1 Department of Medicine West Virginia University Morgantown WV.
2 Department of Medicine Guthrie Health System/Robert Packer Hospital Sayre PA.
J Am Heart Assoc. 2019 Apr 2;8(7):e011581. doi: 10.1161/JAHA.118.011581.
Background The relationship between lowering LDL (low-density lipoprotein) cholesterol with contemporary lipid-lowering therapies and incident diabetes mellitus ( DM ) remains uncertain. Methods and Results Thirty-three randomized controlled trials (21 of statins, 12 of PCSK9 [proprotein convertase subtilisin/kexin type 9] inhibitors, and 0 of ezetimibe) were selected using Medline , Embase, and the Cochrane Central Register of Controlled Trials (inception through November 15, 2018). A total of 163 688 nondiabetic patients were randomly assigned to more intensive (83 123 patients) or less intensive (80 565 patients) lipid-lowering therapy. More intensive lipid-lowering therapy was defined as the more potent pharmacological strategy ( PCSK 9 inhibitors, higher intensity statins, or statins), whereas less intensive therapy corresponded to active control group or placebo/usual care of the trial. Metaregression and meta-analyses were conducted using a random-effects model. No significant association was noted between 1-mmol/L reduction in LDL cholesterol and incident DM for more intensive lipid-lowering therapy (risk ratio: 0.95; 95% CI , 0.87-1.04; P=0.30; R=14%) or for statins or PCSK 9 inhibitors. More intensive lipid-lowering therapy was associated with a higher risk of incident DM compared with less intensive therapy (risk ratio: 1.07; 95% CI , 1.03-1.11; P<0.001; I=0%). These results were driven by higher risk of incident DM with statins (risk ratio: 1.10; 95% CI , 1.05-1.15; P<0.001; I=0%), whereas PCSK 9 inhibitors were not associated with incident DM (risk ratio: 1.00; 95% CI , 0.93-1.07; P=0.96; I=0%; P=0.02 for interaction). Conclusions Among intensive lipid-lowering therapies, there was no independent association between reduction in LDL cholesterol and incident DM . The risk of incident DM was higher with statins, whereas PCSK 9 inhibitors had no association with risk of incident DM .
降低 LDL（低密度脂蛋白）胆固醇与当代降脂治疗和糖尿病（DM）发病之间的关系仍不确定。
使用 Medline、Embase 和 Cochrane 对照试验中心注册库（从建立到 2018 年 11 月 15 日）选择了 33 项随机对照试验（21 项他汀类药物、12 项 PCSK9[前蛋白转化酶枯草溶菌素 9]抑制剂和 0 项依泽替米贝）。共有 163688 名非糖尿病患者被随机分配到更强化（83123 名患者）或较不强化（80565 名患者）的降脂治疗。更强化的降脂治疗定义为更有效的药物治疗策略（PCSK9 抑制剂、更高强度的他汀类药物或他汀类药物），而较不强化的治疗则对应于试验中的活性对照组或安慰剂/常规护理。采用随机效应模型进行荟萃回归和荟萃分析。与更强化的降脂治疗相比，LDL 胆固醇降低 1mmol/L 与 DM 发病之间无显著相关性（风险比：0.95；95%CI，0.87-1.04；P=0.30；R=14%）或与他汀类药物或 PCSK9 抑制剂无关。与较不强化的降脂治疗相比，更强化的降脂治疗与 DM 发病风险较高相关（风险比：1.07；95%CI，1.03-1.11；P<0.001；I=0%）。这些结果是由他汀类药物导致的 DM 发病风险更高所驱动的（风险比：1.10；95%CI，1.05-1.15；P<0.001；I=0%），而 PCSK9 抑制剂与 DM 发病无关（风险比：1.00；95%CI，0.93-1.07；P=0.96；I=0%；P=0.02 用于交互作用）。
在强化降脂治疗中，降低 LDL 胆固醇与 DM 发病之间没有独立的关联。他汀类药物的 DM 发病风险较高，而 PCSK9 抑制剂与 DM 发病风险无关。
