Aulinger Benedikt A, Vahl Torsten P, Prigeon Ron L, D'Alessio David A, Elder Deborah A
Department of Medicine, University of Cincinnati, Cincinnati, Ohio; Department of Internal Medicine II, Ludwig-Maximillian's University, Munich, Germany;
Department of Medicine, University of Cincinnati, Cincinnati, Ohio; Department of Medicine, Columbia University, New York, New York;
Am J Physiol Endocrinol Metab. 2016 May 1;310(9):E774-81. doi: 10.1152/ajpendo.00496.2015. Epub 2016 Mar 15.
The incretin effect reflects the actions of enteral stimuli to promote prandial insulin secretion. Impairment of this measure has been proposed as an early marker of β-cell dysfunction and described in T2D, IGT, and even obesity without IGT. We sought to determine the effects of obesity and diabetes on the incretin effect in young subjects with short exposures to metabolic abnormalities and a few other confounding medical conditions. Subjects with T2D (n = 10; 18.0 ± 0.4 yr) or NGT, either obese (n = 11; 17.7 ± 0.4 yr) or lean (n = 8; 26.5 ± 2.3 yr), had OGTT and iso-iv. The incretin effect was calculated as the difference in insulin secretion during these tests and was decreased ∼50% in both the NGT-Ob and T2D subjects relative to the NGT-Ln group. The T2D group had impaired glucose tolerance and insulin secretion during the OGTT, whereas the lean and obese NGT subjects had comparable glucose excursions and β-cell function. During the iso-iv test, the NGT-Ob subjects had significantly greater insulin secretion than the NGT-Ln and T2D groups. These findings demonstrate that in young subjects with early, well-controlled T2D the incretin effect is reduced, similar to what has been described in diabetic adults. The lower incretin effect calculated for the obese subjects with NGT is driven by a disproportionately greater insulin response to iv glucose and does not affect postprandial glucose regulation. These findings confirm that the incretin effect is an early marker of impaired insulin secretion in persons with abnormal glucose tolerance but suggest that in obese subjects with NGT the incretin effect calculation can be confounded by exaggerated insulin secretion to iv glucose.
肠促胰岛素效应反映了肠内刺激促进餐时胰岛素分泌的作用。这种作用受损被认为是β细胞功能障碍的早期标志物，并在2型糖尿病、糖耐量受损（IGT）甚至无IGT的肥胖症中有所描述。我们试图确定肥胖和糖尿病对年轻受试者肠促胰岛素效应的影响，这些受试者短期暴露于代谢异常及其他一些混杂的医学状况。患有2型糖尿病（n = 10；18.0 ± 0.4岁）或糖耐量正常（NGT）的受试者，包括肥胖者（n = 11；17.7 ± 0.4岁）或瘦者（n = 8；26.5 ± 2.3岁），进行了口服葡萄糖耐量试验（OGTT）和静脉注射葡萄糖试验（iso - iv）。肠促胰岛素效应通过这些试验期间胰岛素分泌的差异来计算，相对于NGT - 瘦组，NGT - 肥胖组和2型糖尿病组的肠促胰岛素效应均降低了约50%。2型糖尿病组在OGTT期间糖耐量和胰岛素分泌受损，而瘦的和肥胖的NGT受试者有相当的血糖波动和β细胞功能。在静脉注射葡萄糖试验中，NGT - 肥胖组受试者的胰岛素分泌显著高于NGT - 瘦组和2型糖尿病组。这些发现表明，在患有早期、控制良好的2型糖尿病的年轻受试者中，肠促胰岛素效应降低，这与糖尿病成年人中所描述的情况相似。NGT肥胖受试者较低的肠促胰岛素效应是由对静脉注射葡萄糖不成比例的更大胰岛素反应所驱动的，并且不影响餐后血糖调节。这些发现证实，肠促胰岛素效应是糖耐量异常者胰岛素分泌受损的早期标志物，但表明在NGT肥胖受试者中，肠促胰岛素效应的计算可能会因对静脉注射葡萄糖的胰岛素分泌过度而混淆。
