The Impact of Diabetes on TB treatment outcomes

糖尿病对结核病治疗结果的影响

• 批准号: 8305333
• 负责人: JONATHAN E. GOLUB
• 金额: $ 59.18万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-02-01 至 2018-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8305333
• 关键词: AIDS/HIV problem; Accounting; Address; Affect; Africa; Age; Alcohol consumption; Antitubercular Agents; Brazil; Cessation of life; Chest; Clinical; Clinical Treatment; Cohort Studies; Complex; Country; Detection; Developing Countries; Diabetes Mellitus; Disease; Dose; Drug Kinetics; Drug usage; Enrollment; Epidemic; Failure; General Population; Glucose; Goals; HIV; HIV Infections; Hyperglycemia; Individual; Interview; Left; Life; Liquid substance; Measures; Modeling; Mycobacterium tuberculosis; Newly Diagnosed; Non-Insulin-Dependent Diabetes Mellitus; Outcome; Outcome Measure; Patients; Pharmaceutical Preparations; Population; Population Attributable Risks; Population Study; Prevalence; Pulmonary Tuberculosis; Recruitment Activity; Relapse; Research; Research Design; Retrospective Studies; Rifampin; Risk; Risk Factors; Sampling; Severities; Smoking; Solid; Sputum; Structure; Surrogate Markers; Techniques; Testing; Time; Treatment Failure; Treatment outcome; Tuberculosis; burden of illness; cohort; diabetic; expectation; fasting glucose; global health; glycemic control; high risk; interdisciplinary approach; mortality; mycobacterial; pharmacodynamic model; prospective; public health relevance; response; sex; treatment response; tuberculosis drugs; tuberculosis treatment

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.

描述（由申请人提供）：在非洲以外，2 型糖尿病 (DM) 在全球结核病负担中所占的比例与艾滋病毒一样多，并且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相关性已得到明确证明，但糖尿病对结核病临床结果产生负面影响的证据尚不明确，因此有几个问题尚未得到解答。糖尿病患者治疗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等——尚未得到严格探讨。我们将在巴西里约热内卢招募并前瞻性跟踪 600 名涂片和培养呈阳性的结核病患者，那里的糖尿病问题正在大幅上升，而结核病流行尚未消退。该研究的具体目的是 1) 评估巴西里约热内卢涂阳肺结核患者的糖尿病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治疗反应的影响结核病合并糖尿病患者的结核病治疗，以及，3) 使用药代动力学/药效学 (PK/PD) 模型，确定接受或不接受肺结核治疗的患者微生物学结果不佳的关键因素DM。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，并为面临这些流行病的发展中国家提供管理策略。