Fegan P G, Shore A C, Mawson D, Tooke J E, MacLeod K M
Clinical Microvascular Research, Peninsula Medical School, Exeter, UK.
Diabet Med. 2005 Dec;22(12):1670-6. doi: 10.1111/j.1464-5491.2005.01719.x.
Abnormalities of microvascular and endothelial function are present in subjects with Type 2 diabetes. Although statin therapy improves cardiovascular risk in diabetes, dyslipidaemia in diabetes may be more responsive to combined statin and fibrate therapy. We examined the effect of cerivastatin and fenofibrate on microvascular function in subjects with Type 2 diabetes with no clinical evidence of cardiovascular disease and near normal lipid levels.
Age-, sex-, lipid- and blood pressure-matched subjects with Type 2 diabetes were randomized in double-blind fashion to one of four treatment groups: group 1 placebo/placebo (n=12), group 2 fenofibrate/placebo (n=10), group 3 cerivastatin/placebo (n=20) and group 4 cerivastatin/fenofibrate (n=11). The subjects were recruited from the Lipid in Diabetes Study. Microvascular function was assessed by skin blood flow response to iontophoresis of acetylcholine and sodium nitroprusside and by skin maximum hyperaemia to local heating. Measurements were carried out at baseline and 3 months later.
Although all lipid parameters improved in groups 2-4 after 3 months' therapy, no difference was detected in skin blood flow to iontophoresis or maximum hyperaemia in any of the groups. Highly sensitive c-reactive protein (Hs-CRP) did not change with therapy.
In conclusion, we were unable to demonstrate any improvement in microvascular endothelial function in non-hyperlipidaemic Type 2 diabetic subjects treated with single or combination lipid-lowering therapy.
2型糖尿病患者存在微血管和内皮功能异常。尽管他汀类药物治疗可改善糖尿病患者的心血管风险,但糖尿病患者的血脂异常可能对他汀类药物与贝特类药物联合治疗反应更佳。我们研究了西立伐他汀和非诺贝特对无心血管疾病临床证据且血脂水平接近正常的2型糖尿病患者微血管功能的影响。
将年龄、性别、血脂和血压匹配的2型糖尿病患者以双盲方式随机分为四个治疗组之一:第1组安慰剂/安慰剂(n = 12),第2组非诺贝特/安慰剂(n = 10),第3组西立伐他汀/安慰剂(n = 20)和第4组西立伐他汀/非诺贝特(n = 11)。这些受试者来自糖尿病血脂研究。通过乙酰胆碱和硝普钠离子导入后皮肤血流反应以及局部加热引起的皮肤最大充血来评估微血管功能。在基线和3个月后进行测量。
尽管治疗3个月后第2 - 4组的所有血脂参数均有所改善,但任何一组中离子导入后皮肤血流或最大充血均未检测到差异。高敏C反应蛋白(Hs-CRP)并未随治疗而改变。
总之,我们未能证明在接受单一或联合降脂治疗的非高脂血症2型糖尿病患者中微血管内皮功能有任何改善。