Szendroedi Julia, Anderwald Christian, Krssak Martin, Bayerle-Eder Michaela, Esterbauer Harald, Pfeiler Georg, Brehm Attila, Nowotny Peter, Hofer Astrid, Waldhäusl Werner, Roden Michael
Department of Internal Medicine 3, Medical University of Vienna, Vienna, Austria.
Diabetes Care. 2009 Feb;32(2):209-14. doi: 10.2337/dc08-1123. Epub 2008 Oct 28.
Statins may exert pleiotropic effects on insulin action that are still controversial. We assessed effects of high-dose simvastatin therapy on peripheral and hepatic insulin sensitivity, as well as on ectopic lipid deposition in patients with hypercholesterolemia and type 2 diabetes.
We performed a randomized, double-blind, placebo-controlled, single-center study. Twenty patients with type 2 diabetes received 80 mg simvastatin (BMI 29 +/- 4 kg/m2, age 55 +/- 6 years) or placebo (BMI 27 +/- 4 kg/m2, age 58 +/- 8 years) daily for 8 weeks and were compared with 10 healthy humans (control subjects; BMI 27 +/- 4 kg/m2, age 55 +/- 7 years). Euglycemic-hyperinsulinemic clamp tests combined with D-[6,6-d2]glucose infusion were used to assess insulin sensitivity (M) and endogenous glucose production (EGP). 1H magnetic resonance spectroscopy was used to quantify intramyocellular and hepatocellular lipids.
High-dose simvastatin treatment lowered plasma total and LDL cholesterol levels by approximately 33 and approximately 48% (P < 0.005) but did not affect M, intracellular lipid deposition in soleus and tibialis anterior muscles and liver, or basal and insulin-suppressed EGP. In simvastatin-treated patients, changes in LDL cholesterol related negatively to changes in M (r = -0.796, P < 0.01). Changes in fasting free fatty acids (FFAs) related negatively to changes in M (r = -0.840, P < 0.01) and positively to plasma retinol-binding protein-4 (r = 0.782, P = 0.008).
High-dose simvastatin treatment has no direct effects on whole-body or tissue-specific insulin action and ectopic lipid deposition. A reduction in plasma FFAs probably mediates alterations in insulin sensitivity in vivo.
他汀类药物可能对胰岛素作用产生多效性影响，而这一点仍存在争议。我们评估了大剂量辛伐他汀治疗对高胆固醇血症合并2型糖尿病患者外周和肝脏胰岛素敏感性以及异位脂质沉积的影响。
我们进行了一项随机、双盲、安慰剂对照的单中心研究。20例2型糖尿病患者每日服用80 mg辛伐他汀（体重指数29±4 kg/m²，年龄55±6岁）或安慰剂（体重指数27±4 kg/m²，年龄58±8岁），持续8周，并与10名健康人（对照受试者；体重指数27±4 kg/m²，年龄55±7岁）进行比较。采用正常血糖-高胰岛素钳夹试验联合D-[6,6-d2]葡萄糖输注来评估胰岛素敏感性（M）和内源性葡萄糖生成（EGP）。采用氢磁共振波谱法对肌细胞内和肝细胞内脂质进行定量分析。
大剂量辛伐他汀治疗使血浆总胆固醇和低密度脂蛋白胆固醇水平分别降低约33%和约48%（P<0.005），但不影响M、比目鱼肌和胫前肌以及肝脏中的细胞内脂质沉积，也不影响基础和胰岛素抑制的EGP。在辛伐他汀治疗的患者中，低密度脂蛋白胆固醇的变化与M的变化呈负相关（r=-0.796，P<0.01）。空腹游离脂肪酸（FFA）的变化与M的变化呈负相关（r=-0.840，P<0.01），与血浆视黄醇结合蛋白-4呈正相关（r=0.782，P=0.008）。
大剂量辛伐他汀治疗对全身或组织特异性胰岛素作用以及异位脂质沉积无直接影响。血浆FFA的降低可能介导了体内胰岛素敏感性的改变。
