The Impact of Diabetes on TB treatment outcomes

描述(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。尽管糖尿病和结核病之间的密切联系已经得到了明确的证明，但糖尿病对结核病临床结果产生负面影响的证据并不明确，留下了几个问题没有得到回答。糖尿病患者对治疗的潜在反应不佳的潜在原因--例如，抗结核药物浓度低、血糖控制不佳、治疗开始时分枝杆菌负荷较高--尚未得到严格的探索。我们将在巴西里约热内卢招募和前瞻性跟踪600名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，结核病疫情尚未消退。这项研究的具体目的是：1)估计巴西里约热内卢涂阳肺结核患者中糖尿病的负担以及糖尿病对结核病治疗结果的影响；2)评估糖尿病控制不良对结核病和糖尿病患者对结核病治疗反应的影响；3)利用药代动力学/药效学(PK/PD)模型，确定在使用或不使用DM治疗肺结核的患者中，导致微生物学结果不佳的关键因素。我们的多学科方法将提供迄今为止解决这两种疾病之间复杂相互作用的最佳证据，并为面临这些集中流行病的发展中国家提供管理战略。

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.