Influence of apolipoprotein E ε4 genotype on the association of glucose-lipid metabolism disorders with the risk of diabetes-related cognitive impairment
Objective This study investigates the influence of the apolipoprotein E ε4(APOE ε4)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(HbA1c)and blood lipid levels.The single nucleotide polymorphisms rs429358 and rs7412 were analyzed to determine the presence of the APOE ε4 genotype.Stepwise Logistic regression was employed to identify independent risk factors for DCI,and subgroup analyses were performed to evaluate the effect of the APOE ε4 genotype on the relationship between HbA1c 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％C1:1.087-1.257,P＜0.001),elevated triglycerides(OR=1.161,95％CI:1.041-1.294,P=0.007),and being an APOE ε4 carrier(OR=1.638,95％C1:1.115-2.405,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 APOE ε4 carriers(OR=1.408,95％CI:1.060-1.870,P=0.018),but not in non-APOE ε4 carriers(P＞0.05).In contrast,elevated HbA1c was independently associated with a higher risk of DCI in non-APOE ε4 carriers(OR=1.220,95％CI:1.040-1.430,P=0.014),but not in APOE ε4 carriers(P＞0.05).Additionally,elevated triglycerides were independently linked to an increased risk of DCI across the entire sample and within each APOE ε4 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.
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