Fundación Biofisika Bizkaia, Barrio Sarriena s/n, 48940 Leioa, Spain.
Biofisika Institute (UPV/EHU, CSIC), Barrio Sarriena s/n, 48940 Leioa, Spain.
Int J Mol Sci. 2020 Jul 2;21(13):4725. doi: 10.3390/ijms21134725.
Statins are the gold-standard treatment for the prevention of primary and secondary cardiovascular disease, which is the leading cause of mortality worldwide. Despite the safety and relative tolerability of statins, observational studies, clinical trials and meta-analyses indicate an increased risk of developing new-onset type 2 diabetes mellitus (T2DM) after long-term statin treatment. It has been shown that statins can impair insulin sensitivity and secretion by pancreatic β-cells and increase insulin resistance in peripheral tissues. The mechanisms involved in these processes include, among others, impaired Ca signaling in pancreatic β-cells, down-regulation of GLUT-4 in adipocytes and compromised insulin signaling. In addition, it has also been described that statins' impact on epigenetics may also contribute to statin-induced T2DM via differential expression of microRNAs. This review focuses on the evidence and mechanisms by which statin therapy is associated with the development of T2DM. This review describes the multifactorial combination of effects that most likely contributes to the diabetogenic effects of statins. Clinically, these findings should encourage clinicians to consider diabetes monitoring in patients receiving statin therapy in order to ensure early diagnosis and appropriate management.
他汀类药物是预防原发性和继发性心血管疾病（全球主要致死原因）的金标准治疗方法。尽管他汀类药物安全性和相对耐受性良好，但观察性研究、临床试验和荟萃分析表明，长期他汀类药物治疗后新发 2 型糖尿病（T2DM）的风险增加。研究表明，他汀类药物可通过破坏胰岛β细胞的 Ca 信号传导、下调脂肪细胞中的 GLUT-4 以及损害胰岛素信号传导，从而损害胰岛素敏感性和β细胞胰岛素分泌。此外，也有研究表明，他汀类药物对表观遗传学的影响也可能通过差异表达 microRNAs 导致他汀类药物引起的 T2DM。本综述重点介绍了他汀类药物治疗与 T2DM 发展相关的证据和机制。本综述描述了可能导致他汀类药物致糖尿病作用的多种因素的综合作用。临床上，这些发现应鼓励临床医生考虑对接受他汀类药物治疗的患者进行糖尿病监测，以确保早期诊断和适当管理。
