Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, University of Colorado at Anschutz (CU-Anschutz), USA; Section of Endocrinology, Department of Pediatrics, School of Medicine, CU-Anschutz, USA.
Biostatistics Center, Milken Institute School of Public Health, George Washington University, Rockville, MD, USA.
J Diabetes Complications. 2024 Jun;38(6):108764. doi: 10.1016/j.jdiacomp.2024.108764. Epub 2024 May 1.
Dysglycemia is a significant risk factor for cognitive impairment. However, which pathophysiologic determinant(s) of dysglycemia, impaired insulin sensitivity (ISens) or the islet β-cell's response (IResp), contribute to poorer cognitive function, independent of dysglycemia is not established. Among 1052 adults with pre-diabetes from the Diabetes Prevention Program Outcomes Study (DPPOS), we investigated the relationship between IResp, ISens and cognitive function.
IResp was estimated by the insulinogenic index (IGI; pmol/mmol) and ISens as 1/fasting insulin from repeated annual oral glucose tolerance tests. The mean IResp and mean ISens were calculated over approximately 12 years of follow-up. Verbal learning (Spanish-English Verbal Learning Test [SEVLT]) and executive function (Digital Symbol Substitution Test [DSST]) were assessed at the end of the follow-up period. Linear regression models were run for each cognitive outcome and were adjusted for dysglycemia and other factors.
Higher IResp was associated with poorer performance on the DSST (-0.69 points per 100 unit increase in IGI, 95 % CI: -1.37, -0.01). ISens was not associated with DSST, nor were IResp or ISens associated with performance on the SEVLT.
These results suggest that a greater β-cell response in people at high risk for type 2 diabetes is associated with poorer executive function, independent of dysglycemia and ISens.
血糖异常是认知障碍的一个重要危险因素。然而，血糖异常的哪些病理生理决定因素——胰岛素敏感性（ISens）或胰岛β细胞的反应（IResp）——在不考虑血糖异常的情况下，与认知功能下降有关，目前尚未确定。在来自糖尿病预防计划结果研究（DPPOS）的 1052 名糖尿病前期成年人中，我们研究了 IResp、ISens 与认知功能之间的关系。
通过胰岛素原指数（IGI；pmol/mmol）和空腹胰岛素的 1/f 来估计 IResp，ISens 是从每年重复的口服葡萄糖耐量试验中得出的。在大约 12 年的随访期间，计算了平均 IResp 和平均 ISens。在随访结束时评估了语言学习（西班牙语-英语语言学习测试[SEVLT]）和执行功能（数字符号替代测试[DSST]）。为每个认知结果运行线性回归模型，并根据血糖异常和其他因素进行调整。
较高的 IResp 与 DSST 上的较差表现相关（IGI 每增加 100 单位，DSST 降低 0.69 分，95%CI：-1.37，-0.01）。ISens 与 DSST 无关，IResp 和 ISens 也与 SEVLT 上的表现无关。
这些结果表明，在 2 型糖尿病高危人群中，β 细胞反应增强与执行功能下降有关，而与血糖异常和 ISens 无关。
