Acarbose slows progression of intima-media thickness of the carotid arteries in subjects with impaired glucose tolerance. (STOP-NIDDM)

Hanefeld M， Chiasson JL， Koehler C， Henkel E， Schaper F， Temelkova-Kurktschiev T. Centre for Clinical Studies， Dresden Technical University， Dresden， Germany. hanefeld@gwt-tud.de

BACKGROUND AND PURPOSE: Impaired glucose tolerance (IGT)-a prediabetic state-is an important risk factor for atherosclerosis. Acarbose， an alpha-glucosidase inhibitor， was shown in the placebo-controlled prospective study to prevent noninsulin-dependent diabetes mellitus (STOP-NIDDM) trial to reduce the risk of diabetes by 36% in IGT subjects. This article reports on a placebo-controlled subgroup analysis of the STOP-NIDDM study to examine the efficacy of acarbose to slow progression of intima-media thickness (IMT) in subjects with IGT.

METHODS: One hundred thirty-two IGT subjects were randomized to placebo (n=66) or acarbose (n=66) 100 mg 3 times daily; the study duration was at least 3 years， mean follow-up time 3.9 (SD 0.6) years. Carotid IMT was determined at study entry and the end of the trial. The intent-to-treat analysis included 56 subjects in the acarbose and 59 in the control group who had a baseline and endpoint measurement.

RESULTS: A significant reduction of the progression of IMT(mean) was observed in the acarbose group versus placebo. After an average time of 3.9 years， IMT(mean) increased by 0.02 (0.07) mm in the acarbose group versus 0.05 (0.06) mm in the placebo group (P=0.027). The annual increase of IMT(mean) was reduced by approximately 50% in the acarbose group versus placebo. Multiple linear regression revealed IMT progression as significantly related to acarbose intake.

CONCLUSIONS: Acarbose slows progression of IMT in IGT subjects， a high-risk population for diabetes and atherosclerosis. This is the first placebo-controlled prospective subgroup analysis， demonstrating that counterbalancing of postprandial hyperglycemia may be vasoprotective.

Stroke. 2004 May;35(5):1073-8.

背景和目的：糖耐量异常（IGT）作为糖尿病的前期状态，是动脉粥样硬化的重要危险 因素.预防胰岛素非依赖型糖尿病的安慰剂对照前瞻性试验 (STOP-NIDDM trial)中，阿卡波糖（Acarbose）作为a糖苷酶抑制剂，能够使IGT患者出现糖尿病的危险性下降36%.本文报告了STOP-NIDDM试验 中安慰剂对照的亚组分析，测定阿卡波糖对延缓IGT患者颈动脉内中膜厚度(intima-media thickness， IMT)进展的作用.

方法：132例糖耐量异常患者随机分成安慰剂对照组（n=66）和阿卡波糖治疗组（n=66， 100mg  3次/日）.试验为期3年，平均随诊时间3.9（SD 0.6）年.在进入试验和试验结束时分别测定颈动脉的IMT.意向性治疗分析（intent-to-treatment analysis）的对象包括阿卡波糖组的56位患者和对照组的59位患者，他们在试验前后都测定了IMT.

结果：阿卡波糖组平均IMT的进展比对照组明显减缓.经过平均3.9年的观察，阿卡波糖组IMTmean 增加0.02(0.07)mm，而对照组增加0.05 (0.06)mm，P=0.027.阿卡波糖组平均每年增加的IMTmean比对照组下降了约50%.多参线性回归分析显示，IMT进展延缓与阿卡波糖治 疗有显著相关性.

结论：IGT患者是糖尿病和动脉粥样硬化的高危人群，阿卡波糖能够减缓IGT患者颈动脉IMT的进展.本实验是第一个安慰剂对照前瞻性亚组分析，结果表明，纠正餐后高血糖可能会带来血管保护作用.