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1.  Low sensitivity of the metabolic syndrome to identify adolescents with impaired glucose tolerance: an analysis of NHANES 1999–2010 
The presence of impaired glucose tolerance (IGT) and metabolic syndrome (MetS) are two risk factors for Type 2 diabetes. The inter-relatedness of these factors among adolescents is unclear.
We evaluated the sensitivity and specificity of MetS for identifying IGT in an unselected group of adolescents undergoing oral glucose tolerance tests (OGTT) in the National Health and Nutrition Evaluation Survey 1999–2010. We characterized IGT as a 2-hour glucose ≥140 mg/dL and MetS using ATP-III-based criteria and a continuous sex- and race/ethnicity-specific MetS Z-score at cut-offs of +1.0 and +0.75 standard deviations (SD) above the mean.
Among 1513 adolescents, IGT was present in 4.8%, while ATP-III-MetS was present in 7.9%. MetS performed poorly in identifying adolescents with IGT with a sensitivity/specificity of 23.7%/92.9% for ATP-III-MetS, 23.6%/90.8% for the MetS Z-score at +1.0 SD and 35.8%/85.0 for the MetS Z-score at +0.75 SD. Sensitivity was higher (and specificity lower) but was still overall poor among overweight/obese adolescents: 44.7%/83.0% for ATP-III-MetS, 43.1%/77.1% for the MetS Z-score at +1.0 SD and 64.3%/64.3% for MetS Z-score at +0.75 SD.
This lack of overlap between MetS and IGT may indicate that assessment of MetS is not likely to be a good indicator of which adolescents to screen using OGTT. These data further underscore the importance of other potential contributors to IGT, including Type 1 diabetes and genetic causes of poor beta-cell function. Practitioners should keep these potential causes of IGT in mind, even when evaluating obese adolescents with IGT.
PMCID: PMC4000320  PMID: 24755002
Insulin resistance; Metabolic syndrome; Impaired glucose tolerance; Type 2 diabetes; Adolescents
2.  Metabolic Syndrome Derived from Principal Component Analysis and Incident Cardiovascular Events: The Multi Ethnic Study of Atherosclerosis (MESA) and Health, Aging, and Body Composition (Health ABC) 
Background. The NCEP metabolic syndrome (MetS) is a combination of dichotomized interrelated risk factors from predominantly Caucasian populations. We propose a continuous MetS score based on principal component analysis (PCA) of the same risk factors in a multiethnic cohort and compare prediction of incident CVD events with NCEP MetS definition. Additionally, we replicated these analyses in the Health, Aging, and Body composition (Health ABC) study cohort. Methods and Results. We performed PCA of the MetS elements (waist circumference, HDL, TG, fasting blood glucose, SBP, and DBP) in 2610 Caucasian Americans, 801 Chinese Americans, 1875 African Americans, and 1494 Hispanic Americans in the multiethnic study of atherosclerosis (MESA) cohort. We selected the first principal component as a continuous MetS score (MetS-PC). Cox proportional hazards models were used to examine the association between MetS-PC and 5.5 years of CVD events (n = 377) adjusting for age, gender, race, smoking and LDL-C, overall and by ethnicity. To facilitate comparison of MetS-PC with the binary NCEP definition, a MetS-PC cut point was chosen to yield the same 37% prevalence of MetS as the NCEP definition (37%) in the MESA cohort. Hazard ratio (HR) for CVD events were estimated using the NCEP and Mets-PC-derived binary definitions. In Cox proportional models, the HR (95% CI) for CVD events for 1-SD (standard deviation) of MetS-PC was 1.71 (1.54–1.90) (P < 0.0001) overall after adjusting for potential confounders, and for each ethnicity, HRs were: Caucasian, 1.64 (1.39–1.94), Chinese, 1.39 (1.06–1.83), African, 1.67 (1.37–2.02), and Hispanic, 2.10 (1.66-2.65). Finally, when binary definitions were compared, HR for CVD events was 2.34 (1.91–2.87) for MetS-PC versus 1.79 (1.46–2.20) for NCEP MetS. In the Health ABC cohort, in a fully adjusted model, MetS-PC per 1-SD (Health ABC) remained associated with CVD events (HR = 1.21, 95%CI 1.12–1.32) overall, and for each ethnicity, Caucasian (HR = 1.24, 95%CI 1.12–1.39) and African Americans (HR = 1.16, 95%CI 1.01–1.32). Finally, when using a binary definition of MetS-PC (cut point 0.505) designed to match the NCEP definition in terms of prevalence in the Health ABC cohort (35%), the fully adjusted HR for CVD events was 1.39, 95%CI 1.17–1.64 compared with 1.46, 95%CI 1.23–1.72 using the NCEP definition. Conclusion. MetS-PC is a continuous measure of metabolic syndrome and was a better predictor of CVD events overall and in individual ethnicities. Additionally, a binary MetS-PC definition was better than the NCEP MetS definition in predicting incident CVD events in the MESA cohort, but this superiority was not evident in the Health ABC cohort.
PMCID: PMC3318892  PMID: 22536533
3.  The value of Apolipoprotein B/Apolipoprotein A1 ratio for metabolic syndrome diagnosis in a Chinese population: a cross-sectional study 
The apoB/apoA1 ratio has been reported to be associated with the metabolic syndrome (MetS), and it may be a more convenient biomarker in MetS predicting. However, whether apoB/apoA1 ratio is a better indicator of metabolic syndrome than other biomarkers and what is the optimal cut-off value of apoB/apoA1 ratio as an indicator of metabolic syndrome in Chinese population remain unknown. Thus, we carried out the current study to assess the predictive value of apoB/apoA1 ratio and determine the optimal cut-off value of apoB/apoA1 ratio for diagnosing MetS in a Chinese population.
We selected 1,855 subjects with MetS and 6,265 individuals without MetS based on the inclusion and exclusion criteria from the China Health Nutrition Survey (CHNS) in 2009. MetS was identified based on the diagnostic criteria of International Diabetes Federation (2005). Logistic regression was used to estimate the association between the apoB/apoA1 ratio and risk of MetS, and receiver operating characteristics (ROC) curve analysis was performed to test the predictive value of apoB/apoA1 ratio and calculate the appropriate cut-off value.
Compared with the lowest quartile of apoB/apoA1 ratio, subjects in the fourth quartile had a higher risk of MetS in both men [odds ratio (OR) = 2.64, 95% confidence interval (CI) =1.82-3.83] and women (OR = 5.18, 95% CI = 3.87-6.92) after adjustment for potential confounders. The optimal cut-off value of apoB/apoA1 ratio for MetS detection was 0.85 in men and 0.80 in women. Comparisons of ROC curves indicated that apoB/apoA1 ratio was better than traditional biomarkers in predicting MetS.
Our results suggest that, apoB/apoA1 ratio has a promising predictive effectiveness in detection of MetS. An apoB/apoA1 ratio higher than 0.85 in men and 0.80 in women may be a promising and convenient marker of MetS.
PMCID: PMC4041140  PMID: 24886173
Metabolic syndrome; Apolipoprotein ratio; ROC curve
4.  Receiver-operating characteristic of adiposity for metabolic syndrome: HANDLS study 
Public health nutrition  2010;14(1):77-92.
To assess the predictive values of various adiposity indices for the metabolic syndrome (MetS) among adults using baseline data from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) cohort.
In a cross-sectional study, body mass index (BMI), waist circumference (WC), body composition by dual-energy x-ray absorptiometry (DXA) and metabolic risk factors such as triglycerides, HDL-cholesterol, blood pressure, fasting glucose and insulin, uric acid and C-reactive protein were measured. Receiver-operating characteristic (ROC) curves and logistic regression analyses were conducted.
Baltimore, Maryland.
1,981 White and African-American US adults, aged 30-64 years.
In predicting risk of MetS using obesity-independent National Cholesterol Education Program Adult Treatment Panel III criteria, % body fat mass (TtFM) assessed using DXA measuring overall adiposity had no added value over WC. This was true among both men (Areas under curve; AUC=0.680 vs. 0.733 for TtFM and WC, respectively, p<0.05) and women (AUC=0.581 vs. 0.686). Rib fat mass (RbFM) was superior to TtFM only in women for MetS (AUC=0.701 and 0.581 for RbFM and TtFM, respectively, p<0.05), particularly among African-American women. Elevated Leg fat mass (LgFM) was protective against MetS among African-American men. Among White men, BMI was inferior to WC in predicting MetS. Optimal WC cut points varied across ethnic-sex groups and differed from those recommended by the NIH/NAASO.
We provide evidence that WC is among the most powerful tools to predict MetS, and that optimal cut-points for various indices including WC may differ by sex and race.
PMCID: PMC3017668  PMID: 20854721
Metabolic syndrome; percent body fat mass; central obesity; body mass index
5.  Low Sensitivity for the Metabolic Syndrome to Detect Uric Acid Elevations in Females and Non-Hispanic-Black Male Adolescents: An Analysis of NHANES 1999-2006 
Atherosclerosis  2011;220(2):575-580.
Uric acid is tightly linked to the metabolic syndrome (MetS) and among adults higher uric acid levels are associated with future risk for diabetes, cardiovascular disease, hypertension and renal disease.
Evaluate the sensitivity of MetS to identify adolescents with elevated uric acid levels on a race/ethnicity and gender-specific basis.
We evaluated 3,296 males and female adolescents 12-19y participating in the National Health and Nutrition Evaluation Survey ‘99-’06, comprised of 67.6% non-Hispanic whites, 15.1% non-Hispanic blacks, and 17.3% Hispanics. We used a definition of MetS modified for use in adolescents and evaluated the sensitivity of a diagnosis of MetS to identify individuals with uric acid elevations (approximately the 95th percentile of uric acid by gender among normal-weight adolescents).
When used as a screening test to identify individuals with uric acid elevations MetS performed more poorly among females (18.0%) than among males (37.0%)(p<0.001). Among males, MetS exhibited a lower sensitivity among non-Hispanic blacks (17.8%) compared to Hispanics (45.9%)(p<0.01) and non-Hispanic whites (37.4%)(p<0.05). There were no race/ethnicity differences in detecting elevated uric acid levels among females (non-Hispanic-white 15.5%, non-Hispanic-black 19.4%, Hispanic 26.5%, p>0.05).
Current criteria to diagnose MetS exhibit racial/ethnic and gender differences in the ability to identify adolescents with elevated uric acid levels, performing poorly among non-Hispanic-black males and among females. Given emerging data regarding the ability of uric acid elevations for predicting future disease, these data may have implications regarding the use of MetS as a marker of risk among all gender and racial/ethnic groups.
PMCID: PMC3321243  PMID: 22178428
metabolic syndrome; uric acid; adolescents; insulin resistance; cardiovascular disease risk
6.  Supplementary use of HbA1c as hyperglycemic criterion to detect metabolic syndrome 
Metabolic syndrome (MetS) refers to a cluster of cardiovascular risk factors including hyperglycemia, dyslipidemia, abdominal obesity and hypertension. An effective detection of MetS not only reflects the prediction risk of diabetes mellitus and cardiovascular diseases but also helps to plan for management strategy which could reduce the healthcare burden of the society. This study aimed to compare the use of hemoglobin A1c (HbA1c) to fasting plasma glucose (FPG) as the hyperglycemic component in MetS diagnosis.
Waist circumference, blood pressure, blood triglyceride, high-density lipoprotein (HDL)-cholesterol, FPG, and HbA1c were examined in 120 Hong Kong Chinese adults with MetS and 120 without MetS. After reviewing the subject basal characteristics, 11 of them were found with undiagnosed diabetes (FPG ≧7.0 mmol/L) and were excluded for further analysis.
The most prevalent MetS components among the included subjects were elevated systolic blood pressure and central obesity. Significant correlation relationships existed between FPG and HbA1c in both subject pools diagnosed with and without MetS (p < 0.001). The diagnostic rate of MetS using HbA1c was compared to FPG by the receiver operating characteristics (ROC) analysis which suggested an area under curve of 0.807 (95% CI: 0.727 to 0.887). The agreement was 90.7% in MetS-positive group with increased FPG as one of the criterion co-existed with elevated HbA1c. If including HbA1c as an additional criterion to FPG in the MetS diagnosis, 30 more participants in MetS-negative group would be MetS-positive leading to an increase in detection rate. Furthermore, 47 subjects (38 from MetS-positive group and 9 from MetS-negative group) were found having HbA1c ≧6.5%, who would have been diagnosed with diabetes based on the diagnostic criteria implemented by the Expert Group in 2009.
These findings suggest that HbA1c enhances the detection of hyperglycemia for the diagnosis of MetS.
PMCID: PMC4232661  PMID: 25400701
7.  Racial/Ethnic and Gender Differences in the Relationship between Uric Acid and Metabolic Syndrome in Adolescents: An Analysis of NHANES 1999–2006 
Metabolism  2011;61(4):554-561.
Among adolescents uric acid is associated with insulin resistance, hypertension and the metabolic syndrome (MetS) and in adults high uric acid levels are an independent risk factor for cardiovascular disease and diabetes.
Determine whether the relationship of uric acid with MetS varies in adolescents by race/ethnicity and gender.
We used linear regression to evaluate associations between uric acid and other MetS-associated clinical and laboratory measures among 3,296 non-Hispanic-white, non-Hispanic-black and Hispanic adolescents age 12–19y participating in the National Health and Nutrition Evaluation Survey (1999–2006).
Overall, non-Hispanic-white males and females had the highest uric acid levels among the three racial/ethnic groups. In each racial/ethnic group there were higher uric acid levels for those adolescents with vs. without MetS. However, the extent of the MetS-related increase in uric acid level varied by race and gender. Among males, MetS was associated with the greatest increases in uric acid among non-Hispanic whites. However, among females, the MetS-related increase in uric acid was greatest among non-whites. Non-Hispanic-white females exhibited the lowest degrees of correlation between levels of uric acid and MetS-associated variables. Uric acid levels did not correlate with insulin levels in non-Hispanic-white females.
These data suggest the relationship between uric acid and MetS varies by race/ethnicity and gender. In particular, non-Hispanic-white males exhibit a strong relationship and non-Hispanic-white females exhibit a relatively poor correlation between uric acid and MetS-related factors. These data may have implications for the use of uric acid as a marker of future risk among adolescents.
PMCID: PMC3262070  PMID: 22000606
obesity; insulin resistance; hypertension
8.  The Metabolic Syndrome and Cognitive Performance: The Northern Manhattan Study 
Neuroepidemiology  2011;37(3-4):153-159.
The metabolic syndrome (MetS) is a risk factor for diabetes, stroke, myocardial infarction, and increased mortality, and has been associated with cognition in some populations. We hypothesized that MetS would be associated with lower Mini-Mental State Examination (MMSE) scores in a multi-ethnic population, and that MetS is a better predictor of cognition than its individual components or diabetes.
We conducted a cross-sectional analysis among 3,150 stroke-free participants. MetS was defined by the modified National Cholesterol Education Program guidelines-Adult Treatment Panel III (NCEP-ATPIII) criteria. Linear regression and polytomous logistic regression estimated the association between MMSE score and MetS, its individual components, diabetes, and inflammatory biomarkers.
MetS was inversely associated with MMSE score (unadjusted β = −0.67; 95% CI −0.92, −0.41). Adjusting for potential confounders, MetS was associated with lower MMSE score (adjusted β = −0.24; 95% CI −0.47, −0.01), but its individual components and diabetes were not. Those with MetS were more likely to have an MMSE score of <18 than a score of ≥24 (adjusted OR = 1.94; 95% CI 1.26, 3.01). There was an interaction between MetS and race-ethnicity, such that MetS was associated with lower MMSE score among non-Hispanic whites and Hispanics but not non-Hispanic blacks.
MetS was associated with lower cognition in a multi-ethnic population. Further studies of the effect of MetS on cognition are warranted, and should account for demographic differences.
PMCID: PMC3214939  PMID: 22005335
Cognitive performance; Cognitive impairment; Vascular dementia; Vascular cognitive impairment; Cerebrovascular disorders; Metabolic syndrome
9.  Metabolic syndrome and the short-term prognosis of acute ischemic stroke: a hospital-based retrospective study 
Metabolic syndrome (MetS) is an important risk factor for cerebral ischemic stroke, yet previous studies on the relationship between MetS or its components and acute cerebral infarction have been inconsistent. This study aims to evaluate the effects of MetS and its components on the short-term prognosis of patients with acute ischemic stroke.
Subjects with ischemic stroke of <7-day duration (530 cases) were enrolled. MetS was defined based on the modified criteria of the International Diabetes Federation and the American Heart Association/National Heart, Lung, and Blood Institute. Demographic data, vascular risk factors, National Institutes of Health Stroke Scale score, the results of physical, laboratory and imaging examinations and clinical outcomes at 30 and 90 days were recorded. Using univariate analysis, we compared different baseline characteristics between patients with MetS and those without MetS. Further, we assessed MetS and its 5 components on the contribution to short-term prognosis of ischemic stroke with multiple logistic regression models after adjusting for age and sex.
The prevalence of MetS among the patients with acute ischemic stroke in the study is 58.3 %, with more in females (70.3 %) than in males (49.7 %, p < 0.001). As expected, among the MetS components, elevated waist circumference, elevated triglyceride, high fasting blood glucose and low high density lipoprotein cholesterol (HDL-C) were significantly more prevalent in patients with MetS than those without MetS (all p < 0.001). There was no correlation between MetS itself and the short-term prognosis of acute ischemic stroke. Only hyperglycemia in the serum was shown to have impact on poor functional outcomes in 30 and 90 days after the onset of stroke.
The occurrence of MetS among patients with acute ischemic stroke in our study is 58.3 %. MetS itself may not be predictive for the short-term prognosis of patients, while hyperglycemia is a significant predictor for poor functional outcomes in our study.
PMCID: PMC4511539  PMID: 26199022
Metabolic syndrome; Acute ischemic stroke; Hyperglycemia; Prognosis
10.  An evaluation of the metabolic syndrome in a large multi-ethnic study: the Family Blood Pressure Program 
The Family Blood Pressure Program is an ongoing, NHLBI-sponsored, multi-center program to study the genetic determinants of high blood pressure. The goal of this particular study was to study patterns of metabolic syndrome (MetS) in four ethnic groups: African Americans, Caucasians, Hispanics, and Asians.
A major part of participants in three networks GENOA, HyperGEN and SAPPHIRe were recruited mainly through hypertensive probands. MetS was defined as a categorical trait following the National Cholesterol Education Program definition (c-MetS). MetS was also characterized quantitatively through multivariate factor analyses (FA) of 10 risk variables (q-MetS). Logistic regression and frequency tables were used for studying associations among traits.
Using the NCEP definition, the Hispanic sample, which by design was enriched for type 2 diabetes (T2D), had a very high prevalence of MetS (73%). In contrast, its prevalence in Chinese was the lowest (17%). In African Americans and Hispanics, c-MetS was more prevalent in women than in men. Association of c-MetS with type 2 diabetes (T2D) was prominent in the Hispanics and African Americans, less pronounced in the Whites and Japanese, (although still significant), and weakest in the Chinese sample.
Using FA without rotation, we found that the main factor loaded obesity (OBS) and blood pressure (BP) in African Americans; OBS and insulin (INS) in Hispanics, in Japanese, and in Whites; and OBS alone in Chinese. In Hispanics, Whites, and Japanese, BP loaded as a separate factor. Lipids in combination with INS also loaded in a separate factor. Using FA with Varimax rotation, 4 independent factors were identified: "Obesity-INS," "Blood pressure," "Lipids-INS," and "Central obesity." They explained about 60% of the variance present in the original risk variables.
MetS ethnic differences were identified. Ascertaining for hypertension or T2D increased the MetS prevalence in networks compared with the one in the US general population. Obesity was the most prominent risk factor contributing to both c-MetS and q-MetS. INS contributed in two important factors (obesity and lipids). The information imbedded into c-MetS trait /q-MetS factors scores can contribute in future research of the MetS, especially its utilization in the genetic analysis.
PMCID: PMC1201342  PMID: 16076393
11.  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
12.  Diagnosis of the Metabolic Syndrome Is Associated With Disproportionately High Levels of High-Sensitivity C-Reactive Protein in Non–Hispanic Black Adolescents 
Diabetes Care  2011;34(3):734-740.
Whereas it is known that the metabolic syndrome (MetS) has a paradoxically lower prevalence in non–Hispanic black adolescents than in non–Hispanic whites or Hispanics, the relative severity of MetS by race/ethnicity is unknown. Inflammation, indicated by high-sensitivity C-reactive protein (hsCRP), is a key factor linking MetS to cardiovascular disease and type 2 diabetes. Our goal was to determine whether elevations of hsCRP vary by race/ethnicity among adolescents with MetS.
We used the National Health and Nutrition Examination Survey (1999–2008) and evaluated adolescents (age 12–19 years) using a pediatric/adolescent adaptation of the ATP III definition of MetS. We used linear regression to evaluate the interaction between MetS status and ethnicity with respect to hsCRP concentration.
For male and female adolescents, MetS was associated with elevated hsCRP levels compared with adolescents without MetS. However, the elevation in hsCRP between adolescents with and without MetS was greater in non–Hispanic blacks compared with that in non–Hispanic whites (P = 0.04) but not that in Hispanics (P = 0.18). hsCRP concentrations correlated with individual MetS components similarly among all ethnicities. In an evaluation of adolescents diagnosed with MetS, non–Hispanic blacks had higher BMI and more hypertension than other ethnicities but there were no other racial/ethnic differences in the features of MetS.
Non–Hispanic black adolescents have a greater differential in hsCRP between those with and those without MetS than the differential in non–Hispanic whites but not that in Hispanics. Therefore, even though MetS has a low prevalence in non–Hispanic blacks, MetS is a particularly good indicator of inflammation in non–Hispanic black adolescents.
PMCID: PMC3041218  PMID: 21285387
13.  The Relationship between Serum Uric Acid Level and Metabolic Syndrome: Differences by Sex and Age in Taiwanese 
Journal of Epidemiology  2010;20(3):219-224.
Metabolic syndrome (MetS) and hyperuricemia are important risk factors for cardiovascular disease. However, findings regarding the relationship between serum uric acid (UA) level and components of MetS have been inconsistent. This study was performed to explore the potential value of UA level as a marker of MetS among male and female Chinese of different ages.
A total of 5896 subjects (2960 females and 2936 males) were recruited from the Department of Health Management at the Chang Gung Medical Center. Hyperuricemia was defined as a serum UA value >7.0 mg/dL for males or >6.0 mg/dL for females. MetS was defined according to the criteria of the Adult Treatment Panel III, as modified for Chinese subjects. Serum UA was used to differentiate MetS and to calculate epidemiological indices by means of discriminate analysis and logistic regression.
The sensitivity and specificity of serum UA concentration as a marker of MetS ranged from 55.2% to 61.4% and 61.9% to 68.4%, respectively. Subjects with high UA had a higher risk of MetS, with odds ratios ranging from 1.23 to 1.82 (P < 0.01). A positive correlation between serum UA and MetS was observed in both sexes. Serum UA and the occurrence of MetS rose with increasing age in females; in males, however, UA values did not vary with age.
Serum UA is more closely associated with MetS in females than in males. High UA among middle-aged women may predict the development of MetS.
PMCID: PMC3900844  PMID: 20308795
serum uric acid; hyperuricemia; metabolic syndrome; discriminate analysis; cardiovascular risk factor
14.  The utility of fat mass index vs. body mass index and percentage of body fat in the screening of metabolic syndrome 
BMC Public Health  2013;13:629.
It has been well documented that obesity is closely associated with metabolic syndrome (MetS). Although body mass index (BMI) is the most frequently used method to assess overweightness and obesity, this method has been criticized because BMI does not always reflect true body fatness, which may be better evaluated by assessment of body fat and fat-free mass. The objective of this study was to investigate the best indicator to predict the presence of MetS among fat mass index, BMI and percentage of body fat (BF %) and determine its optimal cut-off value in the screening of MetS in practice.
A cross-sectional study of 1698 subjects (aged 20–79 years) who participated in the annual health check-ups was employed. Body composition was measured by bioelectrical impedance analysis (BIA). Fat mass index (FMI) was calculated. Sex-specific FMI quartiles were defined as follows: Q1: <4.39, Q2:4.39- < 5.65, Q3:5.65- < 7.03, Q4:≥7.03,in men; and Q1:<5.25, Q2:5.25- < 6.33, Q3:6.33- < 7.93,Q4:≥7.93, in women. MetS was defined by National Cholesterol Education Program/Adult Treatment Panel III criteria. The association between FMI quartiles and MetS was assessed using Binary logistic regression. Receiver operating curve(ROC) analysis was used to determine optimal cutoff points for BMI,BF% and FMI in relation to the area under the curve(AUC),sensitivity and specificity in men and women.
The adjusted odds ratios (95% CI) for the presence of MetS in the highest FMI quartile versus lowest quartile were 79.143(21.243-294.852) for men( P < 0.01) and 52.039(4.144-653.436) for women( P < 0.01) after adjusting age, BMI, BF%, TC, LDL, CRP, smoking status and exercise status, and the odds ratios were 9.166(2.157-38.952) for men( P < 0.01) and 25.574(1.945-336.228) for women( P < 0.05) when WC was also added into the adjustment. It was determined that BMI values of 27.45 and 23.85 kg/m2, BF% of 23.95% and 31.35% and FMI of 7.00 and 7.90 kg/m2 were the optimal cutoff values to predict the presence of MetS among men and women according to the ROC curve analysis. Among the indicators used to predict MetS, FMI was the index that showed the greatest area under the ROC curve in both sexes.
Higher FMI levels appear to be independently and positively associated with the presence of MetS regardless of BMI and BF%. FMI seems to be a better screening tool in prediction of the presence of metabolic syndrome than BMI and percentage of body fat in men and women.
PMCID: PMC3703297  PMID: 23819808
Metabolic syndrome X; Body composition; Fat mass index; Body mass index; Percentage of body fat; Screening
15.  Parent-offspring association of metabolic syndrome in the Framingham Heart Study 
Metabolic syndrome (MetS) is a clustering of five metabolic risk factors including abdominal obesity, elevated blood pressure, hypertriglyceridemia, low high-density lipoprotein cholesterol (HDL-C), and impaired fasting glucose. Few studies have fully reported the strength of clustering of these risk factors in a parent-offspring relationship. This analysis describes the associations between parents and their adult offspring in regard to MetS. It also estimates the association between each risk factor in parents and the presence of MetS in their offspring.
We analyzed data for 1193 offspring (565 sons, and 628 daughters) from the Framingham Offspring Study who attended examinations 5, 6, and 7. Information about their parents was collected from examinations 13, 14 and 15 of the Framingham Original Cohort study. We used pedigree file to combine parental and offspring’s data. Participants were classified as having the MetS according to the Adult Treatment Panel III criteria. Analyses were conducted separately for mothers and fathers. Logistic regression was used to estimate the associations.
After adjusting for age, education, smoking, alcohol consumption and physical activity level of offspring, no significant association was found between father’s and their offspring’s MetS. Mother’s MetS was significantly and positively associated with their daughter’s MetS (adjusted odds ratio or adj OR: 1.63; 95% confidence Interval, CI:1.02-2.61), but not with their sons’ MetS. When analyzed by individual components, maternal impaired glucose (adj OR: 2.03; 95% CI: 1.02- 9.31), abdominal obesity (adj OR: 1.56; 95% CI: 0.98- 2.55) and low HDL-C (adj OR: 2.12; 95% CI: 1.36-3.32) were associated daughter’s MetS. Maternal low HDL-C and raised total cholesterol showed marginal association with son’s MetS. For fathers, only impaired glucose (adj OR: 4.91; 95% CI: 2.07- 11.68) was associated with their daughter’s MetS.
Using the data from Framingham Heart Study, we demonstrate differential association of MetS and its components between parents and offspring. Mother’s MetS was strongly related with daughter’s MetS, but the association was inconsistent with son’s MetS. No association was found between father’s MetS and offspring’s Mets. These results provide evidence that daughters with mother’s MetS are in higher risk than daughters or sons with father’s MetS.
PMCID: PMC4290436  PMID: 25584075
Metabolic syndrome; Parent-offspring; Abdominal obesity; Impaired fasting glucose; Framingham Heart Study
16.  Clinical usefulness of lipid ratios to identify men and women with metabolic syndrome: a cross-sectional study 
Waist circumference, a metabolic syndrome (MetSy) criterion, is not routinely measured in clinical practice making early identification of individuals with MetSy challenging. It has been argued that ratios of commonly measured parameters such as lipids and lipoproteins may be an acceptable alternative for identifying individuals with MetSy. The objective of our study was to explore clinical utility of lipid ratios to identify men and women with MetSy; and to explore the association between lipid ratios and the number of MetSy components.
Men and women (N = 797) of Aboriginal, Chinese, European, and South Asian origin (35–60 years), recruited across ranges of body mass index (BMI), with no diagnosed cardiovascular disease (CVD) or on medications to treat CVD risk factors were assessed for anthropometrics, family history of CVD, MetSy components (waist circumference, blood pressure, glucose, triglycerides (TG), high-density-lipoprotein-cholesterol (HDL-C)), low-density-lipoprotein-cholesterol (LDL-C), nonHDL-C, and health-related behaviours.
Mean levels of lipid ratios significantly increased with increasing number of MetSy components in men and women (p < 0.05). After adjustment for age, ethnicity, smoking, alcohol consumption, physical activity, family history of CVD and BMI, (and menopausal status in women), all lipid ratios were associated with the number of MetSy components in men and women (Poisson regression, p < 0.001). Compared to the rest of the lipid ratios (ROC curve analysis), TG/HDL-C was best able to discriminate between individuals with and without MetSy (AUC = 0.869 (95% CI: 0.830, 0.908) men; AUC = 0.872 (95% CI: 0.832, 0.912) women). The discriminatory power of TC/HDL-C and nonHDL-C/HDL-C to identify individuals with MetSY was the same (for both ratios, AUC = 0.793 (95% CI: 0.744, 0.842) men; 0.818 (95% CI: 0.772, 0.864) women). Additionally, LDL-C/HDL-C was a good marker for women (AUC = 0.759 (95% CI: 0.706, 0.812)), but not for men (AUC = 0.689 (95% CI: 0.631, 0.748)). Based on a multiethnic sample, we identified TG/HDL-C cut-off values of 1.62 in men and 1.18 in women that were best able to discriminate between men and women with and without MetSY.
Our results indicate that TG/HDL-C is a superior marker to identify men and women with MetSy compared to TC/HDL-C, LDL-C/HDL-C, and nonHDL-C/HDL-C.
Electronic supplementary material
The online version of this article (doi:10.1186/1476-511X-13-159) contains supplementary material, which is available to authorized users.
PMCID: PMC4210572  PMID: 25300321
Metabolic syndrome; Lipid ratios; Triglyceride-to-high-density-lipoprotein-cholesterol; Low-density-lipoprotein-cholesterol-to-high-density-lipoprotein-cholesterol; Non-high-density-lipoprotein-cholesterol-to-high-density-lipoprotein-cholesterol; and total cholesterol-to-high-density-lipoprotein-cholesterol
17.  Metabolic Syndrome, Inflammation, and the Incident Heart Failure in the Elderly: the Cardiovascular Health Study 
Circulation. Heart failure  2008;1(4):242-248.
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.
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.
PMCID: PMC2762642  PMID: 19808298
heart failure; metabolism; inflammation
18.  A Cross-sectional Study of Intima-Media Thickness, Ethnicity, Metabolic Syndrome, and Cardiovascular Risk in 2268 Study Participants 
Mayo Clinic Proceedings  2009;84(3):221-228.
OBJECTIVE: To describe the association between intima-media thickness (IMT) and metabolic syndrome (MetS) and to examine if the addition of IMT to a traditional MetS definition adds value to the assessment of predicted cardiovascular disease (CVD) risk in a large multiethnic population.
PARTICIPANTS AND METHODS: In this cross-sectional study, carotid IMT was measured in 2268 men and women as part of a wellness physical examination between August 1, 2000, and October 1, 2001. The wellness examination included a fasting lipid panel, physical examination, and medical history. Mean IMT was described by sex, ethnicity, and the MetS. Predicted risk for CVD was determined with IMT as a component of the diagnostic criteria for MetS.
RESULTS: Intima-media thickness increased with each additional component of the MetS, increasing from 0.516 mm for 0 components to 0.688 mm for 4 or more components (P<.001). In each ethnic group (non-Hispanic whites, blacks, Hispanics, and Asians), those with the MetS had higher mean IMT (increased by 0.084 mm to 0.134 mm) than those without MetS. The addition of IMT as a “new” component in the diagnosis of MetS allowed us to identify 78 (3.4%) participants who were not previously diagnosed as having MetS but who had a high 10-year estimated risk of MetS as measured by the Framingham risk score (11.67%).
CONCLUSION: The addition of IMT to the traditional criteria for the diagnosis of the MetS may help identify individuals who otherwise would not have been identified to be at high risk of CVD.
This article describes the association between intima-media thickness and metabolic syndrome and concludes that the addition of intima-media thickness to the traditional criteria for the diagnosis of the metabolic syndrome may help identify individuals who otherwise would not have been identified to be at high risk of cardiovascular disease.
PMCID: PMC2664597  PMID: 19252108
19.  Ethnic Differences in the Link Between Insulin Resistance and Elevated ALT 
Pediatrics  2013;132(3):e718-e726.
Nonalcoholic fatty liver disease (NAFLD) exhibits tight links with insulin resistance (IR) and the metabolic syndrome (MetS), a cluster of cardiovascular risk factors. Compared with non-Hispanic whites, non-Hispanic black adolescents have more IR but a lower prevalence of NAFLD and MetS. Our hypothesis was that IR would be a better predictor of alanine aminotransferase (ALT) elevations than is MetS among non-Hispanic blacks.
We analyzed data from 4124 adolescents aged 12 to 19 years in the 1999 to 2010 NHANES, using unexplained elevations in ALT (>30 U/L) to characterize presumed NAFLD and using a pediatric adaptation of the Adult Treatment Panel III definition of MetS.
Prevalence of elevated ALT varied by race/ethnicity (Hispanics 13.7%, non-Hispanic white 8.6%, non-Hispanic blacks 5.4%, P < .0001). Among non-Hispanic whites and Hispanics, a classification of MetS performed well in identifying adolescents with elevated ALT (odds ratios [ORs] 9.53 and 5.56, respectively), as did MetS-related indices. However, among non-Hispanic blacks, the association between MetS and ALT elevations was smaller in magnitude and technically nonsignificant (OR = 3.24, P = .051). Furthermore, among non-Hispanic blacks, the presence of IR and elevated waist circumference performed more poorly at identifying ALT elevations (ORs 3.93 and 2.28, respectively: significantly smaller than ORs for non-Hispanic whites, P < .05), with triglyceride elevations being a better predictor (OR = 4.44).
Non-Hispanic black adolescents exhibit a lower relationship between IR and elevated ALT, supporting racial/ethnic differences in the link between MetS and NAFLD. These data may have implications regarding triggers for screening for NAFLD among non-Hispanic black adolescents, focusing particularly on those with triglyceride elevations.
PMCID: PMC3876752  PMID: 23940240
metabolic syndrome; visceral obesity; inflammation; racial/ethnic difference
20.  Metabolic syndrome risk assessment in children: use of a single score 
Revista Paulista de Pediatria  2015;33(2):187-193.
To calculate a score of metabolic syndrome (MetS) in children and set a cutoff point of this score for the prediction of MetS risk.
The study included a random sample of 348 children aged 8 and 9 years of Viçosa, Southeast Brazil. Factor analysis by principal components (PCA) was used to determine, among various risk factors, those with higher degrees of intercorrelation. The chosen variables were: waist circumference (PC), homeostatic model assessment of insulin resistance (HOMA), high density lipoprotein (HDL), triglycerides (TAG) and mean arterial pressure (MAP). Z-scores were created for each one of these parameters and the sum of these z-scores constituted the MetS score. The receiver operating characteristic (ROC) curve was used to identify the cutoff of MetS score, using as gold standard the presence or absence of MetS determined according to criteria age-modified.
The prevalence of MetS in the sample was 8.9% by adopting specific criteria for age, and 24% when considering the cutoff of MetS score. The selected cutoff point of 1.86 was accurate to predict the MetS risk in this sample due to its high sensitivity (96.7%), specificity (82.7%) and AUC of 0.96.
This original Brazilian study presents the MetS score as a suitable alternative for the study of Metabolic Syndrome in children, given the lack of consensus for the definition of this syndrome in childhood.
PMCID: PMC4516373  PMID: 25649382
Metabolic syndrome; Score; Children
21.  Importance of Both Fatness and Aerobic Fitness on Metabolic Syndrome Risk in Japanese Children 
PLoS ONE  2015;10(5):e0127400.
Associations between body mass index (BMI), peak oxygen consumption (VO2peak), and metabolic syndrome (MetS) risk factors have not been adequately studied in Japanese children. Here the relationships between these parameters and the threshold aerobic fitness level necessary for low MetS risk were determined. The participants (299 children; 140 boys and 159 girls, aged 9.1 ± 0.3 years) were divided into four groups using the medians of predicted VO2peak (pVO2peak) and BMI. MetS risk scores were calculated using z-scores. Receiver Operating Characteristic analysis was used to determine the threshold aerobic fitness level necessary for low MetS risk. The MetS risk score of the High BMI group was significantly higher than that of the Low BMI group for both sexes (p < 0.0001). However, the High BMI/High Fitness group had a significantly lower MetS risk score than the High BMI/Low Fitness group for both sexes. The pVO2peak cut-off values for low MetS risk were 47.9 and 44.9 ml/kg/min for boys and girls, respectively. Our results suggest that improvements in both fatness and aerobic fitness are important for decreasing MetS risk. We also confirmed the pVO2peak of cut-off values necessary for low MetS risk in Japanese children.
PMCID: PMC4438983  PMID: 25993528
22.  Optimal cut-off of homeostasis model assessment of insulin resistance (HOMA-IR) for the diagnosis of metabolic syndrome: third national surveillance of risk factors of non-communicable diseases in Iran (SuRFNCD-2007) 
We have recently determined the optimal cut-off of the homeostatic model assessment of insulin resistance for the diagnosis of insulin resistance (IR) and metabolic syndrome (MetS) in non-diabetic residents of Tehran, the capital of Iran. The aim of the present study is to establish the optimal cut-off at the national level in the Iranian population with and without diabetes.
Data of the third National Surveillance of Risk Factors of Non-Communicable Diseases, available for 3,071 adult Iranian individuals aging 25-64 years were analyzed. MetS was defined according to the Adult Treatment Panel III (ATPIII) and International Diabetes Federation (IDF) criteria. HOMA-IR cut-offs from the 50th to the 95th percentile were calculated and sensitivity, specificity, and positive likelihood ratio for MetS diagnosis were determined. The receiver operating characteristic (ROC) curves of HOMA-IR for MetS diagnosis were depicted, and the optimal cut-offs were determined by two different methods: Youden index, and the shortest distance from the top left corner of the curve.
The area under the curve (AUC) (95%CI) was 0.650 (0.631-0.670) for IDF-defined MetS and 0.683 (0.664-0.703) with the ATPIII definition. The optimal HOMA-IR cut-off for the diagnosis of IDF- and ATPIII-defined MetS in non-diabetic individuals was 1.775 (sensitivity: 57.3%, specificity: 65.3%, with ATPIII; sensitivity: 55.9%, specificity: 64.7%, with IDF). The optimal cut-offs in diabetic individuals were 3.875 (sensitivity: 49.7%, specificity: 69.6%) and 4.325 (sensitivity: 45.4%, specificity: 69.0%) for ATPIII- and IDF-defined MetS, respectively.
We determined the optimal HOMA-IR cut-off points for the diagnosis of MetS in the Iranian population with and without diabetes.
PMCID: PMC2857836  PMID: 20374655
23.  Association between Metabolic Syndrome and Sleep-disordered Breathing in Adolescents 
Rationale: Metabolic syndrome (MetS) affects 4 to 10% of adolescents. Risk factors include overweight, male sex, and Hispanic ethnicity. Although sleep-disordered breathing (SDB) has been implicated as a risk factor for MetS in adults, its association with SDB in adolescents is unknown.
Objectives: To define the association of SDB with MetS in adolescents.
Methods: Standardized measurements of SDB, anthropometry and bioassays, were made in 270 adolescents, aged 13.6 ± 0.7 years. MetS was identified if threshold levels were exceeded in three of five areas: waist circumference, blood pressure, triglyceride level, high-density lipoprotein cholesterol level, and glucose levels.
Measurements and Main Results: Although 70% of children with SDB (apnea–hypopnea index ⩾ 5) were overweight and 59% had MetS, 16% of children without SDB had MetS. Twenty-five percent of those with MetS had SDB. After adjusting for age, race, sex, and preterm status, children with SDB had a 6.49 (95% confidence interval, 2.52, 16.70) increased odds of MetS compared with children without SDB. Indices of SDB stress associated with MetS included respiratory event frequency, degree of oxygen desaturation, and sleep efficiency. Analyses of individual metabolic parameters showed that, after adjustment for body mass index, SDB was associated with systolic and diastolic blood pressure, low-density lipoprotein cholesterol, and fasting insulin levels.
Conclusions: A majority of adolescents with SDB are overweight and meet criteria for MetS. The close association between MetS and SDB and their putative interacting pathophysiologies suggests a need to develop screening, prevention, and treatment strategies for both disorders in high-risk, overweight adolescents.
PMCID: PMC1994215  PMID: 17541017
sleep apnea; metabolic syndrome; obesity
24.  γ-Glutamyl Transpeptidase in Men and Alanine Aminotransferase in Women are the Most Suitable Parameters Among Liver Function Tests for the Prediction of Metabolic Syndrome in Nonviral Hepatitis and Nonfatty Liver in the Elderly 
Nonalchoholic fatty liver disease (NAFLD) has been reported as a hepatic manifestation of metabolic syndrome (MetS); it is common and accounts for 80% of the cases with abnormal liver function tests (LFTs). In addition, several studies have proved that there is a correlation between abnormal LFTs and MetS. Therefore, LFTs may represent the abnormal metabolic status of livers in the patients with MetS. To identify the early state of metabolic dysfunction, we investigate the value of LFTs for the future MetS development in the relatively healthy (non-NAFLD) elderly.
Patients and Methods:
A total of 16,912 subjects met the criteria for analysis. In the first stage of this study, subjects were enrolled in the cross-sectional study in order to find out the optimal cutoff value in different LFTs with higher chances to have MetS. In the second stage of the present study, subjects with MetS at baseline were excluded from the same study group, and a median 5.6-year longitudinal study was conducted on the rest of the group.
Among all LFTs, only aspartate aminotransferase in both genders and the α-fetal protein in women failed to show the significance in distinguishing subjects with MetS by the receiver operating characteristic curve. In the Kaplan–Meier plot, only γ-glutamyl transpeptidase (γ-GT) in men and the alanine aminotransferase (ALT) in women could be used to successfully separate subjects with higher risk of developing the MetS from those with lower risk. Finally, in the multivariant Cox regression model, similar results were identified. Still, the hazard ratio (HR) to have future MetS, γ-GT in men, and ALT in women showed significance (HR = 1.511 in men and 1.504 in women).
Among all the different LFTs, γ-GT (>16 U/L) in male and ALT (>21 U/L) in female were the best predictors for the development of MetS in healthy elderly. These two liver markers could be an ancillary test in predicting future MetS development/diagnosis. Elevation of the LFTs without underlying liver diseases should be treated as a warning sign of the possible MetS development in the elderly.
PMCID: PMC4455146  PMID: 26021775
Alanine aminotransferase; elderly; liver function tests; metabolic syndrome; γ-glutamyl transpeptidase
25.  Worksite health screening programs for predicting the development of Metabolic Syndrome in middle-aged employees: a five-year follow-up study 
BMC Public Health  2010;10:747.
Metabolic syndrome (MetS) management programs conventionally focus on the adults having MetS. However, risk assessment for MetS development is also important for many adults potentially at risk but do not yet fulfill MetS criteria at screening. Therefore, we conducted this follow-up study to explore whether initial screening records can be efficiently applied on the prediction of the MetS occurrence in healthy middle-aged employees.
Utilizing health examination data, a five-year follow-up observational study was conducted for 1384 middle-aged Taiwanese employees not fulfilling MetS criteria. Data analyzed included: gender, age, MetS components, uric acid, insulin, liver enzymes, sonographic fatty liver, hepatovirus infections and lifestyle factors. Multivariate logistic regression was used to estimate the adjusted odds ratios (OR) and 95% confidence interval (CI) of risk for MetS development. The synergistic index (SI) values and their confidence intervals of risk factor combinations were calculated; and were used to estimate the interacting effects of coupling MetS components on MetS development.
Within five years, 13% (175 out of 1384) participants fulfilled MetS criteria. The ORs for MetS development among adults initially having one or two MetS components were 2.8 and 7.3, respectively (both p < 0.01), versus the adults having zero MetS component count at screening. Central obesity carried an OR of 7.5 (p < 0.01), which far exceeded other risk factors (all ORs < 2.7). Synergistic effects on MetS development existed between coupling MetS components: 1. High blood pressure plus low-HDL demonstrated an OR of 11.7 (p < 0.01) for MetS development and an SI of 4.7 (95% CI, 2.1-10.9). 2. High blood pressure plus hyperglycemia had an OR of 7.9 (p < 0.01), and an SI of 2.7 (95% CI, 1.2-6.4).
MetS component count and combination can be used in predicting MetS development for participants potentially at risk. Worksite MetS screening programs simultaneously allow for finding out cases and for assessing risk of MetS development.
PMCID: PMC3003648  PMID: 21126351

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