De Wit Stephane, Sabin Caroline A, Weber Rainer, Worm Signe Westring, Reiss Peter, Cazanave Charles, El-Sadr Wafaa, Monforte Antonella d'Arminio, Fontas Eric, Law Matthew G, Friis-Møller Nina, Phillips Andrew
Centre Hospitalier Universitaire Saint-Pierre, Brussels, Belgium.
Diabetes Care. 2008 Jun;31(6):1224-9. doi: 10.2337/dc07-2013. Epub 2008 Feb 11.
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.
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.
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.
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.
本研究旨在确定抗逆转录病毒药物不良事件数据收集（D:A:D）队列中HIV感染患者的糖尿病发病率，识别与糖尿病发病相关的人口统计学、HIV相关及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联的可能机制。
D:A:D是一项对33389例HIV感染患者的前瞻性观察性研究；糖尿病是一个研究终点。在调整已知的糖尿病危险因素、CD4细胞计数、血脂和脂肪代谢障碍后，使用泊松回归模型评估糖尿病与cART暴露之间的关系。
在超过130151人年的随访（PYFU）中，744例患者被诊断为糖尿病（发病率为每1000 PYFU 5.72例[95%CI 5.31 - 6.13]）。糖尿病发病率随cART累积暴露增加，在调整糖尿病潜在危险因素后这种关联仍然显著。与糖尿病关系最密切的是司他夫定暴露；齐多夫定和去羟肌苷暴露也与糖尿病风险增加有关。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有关。分别调整这些变量中的每一个会使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著相关，但对此进行调整并未改变cART与糖尿病之间的关系。
在调整糖尿病和血脂危险因素后，司他夫定和齐多夫定与糖尿病显著相关。对脂肪代谢障碍进行调整并未改变这种关系，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。
