Melander A
Department of Clinical Pharmacology, Lund University, Medical Research Centre, Malmö General Hospital, Sweden.
Diabet Med. 1996 Sep;13(9 Suppl 6):S143-7.
Chronic hyperglycaemia, i.e. impaired glucose tolerance (IGT) and NIDDM, conveys a great risk of macrovascular disease. Both insulin resistance and impaired insulin secretion seem necessary to establish chronic hyperglycaemia, and untreated it appears to promote and worsen both insulin resistance and impaired insulin secretion. The prevention and treatment of chronic hyperglycaemia should include measures directed at both derangements, and the therapeutic goal should be normoglycaemia. As this is rarely achieved by non-pharmacologic treatment alone, addition of oral antidiabetic drugs are often indicated. Their ability to attain euglycaemia is greater the earlier they are employed, but they should never be introduced until after optimization of non-pharmacologic measures. Delayed early insulin response to glucose or a meal always accompanies chronic hyperglycaemia and is not normalized by non-pharmacologic treatment. This justifies the use of insulin-releasing drugs with a rapid onset of action, e.g. the sulphonylurea glipizide. The non-sulphonylureas, repaglinide and A-4166, are even more rapid- and also short-acting, representing a reduced risk of long-lasting, and hence dangerous, hypoglycaemia. Continuous exposure to high concentrations of sulphonylureas may downregulate beta-cell sensitivity. Maximum doses are much lower than previously assumed. The most effective improvers of insulin action seem to be the thiazolidinediones, but they are not yet marketed. Metformin is the only globally available drug for improving insulin action. It is as antihyperglycaemic as sulphonylureas but does not cause hyperinsulinaemia, weight increase or hypoglycaemia. The risk of lactic acidosis can be minimized by avoiding metformin in subjects with renal impairment. Combined treatment with sulphonylurea and metformin can be highly effective even in advanced NIDDM.
慢性高血糖症，即糖耐量受损（IGT）和非胰岛素依赖型糖尿病（NIDDM），会带来患大血管疾病的巨大风险。胰岛素抵抗和胰岛素分泌受损似乎都是导致慢性高血糖症的必要因素，而且未经治疗的慢性高血糖症似乎会促进并加重胰岛素抵抗和胰岛素分泌受损。慢性高血糖症的预防和治疗应包括针对这两种紊乱情况的措施，治疗目标应为血糖正常。由于仅靠非药物治疗很少能达到这一目标，因此常常需要加用口服抗糖尿病药物。尽早使用这些药物，使其达到正常血糖水平的能力就越强，但在优化非药物治疗措施之前绝不应使用。慢性高血糖症总是伴有对葡萄糖或进餐的早期胰岛素反应延迟，且非药物治疗无法使其恢复正常。这就证明了使用起效迅速的胰岛素释放药物是合理的，例如磺酰脲类药物格列吡嗪。非磺酰脲类药物瑞格列奈和A - 4166起效更快且作用时间更短，降低了发生持久且危险的低血糖症的风险。持续暴露于高浓度的磺酰脲类药物可能会下调β细胞敏感性。最大剂量比之前认为的要低得多。胰岛素作用最有效的改善剂似乎是噻唑烷二酮类药物，但它们尚未上市。二甲双胍是唯一全球可用的改善胰岛素作用的药物。它与磺酰脲类药物一样具有降血糖作用，但不会导致高胰岛素血症、体重增加或低血糖症。通过避免在肾功能不全患者中使用二甲双胍，可将乳酸酸中毒的风险降至最低。即使在晚期非胰岛素依赖型糖尿病中，磺酰脲类药物与二甲双胍联合治疗也可能非常有效。
