Kahn S E
University of Washington, Seattle VA Puget Sound Health Care System, Seattle, Washington 98108, USA.
Am J Med. 2000 Apr 17;108 Suppl 6a:2S-8S. doi: 10.1016/s0002-9343(00)00336-3.
beta-cell dysfunction and insulin resistance are two central, interrelated defects in the pathophysiology of type 2 diabetes. By the time a patient's hyperglycemia is recognized, disruption of the normal relationship between beta-cell function and insulin sensitivity is already well established. The pathophysiology and progression of defects in glucose metabolism from normal glucose tolerance to impaired glucose tolerance to frank type 2 diabetes have been studied extensively. Insulin sensitivity has wide intersubject variability, and many individuals at risk for type 2 diabetes are insulin resistant. beta-cell changes in patients with type 2 diabetes include defects in insulin secretion, proinsulin conversion to insulin, and amyloid deposition in the islet. Studies in several ethnic groups have established that the progression from normal glucose tolerance to frank type 2 diabetes results from a gradual deterioration in beta-cell function in the presence of insulin resistance. Furthermore, the recently completed landmark United Kingdom Prospective Diabetes Study demonstrated that type 2 diabetes is a progressive disease and that this progression is due to declining beta-cell function.
β细胞功能障碍和胰岛素抵抗是2型糖尿病病理生理学中的两个核心且相互关联的缺陷。在患者的高血糖被识别出来时，β细胞功能与胰岛素敏感性之间的正常关系已遭到破坏。从正常糖耐受到糖耐量受损再到明显的2型糖尿病，葡萄糖代谢缺陷的病理生理学及进展已得到广泛研究。胰岛素敏感性在个体间存在很大差异，许多有2型糖尿病风险的个体存在胰岛素抵抗。2型糖尿病患者的β细胞变化包括胰岛素分泌缺陷、胰岛素原向胰岛素的转化缺陷以及胰岛淀粉样沉积。对多个种族群体的研究表明，从正常糖耐量发展到明显的2型糖尿病是在存在胰岛素抵抗的情况下β细胞功能逐渐恶化的结果。此外，最近完成的具有里程碑意义的英国前瞻性糖尿病研究表明，2型糖尿病是一种进行性疾病，这种进展是由于β细胞功能下降所致。
