The Impact of Diabetes on TB treatment outcomes

描述（由申请人提供）：在非洲以外，2型糖尿病（DM）占全球结核病负担的比例与艾滋病毒相当，这一比例在发展中国家最高。虽然糖尿病和结核病之间的强相关性已得到明确证明，但糖尿病对结核病临床结局产生负面影响的证据并不明确，因此有几个问题尚未得到解答。糖尿病患者对治疗的潜在次优反应的潜在原因-例如，低浓度的抗结核药物，血糖控制不良，治疗开始时较高的分枝杆菌负荷-尚未得到严格的探索。我们将在巴西里约热内卢招募并前瞻性随访600例涂片和培养阳性结核病患者，那里的糖尿病问题正在大幅攀升，结核病流行尚未消退。该研究的具体目的是：1）估计巴西里约热内卢的涂阳肺结核患者中DM的负担和DM对TB治疗结果的影响，2）评价TB和DM患者中糖尿病控制不良对TB治疗反应的影响，以及3）使用药代动力学/药效学（PK/PD）模型，确定在合并或不合并糖尿病的肺结核患者中导致不良微生物学结局的关键因素。我们的多学科方法将为解决这两种疾病之间复杂的相互作用提供迄今为止最好的证据，并为面临这些趋同流行病的发展中国家的管理战略提供信息。

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.