCEP ATP III criteria, as well as an adapted set of less strict criteria. MHO was defined as obesity, having none of the MetS components, and no previous diagnosis of cardiovascular disease.
Data for 163,517 individuals were available; 17% were obese (11,465 men and 16,612 women). The prevalence of obesity varied from 11.6% in the Italian CHRIS cohort to 26.3% in the German KORA cohort. The age-standardized percentage of obese subjects with MetS ranged in women from 24% in CHRIS to 65% in the Finnish Health2000 cohort, and in men from 43% in CHRIS to 78% in the Finnish DILGOM cohort, with elevated blood pressure the most frequently occurring factor contributing to the prevalence of the metabolic syndrome. The age-standardized prevalence of MHO varied in women from 7% in Health2000 to 28% in NCDS, and in men from 2% in DILGOM to 19% in CHRIS. MHO was more prevalent in women than in men, and decreased with age in both sexes.
Through a rigorous harmonization process, the BioSHaRE-EU consortium was able to compare key characteristics defining the metabolically healthy obese phenotype across ten cohort studies. There is considerable variability in the prevalence of healthy obesity across the different European populations studied, even when unified criteria were used to classify this phenotype.
PMCID: PMC3923238  PMID: 24484869
Harmonization; Obesity; Metabolic syndrome; Cardiovascular disease; Metabolically healthy
17.  Depressive Symptoms and Metabolic Syndrome: Is Inflammation the Underlying Link? 
Biological psychiatry  2008;64(10):896-900.
Behavioral alterations, including depression, are frequent in individuals with the metabolic syndrome (MetS). Recent findings suggest that chronic activation of innate immunity may be involved. The objective of this study was to examine the relationship between MetS and depressive symptoms and to elucidate the involvement of inflammation in this relationship.
Participants were 323 male twins, with and without MetS and free of symptomatic cardiovascular disease, drawn from the Vietnam-Era-Twin Registry. Depressive symptoms were measured with the Beck-Depression-Inventory (BDI). Inflammatory status was assessed using C-reactive protein (CRP) and interleukin-6 (IL-6); twins with both CRP and IL-6 levels above the median were classified as having an elevated inflammatory status. Factor analysis was performed on individual BDI items to extract specific symptom dimensions (neurovegetative, mood, affective-cognitive).
Subjects with MetS had more depressive symptoms than those without. Depressive symptoms with neurovegetative features were more common and more robustly associated with MetS. Both the BDI total score and each symptom subscore were associated with inflammatory biomarkers. After adjusting for age, education and smoking status, the MetS was significantly associated with the BDI total score and the neurovegetative score. After further adjusting for inflammation, the coefficient for MetS decreased somewhat, but remained statistically significant for the BDI neurovegetative subscore. When controlling for the MetS, inflammation remained significantly associated with the BDI mood subscore.
The MetS is associated with higher depressive symptomatology characterized primarily by neurovegetative features. Inflammation is one determinant of depressive symptoms in individuals with MetS.
PMCID: PMC2621309  PMID: 18597739
Metabolic Syndrome; Inflammation; Cytokines; Depression; Mood
18.  Clinical usefulness of the metabolic syndrome for the risk of coronary heart disease does not exceed the sum of its individual components in older men and women. The Three-City (3C) Study 
Heart  2012;98(8):650-655.
To investigate the respective associations and clinical usefulness of the metabolic syndrome (MetS) and its individual components to predict the risk of first coronary heart disease (CHD) events in elderly.
The Three-City is a French prospective multisite community-based cohort.
Three large French cities: Bordeaux, Dijon and Montpellier.
7612 subjects aged 65 and over who were free of CHD at baseline.
Main outcome measures
The MetS was defined by the 2005 National Cholesterol Education Program Adult Treatment Panel III criteria.
During a median follow-up of 5.2 years, 275 first CHD events were adjudicated. The MetS was associated with increased risks of total (adjusted HR: 1.78; 95% CI 1.39 to 2.28), fatal (HR: 2.40; 95% CI 1.41 to 4.09) and non-fatal (HR: 1.64; 95% CI 1.24 to 2.17) CHD events. The association with total CHD was significant in women (HR: 2.56; 95% CI 1.75 to 3.75) but not in men (HR: 1.39; 95% CI 0.99 to 1.94; p for interaction=0.012). When in the same multivariable model, hyperglycemia and abdominal adiposity in women, hyperglycemia, lower HDL cholesterol and abdominal adiposity (inverse association) in men were the components significantly associated with CHD. The components of the MetS but not the MetS itself improved risk prediction beyond traditional risk factors (NRI= 9.35%, p<0;001).
The MetS is a risk marker for CHD in community-dwelling elderly subjects but may not be useful for CHD risk prediction purposes compared to its individual components.
PMCID: PMC3328398  PMID: 22505463
Metabolic syndrome; coronary heart disease; elderly; risk stratification; psychology/psychiatry; epidemiology
19.  Optimal cutoff values of waist circumference and the discriminatory performance of other anthropometric indices to detect the clustering of cardiovascular risk factors for metabolic syndrome in Japanese men and women 
To evaluate the pertinent cutoffs of waist circumference (WC) and the discriminatory performance of other anthropometric indices to detect clustering cardiovascular risk factors for metabolic syndrome (MetS) in Japan, where the current WC cutoffs for MetS (85 cm for men and 90 cm for women) remain controversial.
We analyzed the baseline data from 844 subjects (330 men and 514 women) aged 40–69 years who participated in a cohort study in Saga city, Japan, between November 2005 and December 2007. Receiver operating characteristic (ROC) analyses were performed to find an appropriate cutoff (defined as the point nearest to the upper left corner of the ROC curve) of each anthropometric index for the presence of multiple risk factors among dyslipidemia, hypertension, and hyperglycemia [which was defined as hemoglobin A1c (HbA1c) levels at and above 5.2, 5.5, or 5.8%, values approximately corresponding to fasting plasma glucose levels of 100, 110, and 120 mg/dL, respectively].
The optimal WC cutoff was 88 cm (sensitivity 60%, specificity 70%) for men and 82 cm (sensitivity 78%, specificity 62%) for women; changing the HbA1c cutoff affected the results in women only (~85 cm). For the currently defined WC cutoffs in Japan, specificity was low (53–57%) in men, whereas sensitivity was very low (32–42%) in women. Body mass index, proportion of body fat, waist-to-height ratio, and waist-to-hip ratio showed area under the curve values similar to that of WC.
The current Japanese criteria of WC for MetS may be low for men and too high and insensitive for women in our study population. Other anthropometric indices such as waist-to-height ratio did not confer an improved discriminatory performance compared with WC.
PMCID: PMC2999681  PMID: 21432217
Metabolic syndrome; Waist circumference; Cutoff; Cross-sectional study; ROC analysis
20.  Metabolic Syndrome Model Definitions Predicting Type 2 Diabetes and Cardiovascular Disease 
Diabetes Care  2013;36(2):362-368.
Metabolic syndrome (MetS) is a cluster of abdominal obesity, hyperglycemia, hypertension, and dyslipidemia, which increases the risk for type 2 diabetes and cardiovascular diseases (CVDs). Some argue that MetS is not a single disorder because the traditional MetS features do not represent one entity, and they would like to exclude features from MetS. Others would like to add additional features in order to increase predictive ability of MetS. The aim of this study was to identify a MetS model that optimally predicts type 2 diabetes and CVD while still representing a single entity.
In a random sample (n = 1,928) of the EPIC-NL cohort and a subset of the EPIC-NL MORGEN study (n = 1,333), we tested the model fit of several one-factor MetS models using confirmatory factor analysis. We compared predictive ability for type 2 diabetes and CVD of these models within the EPIC-NL case-cohort study of 545 incident type 2 diabetic subjects, 1,312 incident CVD case subjects, and the random sample, using survival analyses and reclassification.
The standard model, representing the current MetS definition (EPIC-NL comparative fit index [CFI] = 0.95; MORGEN CFI = 0.98); the standard model excluding blood pressure (EPIC-NL CFI = 0.95; MORGEN CFI = 1.00); and the standard model extended with hsCRP (EPIC-NL CFI = 0.95) had an acceptable model fit. The model extended with hsCRP predicted type 2 diabetes (integral discrimination index [IDI]: 0.34) and CVD (IDI: 0.07) slightly better than did the standard model.
It seems valid to represent the traditional MetS features by a single entity. Extension of this entity with hsCRP slightly improves predictive ability for type 2 diabetes and CVD.
PMCID: PMC3554322  PMID: 22933442
21.  Increase of Metabolic Syndrome Score is an Independent Determinant of Increasing Pulse Pressure 
Yonsei Medical Journal  2008;49(1):63-70.
The objective of this study was to determine whether the progressive increase of metabolic syndrome (MetS) score, the number of components of MetS, is correlated significantly with increasing pulse pressure (PP).
Materials and Methods
4,034 subjects were enrolled from the Cardiovascular Genome Center of Yonsei University (M : F = 2344 : 1690, 55.2 ± 10.5). Most of the study population were recruited from hypertension clinics, controlled with medications according to JNC7 guidelines. The Asian modified criteria of MetS were applied and MetS score was estimated. The HOMA index for insulin resistance, cholesterol profiles, and anthropometric measurements were assessed.
Among 4034 participants, 1690 (41.9%) were classified as MetS. Progressive increase in PP was demonstrated for increasing components of the MetS score. Multiple linear regression analysis with PP as the dependent variable showed that age (β = 0.311, p < 0.001), MetS score (β = 0.226, p < 0.001), male gender (β = -0.093, p < 0.001) and HOMA index IR (β = 0.033, p = 0.03) are significantly associated with PP (R2 = 0.207, p < 0.001).
The present results from this study demonstrate that increasing MetS score is an independent determinant of increasing PP. The results also demonstrate the independent role of MetS in increasing arterial stiffness and PP.
PMCID: PMC2615259  PMID: 18306471
Metabolic syndrome; pulse pressure; arterial stiffness; metabolic syndrome scores
22.  Elevated Alanine Aminotransferase Is Strongly Associated with Incident Metabolic Syndrome: A Meta-Analysis of Prospective Studies 
PLoS ONE  2013;8(12):e80596.
The incidence of metabolic syndrome (MetS) is rapidly increasing worldwide and associated with alanine aminotransferase (ALT) activity. However, the impact of ALT activity on MetS incidence is inconsistent in published literature. We therefore estimated the association between elevated ALT activity and incident MetS through a meta-analysis of prospective cohort studies.
Methods/Principal Findings
All published prospective cohort studies on the association between elevated ALT activity and incident MetS were retrieved from Pubmed, Embase, and the Institute for Scientific Information (ISI). In all, seven prospective cohort studies, with 31545 participants and 2873 cases of incident MetS were recruited. If there was insignificant heterogeneity (P-value>0.05 and I2<50%), the fixed-effect model was used to calculate the pooled relative risks (RRs) of incident MetS induced by raised ALT. Otherwise, the random-effect model was used. The calculated RR was 1.81 (95% confidence interval [CI]: 1.49–2.14) when the incidence of MetS was compared between the highest versus the lowest classification of ALT activities. The pooled RR was 1.13 (95% CI: 1.11–1.16) in dose-response analysis with 5 units per liter (U/l) of ALT increment. Subgroup analysis suggested that gender disparity might be the main origin of heterogeneity in overall analysis (P = 0.007 between RRs of gender-specific subgroups evaluated with 5 U/l increments of ALT). Women had a higher dose-response risk of MetS incidence (1.38, 95% CI: 1.20–1.55) than men. Furthermore, sensitivity analysis confirmed the stability of results. No publication bias was found in our meta-analysis.
Current evidence from prospective studies supports the association between ALT elevation and increasing MetS incidence. This association is closer and more consistent in female population. Further studies are needed to confirm this association and to investigate the potential mechanism of ALT activity on MetS occurrence.
PMCID: PMC3851461  PMID: 24324614
23.  Association between physical activity and metabolic syndrome in middle-aged Japanese: a cross-sectional study 
BMC Public Health  2011;11:624.
Although many studies have reported an association between self-reported physical activity and metabolic syndrome (MetS), there is limited information on the optimal level of physical activity required to prevent MetS. This study aimed to determine the association between objectively measured physical activity and MetS in middle-aged Japanese individuals. We also determined the optimal cutoff value for physical activity required to decrease the risk of developing MetS.
A total of 179 men and 304 women, aged between 30 and 64 years, participated in this study. Participants were divided into two groups using the Japanese criteria for MetS as those with MetS or pre-MetS, and those without MetS. Participants were considered to be physically active if they achieved a physical activity level of 23 metabolic equivalents (METs) h/week, measured using a triaxial accelerometer. The association between physical activity and MetS was analyzed using logistic regression with the following covariates: sex, age, sedentary time, low intensity activity, calorie intake, smoking, menopause and body mass index. We also evaluated the factors that determined the association between the prevalence of MetS and pre-MetS and the physical activity cutoff value using classification and regression tree (CART) analysis.
The odds ratio for MetS and pre-MetS was 2.20 for physically inactive participants (< 23 METs h/week), compared with physically active participants (≥ 23 METs h/week). The corresponding odds ratios for men and women were 2.27 (P < 0.01) and 1.95 (not significant), respectively. CART analyses revealed that moderate-vigorous physical activity of > 26.5 METs h/week was sufficient to decrease the prevalence of MetS and pre-MetS in middle-aged Japanese men and women.
The results of this cross-sectional study indicate that the Exercise and Physical Activity Reference for Health Promotion 2006 is inversely associated with the prevalence of MetS in men. Our results also suggest that moderate physical activity of > 26.5 METs h/week may decrease the risk of developing MetS and pre-MetS in middle-aged Japanese individuals.
PMCID: PMC3199599  PMID: 21819591
24.  Leisure-Time Physical Activity and the Metabolic Syndrome in the Finnish Diabetes Prevention Study 
Diabetes Care  2010;33(7):1610-1617.
To assess the effects of leisure-time physical activity (LTPA) and resistance training on metabolic syndrome (MetS) and its components in a post hoc analysis of the Finnish Diabetes Prevention Study, a randomized controlled lifestyle counseling trial.
A cohort of 486 middle-aged overweight men and women with impaired glucose tolerance were followed for an average of 4.1 years. The intervention and control groups were combined in the analyses. LTPA was assessed by questionnaires, dietary intake by food records, and features of the MetS by anthropometric and biochemical measures annually. Resistance training sessions were documented for 137 participants.
Increased moderate-to-vigorous LTPA, even after adjustments for changes in dietary intakes of total and saturated fat, fiber, and energy, and change in BMI was associated with a greater likelihood for resolution (29.7 vs. 19.1%; P = 0.004 in the upper versus lower third of change) and a lesser likelihood for development (23.5 vs. 44.7%; P = 0.041) of the MetS. Of the components of the MetS, the increase in moderate-to-vigorous LTPA was associated most strongly with improvement of glycemia. Among the 137 participants who participated in resistance training, MetS components were favorable in individuals who were in the upper third of participation rate (median 51 times/year) compared with individuals in the lowest third (median 8.5 times/year).
Increased moderate-to-vigorous LTPA was associated with a decreased likelihood of developing the MetS and an increased likelihood of its resolution in individuals at high risk for type 2 diabetes.
PMCID: PMC2890369  PMID: 20413514
25.  Metabolic syndrome in Russian adults: associated factors and mortality from cardiovascular diseases and all causes 
BMC Public Health  2010;10:582.
Metabolic syndrome (MetS) is a cluster of four major obesity-related risk factors for cardiovascular disease (CVD). Russia has one of the highest CVD mortality in the world, but its association with MetS remains unknown. Also little is known about factors associated with MetS and its components in Russia.
Data on 3555 adults aged 18-90 years were collected in a cross-sectional study in 2000. MetS was defined by the International Diabetes Federation (IDF) and National Cholesterol Education Program (NCEP) criteria. Sex-specific associations between the IDF-defined MetS, its components, and life-style, socio-economic factors and laboratory indicators, were analysed using multivariable Poisson regression. Vital status of the study participants was identified by July 2009. Sex-specific associations between MetS and stroke, Coronary Heart Disease (CHD), CVD and all-cause death, were studied by Poisson regression adjusted for age, smoking, alcohol and history of CVDs.
After adjustment for all studied factors except BMI, age, serum GGT, C-reactive protein and AST-to-ALT ratio were associated with MetS in both genders. Additionally, MetS was associated with sedentary lifestyle in women and with smoking in men. In the same regression model drinking alcohol 2-4 times a month and consumption of five or more alcohol units at one occasion in men, and drinking alcohol 5 times or more a month in women were inversely associated with MetS. After a 9-year follow-up, MetS was associated with higher risk of death from stroke (RR = 3.76, 95% CI:1.35-10.46) and from either stroke or myocardial infarction (MI, RR = 2.87, 95% CI:1.32-6.23) in men. No associations between MetS and any of the studied causes of death were observed in women.
Factors associated with MetS in both genders were age, GGT, C-reactive protein, and AST-to-ALT ratio. Moderate frequency of alcohol consumption and binge drinking in men and higher leisure time physical activity in women, were inversely associated with MetS.
Positive associations between MetS and mortality were only observed for deaths from stroke and either stroke or MI in men.
PMCID: PMC2955695  PMID: 20920226

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