载脂蛋白Eε4基因型对糖脂代谢障碍与糖尿病相关认知障碍关系的影响

Influence of apolipoprotein Eε4 genotype on the association of glucose-lipid metabolism disorders with the risk of diabetes-related cognitive impairment

目的研究载脂蛋白E(APOE)ε4基因型对糖脂代谢障碍与糖尿病相关认知障碍(DCI)关系的影响。方法病例对照研究设计, 纳入2017年1月至2022年12月于山西医科大学第一医院接受择期手术的2型糖尿病(T2DM)患者891例, 年龄(62.1±13.8)岁, 包括229例DCI患者(病例组)、662例认知正常的患者(对照组), 采集常规临床信息, 以及外周静脉血检验糖化血红蛋白和血脂, 对APOE基因单核苷酸多态性位点rs429358和rs7412做基因分型以确定APOE ε4基因型。使用逐步Logistic回归筛选DCI发生风险的独立影响因素, 使用亚组分析检验APOE ε4基因型对糖化血红蛋白和血脂与DCI发生风险间关联的影响。结果在所有T2DM患者中, 女性(OR=1.915, 95%CI:1.393~2.631, P<0.001)、T2DM病程延长(OR=1.169, 95%CI:1.087~1.257, P<0.001)、高三酰甘油(OR=1.161, 95%CI:1.041~1.294, P=0.007)和APOEε4携带者(OR=1.638, 95%CI:1.115~2.405, P=0.012)是DCI发生的独立风险因素。高水平低密度脂蛋白在APOE ε4携带者中与DCI的发生风险高独立相关(OR=1.408, 95%CI:1.060~1.870, P=0.018), 但在非APOE ε4携带者中与DCI之间未发现独立相关(P>0.05);相反, 高糖化血红蛋白在非APOE ε4携带者中与高DCI风险独立相关(OR=1.220, 95%CI:1.040~1.430, P=0.014), 但在APOE ε4携带者中与DCI之间未发现独立相关(P>0.05)。高三酰甘油在全样本和各APOE ε4等位基因型亚组中均与高DCI风险独立相关。结论 APOE基因型对糖脂代谢障碍与DCI发生风险间的关联有重要影响, 强调了脂代谢障碍和APOE风险基因在DCI发生和发展中的重要性, 对后续DCI相关临床和机制研究有重要的指导意义。

Objective This study investigates the influence of the apolipoprotein Eε4(APOEε4)genotype on the relationship between glucose-lipid metabolism disorders and diabetes-related cognitive impairment(DCI).Methods A case-control study was conducted involving 891 patients with type 2 diabetes mellitus(T2DM)with a mean age of(62.1±13.8)years,all of whom underwent elective surgery at the First Hospital of Shanxi Medical University between January 2017 and December 2022.Among these participants,229 were diagnosed with DCI(case group),while 662 were cognitively normal(control group).Routine clinical information was collected,and peripheral venous blood samples were analyzed for glycated hemoglobin(HbAlc)and blood lipid levels.The single nucleotide polymorphisms rs429358 and rs7412 were analyzed to determine the presence of the APOEε4 genotype.Stepwise Logistic regression was employed to identify independent risk factors for DCI,and subgroup analyses were performed to evaluate the effect of the APOEε4 genotype on the relationship between HbAlc and blood lipid levels in relation to DCI risk.Results Among all patients,female gender(OR=1.915,95%CI:1.393-2.631,P<0.001),longer duration of T2DM(OR=1.169,95%CI:1.087-1.257,P<0.001),elevated triglycerides(OR=1.161,95%CI:1.041-1.294,P=0.007),and being an APOEε4 carrier(OR=1.638,95%CI:1.115-2.405,P=0.012)were identified as independent risk factors for developing DCI.High levels of low-density lipoprotein(LDL)were found to be independently associated with an increased risk of DCI specifically in APOEε4 carriers(OR=1.408,95%CI:1.060-1.870,P=0.018),but not in non-APOEε4 carriers(P>0.05).In contrast,elevated HbAlc was independently associated with a higher risk of DCI in non-APOEε4 carriers(OR=1.220,95%CI:1.040-1.430,P=0.014),but not in APOEε4 carriers(P>0.05).Additionally,elevated triglycerides were independently linked to an increased risk of DCI across the entire sample and within each APOEε4 genotype subgroup.Conclusions The APOE genotype plays a significant role in modulating the relationship between dyslipidemia and the risk of developing DCI.This highlights the critical importance of lipid metabolism disorders and APOE risk genes in both the development and progression of DCI.These findings offer valuable insights for future clinical and mechanistic studies focused on DCI.