空腹血糖升高与认知功能恶化的代谢关联研究  

Study of metabolic association between elevated fasting blood glucose and cognitive deterioration

作　　者：吴丽蓉 陈瑞华 晁筱雯 郭雨槐 孙涛 李梦慈 陈天璐 WU Lirong;CHEN Ruihua;CHAO Xiaowen;GUO Yuhuai;SUN Tao;LI Mengci;CHEN Tianlu(Center for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus,Shanghai Sixth People's Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200233,China;Sample Bank,Shanghai Sixth People's Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200233,China)

机构地区：[1]上海交通大学医学院附属第六人民医院转化医学中心,上海200233 [2]上海交通大学医学院附属第六人民医院样本库,上海200233

出　　处：《上海交通大学学报（医学版）》2024年第2期212-222,共11页Journal of Shanghai Jiao tong University:Medical Science

基　　金：国家自然科学基金(31972935)。

摘　　要：目的·分析探讨空腹血糖(fasting blood glucose,FBG)升高人群中导致认知功能恶化的影响因素和导致认知功能恶化风险变化的代谢线索。方法·从阿尔茨海默病神经影像学计划数据库中下载阿尔茨海默病队列数据,并筛选出具有FBG数据和随访数据的样本,获得其临床资料[包括年龄、性别、身体质量指数、教育程度、载脂蛋白E4(apolipoprotein E4,APOE4)基因型、人种]和代谢指标数据(包括氨基酸、脂肪酸、蛋白质等)。根据受试者的FBG水平和认知障碍阶段诊断,将其分为正常FBG并无/有认知功能恶化组、FBG升高并无/有认知功能恶化组。采用单因素分析、Cox比例风险回归模型、正交偏最小二乘判别分析、Spearman相关性分析对数据进行分析。结果·共纳入1317例具有FBG数据且具有较为完整的临床资料与代谢物数据的受试者,其中FBG正常(>3.9 mmol/L且<6.1 mmol/L)共1153例,FBG升高(≥6.1 mmol/L)共164例。FBG正常的受试者中,275例有认知功能恶化;FBG升高的受试者中,53例有认知功能恶化。基线人口统计学特征分析结果显示,正常FBG组和高FBG组在性别、人种上差异有统计学意义,无认知功能恶化组和有认知功能恶化组在年龄、性别、APOE4基因携带率上差异有统计学意义(均P<0.05)。Cox回归分析表明,认知功能恶化的主要促进因素依次为APOE4基因阳性、FBG升高和年龄增长(HR=2.22,HR=1.38,HR=1.02;均P<0.05)。不同FBG水平下无认知功能恶化和有恶化组的基线代谢指标,以及认知功能恶化前与认知功能恶化后的代谢指标的差异分析结果显示:在认知功能恶化人群中,高密度脂蛋白(high-density lipoproteins,HDL)携带的磷脂在总脂质中的比值显著升高;低密度脂蛋白(low-density lipoprotein,LDL)颗粒浓度及其携带的脂质含量在认知功能恶化后显著升高。相关性分析结果显示,在认知功能恶化人群中,缬氨酸、亮氨酸不仅与FBG水平�Objective·To analyze and explore the influencing factors that lead to cognitive deterioration in individuals with elevated fasting blood glucose(FBG)and the metabolic clues associated with changes in the risk of cognitive deterioration.Methods·Data from the Alzheimer's Disease Neuroimaging Initiative(ADNI)database were downloaded,and the samples with FBG and follow-up data were selected from the database.Clinical information,including age,gender,body mass index,education years,apolipoprotein E4(APOE4)genotype and race,and corresponding metabolic indicator data,including amino acids,fatty acids,proteins and others were obtained.Based on the FBG levels and diagnosis of cognitive impairment stages in Alzheimer's disease,the subjects were categorized into four groups:normal FBG without/with cognitive deterioration,and elevated FBG without/with cognitive deterioration.The univariate analysis method,the Cox proportional hazards model,orthogonal projections to latent structures discriminant analysis(OPLSDA),and Spearman correlation analysis were employed for data analysis.Results·A total of 1317 subjects were included,among which 1153 had normal FBG level(>3.9 mmol/L and<6.1 mmol/L)and 164 had elevated FBG level(≥6.1 mmol/L).In the normal FBG group,275 subjects showed cognitive deterioration,while in the elevated FBG group,53 subjects showed cognitive deterioration.Univariate analysis revealed significant differences in gender and race between the normal FBG and elevated FBG group,and significant differences in age,gender,and APOE4 genotype between the groups with and without cognitive deterioration(all P<0.05).Cox regression analysis indicated that primary influencing factors for cognitive deterioration were APOE4 positivity,elevated FBG,and increasing age in order(HR=2.22,HR=1.38,HR=1.02;all P<0.05).In the analysis of baseline metabolic indicators in the groups without and with cognitive deterioration,as well as metabolic indicators before and after cognitive deterioration at different FBG levels,the results of t

关 键 词：血糖升高 认知障碍 代谢组学 危险因素 脂蛋白 

分 类 号：R589.9[医药卫生—内分泌] R592[医药卫生—内科学]