Journal of Shandong University (Health Sciences) ›› 2023, Vol. 61 ›› Issue (10): 101-108.doi: 10.6040/j.issn.1671-7554.0.2023.0647

• Public Health & Management Sciences • Previous Articles     Next Articles

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

HAN Mei1, MENG Weijing2, TAO Zikun1, YANG Xi1, XU Yaqi1, MU Huaxia1, BU Weixiao1, WANG Suzhen1, SHI Fuyan1   

  1. 1. School of Public Health, Weifang Medical University, Weifang 261053, Shandong, China;
    2. School of Rehabilitation Medicine, Weifang Medical University, Weifang 261053, Shandong, China
  • Published:2023-11-08

PDF (PC)

69

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

CLC Number: 

  • R587.1
[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.
[1] WUYi-Na, GE Zhi-Ming, LI Fang, HE Hong, JIANG Hong, ZHANG Yun. Expressions of angiotensin converting enzyme 2 mRNA and protein in the kidneys in spontaneously hypertensive rats [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2209, 47(6): 5-.
[2] YU Qingqing, CHANG Kaifeng, LI Jiqing, ZHANG Kai, FU Ping,LIU Xiaowen, ZHAO Yingqi, XUE Fuzhong. Mediation effects of hypertension on the association between exposure to non-steroidal anti-inflammatory drugs and risk of cardio-cerebrovascular diseases in middle-aged and elderly people [J]. Journal of Shandong University (Health Sciences), 2023, 61(8): 79-85.
[3] ZHANG Hengzhe, HOU Xiaohui, Arezou Bikdeli, LI Daqing. Factors influencing the degrees of fatigue after complete revascularization interventions in 152 patients with nonacute myocardial infarction [J]. Journal of Shandong University (Health Sciences), 2023, 61(7): 47-54.
[4] LI Jinquan, GAO Meifang, YAN Fei, DONG Ming. Frequency and risk factors of muscle cramp in 136 cases of type 2 diabetes mellitus [J]. Journal of Shandong University (Health Sciences), 2023, 61(5): 20-24.
[5] HUANG Shan, LOU Nengjun, HAN Xiaolin, LIANG Zhonghao, HUA Mengyu, ZHUANG Xianghua, CHEN Shihong. Effects of Lipin1 on neuronal metabolomics in high glucose environment [J]. Journal of Shandong University (Health Sciences), 2023, 61(2): 1-8.
[6] WU Yujie, ZHANG Mingquan, JI Yongli, ZHAO Lu, WANG Yue, CHEN Shasha. Effects of Hanjingtang and its disassembled prescriptions on serum inflammatory factors, vascular endothelial function and fibrosis in hypertensive rats with cold coagulation syndrome [J]. Journal of Shandong University (Health Sciences), 2022, 60(6): 10-18.
[7] ZHAO Hailong, WANG Hao, FANG Yuqing, MAO Fei, ZHAO Zhangning, TIAN Xiangqi, XU Xinrong, WANG Min, LI Xiuhua. Efficacy of additional idebenone in the treatment of 34 patients with Parkinsons disease with depression [J]. Journal of Shandong University (Health Sciences), 2022, 60(4): 38-44.
[8] SONG Yufeng, NING Hao, YAO Zhigang, WU Haihu, LIU Feifan, LYU Jiaju. Clinical and imaging features of adrenal cavernous hemangioma [J]. Journal of Shandong University (Health Sciences), 2022, 60(2): 37-42.
[9] LYU Yanhong, ZHANG Zhimian. Correlation of helicobacter pylori infection and hypertension in the 2,809 physical examination participants [J]. Journal of Shandong University (Health Sciences), 2022, 60(2): 43-47.
[10] ZENG Yuanyuan, YANG Dongpeng, DONG Zhu, ZHANG Ben, CAO Yiqiu, WANG Xiaowu. Effects and mechanism of tetramethylpyrazine on monocrotaline induced pulmonary arterial hypertension in rats [J]. Journal of Shandong University (Health Sciences), 2022, 60(11): 63-69.
[11] ZHAO Xuan, LI Xiaopeng, LI Jian, TIAN Bin, WANG Guangjun. Therapeutic effects of auricular points sticking with magnetic beads combined with repeated transcranial magnetic stimulation on post-stroke depression [J]. Journal of Shandong University (Health Sciences), 2022, 60(1): 65-70.
[12] FU Wenhao, LI Jiajia, FANG Feng, LI Shixue. Depression status and associated factors among informal caregivers of patients with critical illness [J]. Journal of Shandong University (Health Sciences), 2022, 60(1): 71-77.
[13] LYU Li, JIANG Lu, CHEN Shihong, ZHUANG Xianghua, SONG Yuwen, WANG Dianhui, AN Wenjuan, LI Qian, PAN Zhe. Related factors of osteoporosis in 210 postmenopausal women with type 2 diabetes mellitus [J]. Journal of Shandong University (Health Sciences), 2021, 59(7): 19-25.
[14] SUN Fuyun, WANG Weipeng, ZHANG Huihui, GENG Yan, AN Xiaoxia, LI Shuangshuang, ZHANG Binbin. Correlation among personality traits and depression, anxiety symptoms in patients after colorectal cancer resection [J]. Journal of Shandong University (Health Sciences), 2021, 59(7): 91-96.
[15] ZHENG Fengjie, SONG Yuwen, SUN Aili, PAN Zhe, WANG Dianhui, LOU Nengjun, LYU Li, ZHUANG Xianghua, CHEN Shihong. Correlation between diabetic peripheral neuropathy and sarcopenia [J]. Journal of Shandong University (Health Sciences), 2021, 59(6): 38-44.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
[1] SUO Dongyang, SHEN Fei, GUO Hao, LIU Lichang, YANG Huimin, YANG Xiangdong. Expression and mechanism of Tim-3 in animal model of drug-induced acute kidney injury[J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 1 -6 .
[2] XU Yuxiang, LIU Yudong, ZHANG Peng, DUAN Ruisheng. A retrospective analysis of risk factors of cerebral microbleeds in 101 patients with cerebral small vessel disease[J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 67 -71 .
[3] LYU Longfei, LI Lin, LI Shuhai, QI Lei, LU Ming, CHENG Chuanle, TIAN Hui. Application of laparoscopic fine needle catheter jejunostomy in minimally invasive McKeown resection of esophageal cancer[J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 77 -81 .
[4] ZHANG Juan, ZHANG Lujia, XIAO Wei, LI Shunping. Influencing factors of perceived stress and job retention in national standardized training for resident doctors[J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 108 -114 .
[5] . [J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 122 -124 .
[6] MA Qingyuan, PU Peidong, HAN Fei, WANG Chao, ZHU Zhoujun, WANG Weishan, SHI Chenhui. Effect of miR-27b-3p regulating SMAD1 on osteosarcoma cell proliferation, migration and invasion[J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 32 -37 .
[7] Ju LIU,Qiang WU,Luyue YU,Fengming LIN. Brain tumor image segmentation based on deep learning techniques[J]. Journal of Shandong University (Health Sciences), 2020, 1(8): 42 -49, 73 .
[8] DING Xiangyun, YU Qingmei, ZHANG Wenfang, ZHUANG Yuan, HAO Jing. Correlation of the expression of insulin-like growth factor II in granulosa cells and ovulation induction outcomes of 84 patients with polycystic ovary syndrome[J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 60 -66 .
[9] LONG Tingting, XIE Ming, ZHOU Lu, ZHU Junde. Effect of Noggin protein on learning and memory abilities and the dentate gyrus structure after cerebral ischemia reperfusion injury in mice[J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 15 -23 .
[10] LI Ning, LI Juan, XIE Yan, LI Peilong, WANG Yunshan, DU Lutao, WANG Chuanxin. Expression of LncRNA AL109955.1 in 80 cases of colorectal cancer and its effect on cell proliferation, migration and invasion[J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 38 -46 .
Copyright 2018 © Editorial office of Journal of Shandong University (Health Sciences)
Supported by Beijing Magtech Co.Ltd