Siperstein M D
Medical Service, University of California, San Francisco.
Am J Med. 1988 Nov 28;85(5A):119-30. doi: 10.1016/0002-9343(88)90404-4.
As the major cause of disability and death in insulin-dependent diabetes, microangiopathy is obviously of major concern to diabetologists. Unlike macroangiopathy, which can readily be prevented by means that are currently on hand, the origin and treatment of microangiopathy remain far more problematical. The complexity of this lesion is indicated by the findings in this laboratory that hyperglycemia induced by the rodenticide, vacor, can cause microangiopathy independent of genetic diabetes, yet significant microangiopathic lesions can be detected in genetic diabetic patients before the appearance of hyperglycemia. Further, there is now intriguing evidence based both on basement membrane measurements from our laboratory and on clinical studies showing that significant microangiopathy only rarely occurs prior to the onset of puberty. The evidence that control or even normalization of blood glucose levels does not influence the course of established microangiopathy is becoming increasingly convincing. Five prospective, randomized studies over the past five years have shown that strict regulation of glucose has no consistent benefit on, and in some studies may, at least transiently, accelerate, the retinopathy of diabetes. Moreover, the first controlled study of successful pancreatic transplantation to achieve normalization of blood glucose levels has again demonstrated that established retinopathy is neither prevented nor even delayed by normal glucose levels. This review, therefore, emphasizes that, though hyperglycemia is required for clinically significant microangiopathy to occur, clearly other factors, genetic, environmental, or both, must play major roles in determining the course of microangiopathy. It is toward these nonglycemic factors in the development of diabetic microangiopathy that future research should increasingly be directed.
作为胰岛素依赖型糖尿病导致残疾和死亡的主要原因，微血管病变显然是糖尿病专家主要关注的问题。与大血管病变不同，大血管病变可通过现有的方法轻易预防，而微血管病变的起源和治疗仍然困难得多。本实验室的研究结果表明了这种病变的复杂性，即灭鼠剂华法林诱导的高血糖可导致与遗传性糖尿病无关的微血管病变，但在遗传性糖尿病患者出现高血糖之前就能检测到明显的微血管病变。此外，基于我们实验室对基底膜的测量以及临床研究，现在有有趣的证据表明，明显的微血管病变在青春期开始之前很少发生。血糖水平得到控制甚至恢复正常却不影响已确诊的微血管病变进程，这一证据越来越有说服力。过去五年的五项前瞻性随机研究表明，严格控制血糖对糖尿病视网膜病变没有持续的益处，而且在一些研究中，至少在短期内可能会加速糖尿病视网膜病变。此外，首次成功进行胰腺移植以使血糖水平恢复正常的对照研究再次表明，正常的血糖水平既不能预防已确诊的视网膜病变，甚至也不能延缓其发展。因此，本综述强调，虽然临床上明显的微血管病变发生需要高血糖，但显然其他因素，无论是遗传因素、环境因素还是两者兼而有之，在决定微血管病变的进程中必定起主要作用。未来的研究应越来越多地针对糖尿病微血管病变发展过程中的这些非血糖因素。
