Incidence and risk factors for new-onset diabetes, in HIV-infected patients -: The data collection on adverse events of Anti-HIV drugs (D:A:D) study
Incidence and risk factors for new-onset diabetes, in HIV-infected patients -: The data collection on adverse events of Anti-HIV drugs (D:A:D) study
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DOI：
10.2337/dc07-2013
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发表时间：
2008-06-01
期刊：
影响因子：
16.2
通讯作者：
Phillips, Andrew
中科院分区：
文献类型：
--
作者：
De Wit, Stephane;Sabin, Caroline A.;Phillips, Andrew
目的 - 本研究的目的是确定抗 HIV 药物不良事件数据收集 (D-A:D) 队列中 HIV 感染者的糖尿病发病率，确定与糖尿病发病相关的人口统计学因素、HIV 相关因素和联合抗逆转录病毒治疗 (cART) 相关因素，并确定所发现的任何关系的可能机制。 研究设计和方法 - D:A:D 是一项前瞻性观察性研究33,389 名艾滋病毒感染者；糖尿病是一个研究终点。在调整糖尿病、CD4 计数、血脂和脂肪营养不良的已知危险因素后，使用泊松回归模型评估糖尿病与 cART 暴露之间的关系。 结果 - 在超过 130,151 人年的随访 (PYFU) 中，744 名患者被诊断为糖尿病（发病率为 5.72/1,000 PYFU [95% CI 5.31-6.13]）。糖尿病的发病率随着 cART 的累积暴露而增加，在调整糖尿病的潜在危险因素后，这种关联仍然显着。与糖尿病最密切的关系是服用司他夫定。接触齐多夫定和去羟肌苷也与糖尿病风险增加相关。总胆固醇、高密度脂蛋白胆固醇和甘油三酯的时间更新测量值均与糖尿病相关。分别调整每个变量后，cART 与糖尿病之间的关系略有减弱。尽管脂肪代谢障碍与糖尿病显着相关，但对此进行调整并没有改变 cART 与糖尿病之间的关系。 结论 - 在调整糖尿病和血脂的危险因素后，司他夫定和齐多夫定与糖尿病显着相关。对脂肪营养不良的调整并没有改变这种关系，这表明这两种胸苷类似物可能通过线粒体毒性直接导致胰岛素抵抗。
OBJECTIVE - The aims of this study were to determine the incidence of diabetes among HIV-infected patients in the Data Collection on Adverse Events of Anti-HIV Drugs (D-A:D) cohort, to identify demographic, HIV-related, and combination antiretroviral therapy (cART)-related factors associated with the onset of diabetes, and to identify possible mechanisms for any relationships found.RESEARCH DESIGN AND METHODS - D:A:D is a prospective observational study of 33,389 HIV-infected patients; diabetes is a study end point. Poisson regression models were used to assess the relation between diabetes and exposure to cART after adjusting for known risk factors for diabetes, CD4 count, lipids, and lipodystrophy.RESULTS - Over 130,151 person-years of follow-up (PYFU), diabetes was diagnosed in 744 patients (incidence rate of 5.72 per 1,000 PYFU [95% CI 5.31-6.13]). The incidence of diabetes increased with cumulative exposure to cART, an association that remained significant after adjustment for potential risk factors for diabetes. The strongest relationship with diabetes was exposure to stavudine; exposures to zidovudine and didanosine were also associated with an increased risk of diabetes. Time-updated measurements of total cholesterol, HDL cholesterol, and triglycerides were all associated with diabetes. Adjusting for each of these variables separately reduced the relationship between cART and diabetes slightly. Although lipodystrophy was significantly associated with diabetes, adjustment for this did not modify the relationship between cART and diabetes.CONCLUSION - Stavudine and zidovudine are significantly associated with diabetes after adjustment for risk factors for diabetes and lipids. Adjustment for lipodystrophy did not modify the relationship, suggesting that the two thymidine analogs probably directly contribute to insulin resistance, potentially through mitochondrial toxicity.