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      Metabolic Syndrome and Incident Diabetes : Current state of the evidence

      research-article
      , MD, MPH 1 , , MD, PHD 1 , , MD, PHD 2
      Diabetes Care
      American Diabetes Association

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          Abstract

          OBJECTIVE—Our objective was to perform a quantitative review of prospective studies examining the association between the metabolic syndrome and incident diabetes.

          RESEARCH DESIGN AND METHODS—Using the title terms “diabetes” and “metabolic syndrome” in PubMed, we searched for articles published since 1998.

          RESULTS—Based on the results from 16 cohorts, we performed a meta-analysis of estimates of relative risk (RR) and incident diabetes. The random-effects summary RRs were 5.17 (95% CI 3.99–6.69) for the 1999 World Health Organization definition (ten cohorts); 4.45 (2.41–8.22) for the 1999 European Group for the Study of Insulin Resistance definition (four cohorts); 3.53 (2.84–4.39) for the 2001 National Cholesterol Education Program definition (thirteen cohorts); 5.12 (3.26–8.05) for the 2005 American Heart Association/National Heart, Lung, and Blood Institute definition (five cohorts); and 4.42 (3.30–5.92) for the 2005 International Diabetes Federation definition (nine cohorts). The fixed-effects summary RR for the 2004 National Heart, Lung, and Blood Institute/American Heart Association definition was 5.16 (4.43–6.00) (six cohorts). Higher number of abnormal components was strongly related to incident diabetes. Compared with participants without an abnormality, estimates of RR for those with four or more abnormal components ranged from 10.88 to 24.4. Limited evidence suggests fasting glucose alone may be as good as metabolic syndrome for diabetes prediction.

          CONCLUSIONS—The metabolic syndrome, however defined, has a stronger association with incident diabetes than that previously demonstrated for coronary heart disease. Its clinical value for diabetes prediction remains uncertain.

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          Most cited references35

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          Metabolic syndrome and risk of incident cardiovascular events and death: a systematic review and meta-analysis of longitudinal studies.

          The purpose of this research was to assess the association between the metabolic syndrome (MetSyn) and cardiovascular events and mortality by meta-analyses of longitudinal studies. Controversy exists regarding the cardiovascular risk associated with MetSyn. We searched electronic reference databases through March 2005, studies that referenced Reaven's seminal article, abstracts presented at meetings in 2003 to 2004, and queried experts. Two reviewers independently assessed eligibility. Longitudinal studies reporting associations between MetSyn and cardiovascular events or mortality were eligible. Two reviewers independently used a standardized form to collect data from published reports. Authors were contacted. Study quality was assessed by the control of selection, detection, and attrition biases. We found 37 eligible studies that included 43 cohorts (inception 1971 to 1997) and 172,573 individuals. Random effects meta-analyses showed MetSyn had a relative risk (RR) of cardiovascular events and death of 1.78 (95% confidence interval [CI] 1.58 to 2.00). The association was stronger in women (RR 2.63 vs. 1.98, p = 0.09), in studies enrolling lower risk (<10%) individuals (RR 1.96 vs. 1.43, p = 0.04), and in studies using factor analysis or the World Health Organization definition (RR 2.68 and 2.06 vs. 1.67 for National Cholesterol Education Program definition and 1.35 for other definitions; p = 0.005). The association remained after adjusting for traditional cardiovascular risk factors (RR 1.54, 95% CI 1.32 to 1.79). The best available evidence suggests that people with MetSyn are at increased risk of cardiovascular events. These results can help clinicians counsel patients to consider lifestyle interventions, and should fuel research of other preventive interventions.
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            Risks for all-cause mortality, cardiovascular disease, and diabetes associated with the metabolic syndrome: a summary of the evidence.

            E. Ford (2005)
            In recent years, several major organizations have endorsed the concept of the metabolic syndrome and developed working definitions for it. How well these definitions predict the risk for adverse events in people with the metabolic syndrome is only now being learned. The purpose of this study was to summarize the estimates of relative risk for all-cause mortality, cardiovascular disease, and diabetes reported from prospective studies in samples from the general population using definitions of the metabolic syndrome developed by the National Cholesterol Education Program (NCEP) and World Health Organization (WHO). The author reviewed prospective studies from July 1998 through August 2004. For studies that used the exact NCEP definition of the metabolic syndrome, random-effects estimates of combined relative risk were 1.27 (95% CI 0.90-1.78) for all-cause mortality, 1.65 (1.38-1.99) for cardiovascular disease, and 2.99 (1.96-4.57) for diabetes. For studies that used the most exact WHO definition of the metabolic syndrome, the fixed-effects estimates of relative risk were 1.37 (1.09-1.74) for all-cause mortality and 1.93 (1.39-2.67) for cardiovascular disease; the fixed-effects estimate was 2.60 (1.55-4.38) for coronary heart disease. These estimates suggest that the population-attributable fraction for the metabolic syndrome, as it is currently conceived, is approximately 6-7% for all-cause mortality, 12-17% for cardiovascular disease, and 30-52% for diabetes. Further research is needed to establish the use of the metabolic syndrome in predicting risk for death, cardiovascular disease, and diabetes in various population subgroups.
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              Metabolic syndrome with and without C-reactive protein as a predictor of coronary heart disease and diabetes in the West of Scotland Coronary Prevention Study.

              The National Cholesterol Education Program (NCEP) recently proposed a simple definition for metabolic syndrome. Information on the prospective association of this definition for coronary heart disease (CHD) and type 2 diabetes is currently limited. We used a modified NCEP definition with body mass index in place of waist circumference. Baseline assessments in the West of Scotland Coronary Prevention Study were available for 6447 men to predict CHD risk and for 5974 men to predict incident diabetes over 4.9 years of follow-up. Mean LDL cholesterol was similar but C-reactive protein was higher (P<0.0001) in the 26% of men with the syndrome compared with those without. Metabolic syndrome increased the risk for a CHD event [univariate hazard ratio (HR)=1.76 (95% CI, 1.44 to 2.15)] and for diabetes [univariate HR=3.50 (95% CI 2.51 to 4.90)]. Metabolic syndrome continued to predict CHD events (HR=1.30, 95% CI, 1.00 to 1.67, P=0.045) in a multivariate model incorporating conventional risk factors. Men with 4 or 5 features of the syndrome had a 3.7-fold increase in risk for CHD and a 24.5-fold increase for diabetes compared with men with none (both P<0.0001). C-reactive protein enhanced prognostic information for both outcomes. With pravastatin, men with the syndrome had similar risk reduction for CHD as compared with those without (HR, 0.73 and 0.69; pravastatin versus placebo). A modified NCEP metabolic syndrome definition predicts CHD events, and, more strikingly, new-onset diabetes, and thus helps identify individuals who may receive particular benefit from lifestyle measures to prevent these diseases.
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                Author and article information

                Journal
                Diabetes Care
                diacare
                Diabetes Care
                American Diabetes Association
                0149-5992
                1935-5548
                September 2008
                : 31
                : 9
                : 1898-1904
                Affiliations
                [1 ]Division of Adult and Community Health, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia
                [2 ]BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland
                Author notes

                Corresponding author: Earl Ford, eford@ 123456cdc.gov

                Article
                3191898
                10.2337/dc08-0423
                2518368
                18591398
                da216d04-e68a-4b22-a444-2f29036ca1a4
                Copyright © 2008, DIABETES CARE

                Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

                History
                : 28 February 2008
                : 12 June 2008
                Categories
                Reviews/Commentaries/ADA Statements

                Endocrinology & Diabetes
                Endocrinology & Diabetes

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