The Impact of Diabetes on TB treatment outcomes

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DESCRIPTION (provided by applicant): Outside of Africa, type 2 diabetes (DM) accounts for as much of the global TB burden as HIV and this fraction is highest in the developing world. Though the strong association between DM and TB has been clearly demonstrated, evidence that DM negatively affects TB clinical outcomes is not as clear, leaving several questions unanswered. The potential causes for potential suboptimal response to treatment among diabetics - low concentrations of anti-TB drugs, poor glycemic control, higher mycobacterial burden at the initiation of therapy, for example - have not been rigorously explored. We will recruit and prospectively follow 600 smear and culture positive TB patients in Rio de Janeiro, Brazil where the DM problem is climbing substantially and a TB epidemic has not subsided. The specific aims of the study are 1) To estimate the burden of DM and the impact of DM on TB treatment outcomes among patients with smear- positive pulmonary TB in Rio de Janeiro, Brazil, 2) Evaluate the impact of poor diabetic control on response to TB treatment among patients with TB and DM, and, 3) Using pharmacokinetic/pharmaocdynamic (PK/PD) modeling, determine the key contributing factors to poor microbiologic outcomes among patients being treated for pulmonary TB with or without DM. Our multidisciplinary approach will provide the best evidence to date addressing the complex interactions between these two diseases and inform management strategies for developing countries facing these converging epidemics.