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      Association Between Serum Uric Acid and Development of Type 2 Diabetes

      research-article
      , MD, PHD, , MD, PHD, , RD, , MS, , RD, , RD, , RD, , MD, PHD, FACP
      Diabetes Care
      American Diabetes Association

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          Abstract

          OBJECTIVE

          To systematically evaluate the association between serum uric acid (SUA) level and subsequent development of type 2 diabetes.

          RESEARCH DESIGN AND METHODS

          We searched Medline (31 March from 1966 to 2009) and Embase (31 March from 1980 to 2009) for observational cohort studies examining the association between SUA and the risk of type 2 diabetes by manual literature search. Relative risks (RRs) for each 1 mg/dl increase in SUA were pooled by using a random-effects model. The studies included were stratified into subgroups representing different study characteristics, and meta-regression analyses were performed to investigate the effect of these characteristics on the association between SUA level and type 2 diabetes risk.

          RESULTS

          The search yielded 11 cohort studies (42,834 participants) that reported 3,305 incident cases of type 2 diabetes during follow-up periods ranging from 2.0 to 13.5 years. The pooled RR of a 1 mg/dl increase in SUA was 1.17 (95% CI 1.09–1.25). Study results were consistently significant (i.e., >1) across characteristics of participants and study design. Publication bias was both visually and statistically suggested ( P = 0.03 for Egger's test, 0.06). Adjustment for publication bias attenuated the pooled RR per mg/dl increase in SUA (RR 1.11 [95% CI 1.03–1.20]), but the association remained statistically significant ( P = 0.009).

          CONCLUSIONS

          The current meta-analysis suggests that SUA level is positively associated with the development of type 2 diabetes regardless of various study characteristics. Further research should attempt to determine whether it is effective to utilize SUA level as a predictor of type 2 diabetes for its primary prevention.

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          Most cited references17

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          Active smoking and the risk of type 2 diabetes: a systematic review and meta-analysis.

          Observational studies have suggested an association between active smoking and the incidence of type 2 diabetes. To conduct a systematic review with meta-analysis of studies assessing the association between active smoking and incidence of type 2 diabetes. A search of MEDLINE (1966 to May 2007) and EMBASE (1980 to May 2007) databases was supplemented by manual searches of bibliographies of key retrieved articles, reviews of abstracts from scientific meetings, and contact with experts. Studies were included if they reported risk of impaired fasting glucose, impaired glucose tolerance, or type 2 diabetes in relationship to smoking status at baseline; had a cohort design; and excluded persons with diabetes at baseline. Two authors independently extracted the data, including the presence or absence of active smoking at baseline, the risk of diabetes, methods used to detect diabetes, and key criteria of study quality. Relative risks (RRs) were pooled using a random-effects model. Associations were tested in subgroups representing different patient characteristics and study quality criteria. The search yielded 25 prospective cohort studies (N = 1.2 million participants) that reported 45 844 incident cases of diabetes during a study follow-up period ranging from 5 to 30 years. Of the 25 studies, 24 reported adjusted RRs greater than 1 (range for all studies, 0.82-3.74). The pooled adjusted RR was 1.44 (95% confidence interval [CI], 1.31-1.58). Results were consistent and statistically significant in all subgroups. The risk of diabetes was greater for heavy smokers (> or =20 cigarettes/day; RR, 1.61; 95% CI, 1.43-1.80) than for lighter smokers (RR,1.29; 95% CI, 1.13-1.48) and lower for former smokers (RR, 1.23; 95% CI, 1.14-1.33) compared with active smokers, consistent with a dose-response phenomenon. Active smoking is associated with an increased risk of type 2 diabetes. Future research should attempt to establish whether this association is causal and to clarify its mechanisms.
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            Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease: meta-analyses of prospective studies.

            A large number of epidemiologic studies have reported on associations between various "inflammatory" factors and coronary heart disease (CHD). To assess the associations of blood levels of fibrinogen, C-reactive protein (CRP), and albumin and leukocyte count with the subsequent risk of CHD. Meta-analyses of any long-term prospective studies of CHD published before 1998 on any of these 4 factors. Studies were identified by MEDLINE searches, scanning of relevant reference lists, hand searching of cardiology, epidemiology, and other relevant journals, and discussions with authors of relevant reports. All relevant studies identified were included. The following information was abstracted from published reports (supplemented, in several cases, by the authors): size and type of cohort, mean age, mean duration of follow-up, assay methods, degree of adjustment for confounders, and relationship of CHD risk to the baseline assay results. For fibrinogen, with 4018 CHD cases in 18 studies, comparison of individuals in the top third with those in the bottom third of the baseline measurements yielded a combined risk ratio of 1.8 (95% confidence interval [CI], 1.6-2.0) associated with a difference in long-term usual mean fibrinogen levels of 2.9 pmol/L (0.1 g/dL) between the top and bottom thirds (10.3 vs 7.4 pmol/L [0.35 vs 0.25 g/dL]). For CRP, with 1053 CHD cases in 7 studies, the combined risk ratio of 1.7 (95% CI, 1.4-2.1) was associated with a difference of 1.4 mg/L (2.4 vs 1.0 mg/L). For albumin, with 3770 CHD cases in 8 studies, the combined risk ratio of 1.5 (95% CI, 1.3-1.7) was associated with a difference of 4 g/L (38 vs 42 g/L, ie, an inverse association). For leukocyte count, with 5337 CHD cases in the 7 largest studies, the combined risk ratio of 1.4 (95% CI, 1.3-1.5) was associated with a difference of 2.8 x 10(9)/L (8.4 vs 5.6 x 10(9)/L). Each of these overall results was highly significant (P<.0001). The published results from these prospective studies are remarkably consistent for each factor, indicating moderate but highly statistically significant associations with CHD. Hence, even though mechanisms that might account for these associations are not clear, further study of the relevance of these factors to the causation of CHD is warranted.
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              Components of the metabolic syndrome and risk of cardiovascular disease and diabetes in Beaver Dam.

              To determine whether components of the metabolic syndrome precede the 5-year incidence of cardiovascular disease and diabetes. A population of individuals aged 43-84 years was evaluated from 1988 to 1990 and again 5 years later. Medical history, blood pressure, and laboratory measures were obtained at both examinations following the same protocols. Subjects without diabetes were classified according to level of glycemia, high blood pressure, high-risk lipid levels, high uric acid levels, and proteinuria at baseline. History of incident myocardial infarction, angina, stroke, and diabetes was obtained at follow-up. Of the 4,423 subjects without diabetes, 6.9% had elevated levels of glycemia, 18.4% had high blood pressure, 82.7% had high-risk lipid levels (either high serum total cholesterol or low HDL cholesterol or high ratio of these two levels), 27% had elevated uric acid levels, 33.2% had high BMI, and 3.3% had proteinuria (> or =30 mg/dl). The risk of incident cardiovascular disease 5 years later increased with the number of the components present; 2.5% of those with one component developed cardiovascular disease, whereas 14.9% of those with four or more components developed cardiovascular disease. Of those with one component, diabetes developed in 1.1% 5 years later, whereas diabetes developed in 17.9% of those with four or more components. Components of the metabolic syndrome are common and are associated with incident cardiovascular disease and diabetes after 5 years. Interventions to alter BMI, lipid levels, and blood pressure may decrease incident diabetes and cardiovascular disease.
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                Author and article information

                Journal
                Diabetes Care
                diacare
                dcare
                Diabetes Care
                Diabetes Care
                American Diabetes Association
                0149-5992
                1935-5548
                September 2009
                23 June 2009
                : 32
                : 9
                : 1737-1742
                Affiliations
                [1]From the Department of Internal Medicine, University of Tsukuba Institute of Clinical Medicine, Ibaraki, Japan.
                Author notes
                Corresponding author: Hirohito Sone, hsone@ 123456md.tsukuba.ac.jp .
                Article
                0288
                10.2337/dc09-0288
                2732137
                19549729
                923865b6-5952-4105-bb06-dafb6da31a11
                © 2009 by the American Diabetes Association.

                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
                : 19 February 2009
                : 13 June 2009
                Categories
                Reviews/Commentaries/ADA Statements
                Meta-analyses

                Endocrinology & Diabetes
                Endocrinology & Diabetes

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