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

doi:10.6040/j.issn.1671-7554.0.2023.0647

摘要/Abstract

摘要： 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1 306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。

关键词: G-计算, 因果多中介分析, 2型糖尿病, 认知功能, 高血压, 抑郁症

Abstract: 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 1 306 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.

Key words: G-computation, Causal mediation analysis with multiple mediators, Type 2 diabetes mellitus, Cognitive function, Hypertension, Depression

中图分类号:

R587.1

韩梅,孟维静,陶子琨,杨希,徐雅琪,穆华夏,卜伟晓,王素珍,石福艳. 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[J]. 山东大学学报 (医学版), 2023, 61(10): 101-108.

HAN Mei, MENG Weijing, TAO Zikun, YANG Xi, XU Yaqi, MU Huaxia, BU Weixiao, WANG Suzhen, SHI Fuyan. Causal mediation analysis with multiple-mediator of hypertension and depression between type 2 diabetes mellitus and cognitive function based on G-computation[J]. Journal of Shandong University (Health Sciences), 2023, 61(10): 101-108.

参考文献

[1] Zhang JY, Chen CX, Hua SZ, et al. An updated meta-analysis of cohort studies: diabetes and risk of Alzheimers disease[J]. Diabetes Res Clin Pract, 2017, 124: 41-47. doi:10.1016/j.diabres.2016.10.024.
[2] Biessels GJ, Despa F. Cognitive decline and dementia in diabetes mellitus: mechanisms and clinical implications[J]. Nat Rev Endocrinol, 2018, 14(10): 591-604.
[3] Chatterjee S, Peters SA, Woodward M, et al. Type 2 diabetes as a risk factor for dementia in women compared with men: a pooled analysis of 2.3 million people comprising more than 100,000 cases of dementia[J]. Diabetes Care, 2016, 39(2): 300-307.
[4] 孔令磷, 赵慧敏, 刘玥婷, 等. 社区老年2型糖尿病患者认知衰弱现状及影响因素[J]. 护理学杂志, 2020, 35(7): 89-92. KONG Linglin, ZHAO Huimin, LIU Yueting, et al. Cognitive frailty and its influencing factors among the elderly with type 2 diabetes in community[J]. Journal of Nursing Science, 2020, 35(7): 89-92.
[5] 李修英, 杨湘英, 吴清清, 等. 杭州市社区老年2型糖尿病患者认知衰弱相关因素分析[J]. 中华全科医学, 2022, 20(2): 274-277. LI Xiuying, YANG Xiangying, WU Qingqing, et al. Analysis of related factors of cognitive decline in elderly patients with type 2 diabetes in Hangzhou community[J]. Chinese Journal of General Practice, 2022, 20(2): 274-277.
[6] 刘泳秀, 韩婷, 余莉, 等. 老年2型糖尿病患者认知衰弱现状及影响因素研究[J]. 中国慢性病预防与控制, 2021, 29(6): 426-431. LIU Yongxiu, HAN Ting, YU Li, et al. Cognitive frailty and influencing factors in seniors with type 2 diabetes mellitus[J]. Chinese Journal of Prevention and Control of Chronic Diseases, 2021, 29(6): 426-431.
[7] Pavlou DI, Paschou SA, Anagnostis P, et al. Hypertension in patients with type 2 diabetes mellitus: targets and management[J]. Maturitas, 2018, 112: 71-77. doi: 10.1016/j.maturitas.2018.03.013.
[8] Nilsson PM, Cederholm J, Zethelius BR, et al. Trends in blood pressure control in patients with type 2 diabetes: data from the Swedish National Diabetes Register(NDR)[J]. Blood Press, 2011, 20(6): 348-354.
[9] van Sloten TT, Sedaghat S, Carnethon MR, et al. Cerebral microvascular complications of type 2 diabetes: stroke, cognitive dysfunction, and depression[J]. Lancet Diabetes Endocrinol, 2020, 8(4): 325-336.
[10] Perrin NE, Davies MJ, Robertson N, et al. The prevalence of diabetes-specific emotional distress in people withType 2 diabetes: a systematic review and meta-analysis[J]. Diabet Med, 2017, 34(11): 1508-1520.
[11] Papelbaum M, Moreira RO, Coutinho W, et al. Depression, glycemic control and type 2 diabetes[J]. Diabetol Metab Syndr, 2011, 3(1): 26.
[12] Demakakos P, Muniz-Terrera G, Nouwen A. Type 2 diabetes, depressive symptoms and trajectories of cognitive decline in a national sample of community-dwellers: a prospective cohort study[J]. PLoS One, 2017, 12(4): e0175827. doi:10.1371/journal.pone.0175827.
[13] Gottesman RF, Schneider AL, Albert M, et al. Midlife hypertension and 20-year cognitive change: the atherosclerosis risk in communities neurocognitive study[J]. JAMA Neurol, 2014, 71(10): 1218-1227.
[14] Johar H, Schaefer A, Su TT. Depressive symptoms mediate the longitudinal association between diabetes and subjective cognitive decline. Findings from a semirural multi-ethnic older population in Malaysia[J]. Prev Med, 2023, 167:107390. doi:10.1016/j.ypmed.2022.107390.
[15] Robins J. A new approach to causal inference in mortality studies with a sustained exposure period-application to control of the healthy worker survivor effect[J]. Computers & Mathematics with Applications, 1987, 14(9-12): 923-945.
[16] Taguri M, Featherstone J, Cheng J. Causal mediation analysis with multiple causally non-ordered mediators[J]. Stat Methods Med Res, 2018, 27(1): 3-19.
[17] 李文钊. 因果推理中的潜在结果模型: 起源、逻辑与意蕴[J]. 公共行政评论, 2018, 11(1): 124-149,221-222. LI Wenzhao. The potential outcomes model in the causal inference: origins, logics and implications[J]. Journal of Public Administration, 2018, 11(1): 124-149, 221-222.
[18] Wang AL, Arah OA. G-computation demonstration in causal mediation analysis[J]. Eur J Epidemiol, 2015, 30(10): 1119-1127.
[19] Wu Y, Ding Y, Tanaka Y,et al. Risk factors contributing to type 2 diabetes and recent advances in the treatment and prevention[J]. Int J Med Sci, 2014, 11(11): 1185-1200.
[20] Biessels GJ, Strachan MW, Visseren FL, et al. Dementia and cognitive decline in type 2 diabetes and prediabetic stages: towards targeted interventions[J]. Lancet Diabetes Endocrinol, 2014, 2(3): 246-255.
[21] Sowers JR. Recommendations for special populations: diabetes mellitus and the metabolic syndrome[J]. Am J Hypertens, 2003, 16(11 Pt 2): 41-45.
[22] Kawasoe S, Maruguchi Y, Kajiya S,et al. Mechanism of the blood pressure-lowering effect of sodium-glucose cotransporter 2 inhibitors in obese patients with type 2 diabetes[J]. BMC Pharmacol Toxicol, 2017, 18(1): 23.
[23] Ohishi M. Hypertension with diabetes mellitus: physiology and pathology[J]. Hypertens Res, 2018, 41(6): 389-393.
[24] Thummasorn S, Apichai S, Chupradit S,et al. T2DM patients with depression have higher levels of hyperglycemia and cognitive decline than T2DM patients[J]. PLoS One, 2022, 17(8): e0273327. doi:10.1371/journal.pone.0273327.
[25] Demakakos P, Muniz-Terrera G, Nouwen A. Type 2 diabetes, depressive symptoms and trajectories of cognitive decline in a national sample of community-dwellers: a prospective cohort study[J]. PLoS One, 2017, 12(4): e0175827. doi:10.1371/journal.pone.0175827.
[26] Luchsinger JA, Younes N, Manly JJ, et al. Association of glycemia, lipids, and blood pressure with cognitive performance in people with type 2 diabetes in the glycemia reduction approaches in diabetes: a comparative effectiveness study(GRADE)[J]. Diabetes Care, 2021, 44(10): 2286-2292.
[27] Zilberman JM, Cerezo GH, Del Sueldo M, et al. Association between hypertension, menopause, and cognition in women[J]. J Clin Hypertens Greenwich Conn, 2015, 17(12): 970-976.
[28] Carr AL, Sluiman AJ, Grecian SM, et al. Depression as a risk factor for dementia in older people with type 2 diabetes and the mediating effect of inflammation[J]. Diabetologia, 2021, 64(2): 448-457.
[29] Gonzalez JS, Peyrot M, McCarl LA, et al. Depression and diabetes treatment nonadherence: a meta-analysis[J]. Diabetes Care, 2008, 31(12): 2398-2403.
[30] Jing X, Chen J, Dong Y, et al. Related factors of quality of life of type 2 diabetes patients: a systematic review and meta-analysis[J]. Health Qual Life Outcomes, 2018, 16(1): 189.
[31] Katon WJ, Pedersen HS, Ribe AR, et al. Effect of depression and diabetes mellitus on the risk for dementia: a national population-based cohort study[J]. JAMA Psychiatry, 2015, 72(6): 612-619.
[32] Katon WJ, Lin EH, Russo J, et al. Cardiac risk factors in patients with diabetes mellitus and major depression[J]. J Gen Intern Med, 2004, 19(12): 1192-1199.
[33] Katon WJ, Russo JE, Heckbert SR, et al. The relationship between changes in depression symptoms and changes in health risk behaviors in patients with diabetes[J]. Int J Geriatr Psychiatry, 2010, 25(5): 466-475.

多维度评价

Viewed

Full text

Abstract

Cited

Shared

Discussed