Diabetes, Inflammatory Markers, and Urinary Incontinence in Women
Urinary incontinence (UI) affects over half of women with type 2 diabetes (DM) and has a profound negative impact on quality of life. DM is a strong independent risk factor for prevalent and incident UI, and urologic complications including UI are reported to be more common than other widely recognized complications of DM such as neuropathy, nephropathy, and retinopathy. Yet, the mechanism(s) of how DM promotes UI are poorly understood and research on diabetic uropathy significantly lags behind these other complications of DM. Biomarkers of inflammation, including C-reactive protein (CRP) and adipocytokines, are associated with both DM and UI, and thus may be a mechanism whereby DM increases the risk of UI. We propose to investigate the complex relationship between DM control, obesity, inflammation, and UI in over 1,000 overweight or obese women with DM in the Action for Health in Diabetes (Look AHEAD) study. We will conduct secondary data anlyses to (1) determine the strength and direction of associations between inflammatory biomarker levels (inflammation: CRP (CRP), interleukin 6 (IL-6), plasminogen activator inhibitor-1 (PAI-1); anti-inflammation: adiponectin) and UI, by type and severity, (2) evaluate if and to what extent changes in inflammatory bio-marker levels predict incident UI or change in severity of prevalent UI from baseline to 1 year, and (3) determine whether the association between inflammatory biomarker levels and UI depends on level of diabetes control, measured by HbA1c. This secondary analysis within the large, diverse and well-characterized Look AHEAD cohort is an efficient and innovative study to better understand the mechanisms of urologic complications of diabetes in women. Biomarkers of inflammation may eventually help identify women at higher risk of developing UI, predict response to therapy, and/or inspire new targets for treatment. The proposed analyses could provide a novel contribution to our understanding of inflammation and diabetic uropathy and generate mechanistic hypotheses to explore in the laboratory and in animal models, thus helping to translate laboratory findings to patient care to improve the prevention and treatment of urologic complications of DM.

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