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Jialal I, Adams-Huet B, Remaley AT. A comparison of the ratios of C-reactive protein and triglycerides to high-density lipoprotein-cholesterol as biomarkers of metabolic syndrome in African Americans and non-Hispanic Whites. J Diabetes Complications 2022; 36:108231. [PMID: 35718599 DOI: 10.1016/j.jdiacomp.2022.108231] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Revised: 06/04/2022] [Accepted: 06/10/2022] [Indexed: 10/18/2022]
Abstract
AIMS The ratio of triglycerides (TG) to high density lipoprotein-cholesterol (HDL-C) is a validated biomarker of insulin resistance and metabolic syndrome (MetS). In African-Americans (AA) there is concern about this ratio because their mean TG level is lower than the general population. As an alternative approach, we examined the CRP:HDL-C ratio in both AA and non-Hispanic whites (NHW) in the NHANES study for its association with MetS. METHODS A total of n = 3541 individuals were studied from the NHANES data. Fasting blood samples were obtained for lipids, insulin, and CRP. TG and CRP ratios to HDL-C were calculated. RESULTS The TG:HDL-C ratio was significantly increased in NHW compared to AA, but the CRP:HDL-C ratio did not differ between NHW and AA groups. Both ratios were significantly increased in MetS patients versus controls (both races) and increased with greater severity of MetS. Receiver Operating Characteristic (ROC) curve analysis showed that the TG:HDL-C area under the curve was superior to CRP:HDL-C in predicting MetS in both AA and NHW patients. CONCLUSION In this large NHANES study, the TG:HDL-C ratio is a superior predictor of MetS in both AA and NHW persons despite the lower TG levels in AA persons.
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Affiliation(s)
- Ishwarlal Jialal
- Veterans Affairs Medical Center, Mather, CA, United States of America.
| | | | - Alan T Remaley
- Translational Vascular Medicine Branch, NHLBI, NIH, Bethesda, MD, United States of America
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Jialal I. Letter to the Editor From Jialal: "Higher Incidence of Metabolic Syndrome in Black Women With Polycystic Ovary Syndrome: A Longitudinal Study". J Clin Endocrinol Metab 2022; 107:e2198-e2199. [PMID: 34979022 DOI: 10.1210/clinem/dgab935] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Indexed: 11/19/2022]
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Jialal I, Adams-Huet B. The Ratios of Triglycerides and C-reactive protein to High density-lipoprotein -cholesterol as valid biochemical markers of the Nascent Metabolic Syndrome. Endocr Res 2021; 46:196-202. [PMID: 34080928 DOI: 10.1080/07435800.2021.1930039] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
Aims: Metabolic syndrome (MetS), a cardiometabolic cluster, is a major global problem. The ratio of triglycerides (TG) to high-density lipoprotein cholesterol (HDL-C) is a good biomarker of MetS in certain populations C-reactive protein (CRP) has also been also shown to be a biomarker of MetS. Since CRP captures inflammation, we compared the ratios of TG to HDL-C and CRP to HDL-C in patients with nascent MetS.Methods: Patients with MetS (n = 58) and matched controls (n = 44) were recruited. Fasting blood samples were obtained for routine laboratories, insulin, and adipokines. TG and CRP ratios to HDL-C were calculated. Data were analyzed statistically.Results: Both the TG to HDL-C and CRP to HDL-C ratios were significantly increased in MetS and both increased with increasing severity of MetS. Whilst both correlated with cardiometabolic features and insulin resistance, only the CRP to HDL-C ratio correlated significantly with adiponectin and leptin. Receiver operating characteristic curve analysis showed that both ratios showed excellent discrimination for MetS with no significant differences between ratios.Conclusions: Thus both the TG to HDL-C and CRP to HDL-C ratios are significantly increased in patients with nascent MetS and appear to be valid biomarkers of MetS. However, these preliminary findings with CRP: HDL-C need confirmation in large prospective studies and could have important implications for assessing cardiometabolic risk in African Americans, an under-served population.
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Affiliation(s)
- Ishwarlal Jialal
- Section of Clinical Chemistry, Department of Pathology, Veterans Affairs Medical Center, Mather, CA, USA
| | - Beverley Adams-Huet
- Department of Clinical Sciences , UT Southwestern Medical Center, Dallas, TX, USA
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Sulistyaningsih I, Afifah DN, Juniarto AZ, Anjani G, Rustanti N. The Effect of Tempe Gembus on High-Sensitivity C-Reactive Protein and Adiponectine Levels in Rats with Metabolic Syndrome. J Nutr Sci Vitaminol (Tokyo) 2021; 66:S51-S55. [PMID: 33612648 DOI: 10.3177/jnsv.66.s51] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
Metabolic syndrome can affect the inflammatory state which results in increased high-sensitivity C-reactive protein (hs CRP) and decreased adiponectin levels. Tempe gembus is a functional food that can reduce the risk of metabolic syndrome through the inflammatory pathway. This study applied a quasi experimental method, with a post-test only control group design. Sprague Dawley rats (n=30) were divided into 2 control groups (K- and K+) and 3 treatment groups (P1, P2, P3) which were given a 4-wk diet that included 2.5 g (P1), 5 g (P2), and 7.5 g (P3) of tempe gembus. Adiponectin and hs CRP levels were measured with ELISA. Statistical analysis was done with a one-way ANOVA test and a Kruskal Wallis test. It apprears that administering tempe gembus in these amounts can reduce the hs CRP levels (p=0.037) and increase adiponectin levels in rats with metabolic syndrome (p=0.008). This research has shown that a 2.5 g of tempe gembus can have a strong effect on hs CRP and 5 g of tempe gembus have a strong effect on adiponectin.
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Affiliation(s)
| | - Diana Nur Afifah
- Department of Nutrition Science, Medical Faculty, Diponegoro University
| | | | - Gemala Anjani
- Department of Nutrition Science, Medical Faculty, Diponegoro University
| | - Ninik Rustanti
- Department of Nutrition Science, Medical Faculty, Diponegoro University
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Cardel MI, Guo Y, Sims M, Dulin A, Miller D, Chi X, Pavela G, DeBoer MD, Gurka MJ. Objective and subjective socioeconomic status associated with metabolic syndrome severity among African American adults in Jackson Heart Study. Psychoneuroendocrinology 2020; 117:104686. [PMID: 32361636 PMCID: PMC7304382 DOI: 10.1016/j.psyneuen.2020.104686] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2019] [Revised: 02/12/2020] [Accepted: 04/02/2020] [Indexed: 01/01/2023]
Abstract
PURPOSE To assess independent associations between objective socioeconomic status (OSS) and subjective social status (SSS) with metabolic syndrome (MetS) severity and indicators among African American (AA) adults in the Jackson Heart Study (JHS) at baseline (2000-2004) and eight-year follow-up (2009-2013). METHODS Participants included 1724 AA adults from the JHS cohort (64.4 % women; mean age 53.4 ± 11.8). Associations of OSS (annual household income and school years completed) and SSS (measured with MacArthur Scales) with sex- and race/ethnic-specific MetS severity Z-score were examined after adjustment for demographics and MetS risk factors (i.e., nutrition, physical activity, smoking status, alcohol consumption, and depressive symptoms) at baseline and eight-year follow-up. PRINCIPAL RESULTS Independent of OSS, demographic, psychosocial, and lifestyle factors, individuals with lower US-society SSS had more severe MetS at baseline. A significant interaction existed between sex and US-society SSS such that women with lower perceived social status had more severe MetS severity at baseline, and for every one unit increase in US-society SSS, MetS severity Z-score is estimated to decrease by 0.04. Components of MetS driving the relationship between US-society SSS and MetS severity at baseline were the inverse associations of SSS with glucose levels and the positive associations of SSS with HDL-C. Physical activity was independently associated with MetS severity at baseline, but not at eight-year follow-up. MAJOR CONCLUSIONS Though subjective and objective measures of social status are independently associated with cardiometabolic risk factors and MetS severity among AA adults, SSS may be a stronger predictor of MetS severity than OSS, particularly among women. SSS should be considered in conjunction with OSS when exploring social determinants of cardiometabolic health.
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Affiliation(s)
- Michelle I Cardel
- Department of Health Outcomes and Biomedical Informatics, University of Florida, PO Box 100177, Gainesville, Florida, 32610-0177, USA.
| | - Yi Guo
- Department of Health Outcomes and Biomedical Informatics, University of Florida, PO Box 100177, Gainesville, Florida, 32610-0177, USA.
| | - Mario Sims
- Department of Medicine, University of Mississippi Medical Center, 2500 N. State St., Jackson, Mississippi, 39216, USA.
| | - Akilah Dulin
- Department of Behavioral and Social Sciences, Brown University School of Public Health, Box G-S121-8, 121 S. Main St., Providence, Rhode Island, 02912, USA.
| | - Darci Miller
- Department of Health Outcomes and Biomedical Informatics, University of Florida, PO Box 100177, Gainesville, Florida, 32610-0177, USA.
| | - Xiaofei Chi
- Department of Health Outcomes and Biomedical Informatics, University of Florida, PO Box 100177, Gainesville, Florida, 32610-0177, USA.
| | - Gregory Pavela
- Department of Health Behavior, University of Alabama at Birmingham, 1665 University Blvd., Birmingham, AL 35294, USA.
| | - Mark D DeBoer
- Department of Pediatrics, PO Box 800386, University of Virginia Health System, Charlottesville, Virginia, 22908-0386, USA.
| | - Matthew J Gurka
- Department of Health Outcomes and Biomedical Informatics, University of Florida, PO Box 100177, Gainesville, Florida, 32610-0177, USA.
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Meamar R, Amini M, Aminorroaya A, Nasri M, Abyar M, Feizi A. Severity of the metabolic syndrome as a predictor of prediabetes and type 2 diabetes in first degree relatives of type 2 diabetic patients: A 15-year prospective cohort study. World J Diabetes 2020; 11:202-212. [PMID: 32477456 PMCID: PMC7243485 DOI: 10.4239/wjd.v11.i5.202] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2019] [Revised: 03/16/2020] [Accepted: 03/23/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Type 2 diabetes mellitus (T2DM) has high morbidity and mortality worldwide, therefore there is of paramount importance to identify the risk factors in the populations at risk early in the course of illness. A strong correlation between severity of metabolic syndrome (MetS) and HbA1c, fasting insulin and insulin resistance has been reported. Accordingly, the MetS severity score (or MestS Z-score) can potentially be used to predict the risk of T2DM progression over time. AIM To evaluate the association the of MestS Z-score in first degree relatives (FDRs) of T2DM with the risk of prediabetes and type 2 diabetes in future. METHODS A prospective open cohort study was conducted between 2003-2018. At baseline, the sample comprised of 1766 FDRs of patients with T2DM who had a normal glucose tolerance test. Relative risk (RR) and 95% confidence interval were calculated based on logistic regression. The receiver-operator characteristic analysis and area under the curve based on MetS Z-score were used to evaluate the risk of prediabetes and diabetes among the FDR population. RESULTS Baseline MetS Z-scores were associated with the its latest values (P < 0.0001). Compared with individuals who were T2DM free at the end of follow up, those who developed T2DM had higher MetS Z-score at baseline (P < 0.001). In multivariable logistic regression analyses for every unit elevation in MetS Z-score at the baseline, the RR for developing future T2DM and prediabetes was (RR = 1.94, RR = 3.84), (RR = 1.5, RR = 2.17) in total population and female group, respectively (P < 0.05). The associations remained significant after adjusting the potential confounding variables. A cut off value of 0.97 and 0.94 was defined in the receiver-operator characteristic curve based on the MetS Z-score for differentiating female patients with diabetes and prediabetes from the normal population, respectively. CONCLUSION The MetS Z-score was associated with an increased risk of future T2DM. Appropriate interventions at earlier stages for preventing and attenuating MetS effects may be considered as an effective strategy for FDR as at-risk population.
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Affiliation(s)
- Rokhsareh Meamar
- Isfahan Endocrine and Metabolism Research Center, Isfahan Clinical Toxicology Research Center, Isfahan University of Medical Sciences, Isfahan 81746-73461, Iran
| | - Masoud Amini
- Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan 81746-73461, Iran
| | - Ashraf Aminorroaya
- Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan 81746-73461, Iran
| | - Maryam Nasri
- Grovemead Health Center, London NW4-3EB, United Kingdom
| | - Majid Abyar
- Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan 81746-73461, Iran
| | - Awat Feizi
- Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan 81746-73461, Iran
- Department of Biostatistics and Epidemiology, School of Health, Isfahan University of Medical Sciences, Isfahan 81746-73461, Iran
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Harris CP, von Berg A, Berdel D, Bauer CP, Schikowski T, Koletzko S, Heinrich J, Schulz H, Standl M. Dietary saturated fat and low-grade inflammation modified by accelerometer-measured physical activity in adolescence: results from the GINIplus and LISA birth cohorts. BMC Public Health 2019; 19:818. [PMID: 31238900 PMCID: PMC6593603 DOI: 10.1186/s12889-019-7113-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2019] [Accepted: 06/05/2019] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Saturated fatty acids (SFA) have been reported to promote inflammation. Nevertheless, evidence linking dietary SFA and low-grade inflammation in adolescents is scarce and inconsistent. The modulatory role of physical activity (PA) on fat metabolism and inflammation may provide a potential explanation. Thus, we assessed the association of dietary SFA with high-sensitivity C-reactive protein (hsCRP), a marker of low-grade inflammation, in 15-year-olds, and evaluated possible interactions between dietary SFA and different levels of PA. METHODS Children participating in the 15-year follow-ups of the GINIplus and LISA German birth cohort studies were included (N = 824). SFA intake was estimated by means of a food frequency questionnaire and PA recorded by accelerometers. Average daily minutes of PA were classified into "sedentary", "light" and "moderate-to-vigorous" (MVPA), using Freedson's cut-offs. HsCRP concentrations were measured in serum and categorized into 3 sex-specific levels (below detection limit (I), above 75th percentile (III), in between (II)). Sex-stratified cross-sectional associations between SFA and hsCRP were assessed using multinomial logistic regression, adjusting for potential confounders. Interaction terms were included between SFA and the different PA levels; and if significant interactions were observed, analyses stratified by tertiles of the relevant PA levels were performed. Relative risk ratios (RRR) and 95% confidence intervals (95%CI) were presented for a 1% increase in SFA. RESULTS An inverse association was observed between SFA intake and hsCRP (II vs. I) in males (RRR = 0.85 [95%CI = 0.76;0.96], p = 0.008), whereas no significant association was observed in females. A significant interaction was observed with "sedentary" and "light" PA but not with MVPA in both sexes (p < 0.05). Stratified analyses indicated a significant inverse association between SFA and medium hsCRP levels in males in the highest light PA tertile (hsCRP II vs. I: 0.67 [0.517;0.858], p = 0.002). CONCLUSION Our findings do not support a detrimental role of dietary SFA in low-grade inflammation among adolescents. In males, higher dietary SFA was associated with lower hsCRP, although this should be interpreted in the context of possibly correlated nutrients. Children spending the most time in light PA drove the observed inverse association, suggesting a synergistic effect of SFA and lifestyle PA in the resultant inflammatory response.
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Affiliation(s)
- Carla P. Harris
- Institute of Epidemiology, Helmholtz Zentrum München, Institute of Epidemiology – German Research Centre for Environmental Health, Ingolstädter Landstr. 1, 85764 Neuherberg, Germany
- Dr. von Hauner Children’s Hospital, University Hospital, LMU of Munich, Munich, Germany
| | - Andrea von Berg
- Research Institute, Department of Pediatrics, Marien-Hospital Wesel, Wesel, Germany
| | - Dietrich Berdel
- Research Institute, Department of Pediatrics, Marien-Hospital Wesel, Wesel, Germany
| | - Carl-Peter Bauer
- Department of Pediatrics, Technical University of Munich, Munich, Germany
| | - Tamara Schikowski
- IUF-Leibniz Research Institute for Environmental Medicine (IUF), Düsseldorf, Germany
| | - Sibylle Koletzko
- Dr. von Hauner Children’s Hospital, University Hospital, LMU of Munich, Munich, Germany
| | - Joachim Heinrich
- Institute of Epidemiology, Helmholtz Zentrum München, Institute of Epidemiology – German Research Centre for Environmental Health, Ingolstädter Landstr. 1, 85764 Neuherberg, Germany
- Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, Inner City Clinic, University Hospital of Munich (LMU), Munich, Germany
- Allergy and Lung Health Unit, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia
| | - Holger Schulz
- Institute of Epidemiology, Helmholtz Zentrum München, Institute of Epidemiology – German Research Centre for Environmental Health, Ingolstädter Landstr. 1, 85764 Neuherberg, Germany
- Comprehensive Pneumology Center Munich (CPC-M), German Center for Lung Research, Munich, Germany
| | - Marie Standl
- Institute of Epidemiology, Helmholtz Zentrum München, Institute of Epidemiology – German Research Centre for Environmental Health, Ingolstädter Landstr. 1, 85764 Neuherberg, Germany
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DeBoer MD, Filipp SL, Gurka MJ. Use of a Metabolic Syndrome Severity Z Score to Track Risk During Treatment of Prediabetes: An Analysis of the Diabetes Prevention Program. Diabetes Care 2018; 41:2421-2430. [PMID: 30275282 PMCID: PMC6196828 DOI: 10.2337/dc18-1079] [Citation(s) in RCA: 54] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2018] [Accepted: 08/10/2018] [Indexed: 02/03/2023]
Abstract
OBJECTIVE We assessed whether changes in metabolic syndrome (MetS) severity during the treatment of prediabetes are associated with reduced risk of type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). RESEARCH DESIGN AND METHODS We analyzed data from the Diabetes Prevention Program (DPP) for 2,476 adults in 1996-1999 with prediabetes randomized to receive treatment with lifestyle modification, metformin, or placebo for 2-3 years and followed through 2014 for T2DM and CVD outcomes. We calculated effect sizes from baseline in a MetS severity z score (MetS-Z) and the individual MetS components, and assessed relationships between 1-year effect size and incident T2DM and CVD using hazard ratios (HRs) and mediation analysis. RESULTS Baseline MetS-Z and its components were associated with risk of incident T2DM and CVD. During year 1 of intervention, MetS-Z and its components decreased most with lifestyle modification, followed by treatment with metformin and placebo. Risk of T2DM within 1-5 years was most strongly associated with 1-year changes in MetS-Z and waist circumference (both HRs for a 1 SD increase = 1.80), whereas the risk of CVD was associated with a 1-year change in MetS-Z, glucose, and systolic blood pressure. In mediation analyses, the effect of lifestyle modification on T2DM risk was mediated by 1-year changes in MetS-Z, waist circumference, glucose, and triglycerides, whereas the effect of metformin was mediated by MetS-Z and glucose. CONCLUSIONS Changes in these risk indicators of MetS severity during intervention in the DPP reflect altered disease risk and may help in tracking earlier responses to treatment and in motivating patients.
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Affiliation(s)
- Mark D DeBoer
- Department of Pediatrics, University of Virginia, Charlottesville, VA
| | - Stephanie L Filipp
- Department of Health Outcomes and Biomedical Informatics, College of Medicine, University of Florida, Gainesville, FL
| | - Matthew J Gurka
- Department of Health Outcomes and Biomedical Informatics, College of Medicine, University of Florida, Gainesville, FL
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Abstract
The continued rise of pediatric obesity globally has raised concerns for related sequalae. One marker of risk is the metabolic syndrome, a cluster of cardiovascular risk factors that is associated with future cardiovascular disease and type 2 diabetes. MetS has at its core visceral adipocytes exhibiting dysfunction as a result of excess fat content. MetS in children and adolescents is linked to unhealthy lifestyle practices such as sedentary lifestyles and excess consumption calories. As such, the optimal means of addressing MetS is targeting a decrease in adiposity through lifestyle modification, a decrease in MetS following increases in physical activity and improvements in the quality and content of food intake. Efforts remain needed in increasing motivation to these changes and maintaining adherence to avoid long-term sequelae.
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Affiliation(s)
- Linda X Wang
- Department of Pediatrics, University of Virginia, Charlottesville, VA, USA
| | - Matthew J Gurka
- Department of Health Outcomes and Biomedical Informatics, College of Medicine, University of Florida, Gainesville, FL, USA
| | - Mark D Deboer
- Department of Pediatrics, University of Virginia, Charlottesville, VA, USA -
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Wang LX, Filipp SL, Urbina EM, Gurka MJ, DeBoer MD. Longitudinal Associations of Metabolic Syndrome Severity Between Childhood and Young Adulthood: The Bogalusa Heart Study. Metab Syndr Relat Disord 2018; 16:208-214. [PMID: 29584578 PMCID: PMC5984565 DOI: 10.1089/met.2017.0160] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023] Open
Abstract
BACKGROUND Childhood metabolic syndrome (MetS) is associated with insulin resistance and increased risk for later development of type 2 diabetes (T2DM) and cardiovascular disease (CVD). In using MetS severity z-scores, our objective was to assess longitudinal associations in MetS severity, fasting insulin levels as a sign of insulin resistance and risk for T2DM, and uric acid levels as a biomarker of oxidative stress leading to CVD. METHODS We used linear regression to analyze longitudinal data from 285 white and black participants from the Bogalusa Heart Study evaluated at baseline at ages 5-19 and as young adults after a mean of 12.0 years follow-up. We assessed correlations between childhood MetS severity and young-adult MetS severity, fasting insulin, and uric acid levels, both overall and by sex- and racial subgroups. RESULTS Overall, childhood MetS z-scores were positively associated with young-adult MetS z-scores (r = 0.52), insulin (r = 0.34), and uric acid (r = 0.28) (all P < 0.001). These associations were consistent across all sex- and racial subgroups, except for young adult uric acid in white males in which childhood MetS-z was not associated (r = 0.15, P = 0.243). There was a strong cross-sectional association of young-adult MetS z-scores with insulin (r = 0.70) and uric acid (r = 0.57) (both P < 0.001), which was consistent for all sex- and racial subgroups. CONCLUSIONS These positive longitudinal correlations between childhood MetS z-scores and markers of later insulin resistance and oxidative stress suggest long-term durability of risk for CVD and T2DM. This suggests potential for MetS severity to serve as an indicator to monitor for future risk of T2DM and CVD.
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Affiliation(s)
- Linda X. Wang
- Department of Pediatrics, University of Virginia, Charlottesville, Virginia
| | - Stephanie L. Filipp
- Department of Health Outcomes and Policy, College of Medicine, University of Florida, Gainesville, Florida
| | - Elaine M. Urbina
- Department of Cardiology, Cincinnati Children's Hospital, Cincinnati, Ohio
| | - Matthew J. Gurka
- Department of Health Outcomes and Policy, College of Medicine, University of Florida, Gainesville, Florida
| | - Mark D. DeBoer
- Department of Pediatrics, University of Virginia, Charlottesville, Virginia
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Gurka MJ, Filipp SL, Musani SK, Sims M, DeBoer MD. Use of BMI as the marker of adiposity in a metabolic syndrome severity score: Derivation and validation in predicting long-term disease outcomes. Metabolism 2018; 83:68-74. [PMID: 29410278 PMCID: PMC5960618 DOI: 10.1016/j.metabol.2018.01.015] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2017] [Revised: 12/14/2017] [Accepted: 01/17/2018] [Indexed: 12/17/2022]
Abstract
BACKGROUND Estimates of adiposity in evaluating the metabolic syndrome (MetS) have traditionally utilized measures of waist circumference (WC), whereas body mass index (BMI) is more commonly used clinically. Our objective was to determine if a MetS severity Z-score employing BMI as its measure of adiposity (MetS-Z-BMI) would perform similarly to a WC-based score (MetS-Z-WC) in predicting future disease. METHODS To formulate the MetS-Z-BMI, we performed confirmatory factor analysis on a sex- and race/ethnicity-specific basis on MetS-related data for 6870 adult participants of the National Health and Nutrition Survey 1999-2010. We then validated this score and compared it to MetS-Z-WC in assessing correlations with future coronary heart disease (CHD) and Type 2 diabetes mellitus (T2DM) using Cox proportional hazard analysis of 13,094 participants of the Atherosclerosis Risk in Communities study and Jackson Heart Study. RESULTS Loading factors, which represent the relative contribution of each component to the latent MetS factor, were lower for BMI than for WC in formulating the two respective scores (MetS-Z-BMI and MetS-Z-WC). Nevertheless, MetS-Z-BMI and MetS-Z-WC exhibited similar hazard ratios (HR) toward future disease. For each one standard-deviation-unit increase in MetS-Z-BMI, HR for CHD was 1.76 (95% confidence interval [CI]: 1.65, 1.88) and HR for T2DM was 3.39 (CI 3.16, 3.63) (both p < 0.0001). There were no meaningful differences between the MetS-Z-WC and MetS-Z-BMI scores in their associations with future CHD and T2DM. CONCLUSIONS A MetS severity Z-score utilizing BMI as its measure of adiposity operated similarly to a WC-based score in predicting future CHD and T2DM, suggesting overall similarity in MetS-based risk as estimated by both measures of adiposity. This indicates potential clinical usefulness of MetS-Z-BMI in assessing and following MetS-related risk over time.
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Affiliation(s)
- Matthew J Gurka
- Department of Health Outcomes and Biomedical Informatics, College of Medicine, University of Florida, Gainesville, Florida 32608, United States.
| | - Stephanie L Filipp
- Department of Health Outcomes and Biomedical Informatics, College of Medicine, University of Florida, Gainesville, Florida 32608, United States
| | - Solomon K Musani
- Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39213, United States
| | - Mario Sims
- Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39213, United States
| | - Mark D DeBoer
- Department of Pediatrics, Division of Pediatric Endocrinology, PO Box 800386, University of Virginia, Charlottesville, Virginia 22908, United States
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DeBoer MD, Filipp SL, Musani SK, Sims M, Okusa MD, Gurka MJ. Metabolic Syndrome Severity and Risk of CKD and Worsened GFR: The Jackson Heart Study. Kidney Blood Press Res 2018; 43:555-567. [PMID: 29642060 PMCID: PMC6037309 DOI: 10.1159/000488829] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2017] [Accepted: 03/28/2018] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND/AIMS The metabolic syndrome (MetS), as assessed using dichotomous criteria, is associated with increased risk of future chronic kidney disease (CKD), though this relationship is unclear among African Americans, who have lower risk for MetS but higher risk for CKD. METHODS We performed logistic regression using a sex- and race-specific MetS-severity z-score to assess risk of incident CKD among 2,627 African-American participants of the Jackson Heart Study, assessed at baseline and 8 years later. Based on quartile of baseline MetS severity, we further assessed prevalence of being in the lowest quartile of baseline GFR, the lowest quartile of relative GFR at follow-up, microalbuminuria and incident CKD. RESULTS Higher MetS-severity was associated with higher prevalence of GFR in the lowest quartile at baseline among males and females. Among African-American females but not males, higher baseline MetS-severity was associated with a higher prevalence of baseline elevations in microabuminuria (p<0.01), steep decline in GFR (p<0.001) and a higher incidence of CKD (p<0.0001). Women in increasing quartiles of baseline MetS-severity exhibited a linear trend toward higher odds of future CKD (p<0.05), with those in the 4th quartile of MetS-severity (compared to the 1st) having an odds ratio of 2.47 (95% confidence interval 1.13, 5.37); no such relationship was seen among men (p value for trend 0.49). CONCLUSION MetS-severity exhibited sex-based interactions regarding risk for future GFR deterioration and CKD, with increasing risk in women but not men. These data may have implications for triggering CKD screening among African-American women with higher degrees of MetS-severity.
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Affiliation(s)
- Mark D. DeBoer
- Department of Pediatrics, Division of Pediatric Endocrinology, University of Virginia, Charlottesville, Virginia, United States, 22908
| | - Stephanie L Filipp
- Department of Health Outcomes and Policy, College of Medicine, University of Florida, Gainesville, Florida, United States, 32608
| | - Solomon K. Musani
- Department of Medicine, Jackson Heart Study, University of Mississippi Medical Center, Jackson, MS, United States 39213
| | - Mario Sims
- Department of Medicine, Jackson Heart Study, University of Mississippi Medical Center, Jackson, MS, United States 39213
| | - Mark D. Okusa
- Department of Medicine, Division of Nephrology, University of Virginia, Charlottesville, Virginia, United States, 22908
| | - Matthew J. Gurka
- Department of Health Outcomes and Policy, College of Medicine, University of Florida, Gainesville, Florida, United States, 32608
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Geographical variation in the prevalence of obesity, metabolic syndrome, and diabetes among US adults. Nutr Diabetes 2018; 8:14. [PMID: 29549249 PMCID: PMC5856741 DOI: 10.1038/s41387-018-0024-2] [Citation(s) in RCA: 92] [Impact Index Per Article: 13.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2017] [Revised: 12/06/2017] [Accepted: 12/28/2017] [Indexed: 01/28/2023] Open
Abstract
Cardiovascular disease (CVD) and type 2 diabetes remain significant public health concerns. Targeting of prevention efforts by geographical location has been suggested by the Institute of Medicine to coincide with the presence of area-based risk. The metabolic syndrome (MetS) is a stronger risk factor than is obesity for the prediction of future CVD and diabetes, yet its prevalence has not previously been described geographically. Our objective is to determine geographical variation in the prevalence of obesity, MetS, and diabetes among US adults. We assessed the prevalence of obesity, MetS, and diabetes by US census division, and the prevalence of obesity, MetS, and diabetes for each sex and racial/ethnic group by US region among 9826 US non-Hispanic white, non-Hispanic black, and Hispanic adults aged 20–65 years participating in the National Health and Nutrition Examination Survey 1999–2014. We also compared a sex- and race/ethnicity-specific MetS severity score by geographical area. The prevalence of obesity, MetS, and diabetes varied by US census division and region, with overall similarity by geographical area in the prevalence of each of these conditions. The prevalence of MetS was particularly high (≥35%) in the West North Central, West South Central, and East South Central and low (30%) in the Pacific, New England, and Mid-Atlantic divisions. Some of the geographical variation appeared due to differences among non-Hispanic white females, who had a high prevalence of MetS (>32%) in the Midwest and South and a low prevalence of MetS (24%) in the West and Northeast. Geographical differences in MetS imply variation in the risk for future CVD and diabetes, with more elevated risk in the center of the United States. As MetS is a stronger risk factor for prediction of CVD and T2DM than is obesity, these differences are potentially important for prompting public health efforts toward surveillance and prevention in high-risk areas.
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Gurka MJ, Guo Y, Filipp SL, DeBoer MD. Metabolic syndrome severity is significantly associated with future coronary heart disease in Type 2 diabetes. Cardiovasc Diabetol 2018; 17:17. [PMID: 29351794 PMCID: PMC5775549 DOI: 10.1186/s12933-017-0647-y] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2017] [Accepted: 12/23/2017] [Indexed: 02/06/2023] Open
Abstract
Background The severity of the metabolic syndrome (MetS) is significantly associated with future coronary heart disease (CHD) among individuals without baseline Type 2 diabetes. However, the validity of assessing MetS severity among individuals with diabetes is unknown. Objective To assess for differences in MetS severity by timing of Type 2 diabetes diagnosis and to assess for associations between MetS severity and future CHD among individuals with diabetes. Methods We analyzed data from participants of the Atherosclerosis Risk in Communities study, including 1419 with- and 7241 without diabetes, followed during 4 visits and adjudicated CHD diagnoses over a 20-year period. We used Cox-regression techniques to assess hazard ratios (HR) of CHD based on a sex- and race/ethnicity-specific MetS-severity Z-score (standard MetS score) and a similar MetS-severity score formulated without incorporating glucose as a component of MetS (no-glucose MetS score). Results For both the standard- and no-glucose MetS-severity scores, scores were highest in the baseline-diabetes group, lowest in the never-diabetes group and intermediate in the incident-diabetes groups. Among participants with diabetes, increasing MetS-severity score at baseline was associated with incident CHD, using both the standard MetS score (HR 1.29, 95% confidence interval [CI] 1.21, 1.39) and the no-glucose score (HR 1.42, CI 1.24, 1.62) (both p < 0.001). For the baseline-diabetes group, this relationship remained significant when Visit 2 Hemoglobin-A1c was included in the model, both for the standard MetS score (HR 1.21, CI 1.09, 1.34; p < 0.001) and the no-glucose score (HR 1.25, CI 1.04, 1.51; p = 0.02). Conclusions MetS severity appears to provide an estimate of metabolic disarray in the setting of diabetes and is predictive of future CHD events beyond HbA1c. Identifying MetS severity among individuals with diabetes may help in identifying those at higher risk, who could then receive further preventative treatment. Electronic supplementary material The online version of this article (10.1186/s12933-017-0647-y) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Matthew J Gurka
- Department of Health Outcomes and Policy, College of Medicine, University of Florida, Gainesville, FL, 32608, USA
| | - Yi Guo
- Department of Health Outcomes and Policy, College of Medicine, University of Florida, Gainesville, FL, 32608, USA
| | - Stephanie L Filipp
- Department of Health Outcomes and Policy, College of Medicine, University of Florida, Gainesville, FL, 32608, USA
| | - Mark D DeBoer
- Department of Pediatrics, Division of Pediatric Endocrinology, University of Virginia, 409 Lane Rd, Room 2017, P.O. Box 800386, Charlottesville, VA, 22908, USA.
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Guo Y, Musani SK, Sims M, Pearson TA, DeBoer MD, Gurka MJ. Assessing the added predictive ability of a metabolic syndrome severity score in predicting incident cardiovascular disease and type 2 diabetes: the Atherosclerosis Risk in Communities Study and Jackson Heart Study. Diabetol Metab Syndr 2018; 10:42. [PMID: 29796112 PMCID: PMC5956946 DOI: 10.1186/s13098-018-0344-3] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2018] [Accepted: 05/08/2018] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The severity of the metabolic syndrome (MetS) predicts future coronary heart disease (CHD) and diabetes independent of the individual MetS components. Our aim was to evaluate whether MetS severity conferred additional discrimination to existing scoring systems for cardiovascular disease (CVD) and diabetes risk. METHODS We assessed Cox proportional hazard models of CHD- and diabetes risk among 13,141 participants of the Atherosclerosis Risk in Communities Study and the Jackson Heart Study, using the Framingham Risk Calculator, the American Heart Association's Atherosclerotic CVD calculator, the American Diabetes Association diabetes risk score and an additional diabetes risk score derived from ARIC data. We then added a MetS-severity Z-score to these models and assessed for added risk discrimination by assessing Akaike information criterion, c-statistic, integrated discrimination improvement (IDI) and continuous net reclassification improvement (NRI). RESULTS The MetS severity score appears to add to the predictive ability of individual CHD and diabetes risk scores. Using the IDI, MetS improved risk prediction for diabetes but not CHD risk. In all 4 scoring systems, MetS severity had a significant non-event NRI, improving the ability to exclude individuals without events. Assessing interactions between risk scores and MetS severity revealed that MetS severity was more highly associated with disease risk among those in the lowest quintiles of risk score, suggesting that MetS was particularly able to identify risk among individuals judged to be of low risk by existing algorithms. CONCLUSIONS Mets severity improved prediction of diabetes more so than CHD. Incorporation of multiple risk predictors into electronic health records may help in better identifying those at high disease risk, who can then be placed earlier on preventative therapy.
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Affiliation(s)
- Yi Guo
- Department of Health Outcomes and Biomedical Informatics, College of Medicine, University of Florida, Gainesville, FL 32608 USA
| | - Solomon K. Musani
- Department of Medicine, Jackson Heart Study, University of Mississippi Medical Center, Jackson, MS 39213 USA
| | - Mario Sims
- Department of Medicine, Jackson Heart Study, University of Mississippi Medical Center, Jackson, MS 39213 USA
| | - Thomas A. Pearson
- Department of Epidemiology, College of Public Health and Health Professions, University of Florida, Gainesville, FL 32608 USA
| | - Mark D. DeBoer
- Division of Pediatric Endocrinology, Department of Pediatrics, University of Virginia, Charlottesville, VA 22908 USA
| | - Matthew J. Gurka
- Department of Health Outcomes and Biomedical Informatics, College of Medicine, University of Florida, Gainesville, FL 32608 USA
- 2004 Mowry Rd Room 3211, PO Box 100177, Gainesville, FL 32610-0177 USA
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Gurka MJ, Golden SH, Musani SK, Sims M, Vishnu A, Guo Y, Cardel M, Pearson TA, DeBoer MD. Independent associations between a metabolic syndrome severity score and future diabetes by sex and race: the Atherosclerosis Risk In Communities Study and Jackson Heart Study. Diabetologia 2017; 60:1261-1270. [PMID: 28378033 PMCID: PMC5481783 DOI: 10.1007/s00125-017-4267-6] [Citation(s) in RCA: 72] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2016] [Accepted: 03/14/2017] [Indexed: 01/08/2023]
Abstract
AIMS/HYPOTHESIS The study aimed to assess for an association between the degree of severity of the metabolic syndrome and risk of type 2 diabetes beyond that conferred by the individual components of the metabolic syndrome. METHODS We assessed HRs for an Adult Treatment Panel III (ATP-III) metabolic syndrome score (ATP-III MetS) and a sex- and race-specific continuous metabolic syndrome severity z score related to incident diabetes over a median of 7.8 years of follow-up among participants of two observational cohorts, the Atherosclerosis Risk in Communities study (n = 10,957) and the Jackson Heart Study (n = 2137). RESULTS The ATP-III MetS had an HR for incident diabetes of 4.36 (95% CI 3.83, 4.97), which was attenuated in models that included the individual metabolic syndrome components. By contrast, participants in the fourth quartile of metabolic syndrome severity (compared with the first quartile) had an HR of 17.4 (95% CI 12.6, 24.1) for future diabetes; in models that also included the individual metabolic syndrome components, this remained significant, with an HR of 3.69 (95% CI 2.42, 5.64). There was a race × metabolic syndrome interaction in these models such that HR was greater for black participants (5.30) than white participants (2.24). When the change in metabolic syndrome severity score was included in the hazard models, this conferred a further association, with changes in metabolic syndrome severity score of ≥0.5 having a HR of 2.66 compared with changes in metabolic syndrome severity score of ≤0. CONCLUSIONS/INTERPRETATION Use of a continuous sex- and race-specific metabolic syndrome severity z score provided an additional prediction of risk of diabetes beyond that of the individual metabolic syndrome components, suggesting an added risk conferred by the processes underlying the metabolic syndrome. Increases in this score over time were associated with further risk, supporting the potential clinical utility of following metabolic syndrome severity over time.
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Affiliation(s)
- Matthew J Gurka
- Department of Health Outcomes and Policy, College of Medicine, University of Florida, Gainesville, FL, USA
| | - Sherita H Golden
- Department of Medicine, Johns Hopkins University, Baltimore, MD, USA
- Department of Epidemiology, Johns Hopkins University, Baltimore, MD, USA
| | - Solomon K Musani
- Department of Medicine, Jackson Heart Study, University of Mississippi Medical Center, Jackson, MS, USA
| | - Mario Sims
- Department of Medicine, Jackson Heart Study, University of Mississippi Medical Center, Jackson, MS, USA
| | - Abhishek Vishnu
- Department of Health Outcomes and Policy, College of Medicine, University of Florida, Gainesville, FL, USA
- Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Yi Guo
- Department of Health Outcomes and Policy, College of Medicine, University of Florida, Gainesville, FL, USA
| | - Michelle Cardel
- Department of Health Outcomes and Policy, College of Medicine, University of Florida, Gainesville, FL, USA
| | - Thomas A Pearson
- Department of Epidemiology, College of Medicine, University of Florida, Gainesville, FL, USA
| | - Mark D DeBoer
- Department of Pediatrics, Division of Pediatric Endocrinology, University of Virginia, 409 Lane Road, Room 2017, PO Box 800386, Charlottesville, VA, 22908, USA.
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C-reactive protein in Brazilian adolescents: distribution and association with metabolic syndrome in ERICA survey. Eur J Clin Nutr 2017; 71:1206-1211. [PMID: 28537577 DOI: 10.1038/ejcn.2017.74] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2016] [Revised: 02/07/2017] [Accepted: 04/14/2017] [Indexed: 12/11/2022]
Abstract
BACKGROUND/OBJECTIVES C-reactive protein (CRP) is a marker of inflammation that has been shown to be predictive of cardiovascular diseases in adults. To evaluate the distribution of CRP as well as its association with metabolic syndrome and its components. SUBJECTS/METHODS This is a cross-sectional study on adolescents aged 12-17, participants in the Study of Cardiovascular Risk in Adolescents (ERICA). Anthropometric, biochemical and blood pressure data were collected from 6316 adolescents, selected from a random sample of students in the cities of Brasilia, Fortaleza, João Pessoa, Manaus, Porto Alegre and Rio de Janeiro. Metabolic syndrome was defined by the criteria proposed by International Diabetes Federation for adolescent. Poisson regression model with robust variance, taking into consideration the study's complex sampling design, was used to determine multivariate-adjusted prevalence rate ratios expressing the relationship of metabolic syndrome with CRP. RESULTS In adolescents with metabolic syndrome, CRP concentrations were five times higher (1.01 mg/l; interquartile range (IQR): 0.54-3.47) compared with those without metabolic syndrome (0.19 mg/l; IQR: 0.10-0.78). In multivariate Poisson regression analysis adjusted by sex, age and skin color, the prevalence of elevated CRP (>3.0 mg/l) was almost three times higher in adolescents with metabolic syndrome than in those without this condition (prevalence ratio (PR): 2.9; 95%CI: 2.0-4.3; P<0.001). Of the metabolic syndrome components, elevated waist circumference, low high-density lipoprotein-cholesterol and high triglycerides were significantly related to CRP in a graded (dose-response) manner. CONCLUSIONS The association of CRP with metabolic syndrome and its components suggests that inflammation may be useful in assessing cardiovascular risk in adolescents.
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Musani SK, Martin LJ, Woo JG, Olivier M, Gurka MJ, DeBoer MD. Heritability of the Severity of the Metabolic Syndrome in Whites and Blacks in 3 Large Cohorts. CIRCULATION. CARDIOVASCULAR GENETICS 2017; 10:e001621. [PMID: 28408709 PMCID: PMC5481724 DOI: 10.1161/circgenetics.116.001621] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/16/2016] [Accepted: 03/06/2017] [Indexed: 02/02/2023]
Abstract
BACKGROUND Although dichotomous criteria for the metabolic syndrome (MetS) appear heritable, it is not known whether MetS severity as assessed by a continuous MetS score is heritable and whether this varies by race. METHODS AND RESULTS We used SOLAR (Sequential Oligogenic Linkage Analysis Routines) to evaluate heritability of Adult Treatment Panel-III MetS and a sex- and race-specific MetS severity Z score among 3 large familial cohorts: the JHS (Jackson Heart Study, 1404 black participants), TOPS (Take Off Pounds Sensibly, 1947 white participants), and PLRS (Princeton Lipid Research Study, 229 black and 527 white participants). Heritability estimates were larger for Adult Treatment Panel-III MetS among black compared with white cohort members (JHS 0.48; 95% confidence interval [CI], 0.28-0.68 and PLRS blacks 0.93 [95% CI, 0.73-1.13] versus TOPS 0.21 [95% CI, -0.18 to 0.60] and PLRS whites 0.27 [95% CI, -0.04 to 0.58]). The difference by race narrowed when assessing heritability of the MetS severity score (JHS 0.52 [95% CI, 0.38, 0.66] and PLRS blacks 0.64 [95% CI, 0.13-1.15] versus TOPS 0.23 [95% CI, 0.15-0.31] and PLRS whites 0.60 [95% CI, 0.33-0.87]). There was a high degree of genetic and phenotypic correlation between MetS severity and the individual components of MetS among all groups, although the genetic correlations failed to reach statistical significance among PLRS blacks. Meta-analyses revealed a combined heritability estimate for Adult Treatment Panel-III MetS of 0.24 (95% CI, 0.11-0.36) and for the MetS severity score of 0.50 (95% CI, -0.05 to 0.99). CONCLUSIONS MetS severity seems highly heritable among whites and blacks. This continuous MetS severity Z score may provide a more useful means of characterizing phenotypic MetS in genetic studies by minimizing racial differences.
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Affiliation(s)
- Solomon K Musani
- From the Jackson Heart Study, University of Mississippi Medical Center, Jackson (S.K.M.); Division of Human Genetics (L.J.M.) and Division of Epidemiology & Biostatistics (J.G.W.), Cincinnati Children's Hospital Medical Center, OH; Department of Pediatrics, University of Cincinnati, OH (L.J.M., J.G.W.); Texas Biomedical Research Institute, San Antonio (M.O.); Department of Health Outcomes & Policy, University of Florida, Gainesville (M.J.G.); and Department of Pediatrics, University of Virginia, Charlottesville (M.D.D.)
| | - Lisa J Martin
- From the Jackson Heart Study, University of Mississippi Medical Center, Jackson (S.K.M.); Division of Human Genetics (L.J.M.) and Division of Epidemiology & Biostatistics (J.G.W.), Cincinnati Children's Hospital Medical Center, OH; Department of Pediatrics, University of Cincinnati, OH (L.J.M., J.G.W.); Texas Biomedical Research Institute, San Antonio (M.O.); Department of Health Outcomes & Policy, University of Florida, Gainesville (M.J.G.); and Department of Pediatrics, University of Virginia, Charlottesville (M.D.D.)
| | - Jessica G Woo
- From the Jackson Heart Study, University of Mississippi Medical Center, Jackson (S.K.M.); Division of Human Genetics (L.J.M.) and Division of Epidemiology & Biostatistics (J.G.W.), Cincinnati Children's Hospital Medical Center, OH; Department of Pediatrics, University of Cincinnati, OH (L.J.M., J.G.W.); Texas Biomedical Research Institute, San Antonio (M.O.); Department of Health Outcomes & Policy, University of Florida, Gainesville (M.J.G.); and Department of Pediatrics, University of Virginia, Charlottesville (M.D.D.)
| | - Michael Olivier
- From the Jackson Heart Study, University of Mississippi Medical Center, Jackson (S.K.M.); Division of Human Genetics (L.J.M.) and Division of Epidemiology & Biostatistics (J.G.W.), Cincinnati Children's Hospital Medical Center, OH; Department of Pediatrics, University of Cincinnati, OH (L.J.M., J.G.W.); Texas Biomedical Research Institute, San Antonio (M.O.); Department of Health Outcomes & Policy, University of Florida, Gainesville (M.J.G.); and Department of Pediatrics, University of Virginia, Charlottesville (M.D.D.)
| | - Matthew J Gurka
- From the Jackson Heart Study, University of Mississippi Medical Center, Jackson (S.K.M.); Division of Human Genetics (L.J.M.) and Division of Epidemiology & Biostatistics (J.G.W.), Cincinnati Children's Hospital Medical Center, OH; Department of Pediatrics, University of Cincinnati, OH (L.J.M., J.G.W.); Texas Biomedical Research Institute, San Antonio (M.O.); Department of Health Outcomes & Policy, University of Florida, Gainesville (M.J.G.); and Department of Pediatrics, University of Virginia, Charlottesville (M.D.D.)
| | - Mark D DeBoer
- From the Jackson Heart Study, University of Mississippi Medical Center, Jackson (S.K.M.); Division of Human Genetics (L.J.M.) and Division of Epidemiology & Biostatistics (J.G.W.), Cincinnati Children's Hospital Medical Center, OH; Department of Pediatrics, University of Cincinnati, OH (L.J.M., J.G.W.); Texas Biomedical Research Institute, San Antonio (M.O.); Department of Health Outcomes & Policy, University of Florida, Gainesville (M.J.G.); and Department of Pediatrics, University of Virginia, Charlottesville (M.D.D.).
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Lee AM, Gurka MJ, DeBoer MD. Correlation of metabolic syndrome severity with cardiovascular health markers in adolescents. Metabolism 2017; 69:87-95. [PMID: 28285655 PMCID: PMC5394425 DOI: 10.1016/j.metabol.2017.01.008] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2016] [Revised: 12/15/2016] [Accepted: 01/08/2017] [Indexed: 12/16/2022]
Abstract
BACKGROUND AND OBJECTIVES The presence of metabolic syndrome (MetS) in childhood is a significant risk factor for later cardiovascular disease (CVD). Recent data showed temporal decreases in a sex- and race/ethnicity-specific MetS severity z-score among U.S. adolescents. Our goal was to characterize the relationship of this MetS z-score with other CVD risk indicators and assess their temporal trends and lifestyle influences. METHODS We analyzed 4837 participants aged 12-20years from the National Health and Nutrition Examination Survey by 2-year waves from 1999 to 2012. We used linear regression to compare MetS z-score and dietary factors with serum levels of low-density lipoprotein (LDL), apolipoprotein-B (ApoB), high-sensitivity C-reactive protein (hsCRP) and uric acid. RESULTS MetS severity z-score was positively correlated with LDL, ApoB, hsCRP, and uric acid measurements (p<0.0001 for all). These correlations held true among individual racial/ethnic groups. LDL, ApoB, and hsCRP measurements decreased over time among U.S. adolescents (p=0.002, p<0.0001, and p=0.024, respectively). Saturated fat consumption was positively correlated with LDL (p=0.005) and ApoB (p=0.012) and inversely related to serum uric acid (p=0.001). Total caloric intake was inversely related to LDL (p=0.003) and serum uric acid (p=0.003). Unsaturated fat, carbohydrate, and protein consumption were not related to LDL, ApoB, hsCRP, or serum uric acid. CONCLUSIONS There is a positive correlation between MetS severity and all four CVD risk indicators studied. LDL, ApoB, and hsCRP showed favorable temporal trends, which could be related to similar trends in MetS z-score. These data support the importance of considering multiple inter-related factors in clinical CVD risk assessment.
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Affiliation(s)
- Arthur M Lee
- Department of Pediatrics, University of Virginia, Charlottesville, VA 22908, United States
| | - Matthew J Gurka
- Department of Health Outcomes and Policy, College of Medicine, University of Florida, Gainesville, FL 32608, United States
| | - Mark D DeBoer
- Department of Pediatrics, University of Virginia, Charlottesville, VA 22908, United States.
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DeBoer MD, Gurka MJ. Clinical utility of metabolic syndrome severity scores: considerations for practitioners. Diabetes Metab Syndr Obes 2017; 10:65-72. [PMID: 28255250 PMCID: PMC5325095 DOI: 10.2147/dmso.s101624] [Citation(s) in RCA: 59] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
The metabolic syndrome (MetS) is marked by abnormalities in central obesity, high blood pressure, high triglycerides, low high-density lipoprotein-cholesterol, and high fasting glucose and appears to be produced by underlying processes of inflammation, oxidative stress, and adipocyte dysfunction. MetS has traditionally been classified based on dichotomous criteria that deny that MetS-related risk likely exists as a spectrum. Continuous MetS scores provide a way to track MetS-related risk over time. We generated MetS severity scores that are sex- and race/ethnicity-specific, acknowledging that the way MetS is manifested may be different by sex and racial/ethnic subgroup. These scores are correlated with long-term risk for type 2 diabetes mellitus and cardiovascular disease. Clinical use of scores like these provide a potential opportunity to identify patients at highest risk, motivate patients toward lifestyle change, and follow treatment progress over time.
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Affiliation(s)
- Mark D DeBoer
- Division of Pediatric Endocrinology, Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, VA
- Department of Health Outcomes and Policy, College of Medicine, University of Florida, Gainesville, FL, USA
- Correspondence: Mark D DeBoer, Division of Pediatric Endocrinology, Department of Pediatrics, University of Virginia School of Medicine, 409 Lane Road, Room 2017, PO Box 800386, Charlottesville, VA 22908, USA, Tel +1 434 924 9833, Fax +1 434 924 9181, Email
| | - Matthew J Gurka
- Department of Health Outcomes and Policy, College of Medicine, University of Florida, Gainesville, FL, USA
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Gurka MJ, Vishnu A, Santen RJ, DeBoer MD. Progression of Metabolic Syndrome Severity During the Menopausal Transition. J Am Heart Assoc 2016; 5:JAHA.116.003609. [PMID: 27487829 PMCID: PMC5015287 DOI: 10.1161/jaha.116.003609] [Citation(s) in RCA: 104] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/02/2022]
Abstract
Background After menopause, women exhibit a higher prevalence of the metabolic syndrome (MetS) and higher risk of cardiovascular disease. However, the timing of changes in MetS severity over the menopausal transition and whether these changes differ by racial/ethnic group remain unclear. Methods and Results We assessed data from 1470 women from the Atherosclerosis Risk in Communities cohort who experienced transition in menopausal status over 10 years (visits 1–4). We used linear mixed models to evaluate changes by menopausal status (premenopause, perimenopause, and postmenopause) in a MetS severity Z‐score and in the individual MetS components. While there were gradual increases in MetS severity over time across menopause stages, black women in particular exhibited more rapid progression in MetS severity during the premenopausal and perimenopausal periods than during the postmenopausal period. In the postmenopausal period (compared with prior periods), white women exhibited unfavorable decreases in high‐density lipoprotein, while black women exhibited favorable alterations in the rate of change for waist circumference, triglycerides, high‐density lipoprotein, and glucose, contributing to the slowed progression of MetS severity. These changes were all observed after adjusting for hormone replacement treatment. Conclusions During menopausal transition, women exhibited rapid increases in MetS severity during the premenopausal and perimenopausal periods, with black women having significant reductions in this increase in severity during the postmenopausal period. These data suggest that the higher prevalence of MetS in postmenopausal women may be caused more by changes during the menopausal transition than by postmenopause. These findings may thus have implications regarding the timing of cardiovascular risk relative to menopause.
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Affiliation(s)
- Matthew J Gurka
- Department of Health Outcomes and Policy, College of Medicine, University of Florida, Gainesville, FL
| | - Abhishek Vishnu
- Department of Health Outcomes and Policy, College of Medicine, University of Florida, Gainesville, FL
| | - Richard J Santen
- Division of Endocrinology, Department of Medicine, University of Virginia, Charlottesville, VA
| | - Mark D DeBoer
- Division of Pediatric Endocrinology, Department of Pediatrics, University of Virginia, Charlottesville, VA
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Sah SK, Khatiwada S, Pandey S, Kc R, Das BKL, Baral N, Lamsal M. Association of high-sensitivity C-reactive protein and uric acid with the metabolic syndrome components. SPRINGERPLUS 2016; 5:269. [PMID: 27006878 PMCID: PMC4777974 DOI: 10.1186/s40064-016-1933-y] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 01/11/2016] [Accepted: 02/24/2016] [Indexed: 11/16/2022]
Abstract
Metabolic syndrome (MetS) has been found to be associated with inflammatory molecules. This study was conducted among 125 MetS patients at B P Koirala Institute of Health Sciences, Dharan, Nepal to find an association of high-sensitivity C-reactive protein (hs-CRP) and serum uric acid with MetS components. Anthropometric measurements, blood pressure, medical history and blood samples were taken. Estimation of hs-CRP, serum uric acid, blood glucose, triglyceride and high density lipoprotein (HDL) cholesterol was done. hs-CRP had positive correlation with blood glucose (r = 0.2, p = 0.026) and negative with HDL cholesterol (r = −0.361, p < 0.001). Serum uric acid had positive correlation with waist circumference (r = 0.178, p = 0.047). Patients with elevated hs-CRP and uric acid had higher waist circumference (p = 0.03), diastolic BP (p = 0.002) and lower HDL cholesterol (p = 0.004) than others. Elevated hs-CRP and high uric acid were individually associated with higher odds for low HDL cholesterol (7.992; 1.785–35.774, p = 0.002) and hyperglycemia (2.471; 1.111–5.495, p = 0.029) respectively. Combined rise of hs-CRP and uric acid was associated with severity of MetS (p < 0.001) and higher odds for hyperglycemia (8.036; 2.178–29.647, p = 0.001) as compared to individual rise of hs-CRP or uric acid. The present study demonstrates that hs-CRP and serum uric acid are associated with MetS components, and the combined rise of hs-CRP and uric acid is associated with the increase in severity of MetS.
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Affiliation(s)
- Santosh Kumar Sah
- Department of Biochemistry, Universal College of Medical Sciences, Bhairahawa, Nepal
| | - Saroj Khatiwada
- Department of Biochemistry, Modern Technical College, Sanepa, Lalitpur, Nepal
| | - Sunil Pandey
- Department of Biochemistry, B P Koirala Institute of Health Sciences, Dharan, Nepal
| | - Rajendra Kc
- Department of Biochemistry, Modern Technical College, Sanepa, Lalitpur, Nepal
| | - Binod Kumar Lal Das
- Department of Biochemistry, B P Koirala Institute of Health Sciences, Dharan, Nepal
| | - Nirmal Baral
- Department of Biochemistry, B P Koirala Institute of Health Sciences, Dharan, Nepal
| | - Madhab Lamsal
- Department of Biochemistry, B P Koirala Institute of Health Sciences, Dharan, Nepal
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Lee AM, Gurka MJ, DeBoer MD. Trends in Metabolic Syndrome Severity and Lifestyle Factors Among Adolescents. Pediatrics 2016; 137:e20153177. [PMID: 26908664 PMCID: PMC4771130 DOI: 10.1542/peds.2015-3177] [Citation(s) in RCA: 67] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/23/2015] [Indexed: 11/24/2022] Open
Abstract
BACKGROUND AND OBJECTIVES Childhood metabolic syndrome (MetS) is a risk factor for adverse outcomes later in life. Our goal was to identify temporal trends among US adolescents in the severity of MetS, its individual components, and factors related to diet and physical activity. METHODS We analyzed 5117 participants aged 12 to 19 from NHANES. We used regression analysis of individual waves of data, 1999 to 2012. MetS severity was calculated using a gender- and race/ethnicity-specific MetS severity z score. RESULTS There was a linear trend of decreasing MetS severity in US adolescents from 1999 to 2012 (P = .030). This occurred despite a trend of increasing BMI z score (P = .005); instead, the decrease in MetS severity appeared to be due to trends in increasing high-density lipoprotein (HDL; P < .0001) and decreasing triglyceride (P = .0001) levels. In considering lifestyle factors, there was no change in physical activity over the time period. Regarding dietary patterns, total calorie consumption and carbohydrate consumption were positively associated with triglyceride levels and negatively associated with HDL levels, whereas unsaturated fat consumption exhibited the opposite associations. Consistent with these associations, there was a trend of decreasing total calorie consumption (P < .0001), decreasing carbohydrate consumption (P < .0001), and increasing unsaturated fat consumption (P = .002). CONCLUSIONS The healthier trend of declining MetS severity in adolescents appeared to be due to favorable increases in HDL and decreases in fasting triglyceride measurements. These were in turn associated with favorable changes in dietary patterns among US adolescents. Future studies should investigate the causality of dietary differences on changes in MetS severity in adolescents.
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Affiliation(s)
- Arthur M. Lee
- Department of Pediatrics, University of Virginia, Charlottesville, Virginia; and
| | - Matthew J. Gurka
- Department of Health Outcomes and Policy, College of Medicine, University of Florida, Gainesville, Florida
| | - Mark D. DeBoer
- Department of Pediatrics, University of Virginia, Charlottesville, Virginia; and
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24
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Lee AM, Gurka MJ, DeBoer MD. A metabolic syndrome severity score to estimate risk in adolescents and adults: current evidence and future potential. Expert Rev Cardiovasc Ther 2016; 14:411-3. [PMID: 26783022 DOI: 10.1586/14779072.2016.1143360] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Affiliation(s)
- Arthur M Lee
- a Division of Pediatric Endocrinology , University of Virginia , Charlottesville , VA , USA
| | - Matthew J Gurka
- b Department of Health Outcomes and Policy, College of Medicine , University of Florida , Gainesville , FL , USA
| | - Mark D DeBoer
- a Division of Pediatric Endocrinology , University of Virginia , Charlottesville , VA , USA.,b Department of Health Outcomes and Policy, College of Medicine , University of Florida , Gainesville , FL , USA
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25
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DeBoer MD, Gurka MJ, Woo JG, Morrison JA. Severity of the metabolic syndrome as a predictor of type 2 diabetes between childhood and adulthood: the Princeton Lipid Research Cohort Study. Diabetologia 2015; 58:2745-52. [PMID: 26380985 PMCID: PMC4734129 DOI: 10.1007/s00125-015-3759-5] [Citation(s) in RCA: 91] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2015] [Accepted: 08/25/2015] [Indexed: 11/25/2022]
Abstract
AIMS/HYPOTHESIS The aim of this study was to determine the long-term associations of a sex- and race/ethnicity-specific metabolic syndrome (MetS) severity z score from childhood and adulthood with a future diagnosis of type 2 diabetes mellitus. METHODS We performed a prospective cohort study with evaluations from the Cincinnati Clinic of the National Heart Lung and Blood Institute Lipids Research Clinic (LRC) 1973-1976 and Princeton Follow-up Study (PFS) 1998-2003, and further disease status from the Princeton Health Update (PHU) 2010-2014. We assessed MetS severity as a predictor of incident type 2 diabetes among 629 cohort participants assessed at both the LRC and PFS and 354 participants at the PHU. RESULTS Cohort participants had a mean age of 12.9 years at baseline (LRC), 38.4 years at the PFS and 49.6 years at the most recent follow-up. Childhood MetS z scores were associated with adult MetS z scores (p < 0.01). Compared with individuals who were disease-free at all time-points, those who developed type 2 diabetes by 1998-2003 and 2010-2014 had higher MetS severity z scores in childhood (p < 0.05). For every one-unit elevation in childhood MetS z score, the OR of developing future type 2 diabetes was 2.7 for incident disease by a mean age of 38.5 years (p < 0.01) and 2.8 for incident disease by a mean age of 49.6 years (p < 0.05). Regarding associations with the change in z score from childhood to adulthood, for every one-unit increase in MetS z score over time the OR of developing incident type 2 diabetes by a mean age of 49.6 years was 7.3 (p < 0.01). CONCLUSIONS/INTERPRETATION The severity of MetS in childhood was associated with the incidence of adult type 2 diabetes and the degree of increase in this severity predicted future disease. These findings provide evidence of potential clinical utility in assessing MetS severity to detect risk and follow clinical progress over time.
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Affiliation(s)
- Mark D DeBoer
- Division of Pediatric Endocrinology, University of Virginia, P.O. Box 800386, Charlottesville, VA, 22908, USA.
| | - Matthew J Gurka
- Department of Biostatistics, School of Public Health, West Virginia University, Morgantown, WV, USA
| | - Jessica G Woo
- Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - John A Morrison
- Division of Cardiology, University of Cincinnati, Cincinnati, OH, USA
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Weinstock RS, Drews KL, Caprio S, Leibel NI, McKay SV, Zeitler PS. Metabolic syndrome is common and persistent in youth-onset type 2 diabetes: Results from the TODAY clinical trial. Obesity (Silver Spring) 2015; 23:1357-61. [PMID: 26047470 PMCID: PMC4482791 DOI: 10.1002/oby.21120] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2014] [Revised: 02/24/2015] [Accepted: 03/07/2015] [Indexed: 01/20/2023]
Abstract
OBJECTIVE To examine the prevalence of metabolic syndrome (MetS) in youth-onset type 2 diabetes in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study. METHODS Prevalence of MetS (ATP III definition) was compared at baseline (n = 679) and at 6 (n = 625) and 24 months (n = 545) using chi-square tests. Laboratory data were examined between MetS classifications at each time point using ANOVA. RESULTS Baseline prevalence of MetS was 75.8% and did not differ by treatment group or change over time. MetS was more common in females (83.1%) than males (62.3%; P < 0.0001) at baseline; this difference persisted over 24 months. Prevalence of MetS was similar between ethnic groups at baseline but greater in Hispanics (82.7%) vs. non-Hispanic Whites (67.5%; P = 0.0017) and non-Hispanic Blacks (72.7%; P = 0.0164) at 24 months. Although MetS was common in participants with hemoglobin A1c < 7.0% (74.4% at baseline; no significant change over 24 months), it was more common in those who did not maintain glycemic control at 6 months (80.3%; P = 0.0081). Elevated C-reactive protein, ALT, IL-6, and PAI-1 levels were more frequent with MetS. CONCLUSIONS Persistent high prevalence of MetS in youth-onset diabetes, even with excellent glycemic control, is of concern given the associated increased cardiovascular risk.
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Affiliation(s)
- Ruth S Weinstock
- Department of Medicine, SUNY Upstate Medical University, Syracuse, New York, USA
| | - Kimberly L Drews
- Department of Epidemiology and Biostatistics, Biostatistics Center, George Washington University, Rockville, Maryland, USA
| | - Sonia Caprio
- Department of Pediatrics, Yale University, New Haven, Connecticut, USA
| | - Natasha I Leibel
- Department of Pediatrics, Naomi Berrie Diabetes Center, Columbia University Medical Center, New York, New York, USA
| | | | - Philip S Zeitler
- Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
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Khan UI, McGinn AP, Isasi CR, Groisman-Perelstein A, Diamantis PM, Ginsberg M, Wylie-Rosett J. Differences in Cardiometabolic Risk between Insulin-Sensitive and Insulin-Resistant Overweight and Obese Children. Child Obes 2015; 11:289-96. [PMID: 25774664 PMCID: PMC4485365 DOI: 10.1089/chi.2014.0112] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND It is known that 15-30% overweight/obese adults do not suffer cardiometabolic consequences. There is limited literature examining factors that can be used to assess cardiometabolic health in overweight/obese children. If such factors can be identified, they would aid in differentiating those most in need for aggressive management. METHODS Baseline data from 7- to 12-year-old, overweight, and obese children enrolled in a weight management program at an urban hospital were analyzed. Homeostatic model assessment for insulin resistance (HOMA-IR) <2.6 was used to define insulin-sensitive and HOMA-IR ≥2.6 was used to defined insulin-resistant participants. Demographics, physical activity measures, and cardiometabolic risk factors were compared between the two phenotypes. Odds ratios (ORs) examining the association between intermediate endpoints (metabolic syndrome [MetS], nonalcoholic fatty liver disease [NAFLD], systemic inflammation, and microalbuminuria) and the two metabolic phenotypes were evaluated. RESULTS Of the 362 overweight/obese participants, 157 (43.5%) were insulin sensitive and 204 (56.5%) were insulin resistant. Compared to the insulin-sensitive group, the insulin-resistant group was older (8.6±1.6 vs. 9.9±1.7; p<0.001) and had a higher BMI z-score (1.89±0.42 vs. 2.04±0.42; p=0.001). After multivariable adjustment, compared to the insulin-sensitive group, the insulin-resistant group had higher odds of having MetS (OR, 5.47; 95% confidence interval [CI]: 1.72, 17.35; p=0.004) and NAFLD (OR, 8.66; 95% CI, 2.48, 30.31; p=0.001), but not systemic inflammation (OR, 1.06; 95% CI: 0.56, 2.03; p=0.86) or microalbuminuria (OR, 1.71; 95% CI, 0.49, 6.04; p=0.403). CONCLUSIONS Using a HOMA-IR value of ≥2.6, clinical providers can identify prepubertal and early pubertal children most at risk. Focusing limited resources on aggressive weight interventions may lead to improvement in cardiometabolic health.
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Affiliation(s)
- Unab I. Khan
- Department of Pediatrics, Albert Einstein College of Medicine, Bronx, NY
- Department of Family and Social Medicine, Albert Einstein College of Medicine, Bronx, NY
| | - Aileen P. McGinn
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY
| | - Carmen R. Isasi
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY
| | | | | | - Mindy Ginsberg
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY
| | - Judith Wylie-Rosett
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY
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Agirbasli M, Tanrikulu A, Acar Sevim B, Azizy M, Bekiroglu N. Total cholesterol-to-high-density lipoprotein cholesterol ratio predicts high-sensitivity C-reactive protein levels in Turkish children. J Clin Lipidol 2014; 9:195-200. [PMID: 25911075 DOI: 10.1016/j.jacl.2014.12.010] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2014] [Revised: 12/13/2014] [Accepted: 12/18/2014] [Indexed: 10/24/2022]
Abstract
BACKGROUND High-sensitivity C-reactive protein (hs-CRP) is a biomarker of continued long-term systemic inflammation and cardiovascular (CV) risk. OBJECTIVE To analyze the association of hs-CRP levels with CV risk factors in healthy school children. METHODS The study sample was derived from a survey on the prevalence of CV risk factors (dyslipidemia, obesity, high blood pressure, and insulin resistance in school children. Along with anthropometry, hs-CRP levels, lipids, glucose levels, and insulin levels were measured. RESULTS Ninety-one male (12.5 ± 3.4 years) and 77 female students (12.7 ± 3.4; P = .624) were included. Median (interquartile range) hs-CRP levels were similar among boys and girls (0.4 [1.2] vs 0.5 [0.7]; P = .928). Risk factors such as obesity (16%), high triglycerides (20%), low high-density lipoprotein cholesterol (HDL-C, 16%), and elevated blood pressure (25%) were commonly observed in study participants. Gender-stratified analysis displayed that insulin resistance (18 [19.8%] vs 3 [3.9%]; P = .002) and high triglycerides (26 [28.6%] vs 8 [10.4%]; P = .003) were more commonly observed among boys compared with girls. hs-CRP levels correlated positively with cardiometabolic risk factors such as waist circumference (boys) and total cholesterol (TC)-to-HDL-C ratio. Linear regression analysis displayed that among the covariates of age, body mass index, and glucose, TC-to-HDL-C ratio was the most significant determinant of hs-CRP levels (P = .004). CONCLUSION Cardiometabolic risk factors such as TC-to-HDL-C ratio correlate with hs-CRP levels in children and adolescents. Long-term prospective studies are needed to confirm the association between hs-CRP and cardiometabolic risk in children.
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Affiliation(s)
- Mehmet Agirbasli
- Department of Cardiology, Marmara University School of Medicine, Istanbul, Turkey.
| | - Azra Tanrikulu
- Department of Cardiology, Maltepe State Hospital, Istanbul, Turkey
| | | | - Munir Azizy
- Marmara University School of Medicine, Istanbul, Turkey
| | - Nural Bekiroglu
- Department of Biostatistics, Marmara University School of Medicine, Istanbul, Turkey
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Middleton JP, Wiener RC, Barnes BH, Gurka MJ, DeBoer MD. Clinical features of pediatric nonalcoholic fatty liver disease: a need for increased awareness and a consensus for screening. Clin Pediatr (Phila) 2014; 53:1318-25. [PMID: 24477713 PMCID: PMC4450252 DOI: 10.1177/0009922813520072] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Affiliation(s)
- Jeremy P. Middleton
- Division of Pediatric Gastroenterology, Department of Pediatrics, University of Virginia, Charlottesville, VA
| | | | - Barrett H. Barnes
- Division of Pediatric Gastroenterology, Department of Pediatrics, University of Virginia, Charlottesville, VA
| | - Matthew J. Gurka
- Department of Biostatistics, School of Public Health, West Virginia University, Morgantown, WV, USA
| | - Mark D. DeBoer
- Division of Pediatric Endocrinology, Department of Pediatrics, University of Virginia, Charlottesville, Virginia, USA
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Abstract
The ever growing prevalence of childhood obesity is being accompanied by an increase in the pediatric population of diseases once believed to be exclusive of the adulthood such as the metabolic syndrome (MS). The MS has been defined as the link between insulin resistance, hypertension, dyslipidemia, impaired glucose tolerance, and other metabolic abnormalities associated with an increased risk of atherosclerotic cardiovascular diseases in adults. In this review, we will discuss the peculiar aspects of the pediatric MS and the role of novel molecules and biomarkers in its pathogenesis.
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31
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Maahs DM, Daniels SR, de Ferranti SD, Dichek HL, Flynn J, Goldstein BI, Kelly AS, Nadeau KJ, Martyn-Nemeth P, Osganian SK, Quinn L, Shah AS, Urbina E. Cardiovascular disease risk factors in youth with diabetes mellitus: a scientific statement from the American Heart Association. Circulation 2014; 130:1532-58. [PMID: 25170098 DOI: 10.1161/cir.0000000000000094] [Citation(s) in RCA: 126] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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DeBoer MD, Gurka MJ. Low sensitivity of the metabolic syndrome to identify adolescents with impaired glucose tolerance: an analysis of NHANES 1999-2010. Cardiovasc Diabetol 2014; 13:83. [PMID: 24755002 PMCID: PMC4000320 DOI: 10.1186/1475-2840-13-83] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2014] [Accepted: 04/15/2014] [Indexed: 01/21/2023] Open
Abstract
BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSION 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.
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Affiliation(s)
- Mark D DeBoer
- Department of Pediatrics, University of Virginia, Charlottesville, Virginia 22908, USA
| | - Matthew J Gurka
- Department of Biostatistics, School of Public Health, West Virginia University, Morgantown, WV 26506, USA
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Voils SA, Cooper-DeHoff RM. Association between high sensitivity C-reactive protein and metabolic syndrome in subjects completing the National Health and Nutrition Examination Survey (NHANES) 2009-10. Diabetes Metab Syndr 2014; 8:88-90. [PMID: 24907172 DOI: 10.1016/j.dsx.2014.04.021] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
AIMS Metabolic syndrome and elevated high-sensitivity (hs) C-reactive protein (CRP) have been associated with an increase in risk of coronary artery disease, stroke, and diabetes but the relationship between the two is unclear. The purpose of this study is to identify any association between metabolic syndrome and hs-CRP concentrations. METHODS Subjects 20 years or older completing the 2009-10 National Health and Nutrition Examination Survey (NHANES) were included. Metabolic syndrome was defined as having at least 3 of the following: hypertension, insulin resistance, hypertriglyceridemia, low high-density lipoprotein cholesterol, or high waist circumference. Elevated hs-CRP was defined as >3 mg/L. Multivariate logistic regression modeling was used to assess the relationship between hs-CRP and metabolic syndrome while controlling for potential confounders. RESULTS A total of 5728 subjects met the inclusion criteria, of which 69% were 20-55 years old, and 52% were female. Overall prevalence of metabolic syndrome was 34% and hs-CRP concentrations were elevated in 32% of subjects. Number of metabolic syndrome conditions was significantly associated with increasing odds of elevated hs-CRP concentrations. Subjects with one, two, three, four, or five metabolic syndrome conditions had 2.4, 3.3, 5.1, 10.7 and 11.1 times greater odds of elevated hs-CRP as compared to subjects with no metabolic syndrome conditions (p<0.05 for all comparisons). CONCLUSIONS Presence of metabolic syndrome was common in subjects from NHANES 2009-10 and a significant "dose-related" association was confirmed between number of metabolic syndrome conditions and increasing odds of elevated hs-CRP concentration.
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Affiliation(s)
- Stacy A Voils
- Department of Pharmacotherapy and Translational Research, University of Florida College of Pharmacy, 1225 Center Drive, HPNP Building, Room 3315, P.O. Box 100486, Gainesville, FL 32610-0486, United States.
| | - Rhonda M Cooper-DeHoff
- Department of Pharmacotherapy and Translational Research and Division of Cardiovascular Medicine, Colleges of Pharmacy and Medicine, Center for Pharmacogenomics, University of Florida, Health Science Center, Room PG-25, P.O. Box 100486, Gainesville, FL 32610-0486, United States.
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Gurka MJ, Lilly CL, Oliver MN, DeBoer MD. An examination of sex and racial/ethnic differences in the metabolic syndrome among adults: a confirmatory factor analysis and a resulting continuous severity score. Metabolism 2014; 63:218-25. [PMID: 24290837 PMCID: PMC4071942 DOI: 10.1016/j.metabol.2013.10.006] [Citation(s) in RCA: 186] [Impact Index Per Article: 16.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2013] [Revised: 09/24/2013] [Accepted: 10/15/2013] [Indexed: 12/17/2022]
Abstract
OBJECTIVE The metabolic syndrome (MetS) is typically diagnosed based on abnormalities in specific clustered clinical measures that are associated with increased risk for coronary heart disease (CHD) and Type 2 diabetes mellitus (T2DM). However, current MetS criteria result in racial/ethnic discrepancies. Our goals were to use confirmatory factor analysis (CFA) to delineate differential contributions to MetS by sub-group, and if contributions were discovered, develop sex and racial/ethnic-specific equations to calculate MetS severity. RESEARCH DESIGN AND METHODS Using data on adults from the National Health and Nutrition Examination Survey 1999-2010, we performed a CFA of a single MetS factor that allowed differential loadings across groups, resulting in a sex and race/ethnicity-specific continuous MetS severity score. RESULTS Loadings to the single MetS factor differed by sub-group for each MetS component (p<0.001), with lower factor loadings among non-Hispanic-blacks for triglycerides and among Hispanics for waist circumference. Systolic blood pressure exhibited low factor loadings among all groups. MetS severity scores were correlated with biomarkers of future disease (high-sensitivity C-reactive-protein, uric acid, insulin resistance). Non-Hispanic-black-males with diabetics had a low prevalence of MetS but high MetS severity scores that were not significantly different from other racial/ethnic groups. CONCLUSIONS This analysis among adults uniquely demonstrated differences between sexes and racial/ethnic groups regarding contributions of traditional MetS components to an assumed single factor. The resulting equations provide a clinically-accessible and interpretable continuous measure of MetS for potential use in identifying adults at higher risk for MetS-related diseases and following changes within individuals over time. These equations hold potential to be a powerful new outcome for use in MetS-focused research and interventions.
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Affiliation(s)
- Matthew J Gurka
- Department of Biostatistics, School of Public Health, West Virginia University, Morgantown, West Virginia.
| | - Christa L Lilly
- Department of Biostatistics, School of Public Health, West Virginia University, Morgantown, West Virginia
| | - M Norman Oliver
- Department of Family Medicine, School of Medicine, University of Virginia, Charlottesville, Virginia
| | - Mark D DeBoer
- Department of Pediatrics, School of Medicine, University of Virginia, Charlottesville, Virginia
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35
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DeBoer MD, Wiener RC, Barnes BH, Gurka MJ. Ethnic differences in the link between insulin resistance and elevated ALT. Pediatrics 2013; 132:e718-26. [PMID: 23940240 PMCID: PMC3876752 DOI: 10.1542/peds.2012-3584] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND 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. METHODS 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. RESULTS 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). CONCLUSIONS 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.
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Affiliation(s)
- Mark D. DeBoer
- Department of Pediatrics, University of Virginia, Charlottesville, Virginia; and
| | | | - Barrett H. Barnes
- Department of Pediatrics, University of Virginia, Charlottesville, Virginia; and
| | - Matthew J. Gurka
- Biostatistics, School of Public Health, West Virginia University, Morgantown, West Virginia
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DeBoer MD. Obesity, systemic inflammation, and increased risk for cardiovascular disease and diabetes among adolescents: a need for screening tools to target interventions. Nutrition 2013; 29:379-86. [PMID: 23022122 PMCID: PMC3578702 DOI: 10.1016/j.nut.2012.07.003] [Citation(s) in RCA: 178] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2012] [Revised: 07/03/2012] [Accepted: 07/03/2012] [Indexed: 12/16/2022]
Abstract
Cardiovascular disease (CVD) and type 2 diabetes mellitus have their roots in childhood, particularly in obese children and adolescents, raising important opportunities for early lifestyle intervention in at-risk individuals. However, not all obese individuals are at the same risk for disease progression. Accurate screening of obese adolescents may identify those in greatest need for intensive intervention to prevent or delay future disease. One potential screening target is obesity-related inflammation, which contributes to insulin resistance, metabolic syndrome, and CVD. In adults, the inflammatory marker high-sensitivity C-reactive protein (hsCRP) has utility for risk stratification and treatment initiation in individuals of intermediate CVD risk. In adolescents, hsCRP shares many of the associations of hsCRP in adults regarding the degree of insulin resistance, metabolic syndrome, and carotid artery media thickness. However, long-term data linking increased hsCRP levels-and increased insulin or decreased adiponectin-in childhood to adult disease outcomes are lacking at this time. Future efforts continue to be needed to identify childhood clinical and laboratory characteristics that could be used as screening tests to predict adult disease progression. Such tests may have utility in motivating physicians and patients' families toward lifestyle changes, ultimately improving prevention efforts.
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Affiliation(s)
- Mark D DeBoer
- Department of Pediatrics, University of Virginia, Charlottesville, Virginia, USA.
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Obesity and african americans: physiologic and behavioral pathways. ISRN OBESITY 2013; 2013:314295. [PMID: 24533220 PMCID: PMC3901988 DOI: 10.1155/2013/314295] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/13/2012] [Accepted: 12/31/2012] [Indexed: 01/21/2023]
Abstract
Although progress has been made to understand the association between physiological and lifestyle behaviors with regard to obesity, ethnic differences in markers of obesity and pathways towards obesity remain somewhat unexplained. However, obesity remains a serious growing concern. This paper highlights ethnic differences in African Americans and Caucasians that may contribute to the higher prevalence of obesity among African Americans. Understanding ethnic differences in metabolic syndrome criteria, functioning of the hypothalamic pituitary adrenal axis, variations in glucocorticoid sensitivity and insulin resistance, and physical activity and cardiovascular fitness levels may help to inform practical clinical and public health interventions and reduce obesity disparities.
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Rodriguez F, Naderi S, Wang Y, Johnson CE, Foody JM. High prevalence of metabolic syndrome in young Hispanic women: findings from the national Sister to Sister campaign. Metab Syndr Relat Disord 2012; 11:81-6. [PMID: 23259587 DOI: 10.1089/met.2012.0109] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023] Open
Abstract
BACKGROUND Hispanics are the fastest growing segment of the U.S. population and have a higher prevalence of cardiometabolic risk factors as compared with non-Hispanic whites. Further data suggests that Hispanics have undiagnosed complications of metabolic syndrome, namely diabetes mellitus, at an earlier age. We sought to better understand the epidemiology of metabolic syndrome in Hispanic women using data from a large, community-based health screening program. METHODS Using data from the Sister to Sister: The Women's Heart Health Foundation community health fairs from 2008 to 2009 held in 17 U.S. cities, we sought to characterize how cardiometabolic risk profiles vary across age for women by race and ethnicity. Metabolic syndrome was defined using the updated National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) guidelines, which included three or more of the following: Waist circumference ≥35 inches, triglycerides ≥150 mg/dL, high-density lipoprotein (HDL) <50 mg/dL, systolic blood pressure ≥130 mmHg or diastolic blood pressure ≥85 mmHg, or a fasting glucose ≥100 mg/dL. RESULTS A total of 6843 community women were included in the analyses. Metabolic syndrome had a prevalence of 35%. The risk-adjusted odds ratio for metabolic syndrome in Hispanic women versus white women was 1.7 (95% confidence interval, 1.4, 2.0). Dyslipidemia was the strongest predictor of metabolic syndrome among Hispanic women. This disparity appeared most pronounced for younger women. Additional predictors of metabolic syndrome included black race, increasing age, and smoking. CONCLUSIONS In a large, nationally representative sample of women, we found that metabolic syndrome was highly prevalent among young Hispanic women. Efforts specifically targeted to identifying these high-risk women are necessary to prevent the cardiovascular morbidity and mortality associated with metabolic syndrome.
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Affiliation(s)
- Fátima Rodriguez
- Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA
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Gurka MJ, Ice CL, Sun SS, Deboer MD. A confirmatory factor analysis of the metabolic syndrome in adolescents: an examination of sex and racial/ethnic differences. Cardiovasc Diabetol 2012; 11:128. [PMID: 23062212 PMCID: PMC3489601 DOI: 10.1186/1475-2840-11-128] [Citation(s) in RCA: 120] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2012] [Accepted: 10/10/2012] [Indexed: 01/21/2023] Open
Abstract
Objective The metabolic syndrome (MetS) is a cluster of clinical indices that signals increased risk for cardiovascular disease and Type 2 diabetes. The diagnosis of MetS is typically based on cut-off points for various components, e.g. waist circumference and blood pressure. Because current MetS criteria result in racial/ethnic discrepancies, our goal was to use confirmatory factor analysis to delineate differential contributions to MetS by sub-group. Research Design and Methods Using 1999–2010 data from the National Health and Nutrition Examination Survey (NHANES), we performed a confirmatory factor analysis of a single MetS factor that allowed differential loadings across sex and race/ethnicity, resulting in a continuous MetS risk score that is sex and race/ethnicity-specific. Results Loadings to the MetS score differed by racial/ethnic and gender subgroup with respect to triglycerides and HDL-cholesterol. ROC-curve analysis revealed high area-under-the-curve concordance with MetS by traditional criteria (0.96), and with elevations in MetS-associated risk markers, including high-sensitivity C-reactive protein (0.71), uric acid (0.75) and fasting insulin (0.82). Using a cut off for this score derived from ROC-curve analysis, the MetS risk score exhibited increased sensitivity for predicting elevations in ≥2 of these risk markers as compared with traditional pediatric MetS criteria. Conclusions The equations from this sex- and race/ethnicity-specific analysis provide a clinically-accessible and interpretable continuous measure of MetS that can be used to identify children at higher risk for developing adult diseases related to MetS, who could then be targeted for intervention. These equations also provide a powerful new outcome for use in childhood obesity and MetS research.
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Affiliation(s)
- Matthew J Gurka
- Department of Biostatistics, School of Public Health, West Virginia University, Morgantown, West Virginia, USA.
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Reiner AP, Beleza S, Franceschini N, Auer PL, Robinson JG, Kooperberg C, Peters U, Tang H. Genome-wide association and population genetic analysis of C-reactive protein in African American and Hispanic American women. Am J Hum Genet 2012; 91:502-12. [PMID: 22939635 DOI: 10.1016/j.ajhg.2012.07.023] [Citation(s) in RCA: 100] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2012] [Revised: 07/08/2012] [Accepted: 07/26/2012] [Indexed: 11/29/2022] Open
Abstract
C-reactive protein (CRP) is a systemic inflammation marker that predicts future cardiovascular risk. CRP levels are higher in African Americans and Hispanic Americans than in European Americans, but the genetic determinants of CRP in these admixed United States minority populations are largely unknown. We performed genome-wide association studies (GWASs) of 8,280 African American (AA) and 3,548 Hispanic American (HA) postmenopausal women from the Women's Health Initiative SNP Health Association Resource. We discovered and validated a CRP-associated variant of triggering receptors expressed by myeloid cells 2 (TREM2) in chromosomal region 6p21 (p = 10(-10)). The TREM2 variant associated with higher CRP is common in Africa but rare in other ancestral populations. In AA women, the CRP region in 1q23 contained a strong admixture association signal (p = 10(-17)), which appears to be related to several independent CRP-associated alleles; the strongest of these is present only in African ancestral populations and is associated with higher CRP. Of the other genomic loci previously associated with CRP through GWASs of European populations, most loci (LEPR, IL1RN, IL6R, GCKR, NLRP3, HNF1A, HNF4A, and APOC1) showed consistent patterns of association with CRP in AA and HA women. In summary, we have identified a common TREM2 variant associated with CRP in United States minority populations. The genetic architecture underlying the CRP phenotype in AA women is complex and involves genetic variants shared across populations, as well as variants specific to populations of African descent.
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Affiliation(s)
- Alex P Reiner
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
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Koebnick C, Smith N, Huang K, Martinez MP, Clancy HA, Kushi LH. The prevalence of obesity and obesity-related health conditions in a large, multiethnic cohort of young adults in California. Ann Epidemiol 2012; 22:609-16. [PMID: 22766471 DOI: 10.1016/j.annepidem.2012.05.006] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2011] [Revised: 04/19/2012] [Accepted: 05/25/2012] [Indexed: 12/22/2022]
Abstract
PURPOSE To identify population groups that are most susceptible to obesity-related health conditions at young age. METHODS For this population-based cross-sectional study, measured weight and height, diagnosis, laboratory, and drug prescription information were extracted from electronic medical records of 1,819,205 patients aged 20 to 39 years enrolled in two integrated health plans in California in 2007 through 2009. RESULTS Overall, 29.9% of young adults were obese. Extreme obesity (body mass index [BMI] ≥ 40 kg/m(2)) was observed in 6.1% of women and 4.5% of men. The adjusted relative risk (RR) for diabetes, hypertension, dyslipidemia, and the metabolic syndrome increased sharply for those individuals with a BMI of 40 or greater, with the sharpest increase in the adjusted RR for hypertension and the metabolic syndrome. The association between weight class and dyslipidemia, hypertension, and the metabolic syndrome but not diabetes was stronger among 20.0- to 29.9-year-olds compared with 30.0- to 39.9-year-olds (P for interaction < .05). For example, compared with their normal weight counterparts of the same age group, young adults with a BMI of 40.0 to 49.9, 50.0 to 59.9, and 60 or greater kg/m(2) had a RR for hypertension of 11.73, 19.88, and 30.47 (95% confidence interval [CI], 26.39-35.17) at 20 to 29 years old, and 9.31, 12.41, and 15.43 (95% CI, 14.32-16.63) at 30 to 39 years old. CONCLUSIONS Although older individuals were more likely to be extremely obese, the association between obesity-related health conditions was stronger in younger individuals. Hispanics and Blacks are also more likely to be obese, including extremely obese, putting them at an elevated risk for premature cardiovascular disease and some cancers relative to non-Hispanic Whites.
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Affiliation(s)
- Corinna Koebnick
- Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, CA 91101, USA.
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DeBoer MD, Dong L, Gurka MJ. Racial/ethnic and sex differences in the relationship between uric acid and metabolic syndrome in adolescents: an analysis of National Health and Nutrition Survey 1999-2006. Metabolism 2012; 61:554-61. [PMID: 22000606 PMCID: PMC3262070 DOI: 10.1016/j.metabol.2011.09.003] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2011] [Revised: 08/12/2011] [Accepted: 09/06/2011] [Indexed: 02/07/2023]
Abstract
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. The objective was to determine whether the relationship of uric acid with MetS varies in adolescents by race/ethnicity and sex. We used linear regression to evaluate associations between uric acid and other MetS-associated clinical and laboratory measures among 3296 non-Hispanic white, non-Hispanic black, and Hispanic adolescents aged 12 to 19 years 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 3 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 sex. 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 greater among non-Hispanic blacks and Hispanics. 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 that the relationship between uric acid and MetS varies by race/ethnicity and sex. 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.
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Affiliation(s)
- Mark D DeBoer
- Department of Pediatrics, University of Virginia, PO Box 800386, Charlottesville, VA 22908, USA.
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DeBoer MD, Dong L, Gurka MJ. Racial/ethnic and sex differences in the ability of metabolic syndrome criteria to predict elevations in fasting insulin levels in adolescents. J Pediatr 2011; 159:975-81.e3. [PMID: 21784441 PMCID: PMC3202665 DOI: 10.1016/j.jpeds.2011.05.023] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2011] [Revised: 03/28/2011] [Accepted: 05/16/2011] [Indexed: 01/01/2023]
Abstract
OBJECTIVE To evaluate racial/ethnic and sex differences in the relationship between metabolic syndrome (MetS) diagnosis and fasting insulin in adolescents. STUDY DESIGN We analyzed data from the National Health and Nutrition Evaluation Survey 1999-2008 for 3693 non-Hispanic-white, non-Hispanic-black, and Hispanic adolescents (12 to 19 years of age). We used linear regression to evaluate differences in fasting insulin levels between those with and without an adolescent adaptation of ATPIII-MetS in a sex- and race/ethnicity-specific basis. RESULTS Females had higher insulin levels than males, and non-Hispanic blacks and Hispanics had higher levels than non-Hispanic whites. Adolescents with MetS had higher insulin levels than those without MetS. The difference in insulin levels between those with and without MetS was greater in non-Hispanic blacks than in non-Hispanic whites (P < .05) but not Hispanics (P = .10). The sensitivity of MetS in detecting elevated insulin levels was lower in non-Hispanic blacks and females than in other ethnicities and males, respectively. Correlations between insulin and individual MetS components were similar among ethnicities. CONCLUSION MetS diagnosis performed more poorly in predicting elevated insulin levels in non-Hispanic blacks and in females. These data support the hypothesis that non-Hispanic blacks do not meet current criteria for MetS until they have reached a more advanced degree of insulin resistance.
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Affiliation(s)
- Mark D. DeBoer
- Department of Pediatrics, University of Virginia, Charlottesville, Virginia, United States, 22908,Author to whom correspondence should be addressed: Mark D. DeBoer, P.O. Box 800386, Charlottesville, VA 22908, Phone: 434-924-9833, Fax: 434-924-9181,
| | - Lili Dong
- Department of Community Medicine, West Virginia University, Morgantown, WV, United States, 26506
| | - Matthew J. Gurka
- Department of Community Medicine, West Virginia University, Morgantown, WV, United States, 26506
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DeBoer MD, Gurka MJ. 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; 220:575-80. [PMID: 22178428 DOI: 10.1016/j.atherosclerosis.2011.11.033] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2011] [Revised: 11/06/2011] [Accepted: 11/21/2011] [Indexed: 11/26/2022]
Abstract
BACKGROUND 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. OBJECTIVE Evaluate the sensitivity of MetS to identify adolescents with elevated uric acid levels on a race/ethnicity and gender-specific basis. METHODS We evaluated 3296 male and female adolescents 12-19 y participating in the National Health and Nutrition Evaluation Survey 1999-06, 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). RESULTS 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). CONCLUSION 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.
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Affiliation(s)
- Mark D DeBoer
- Department of Pediatrics, University of Virginia, Charlottesville, VA 22908, United States.
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Deboer MD. Ethnicity, obesity and the metabolic syndrome: implications on assessing risk and targeting intervention. Expert Rev Endocrinol Metab 2011; 6:279-289. [PMID: 21643518 PMCID: PMC3105461 DOI: 10.1586/eem.11.17] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Pediatric obesity threatens the future health of a growing number of children worldwide. An added challenge in identifying the patients at greatest need for intervention due to their elevated risk for future disease is that pediatric obesity and the associated metabolic syndrome manifest differently among different ethnic groups. African-Americans and Hispanics are more likely to exhibit obesity and insulin resistance and are at a higher risk for developing Type 2 diabetes. Nevertheless, using current criteria, African-American adolescents are much less likely to be diagnosed with metabolic syndrome, largely owing to lower rates of dyslipidemia. Further development is needed in ethnicity-inclusive means of risk identification among adolescents to accurately target treatment toward children at highest risk for future disease and to motivate adolescent patients and their families towards lifestyle improvement. Effective targeting and intensive treatment efforts may help in avoiding future sequelae of obesity among all ethnicities.
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Affiliation(s)
- Mark D Deboer
- Department of Pediatrics, Division of Pediatric Endocrinology, University of Virginia School of Medicine, PO Box 800386, Charlottesville, VA 22908, USA Tel.: +1 434 924 9833
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