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      Alcohol Consumption, Mediating Biomarkers, and Risk of Type 2 Diabetes Among Middle-Aged Women

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          Abstract

          OBJECTIVE—The purpose of this study was to investigate whether adiponectin concentrations and biomarkers of inflammation, endothelial dysfunction, and insulin resistance mediate the association between alcohol consumption and diabetes.

          RESEARCH DESIGN AND METHODS—In a nested case-control study of 705 women with incident diabetes and 787 matched control subjects, we examined the adjusted relationship between baseline alcohol consumption and risk of diabetes before and after adjustment for markers of inflammation/endothelial dysfunction (C-reactive protein, vascular cell adhesion molecule-1, intercellular adhesion molecule-1, E-selectin, tumor necrosis factor-α receptor 2, and interleukin-6), fasting insulin, and adiponectin concentrations.

          RESULTS—Alcohol consumption was associated with a decreased risk of diabetes (odds ratio per 12.5 g/day increment in alcohol use 0.58; 95% CI 0.49–0.69; P < 0.001). Adjustment for BMI attenuated the association by 25%. None of the markers of inflammation or fasting insulin appeared to account for >2% of the observed relationship. Without adjustment for BMI, these biomarkers individually explained slightly more of the association, but <10% in all cases. Adiponectin accounted for 25% in a fully adjusted model and for 29% without adjustment for BMI.

          CONCLUSIONS—In this population of women, alcohol consumption was inversely associated with risk of type 2 diabetes. Adiponectin appeared to be a mediator of this association, but circulating biomarkers of inflammation, endothelial dysfunction, and fasting insulin did not explain this association. These results suggest that further research is needed into the potentially mediating roles of other biomarkers affected by alcohol consumption.

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          Most cited references29

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          Inflammatory markers and risk of developing type 2 diabetes in women.

          We conducted a prospective, nested, case-control study of inflammatory markers as predictors of type 2 diabetes among 32,826 women who provided blood samples in 1989 through 1990 in the Nurses' Health Study. Among women free of diabetes, cardiovascular disease, or cancer at baseline, 737 had developed diabetes by 2000. Control women (n = 785) were selected matched on age, fasting status, race, and BMI for cases in the top BMI decile. Baseline levels of tumor necrosis factor (TNF)-alpha receptor 2, interleukin (IL)-6, and C-reactive protein (CRP) were significantly higher among case than control subjects (all P
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            Biomarkers of endothelial dysfunction and risk of type 2 diabetes mellitus.

            Endothelial dysfunction occurs in diagnosed type 2 diabetes mellitus but may also precede development of diabetes. To determine whether elevated plasma levels of biomarkers reflecting endothelial dysfunction (E-selectin; intercellular adhesion molecule 1 [ICAM-1]; and vascular cell adhesion molecule 1 [VCAM-1]) predict development of type 2 diabetes in initially nondiabetic women. Prospective, nested case-control study within the Nurses' Health Study, an ongoing US study initiated in 1976. Of 121 700 women initially enrolled, 32 826 provided blood samples in 1989-1990; of those free of diabetes, cardiovascular disease, or cancer at baseline, 737 developed incident diabetes by 2000. Controls (n = 785) were selected according to matched age, fasting status, and race. Risk of confirmed clinically diagnosed type 2 diabetes by baseline levels of E-selectin, ICAM-1, and VCAM-1. Baseline median levels of the biomarkers were significantly higher among cases than among controls (E-selectin, 61.2 vs 45.4 ng/mL; ICAM-1, 264.9 vs 247.0 ng/mL; VCAM-1, 545.4 vs 526.0 ng/mL [all P values < or =.004]). Elevated E-selectin and ICAM-1 levels predicted incident diabetes in logistic regression models conditioned on matching criteria and adjusted for body mass index (BMI), family history of diabetes, smoking, diet score, alcohol intake, activity index, and postmenopausal hormone use. The adjusted relative risks for incident diabetes in the top quintile vs the bottom quintiles were 5.43 for E-selectin (95% confidence interval [CI], 3.47-8.50), 3.56 for ICAM-1 (95% CI, 2.28-5.58), and 1.12 for VCAM-1 (95% CI, 0.76-1.66). Adjustment for waist circumference instead of BMI or further adjustment for baseline levels of C-reactive protein, fasting insulin, and hemoglobin A(1c) or exclusion of cases diagnosed during the first 4 years of follow-up did not alter these associations. Endothelial dysfunction predicts type 2 diabetes in women independent of other known risk factors, including obesity and subclinical inflammation.
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              Moderate alcohol intake, increased levels of high-density lipoprotein and its subfractions, and decreased risk of myocardial infarction.

              Previous studies have suggested that moderate alcohol intake exerts a protective effect against coronary heart disease. Alterations in plasma lipoprotein levels represent one plausible mechanism of this apparent protective effect. We therefore examined the interrelation among alcohol consumption, plasma lipoprotein levels, and the risk of myocardial infarction in 340 patients who had had myocardial infarctions and an equal number of age- and sex-matched controls. The case patients were men or women less than 76 years of age with no history of coronary disease who were discharged from one of six hospitals in the Boston area with a diagnosis of a confirmed myocardial infarction. Alcohol consumption was estimated by means of a food-frequency questionnaire. We observed a significant inverse association between alcohol consumption and the risk of myocardial infarction (P for trend, < 0.001 after control for known coronary risk factors). In multivariate analyses, the relative risk for the highest intake category (subjects who consumed three or more drinks per day) as compared with the lowest (those who had less than one drink a month) was 0.45 (95 percent confidence interval, 0.26 to 0.80). The levels of total high-density lipoprotein cholesterol (HDL) and its HDL2 and HDL3 subfractions were strongly associated with alcohol consumption (P for trend, < 0.001 for each). The addition of HDL or either of its subfractions to the multivariate model substantially reduced the inverse association between alcohol intake and myocardial infarction, whereas the addition of the other plasma lipid measurements did not materially alter the relation. These data confirm the inverse association of moderate alcohol intake with the risk of myocardial infarction and support the view that the effect is mediated, in large part, by increases in both HDL2 and HDL3.
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                Author and article information

                Journal
                Diabetes Care
                diacare
                Diabetes Care
                American Diabetes Association
                0149-5992
                1935-5548
                October 2008
                : 31
                : 10
                : 2050-2055
                Affiliations
                [1 ]Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands
                [2 ]Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts
                [3 ]Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts
                [4 ]Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts
                [5 ]Business Unit Biosciences, TNO Quality of Life, Zeist, the Netherlands
                [6 ]Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, Boston, Massachusetts
                Author notes

                Corresponding author: Joline W.J. Beulens, j.beulens@ 123456umcutrecht.nl

                Article
                31102050
                10.2337/dc08-0814
                2551653
                18628567
                345ddb71-cb6b-4706-a880-0ca095cbb82e
                Copyright © 2008, 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
                : 29 April 2008
                : 10 July 2008
                Categories
                Cardiovascular and Metabolic Risk

                Endocrinology & Diabetes
                Endocrinology & Diabetes

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