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阿卡波糖抑制餐后高血糖是治疗代谢综合征患者的一种有前景的治疗策略。

Inhibition of postprandial hyperglycemia by acarbose is a promising therapeutic strategy for the treatment of patients with the metabolic syndrome.

作者信息

Yamagishi S, Nakamura K, Takeuchi M

机构信息

Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan.

出版信息

Med Hypotheses. 2005;65(1):152-4. doi: 10.1016/j.mehy.2004.12.008. Epub 2005 Jan 28.

Abstract

The metabolic syndrome is strongly associated with insulin resistance and has been recognized as a cluster of risk factors for cardiovascular diseases such as visceral obesity, hypertension, diabetes, and atherogenic dyslipidemia. Recently, insulin resistance in the absence of overt diabetes or the metabolic syndrome itself has been associated with endothelial dysfunction, one of the initial steps in the process of atherosclerosis. Postprandial hyperglycemia, one of the characteristic features of insulin resistance, induces oxidative stress generation and elicits vascular inflammation and platelet activation, thus being involved in the pathogenesis of atherosclerosis. A recent multicenter, placebo-controlled randomized trial, STOP-NIDDM trial, revealed that acarbose (Glucobay R), an alpha-glucosidase inhibitor, improved postprandial hyperglycemia and subsequently reduced the risk of development of type 2 diabetes in patients with impaired glucose tolerance (IGT). In this study, acarbose treatment was also found to slow the progression of intima-media thickness of the carotid arteries, a surrogate marker for atherosclerosis, and to reduce the incidence of cardiovascular diseases and newly diagnosed hypertension in subjects with IGT. Acarbose significantly reduced body mass index and waist circumference in these patients over 3 years. Furthermore, a meta-analysis of seven long-term studies has also shown that intervention with acarbose prevents myocardial infarction and cardiovascular diseases in type 2 diabetic patients. In this analysis, glycemic control, triglyceride levels, body weight and systolic blood pressure was also significantly improved during acarbose treatment. These observations suggest that prevention of postprandial hyperglycemia by acarbose may be a promising therapeutic strategy for reducing the increased risk for diabetes, hypertension, dyslipidemia, obesity, and cardiovascular diseases in patients with the metabolic syndrome. Acarbose improves postprandial hyperglycemia by delaying the release of glucose from complex carbohydrates in the absence of an increase in insulin secretion. Therefore, we would like to hypothesize here that this improvement in glucose metabolism could be associated with amelioration in insulin sensitivity, thus explaining the above-mentioned beneficial cardiometabolic actions of acarbose. Large clinical trials will provide us with more definite information whether acarbose treatment can improve insulin sensitivity and resultantly reduce the risk of diabetes, hypertension and cardiovascular diseases in patients with the metabolic syndrome.

摘要

代谢综合征与胰岛素抵抗密切相关,并且已被公认为是心血管疾病的一组危险因素,如内脏肥胖、高血压、糖尿病和致动脉粥样硬化性血脂异常。最近,在无明显糖尿病或代谢综合征本身的情况下,胰岛素抵抗已与内皮功能障碍相关,内皮功能障碍是动脉粥样硬化过程中的初始步骤之一。餐后高血糖是胰岛素抵抗的特征之一,可诱导氧化应激产生,并引发血管炎症和血小板活化,从而参与动脉粥样硬化的发病机制。最近一项多中心、安慰剂对照的随机试验——STOP-NIDDM试验表明,α-葡萄糖苷酶抑制剂阿卡波糖(拜糖平®)可改善餐后高血糖,并随后降低糖耐量受损(IGT)患者发生2型糖尿病的风险。在这项研究中,还发现阿卡波糖治疗可减缓颈动脉内膜中层厚度(动脉粥样硬化的替代标志物)的进展,并降低IGT受试者心血管疾病和新诊断高血压的发生率。在3年时间里,阿卡波糖显著降低了这些患者的体重指数和腰围。此外,一项对7项长期研究的荟萃分析也表明,阿卡波糖干预可预防2型糖尿病患者发生心肌梗死和心血管疾病。在此分析中,阿卡波糖治疗期间血糖控制、甘油三酯水平、体重和收缩压也得到了显著改善。这些观察结果表明,通过阿卡波糖预防餐后高血糖可能是一种有前景的治疗策略,可降低代谢综合征患者患糖尿病、高血压、血脂异常、肥胖和心血管疾病的风险。阿卡波糖通过在不增加胰岛素分泌的情况下延迟复合碳水化合物中葡萄糖的释放来改善餐后高血糖。因此,我们在此推测,这种葡萄糖代谢的改善可能与胰岛素敏感性的改善相关,从而解释了阿卡波糖上述有益的心脏代谢作用。大型临床试验将为我们提供更确切的信息,即阿卡波糖治疗是否能改善胰岛素敏感性,并最终降低代谢综合征患者患糖尿病、高血压和心血管疾病的风险。

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