Dogra G K, Watts G F, Chan D C, Stanton K
School of Medicine and Pharmacology, Royal Perth Hospital Unit, Western Australian Heart Research Institute, University of Western Australia, Perth, Western Australia.
Diabet Med. 2005 Mar;22(3):239-42. doi: 10.1111/j.1464-5491.2004.01382.x.
Type 1 diabetes mellitus patients with microalbuminuria have endothelial dysfunction associated with the degree of albuminuria but not with LDL-cholesterol levels. Lipid-lowering agents such as statins may still be of benefit as they can correct endothelial dysfunction by both lipid and non-lipid mechanisms. We therefore examined the effects of atorvastatin on brachial artery endothelial dysfunction in these patients.
In a double-blind, randomized crossover study, 16 Type 1 diabetes mellitus patients with microalbuminuria received 6 weeks of atorvastatin 40 mg/day or placebo, separated by a 4-week washout. Brachial artery, endothelium-dependent, flow-mediated dilatation (FMD) and endothelium-independent, glyceryl trinitrate-mediated dilatation (GTNMD) were measured.
Compared with placebo, atorvastatin produced a significant decrease in apolipoprotein B (34.2%), LDL-cholesterol (44.1%) (all P < 0.001), and oxidized-LDL (35.7%, P = 0.03). There was a non-significant increase in plasma cGMP (P = 0.13) on atorvastatin. FMD and GTNMD increased significantly on atorvastatin (FMD: atorvastatin +1.8 +/- 0.4%; placebo +0.2 +/- 0.4%, P = 0.007); (GTNMD: atorvastatin +1.3 +/- 0.9%; placebo -1.2 +/- 0.6%, P = 0.04). An increase in cGMP was independently correlated with an increase in FMD on atorvastatin (adjusted (R2) 0.41, P = 0.02).
Atorvastatin improves endothelium-dependent and independent vasodilator function of the brachial artery in Type 1 diabetes mellitus patients with microalbuminuria. This may relate to pleiotropic effects of statins, in particular reduced oxidative stress and increased availability of nitric oxide.
1型糖尿病伴微量白蛋白尿患者存在内皮功能障碍，且与白蛋白尿程度相关，但与低密度脂蛋白胆固醇水平无关。他汀类等降脂药物可能仍有益处，因为它们可通过脂质和非脂质机制纠正内皮功能障碍。因此，我们研究了阿托伐他汀对这些患者肱动脉内皮功能障碍的影响。
在一项双盲、随机交叉研究中，16例1型糖尿病伴微量白蛋白尿患者接受为期6周的阿托伐他汀40mg/天治疗或安慰剂治疗，中间间隔4周的洗脱期。测量肱动脉内皮依赖性血流介导的舒张功能（FMD）和内皮非依赖性硝酸甘油介导的舒张功能（GTNMD）。
与安慰剂相比，阿托伐他汀使载脂蛋白B显著降低（34.2%）、低密度脂蛋白胆固醇显著降低（44.1%）（均P<0.001），氧化型低密度脂蛋白降低（35.7%，P=0.03）。阿托伐他汀治疗后血浆环磷酸鸟苷（cGMP）有非显著性升高（P=0.13）。阿托伐他汀治疗后FMD和GTNMD显著增加（FMD：阿托伐他汀组增加1.8±0.4%；安慰剂组增加0.2±0.4%，P=0.007）；（GTNMD：阿托伐他汀组增加1.3±0.9%；安慰剂组降低1.2±0.6%，P=0.04）。阿托伐他汀治疗后cGMP升高与FMD增加独立相关（校正R2 0.41，P=0.02）。
阿托伐他汀可改善1型糖尿病伴微量白蛋白尿患者肱动脉的内皮依赖性和非依赖性血管舒张功能。这可能与他汀类药物的多效性有关，尤其是氧化应激降低和一氧化氮可用性增加。
