Lancet. 2001 Mar 24;357(9260):905-10.
Atherosclerosis is the most common complication of diabetes. Correction of hyperglycaemia helps to prevent microvascular complications but has little effect on macrovascular disease. Post-hoc analyses of diabetic subpopulations in lipid intervention trials suggest that correction of lipoprotein abnormalities will lead to a decrease in coronary-artery disease. The Diabetes Atherosclerosis Intervention Study (DAIS) was specifically designed to assess the effects of correcting lipoprotein abnormalities on coronary atherosclerosis in type 2 diabetes.
731 men and women with type 2 diabetes were screened by metabolic and angiographic criteria. 418 were randomly assigned micronised fenofibrate (200 mg/day) or placebo for at least 3 years. They were in good glycaemic control (mean haemoglobin A1c 7.5%), had mild lipoprotein abnormalities, typical of type 2 diabetes, and at least one visible coronary lesion. Half had no previous clinical coronary disease. Initial and final angiograms followed a standard protocol and were analysed by a computer-assisted quantitative approach. Missing data for the primary endpoints (minimum lumen diameter, mean segment diameter, and mean percentage stenosis) were imputed. Analyses were by intention to treat.
Total plasma cholesterol, HDL-cholesterol, LDL-cholesterol, and triglyceride concentrations all changed significantly more from baseline in the fenofibrate group (n=207) than in the placebo group (n=211). The fenofibrate group showed a significantly smaller increase in percentage diameter stenosis than the placebo group (mean 2.11 [SE 0.594] vs 3.65 [0.608]%, p=0.02), a significantly smaller decrease in minimum lumen diameter (-0.06 [0.016] vs -0.10 [0.016] mm, p=0.029), and a non-significantly smaller decrease in mean segment diameter (-0.06 [0.017] vs -0.08 [0.018] mm, p=0.171). The trial was not powered to examine clinical endpoints, but there were fewer in the fenofibrate group than the placebo group (38 vs 50).
DAIS suggests that treatment with fenofibrate reduces the angiographic progression of coronary-artery disease in type 2 diabetes. This effect is related, at least partly, to the correction of lipoprotein abnormalities, even those previously judged not to need treatment.
动脉粥样硬化是糖尿病最常见的并发症。纠正高血糖有助于预防微血管并发症，但对大血管疾病影响甚微。脂质干预试验中糖尿病亚组的事后分析表明，纠正脂蛋白异常将导致冠状动脉疾病减少。糖尿病动脉粥样硬化干预研究（DAIS）专门设计用于评估纠正脂蛋白异常对2型糖尿病患者冠状动脉粥样硬化的影响。
根据代谢和血管造影标准对731名2型糖尿病男性和女性进行筛查。418人被随机分配接受微粒化非诺贝特（200毫克/天）或安慰剂治疗至少3年。他们血糖控制良好（平均糖化血红蛋白7.5%），有2型糖尿病典型的轻度脂蛋白异常，且至少有一处可见冠状动脉病变。一半人既往无临床冠心病。初始和最终血管造影遵循标准方案，并采用计算机辅助定量方法进行分析。主要终点（最小管腔直径、平均节段直径和平均狭窄百分比）的缺失数据进行了估算。分析采用意向性分析。
非诺贝特组（n = 207）的总血浆胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇和甘油三酯浓度较基线的变化均显著大于安慰剂组（n = 211）。非诺贝特组的直径狭窄百分比增加显著小于安慰剂组（平均2.11 [标准误0.594] 对3.65 [0.608]%，p = 0.02），最小管腔直径减少显著更小（-0.06 [0.016] 对-0.10 [0.016] 毫米，p = 0.029），平均节段直径减少无显著更小（-0.06 [0.017] 对-0.08 [0.018] 毫米，p = 0.171）。该试验无足够效力检验临床终点，但非诺贝特组的临床终点事件少于安慰剂组（38例对50例）。
DAIS表明，非诺贝特治疗可降低2型糖尿病患者冠状动脉疾病的血管造影进展。这种作用至少部分与脂蛋白异常的纠正有关，即使是那些先前被认为无需治疗的异常。
