Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
China National Clinical Research Center for Neurological Diseases, Beijing, China.
Aging (Albany NY). 2020 Nov 16;12(22):22688-22699. doi: 10.18632/aging.103887.
Previous observational studies have reported an association between impaired glucose metabolism and Alzheimer's disease. This study aimed to examine the causal association of glycemic traits with Alzheimer's disease. We used a two-sample Mendelian randomization approach to evaluate the causal effect of six glycemic traits (type 2 diabetes, fasting glucose, fasting insulin, hemoglobin A1c, homeostasis model assessment- insulin resistance and HOMA-β-cell function) on Alzheimer's disease. Summary data on the association of single nucleotide polymorphisms with these glycemic traits were obtained from genome-wide association studies of the DIAbetes Genetics Replication And Meta-analysis and Meta-Analyses of Glucose and Insulin-related traits Consortium. Summary data on the association of single nucleotide polymorphisms with Alzheimer's disease were obtained from the International Genomics of Alzheimer's Project. The Mendelian randomization analysis showed that 1-standard deviation higher fasting glucose and lower HOMA-β-cell function (indicating pancreatic β-cell dysfunction) were causally associated with a substantial increase in risk of Alzheimer's disease (odds ratio=1.33, 95% confidence interval: 1.04-1.68, p=0.02; odds ratio=1.92, 95% confidence interval: 1.15-3.21, p=0.01). However, no significant association was observed for other glycemic traits. This Mendelian randomization analysis provides evidence of causal associations between glycemic traits, especially high fasting glucose and pancreatic β-cell dysfunction, and high risk of Alzheimer's disease.
先前的观察性研究报告称，葡萄糖代谢受损与阿尔茨海默病之间存在关联。本研究旨在检验血糖特征与阿尔茨海默病之间的因果关系。我们使用两样本孟德尔随机化方法来评估 6 种血糖特征（2 型糖尿病、空腹血糖、空腹胰岛素、糖化血红蛋白、稳态模型评估-胰岛素抵抗和 HOMA-β 细胞功能）与阿尔茨海默病的因果关系。单核苷酸多态性与这些血糖特征关联的汇总数据来自糖尿病遗传学复制和代谢分析以及血糖和胰岛素相关特征荟萃分析联盟的全基因组关联研究。单核苷酸多态性与阿尔茨海默病关联的汇总数据来自国际阿尔茨海默病基因组学项目。孟德尔随机化分析表明，空腹血糖升高 1 个标准差和 HOMA-β 细胞功能降低（提示胰岛β细胞功能障碍）与阿尔茨海默病风险显著增加相关（比值比=1.33，95%置信区间：1.04-1.68，p=0.02；比值比=1.92，95%置信区间：1.15-3.21，p=0.01）。然而，其他血糖特征与阿尔茨海默病之间没有显著关联。这项孟德尔随机化分析提供了证据，表明血糖特征，尤其是空腹血糖升高和胰岛β细胞功能障碍与阿尔茨海默病高风险之间存在因果关系。
