Wolffenbuttel B H, van Haeften T W
Department of Internal Medicine, University Hospital Maastricht, The Netherlands.
Drugs. 1995 Aug;50(2):263-88. doi: 10.2165/00003495-199550020-00006.
It is expected that the number of patients with diabetes mellitus will increase in the near future. The high rate of microvascular and macrovascular complications developing in these patients will place an even higher burden on our healthcare systems. Several pathophysiological factors are involved in the development of complications, among which are hyperglycaemia per se, the consequent formation of advanced glycation end-products (AGEs) and the intracellular accumulation of sorbitol. In addition, hypertension and dyslipidaemia also play an important role, especially in the development of coronary heart disease and stroke. The major therapeutic goals in patients with non-insulin-dependent diabetes mellitus (NIDDM) are to reduce obesity and normalise lipid disturbances and increased blood pressure, in order to improve the well-being of the patient and reduce the risk of the development of late diabetic complications. Often, pharmacological treatment of the hyperglycaemia is necessary, in which case sulphonylureas, metformin, alpha-glucosidase inhibitors such as acarbose, or insulin may be employed. It is believed that medical interventions, by their effect on improving metabolic control, reduce the incidence and severity of diabetic complications, especially when considering the toxic effects of glucose and the accumulation of AGEs as a consequence of raised tissue glucose levels. This concept is also based on extrapolation of the finding of the Diabetes Control and Complications Trial that intensive glycaemic control in IDDM will prevent the progression of at least the microvascular complications like retinopathy and nephropathy. There are, however, no long term studies in NIDDM patients to show that treatment with oral antihyperglycaemic agents helps to postpone or prevent complications. It is expected that the UK Prospective Diabetes Study will show whether better metabolic control, either with oral antihyperglycaemics or with insulin, will indeed improve outcome. Several other studies aiming at specific risk factor intervention (hypertension, hyperlipidaemia, lipid oxidation) in NIDDM patients are currently ongoing.
预计在不久的将来,糖尿病患者的数量将会增加。这些患者中微血管和大血管并发症的高发生率将给我们的医疗系统带来更高的负担。并发症的发生涉及多种病理生理因素,其中包括高血糖本身、由此导致的晚期糖基化终产物(AGEs)的形成以及山梨醇在细胞内的蓄积。此外,高血压和血脂异常也起着重要作用,尤其是在冠心病和中风的发生发展过程中。非胰岛素依赖型糖尿病(NIDDM)患者的主要治疗目标是减轻肥胖、使脂质紊乱和血压升高恢复正常,以改善患者的健康状况并降低晚期糖尿病并发症的发生风险。通常,高血糖的药物治疗是必要的,在这种情况下可使用磺脲类药物、二甲双胍、阿卡波糖等α-葡萄糖苷酶抑制剂或胰岛素。人们认为,医疗干预通过改善代谢控制,可降低糖尿病并发症的发生率和严重程度,特别是考虑到葡萄糖的毒性作用以及组织葡萄糖水平升高导致的AGEs蓄积时。这一概念也是基于糖尿病控制与并发症试验的研究结果推断而来,该试验表明,强化血糖控制可预防IDDM患者至少如视网膜病变和肾病等微血管并发症的进展。然而,目前尚无针对NIDDM患者的长期研究表明口服降糖药治疗有助于延缓或预防并发症。预计英国前瞻性糖尿病研究将表明,无论是使用口服降糖药还是胰岛素进行更好的代谢控制,是否真的能改善预后。目前,其他几项针对NIDDM患者特定危险因素干预(高血压、高脂血症、脂质氧化)的研究正在进行中。