基于G-计算的高血压、抑郁在2型糖尿病与认知功能之间的因果多中介分析

Causal mediation analysis with multiple-mediator of hypertension and depression between type 2 diabetes mellitus and cognitive function based on G-computation

目的探究2型糖尿病(T2DM)与认知功能之间的直接因果效应,以及高血压和抑郁在其因果关系中的中介效应。方法选取美国国家健康和营养检查调查(NHANES)数据库2013年至2014年60~80岁研究对象1306例,根据是否患T2DM分为对照组和T2DM组。采用G-计算因果多中介分析方法,分析二分类中介高血压、连续型中介抑郁两变量在T2DM与认知功能间的中介效应,并根据性别进行亚组分析。结果T2DM与动物词语流畅性测试、数字符号替换测试之间直接效应差异均有统计学意义,b和95%CI分别为-0.75(95%CI:-1.45~-0.04)和-4.10(95%CI:-6.02~-2.18)。高血压、抑郁在T2DM暴露与认知功能关系中起到部分中介作用,b和95%CI分别为-0.11(95%CI:-0.21~0.00)和-0.50(95%CI:-0.94~-0.05)。亚组分析结果显示,不同性别的直接、间接效应不同。结论T2DM引起认知功能下降可能由高血压和抑郁介导,性别可能是调节变量,预防、管理及治疗合并症对降低认知功能障碍发生风险有重要作用。

Objective To explore the direct causal effect between type 2 diabetes mellitus(T2DM)and cognitive function,as well as the mediating effect of hypertension and depression in the causal relationship.Methods A total of 1306 participants aged 60 to 80 years were selected from the National Health and Nutrition Examination Survey(NHANES)database for the years 2013-2014 and divided into the control group and T2DM group according to whether they had T2DM.The mediating effects of binary mediator hypertension and continuous mediator depression on the relationship between T2DM and cognitive function was analyzed with G-computation causal multi-mediation,and subgroup analysis was performed according to genders.Results There was a statistically significant direct effect between T2DM and Animal Verbal Fluency Test and Digit Symbol Substitution Test,with b and 95%CI of-0.75(95%CI:-1.45-0.04)and-4.10(95%CI:-6.02-2.18),respectively.Hypertension and depression played a partial mediating role in the relationship between T2DM and cognitive function,and b and 95%CI were-0.11(95%CI:-0.21-0.00)and-0.50(95%CI:-0.94-0.05),respectively.Subgroup analysis showed that the direct and indirect effects were statistically different between genders.Conclusion The cognitive decline induced by T2DM may be mediated by hypertension and depression,and gender may be a moderating variable.Prevention,management and treatment of the complications play an important role in reducing the risk of cognitive dysfunction.