血糖谱、遗传易感性与慢性肾病风险的前瞻性队列研究  

Prospective cohort study on the glycemic profile,genetic susceptibility,and risk of chronic kidney disease

作　　者：张婷 陈红宇 程盼 赵星 郭冰 吴功华 ZHANG Ting;CHEN Hong-yu;CHENG Pan;ZHAO Xing;GUO Bing;WU Gong-hua(Department of Epidemiology and Health Statistics,West China School of Public Health/West China Fourth Hospital,Sichuan University,Chengdu,Sichuan 610041,China)

机构地区：[1]四川大学华西公共卫生学院/华西第四医院流行病与卫生统计学系,四川成都610041

出　　处：《现代预防医学》2025年第3期385-391,共7页Modern Preventive Medicine

基　　金：国家自然科学基金(82273740,82073667);2022年引导专项四川省配套-主动健康精准预防医学。

摘　　要：目的探究血糖谱与新发慢性肾病(chronic kidney disease,CKD)的纵向关联,以及遗传易感性对这种关联的影响。方法基于英国生物银行(UK Biobank)的基线调查及基因检测数据,使用Cox比例风险模型评估基线糖化血红蛋白(hemoglobin A1c,HbA1c)和血糖状态与新发CKD的相关性,以及遗传易感性在这种关联中的作用。结果本研究共纳入81059名研究对象,其中糖尿病前期和糖尿病患者各占15.2%和6.9%。中位随访时间13.5年期间,共观察到3637例新发CKD。多变量调整模型显示,与血糖正常的参与者相比,2型糖尿病(T2D)和糖尿病前期均增加CKD的发病风险,风险比(hazard ratios,HR)及95%CI分别为2.04(95%CI:1.85~2.25)和1.09(95%CI:1.00~1.18)。在HbA1c低于糖尿病阈值时,可观察到明显的风险梯度;与HbA1c<5.0%相比,HbA1c≥6.6%的参与者CKD风险增大约2倍。血糖状态与遗传风险之间存在显著的乘法交互作用(P interaction<0.001)。在不同遗传风险组中,高血糖均显著增加CKD风险。与低遗传风险且血糖正常的参与者相比,同时患有T2D和高遗传风险参与者的CKD风险最高(HR=6.67,95%CI:5.75~7.74)。结论在所有遗传风险组的人群中,血糖状态均与CKD风险相关。Objective To investigate the longitudinal association between glycemic profile and the incidence of chronic kidney disease(CKD),as well as the impact of genetic susceptibility on this association.Methods Utilizing baseline survey and genetic data from the UK Biobank,Cox proportional hazards models were employed to assess the correlation between baseline hemoglobin A1c(HbA1c)levels and glycemic status with the onset of CKD,along with the role of genetic susceptibility in this relationship.Results A total of 81059 participants were included in this study,with 15.2% classified as prediabetic and 6.9% as diabetic.During a median follow-up period of 13.5 years,3637 new cases of CKD were observed.Multivariable-adjusted models indicated that both type 2 diabetes(T2D)and prediabetes significantly increased the risk of developing CKD compared to participants with normal blood glucose levels,with hazard ratios(HRs)and 95% confidence intervals(CIs)of 2.04(95%CI:1.85-2.25)and 1.09(95%CI:1.00-1.18),respectively.A clear risk gradient was observed when HbA1c was below the diabetes threshold;participants with HbA1c≥6.6% had approximately double the risk of CKD compared to those with HbA1c<5.0%.A significant multiplicative interaction between glycemic status and genetic risk was found(P interaction<0.001).In all genetic risk groups,hyperglycemia significantly increased the risk of CKD.Among participants with high genetic risk,those with both T2D and high genetic risk exhibited the highest CKD risk(HR=6.67,95%CI:5.75-7.74)compared to those with low genetic risk and normal blood glucose.Conclusion Glycemic status is associated with the risk of CKD across all genetic risk groups.

关 键 词：血糖 糖尿病前期 遗传易感性 慢性肾脏疾病 

分 类 号：R692[医药卫生—泌尿科学]