A high fasting plasma insulin concentration predicts type 2 diabetes independent of insulin resistance - Evidence for a pathogenic role of relative hyperinsulinemia
A high fasting plasma insulin concentration predicts type 2 diabetes independent of insulin resistance - Evidence for a pathogenic role of relative hyperinsulinemia
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DOI：
10.2337/diabetes.49.12.2094
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发表时间：
2000-12-01
期刊：
影响因子：
7.7
通讯作者：
Pratley, RE
中科院分区：
文献类型：
--
作者：
Weyer, C;Hanson, RL;Pratley, RE
空腹高胰岛素血症是广泛使用的胰岛素抵抗的替代指标，可预测各种人群中的2型糖尿病，空腹高胰岛素血症是否独立于胰岛素抵抗预测糖尿病尚不清楚。在319皮马印第安人与。正常葡萄糖耐量、空腹血浆胰岛素浓度和胰岛素刺激的葡萄糖处置（M）（高胰岛素钳夹）呈负相关，但在任何给定的M下，存在实质性变化，相对于胰岛素敏感性程度，一些受试者是高胰岛素血症的，而另一些是低胰岛素血症的。在319名受试者中，有262名前瞻性随访了6.4 +/- 3.9年，除了低M和低急性胰岛素反应（AIR）（静脉葡萄糖激发）外，高空腹血浆胰岛素浓度是糖尿病的重要独立预测因子。在319名随访测量M和AIR（5.1 ± 3.9年）的受试者中，161名受试者的相对空腹血浆胰岛素浓度较高可预测糖尿病发作前AIR的下降，但不能预测M的下降。调整后的空腹血浆胰岛素浓度是一种家族性特征（遗传力为0.52），在全基因组扫描中，有证据表明与染色体3q上的一个区域存在连锁（比值分数的对数为1.77），该区域含有编码GLUT 2的基因。这些结果提供了第一个前瞻性的证据，在人类中，空腹高胰岛素血症本身在糖尿病的发病机制中具有主要作用，独立于胰岛素抵抗。改善基础胰岛素分泌过多是否能预防糖尿病仍有待阐明。
Fasting hyperinsulinemia is a widely used surrogate measure of insulin resistance and predicts type 2 diabetes in various populations, whether fasting hyperinsulinemia predicts diabetes independent of insulin resistance is unknown. In 319 Pima Indians with. normal glucose tolerance, fasting plasma insulin concentration and insulin-stimulated glucose disposal (M) (hyperinsulinemic clamp) were inversely related, but at any given M, there was substantial variation, with some subjects being hyperinsulinemic and others being hypoinsulinemic relative to their degree of insulin sensitivity. In 262 of the 319 subjects followed prospectively over 6.4 +/- 3.9 years, a high fasting plasma insulin concentration was a significant independent predictor of diabetes, in addition to low M and low acute insulin response (AIR) (intravenous glucose challenge). In 161 of the 319 subjects with follow-up measurements of M and AIR (5.1 +/- 3.9 years), a high relative fasting plasma insulin concentration predicted a decline in AIR but not in M before the onset of diabetes. The adjusted fasting plasma insulin concentration was a familial trait (heritability of 0.52) and in a genome-wide scan, there was suggestive evidence of linkage (logarithm of odds score 1.77) to a region on chromosome 3q, which harbors the gene encoding GLUT2. These results provide the first prospective evidence in humans that fasting hyperinsulinemia itself has a primary role in the pathogenesis of diabetes, independent of insulin resistance. Whether amelioration of basal insulin hypersecretion will prevent diabetes remains to be elucidated.