Rajpathak Swapnil N, Kumbhani Dharam J, Crandall Jill, Barzilai Nir, Alderman Michael, Ridker Paul M
Department of Epidemiology and Population Health and Department of Medicine, Albert Einstein College of Medicine, New York, New York.
Diabetes Care. 2009 Oct;32(10):1924-9. doi: 10.2337/dc09-0738.
Although statin therapy reduces cardiovascular risk, its relationship with the development of diabetes is controversial. The first study (West of Scotland Coronary Prevention Study [WOSCOPS]) that evaluated this association reported a small protective effect but used nonstandardized criteria for diabetes diagnosis. However, results from subsequent hypothesis-testing trials have been inconsistent. The aim of this meta-analysis is to evaluate the possible effect of statin therapy on incident diabetes.
A systematic literature search for randomized statin trials that reported data on diabetes through February 2009 was conducted using specific search terms. In addition to the hypothesis-generating data from WOSCOPS, hypothesis-testing data were available from the Heart Protection Study (HPS), the Long-Term Intervention with Pravastatin in Ischemic Disease (LIPID) Study, the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT), the Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER), and the Controlled Rosuvastatin Multinational Study in Heart Failure (CORONA), together including 57,593 patients with mean follow-up of 3.9 years during which 2,082 incident diabetes cases accrued. Weighted averages were reported as risk ratios (RRs) with 95% CIs using a random-effects model. Statistical heterogeneity scores were assessed with the Q and I(2) statistic.
In the meta-analysis of the hypothesis-testing trials, we observed a small increase in diabetes risk (RR 1.13 [95% CI 1.03-1.23]) with no evidence of heterogeneity across trials. However, this estimate was attenuated and no longer significant when the hypothesis-generating trial WOSCOPS was included (1.06 [0.93-1.25]) and also resulted in significant heterogeneity (Q 11.8 [5 d.f.], P = 0.03, I(2) = 57.7%).
Although statin therapy greatly lowers vascular risk, including among those with and at risk for diabetes, the relationship of statin therapy to incident diabetes remains uncertain. Future statin trials should be designed to formally address this issue.
尽管他汀类药物治疗可降低心血管疾病风险，但其与糖尿病发生之间的关系仍存在争议。第一项评估此关联的研究（苏格兰西部冠心病预防研究[WOSCOPS]）报告称有轻微的保护作用，但使用的糖尿病诊断标准不规范。然而，后续假设检验试验的结果并不一致。本荟萃分析的目的是评估他汀类药物治疗对新发糖尿病的可能影响。
使用特定检索词对截至2009年2月报告糖尿病数据的随机他汀类药物试验进行系统文献检索。除了来自WOSCOPS的产生假设的数据外，还可获得来自心脏保护研究（HPS）、普伐他汀长期干预缺血性疾病研究（LIPID）、盎格鲁-斯堪的纳维亚心脏结局试验（ASCOT）、瑞舒伐他汀用于预防的合理性：一项评估瑞舒伐他汀的干预试验（JUPITER）以及瑞舒伐他汀治疗心力衰竭的多中心对照研究（CORONA）的假设检验数据，这些研究共纳入57593例患者，平均随访3.9年，期间有2082例新发糖尿病病例。采用随机效应模型将加权平均值报告为风险比（RRs）及95%置信区间（CIs）。使用Q和I²统计量评估统计异质性得分。
在对假设检验试验的荟萃分析中，我们观察到糖尿病风险有小幅增加（RR 1.13[95%CI 1.03 - 1.23]），且各试验间无异质性证据。然而，当纳入产生假设的试验WOSCOPS时，该估计值减弱且不再显著（1.06[0.93 - 1.25]），并且还导致了显著的异质性（Q 11.8[5个自由度]，P = 0.03，I² = 57.7%）。
尽管他汀类药物治疗可大幅降低血管风险，包括糖尿病患者及糖尿病高危人群，但他汀类药物治疗与新发糖尿病之间的关系仍不确定。未来的他汀类药物试验应设计用于正式解决这一问题。
