Jialal Ishwarlal, Miguelino Eric, Griffen Steven C, Devaraj Sridevi
Laboratory for Atherosclerosis and Metabolic Research, University of California, Davis, Medical Center, Sacramento, California 95817, USA.
J Clin Endocrinol Metab. 2007 Aug;92(8):3136-40. doi: 10.1210/jc.2007-0453. Epub 2007 May 22.
Cardiovascular disease is a major cause of mortality in type 1 diabetes (TIDM). TIDM is a proinflammatory state. Whereas there is consensus on lipid management in type 2 diabetes, there is a lack of data in type 1 diabetes. In addition to benefits on the lipid profile, statin therapy is antiinflammatory.
There are scant data on statin therapy in T1DM. Thus, we tested the effect of simvastatin, compared with placebo, on biomarkers of inflammation and monocyte function in TIDM patients.
This was a double-blind, randomized, placebo-controlled study of T1DM patients, randomized to placebo or simvastatin, 20 mg/d for 3 months.
The study was conducted at the University of California, Davis, Medical Center.
Participants included patients with T1DM.
Analytes measured at baseline and 3 months included liver function tests, creatinine, hemoglobin AIC, high-sensitivity C-reactive protein, soluble CD40 ligand, monocyte O(2)(-), cytokines, nuclear factor-kappaB. Simvastatin therapy resulted in significant reduction in low-density lipoprotein and non-high-density lipoprotein cholesterol, high-sensitivity C-reactive protein (18% reduction, P < 0.001) and soluble CD40 ligand (22% reduction, P < 0.05), compared with placebo. Simvastatin therapy significantly inhibited lipopolysaccharide-activated monocyte release of O(2)(-) (P < 0.0005), IL-8 (P < 0.03), and TNF (P < 0.02). Simvastatin therapy significantly inhibited monocyte IL-6 release, compared with baseline (P = 0.02). Simvastatin therapy also significantly reduced monocytic nuclear factor-kappaB p65 activity, compared with placebo (P < 0.01).
This study demonstrates that simvastatin (20 mg/d) is safe in T1DM patients and has concomitant benefits on the lipid profile and biomarkers of inflammation. These novel findings could have implications for developing policy guidelines for statin therapy in forestalling vascular complications in young T1DM.
心血管疾病是1型糖尿病（TIDM）患者死亡的主要原因。TIDM是一种促炎状态。虽然2型糖尿病患者的血脂管理已达成共识，但1型糖尿病患者的数据却很缺乏。除了对血脂有益外，他汀类药物治疗还具有抗炎作用。
关于T1DM患者使用他汀类药物治疗的数据很少。因此，我们测试了辛伐他汀与安慰剂相比，对TIDM患者炎症生物标志物和单核细胞功能的影响。
这是一项针对T1DM患者的双盲、随机、安慰剂对照研究，随机分为安慰剂组或辛伐他汀组，辛伐他汀剂量为20mg/d，持续3个月。
该研究在加利福尼亚大学戴维斯分校医学中心进行。
参与者包括T1DM患者。
在基线和3个月时测量的分析物包括肝功能测试、肌酐、糖化血红蛋白、高敏C反应蛋白、可溶性CD40配体、单核细胞O(2)(-)、细胞因子、核因子-κB。与安慰剂相比，辛伐他汀治疗使低密度脂蛋白和非高密度脂蛋白胆固醇、高敏C反应蛋白（降低18%，P<0.001）和可溶性CD40配体（降低22%，P<0.05）显著降低。辛伐他汀治疗显著抑制脂多糖激活的单核细胞释放O(2)(-)（P<0.0005）、IL-8（P<0.03）和TNF（P<0.02）。与基线相比，辛伐他汀治疗显著抑制单核细胞IL-6释放（P=0.02）。与安慰剂相比，辛伐他汀治疗还显著降低单核细胞核因子-κB p65活性（P<0.01）。
本研究表明，辛伐他汀（20mg/d）对T1DM患者是安全的，并且对血脂和炎症生物标志物有协同益处。这些新发现可能对制定他汀类药物治疗政策指南以预防年轻T1DM患者的血管并发症有启示意义。
