The natural history of insulin secretory dysfunction and insulin resistance in the pathogenesis of type 2 diabetes mellitus
The natural history of insulin secretory dysfunction and insulin resistance in the pathogenesis of type 2 diabetes mellitus
复制标题
DOI：
10.1172/jci7231
复制
发表时间：
1999-09-01
影响因子：
15.9
通讯作者：
Pratley, RE
中科院分区：
文献类型：
--
作者：
Weyer, C;Bogardus, C;Pratley, RE
2型糖尿病的发病机制涉及胰岛素作用、胰岛素分泌和内源性葡萄糖输出（EGO）的异常。然而，由于缺乏详细的纵向研究，这些异常发生的顺序及其对糖耐量恶化的相对贡献仍不清楚。我们纵向测量了17名皮马印第安人的胰岛素作用、胰岛素分泌和EGO，这些人的糖耐量在5.1 +/- 1.4年内从正常（NGT）到受损（IGT）再到糖尿病。从NGT到IGT的转变与体重增加、胰岛素刺激的葡萄糖处置下降和静脉注射葡萄糖的急性胰岛素分泌反应（AIR）下降有关，但EGO没有变化。从IGT到糖尿病的进展伴随着体重的进一步增加，胰岛素刺激的葡萄糖处理和AIR的进一步减少，以及基础EGO的增加。31名在相同时间内保持NGT的受试者体重也增加了，但他们的AIR随着胰岛素刺激的葡萄糖处理的减少而增加。因此，胰岛素分泌和胰岛素作用的缺陷在糖尿病发病早期就出现了。预防糖尿病的干预应针对这两种异常。
The pathogenesis of type 2 diabetes involves abnormalities in insulin action, insulin secretion, and endogenous glucose output (EGO). However, the sequence with which these abnormalities develop and their relative contributions to the deterioration in glucose tolerance remain unclear in the absence of a detailed longitudinal study. We measured insulin action, insulin secretion, and EGO longitudinally in 17 Pima Indians, in whom glucose tolerance deteriorated from normal (NGT) to impaired (IGT) to diabetic over 5.1 +/- 1.4 years. Transition from NGT to IGT was associated with an increase in body weight, a decline in insulin-stimulated glucose disposal, and a decline in the acute insulin secretory response (AIR) to intravenous glucose, but no change in EGO. Progression from IGT to diabetes was accompanied by a further increase in bodyweight, further decreases in insulin-stimulated glucose disposal and AIR, and an increase in basal EGO. Thirty-one subjects who retained NGT over a similar period also gained weight, but their AIR increased with decreasing insulin-stimulated glucose disposal. Thus, defects in insulin secretion and insulin action occur early in the pathogenesis of diabetes. Intervention to prevent diabetes should target both abnormalities.