Robinson Jennifer G
aDepartment of Epidemiology bDepartment of Medicine cPrevention Intervention Center, University of Iowa, Iowa City, Iowa, USA.
Curr Opin Lipidol. 2015 Jun;26(3):228-35. doi: 10.1097/MOL.0000000000000172.
In randomized trials and many observational studies, statins are associated with a modest excess of type 2 diabetes mellitus. High-intensity statins, such as atorvastatin 80 mg and rosuvastatin 20 mg, are associated with a higher excess risk of diabetes than moderate-intensity statins, such as atorvastatin 10 mg, simvastatin 20-40 mg, or pravastatin 40 mg.
Multiple mechanisms have been proposed for statin-associated diabetes risk, primarily related to increased insulin resistance or impaired insulin secretion. Genetic polymorphisms with reduced HMG CoA reductase function are associated with weight gain, insulin resistance, and diabetes. Animal models have shown that HMG CoA inhibition has multiple downstream effects that may increase diabetes risk. Statin impairment of insulin signaling, decreased adipocyte differentiation, decreased pancreatic β-cell insulin secretion, and other effects have also been found. The excess risk of diabetes appears to be confined to those who are already at risk for developing diabetes. Diabetes is diagnosed only 2-4 months earlier in statin-treated patients and therefore is unlikely to have no long-term adverse consequences.
The clinical impact of statin-associated diabetes is likely unimportant. The cardiovascular risk reduction benefit from statin far outweighs the potential for adverse effects in all but the very lowest risk individuals.
在随机试验和许多观察性研究中，他汀类药物与2型糖尿病的适度增加有关。高强度他汀类药物，如80毫克阿托伐他汀和20毫克瑞舒伐他汀，与糖尿病的额外风险高于中等强度他汀类药物，如10毫克阿托伐他汀、20 - 40毫克辛伐他汀或40毫克普伐他汀。
已提出多种与他汀类药物相关糖尿病风险的机制，主要与胰岛素抵抗增加或胰岛素分泌受损有关。HMG CoA还原酶功能降低的基因多态性与体重增加、胰岛素抵抗和糖尿病有关。动物模型表明，HMG CoA抑制有多种下游效应，可能增加糖尿病风险。还发现了他汀类药物对胰岛素信号传导的损害、脂肪细胞分化减少、胰腺β细胞胰岛素分泌减少及其他影响。糖尿病的额外风险似乎仅限于那些已有糖尿病发病风险的人。在接受他汀类药物治疗的患者中，糖尿病仅提前2 - 4个月被诊断出来，因此不太可能没有长期不良后果。
他汀类药物相关糖尿病的临床影响可能并不重要。除了风险极低的个体外，他汀类药物降低心血管风险的益处远远超过潜在的不良反应。
