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Sex Differences in the Prediction of Type 2 Diabetes by Inflammatory Markers

Results from the MONICA/KORA Augsburg case-cohort study, 1984–2002

¹ Institute of Epidemiology, GSF National Research Center for Environment and Health, Neuherberg, Germany
² German Diabetes Centre, German Diabetes Clinic, Leibniz Centre at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
³ University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
⁴ Department of Internal Medicine II-Cardiology, University of Ulm Medical Center, Ulm, Germany

Address correspondence and reprint requests to Wolfgang Koenig, MD, FRCP, Department of Internal Medicine II-Cardiology, University of Ulm Medical Center, Robert Koch Str. 8, D-89081 Ulm, Germany. E-mail: wolfgang.koenig{at}uniklinik-ulm.de

OBJECTIVE—Although sex differences have been reported for associations between obesity and inflammation, the question of whether there is an effect modification by sex in the association between inflammation and type 2 diabetes has not been investigated in detail. Therefore, the aim of this study was to compare associations of markers of inflammation with type 2 diabetes risk between men and women.

RESEARCH DESIGN AND METHODS—Following a case-cohort design, cases of incident type 2 diabetes were identified from 7,936 subjects aged 35–74 years at baseline who participated in the population-based Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA)/Cooperative Research in the Region of Augsburg (KORA) studies conducted between 1984 and 2002. Concentrations of C-reactive protein (CRP) and interleukin (IL)-6 were measured in 527 cases of incident type 2 diabetes (305 men and 222 women) and 1,698 noncases (889 men and 809 women).

RESULTS—After adjustment for age and survey and lifestyle factors including smoking, alcohol intake, and physical activity, elevated concentrations of CRP showed a considerably stronger association with risk of type 2 diabetes in women (hazard ratio comparing tertile extremes 7.60 [95% CI 4.43–13.04]) than in men (1.84 [1.27–2.67]). The P value for the sex interaction was <0.001. Further adjustment for metabolic risk factors considerably attenuated these associations, and they became nonsignificant in men but remained significant in women. IL-6 was also more strongly associated with type 2 diabetes in women, but there was no significant sex interaction.

CONCLUSIONS—Our data suggest that inflammatory processes may be of particular importance in the pathogenesis of type 2 diabetes in women.

Abbreviations: CRP, C-reactive protein • IL, interleukin • IRMA, immunoradiometric assay • KORA, Cooperative Research in the Region of Augsburg • MONICA, Monitoring of Trends and Determinants in Cardiovascular Disease • SHBG, sex hormone–binding globulin • WHR, waist-to-hip ratio

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