Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, U.K.
Diabetes. 2022 Oct 1;71(10):2222-2232. doi: 10.2337/db21-0905.
We conducted a Mendelian randomization analysis to differentiate associations of four glycemic indicators with a broad range of atherosclerotic and thrombotic diseases. Independent genetic variants associated with fasting glucose (FG), 2 h glucose after an oral glucose challenge (2hGlu), fasting insulin (FI), and glycated hemoglobin (HbA1c) at the genome-wide significance threshold were used as instrumental variables. Summary-level data for 12 atherosclerotic and 4 thrombotic outcomes were obtained from large genetic consortia and the FinnGen and UK Biobank studies. Higher levels of genetically predicted glycemic traits were consistently associated with increased risk of coronary atherosclerosis-related diseases and symptoms. Genetically predicted glycemic traits except HbA1c showed positive associations with peripheral artery disease risk. Genetically predicted FI levels were positively associated with risk of ischemic stroke and chronic kidney disease. Genetically predicted FG and 2hGlu were positively associated with risk of large artery stroke. Genetically predicted 2hGlu levels showed positive associations with risk of small vessel stroke. Higher levels of genetically predicted glycemic traits were not associated with increased risk of thrombotic outcomes. Most associations for genetically predicted levels of 2hGlu and FI remained after adjustment for other glycemic traits. Increase in glycemic status appears to increase risks of coronary and peripheral artery atherosclerosis but not thrombosis.
我们进行了孟德尔随机化分析，以区分四种血糖指标与广泛的动脉粥样硬化和血栓形成疾病的关联。用于作为工具变量的是与空腹血糖（FG）、口服葡萄糖耐量试验后 2 小时血糖（2hGlu）、空腹胰岛素（FI）和糖化血红蛋白（HbA1c）相关的全基因组显著阈值的独立遗传变异。从大型遗传联盟以及 FinnGen 和 UK Biobank 研究中获得了 12 种动脉粥样硬化和 4 种血栓形成结局的汇总水平数据。遗传预测的血糖特征水平与冠状动脉粥样硬化相关疾病和症状的风险增加呈一致相关性。除 HbA1c 外，遗传预测的血糖特征与外周动脉疾病风险呈正相关。遗传预测的 FI 水平与缺血性中风和慢性肾脏病的风险呈正相关。遗传预测的 FG 和 2hGlu 与大动脉中风风险呈正相关。遗传预测的 2hGlu 水平与小血管中风风险呈正相关。遗传预测的血糖特征水平升高与血栓形成结局的风险增加无关。调整其他血糖特征后，遗传预测的 2hGlu 和 FI 水平的大多数关联仍然存在。血糖状况的升高似乎会增加冠状动脉和外周动脉粥样硬化的风险，但不会增加血栓形成的风险。
