Are statins diabetogenic?
Are statins diabetogenic?
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DOI：
10.1097/hco.0b013e3283470359
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发表时间：
2011-07
影响因子：
2.3
通讯作者：
Fazio S
中科院分区：
文献类型：
--
作者：
Sampson UK;Linton MF;Fazio S
他汀类药物被广泛用于降低低密度脂蛋白和预防动脉粥样硬化性心血管疾病。虽然这些药物有良好的安全记录，但在长期使用期间发生糖尿病的风险增加最近引起了人们的关注。在这里，我们回顾了与他汀类药物使用和糖尿病事件相关的临床试验证据，以及这种关联的潜在机制。瑞舒伐他汀治疗的糖尿病发病率增加在他汀类药物用于一级预防的合理性：一项评价瑞舒伐他汀的干预试验（JUPITER）中再次引起了对他汀类药物治疗与糖尿病之间联系的关注。JUPITER的发现得到了最近两项大规模安慰剂对照和标准护理对照试验的荟萃分析的支持，这两项试验分别观察到与他汀类药物治疗相关的糖尿病事件风险增加9% [比值比1.09; 95%置信区间（CI）1.02-1.17]和13%（风险比1.13; 95% CI 1.03-1.23）。然而，这种关联的潜在机制仍不清楚。实验证据支持涉及抑制β细胞葡萄糖转运蛋白、延迟ATP产生、血浆来源胆固醇的促炎和氧化β细胞作用、抑制钙通道依赖性胰岛素分泌和β细胞凋亡的范例。大型临床试验的汇总支持他汀类药物适度增加糖尿病发病风险的观点。由于糖尿病是冠状动脉和外周动脉疾病的风险等同条件，这些发现产生了一个悖论，即所需的他汀类药物治疗可能会被扣留，以避免糖尿病的过度风险，同时代表糖尿病患者最强的心血管风险降低工具。我们只是建议服用他汀类药物的患者定期监测血糖。
Statins are widely utilized for low-density lipoprotein lowering and for prevention of atherosclerotic cardiovascular disease. Although these drugs have a good safety record, increased risk of developing diabetes during extended use has recently garnered attention. Here we review clinical trial evidence related to statin use and incident diabetes, and the potential mechanisms for this association. The increased incidence of diabetes with rosuvastatin treatment in Justification for the Use of Statins in Primary Prevention: an intervention Trial Evaluating Rosuvastatin (JUPITER) reignited attention on the link between statin therapy and diabetes. The JUPITER findings are supported by two recent meta-analyses of large-scale placebo-controlled and standard care-controlled trials, which, respectively, observed a 9% [odds ratio 1.09; 95% confidence interval (CI) 1.02–1.17] and 13% (risk ratio 1.13; 95% CI 1.03–1.23) increased risk for incident diabetes associated with statin therapy. However, the underlying mechanisms for this association remain unclear. Experimental evidence supports a paradigm implicating inhibition of β-cell glucose transporters, delayed ATP production, pro-inflammatory and oxidative β-cell effects of plasma-derived cholesterol, inhibition of calcium channel-dependent insulin secretion, and β-cell apoptosis. The aggregate of large clinical trials supports the notion that statins modestly increase the risk of incident diabetes. Because diabetes is a risk equivalent condition for coronary and peripheral arterial diseases, these findings create a paradox whereby needed statin therapy may be withheld to avoid excess risk of diabetes while representing the strongest cardiovascular risk reduction tool in diabetics. We simply recommend regular glucose monitoring in patients taking statins.