Abdella N A
Department of Medicine, Faculty of Medicine, Kuwait University, Kuwait.
Med Princ Pract. 2002;11 Suppl 2:69-74. doi: 10.1159/000066410.
A global epidemic of type 2 diabetes exists and in the near future it may be closely associated with an epidemic of cardiovascular disease. Since the diabetic population is at risk of developing cardiovascular disease, diabetes management should target tight glycaemic control. Two controversial issues in the management of diabetics with coronary heart disease (CHD) are discussed in this review. Firstly, exogenous insulin administration and increased risk of cardiovascular disease, and, secondly, the effect of sulphonylurea treatment on potassium ATP channels and risk of myocardial ischaemia. The consensus of opinion is that high circulating serum insulin level is simply a marker of an insulin-resistant state and therefore does not have a direct role in the pathogenesis of atherosclerosis in diabetic patients. However, overwhelming evidence exists for the linear association between worsening glycaemic control and increased risk for coronary heart disease. The United Kingdom Prospective Diabetes Study reported intensive blood glucose control decreased the risk of myocardial infarction by 16%. The benefits of tight glycaemic control outweighs the theoretical concept of hyperinsulinaemia being atherogenic. Safety concerns about sulphonylureas date back to 1970. The mechanism of action of sulphonylureas by closure of potassium ATP channels identified in pancreatic beta cells, cardiomyocytes and vascular smooth muscle cells caused great concern about safety because of the risk of developing myocardial ischaemia. Brief episodes of cardiac ischaemia render the heart more resistant to subsequent ischaemic events, this phenomenon is called 'ischaemic preconditioning'. Activation of potassium ATP channels completely mimicked the preconditioning phenomena; moreover, blocking these channels with some of the sulphonylurea compounds abolished this protective effect. The concept of selectivity of sulphonylurea compounds therefore emerged and the choice of drug should be based on this fact. Every compound should be studied individually for its efficacy and safety vis-à-vis the relevant end points for type 2 diabetes, i.e. cardiovascular morbidity and mortality.
2型糖尿病在全球流行，且在不久的将来可能与心血管疾病的流行密切相关。由于糖尿病患者有发生心血管疾病的风险，糖尿病管理应以严格控制血糖为目标。本文综述了冠心病（CHD）糖尿病患者管理中的两个有争议的问题。首先，外源性胰岛素的使用与心血管疾病风险增加，其次，磺脲类药物治疗对钾离子ATP通道的影响以及心肌缺血风险。目前的共识是，循环血清胰岛素水平升高仅仅是胰岛素抵抗状态的一个标志，因此在糖尿病患者动脉粥样硬化的发病机制中没有直接作用。然而，有大量证据表明血糖控制恶化与冠心病风险增加之间存在线性关联。英国前瞻性糖尿病研究报告称，强化血糖控制可使心肌梗死风险降低16%。严格控制血糖的益处超过了高胰岛素血症具有致动脉粥样硬化作用这一理论概念。对磺脲类药物的安全担忧可追溯到1970年。磺脲类药物通过关闭胰腺β细胞、心肌细胞和血管平滑肌细胞中的钾离子ATP通道发挥作用，由于存在发生心肌缺血的风险，这引起了人们对安全性的极大关注。短暂的心脏缺血发作可使心脏对随后的缺血事件更具抵抗力，这种现象称为“缺血预处理”。钾离子ATP通道的激活完全模拟了预处理现象；此外，用一些磺脲类化合物阻断这些通道会消除这种保护作用。因此出现了磺脲类化合物选择性的概念，药物的选择应基于这一事实。每种化合物都应针对2型糖尿病的相关终点，即心血管发病率和死亡率，单独研究其疗效和安全性。
