Additional Evidence for the Relationship Between Type 2 Diabetes and Stroke Through Observational and Genetic Analyses

Wenqiang Zhang; Li Zhang; Jingwei Zhu; Chenghan Xiao; Huijie Cui; Chao Yang; Peijing Yan; Mingshuang Tang; Yutong Wang; Lin Chen; Yunjie Liu; Yanqiu Zou; Xueyao Wu; Ling Zhang; Chunxia Yang; Yuqin Yao; Jiayuan Li; Zhenmi Liu; Xia Jiang; Ben Zhang

doi:10.2337/db22-0954

Additional Evidence for the Relationship Between Type 2 Diabetes and Stroke Through Observational and Genetic Analyses

Diabetes. 2023 Nov 1;72(11):1671-1681. doi: 10.2337/db22-0954.

Authors

Wenqiang Zhang¹, Li Zhang¹, Jingwei Zhu¹, Chenghan Xiao^{1

2}, Huijie Cui¹, Chao Yang¹, Peijing Yan¹, Mingshuang Tang¹, Yutong Wang¹, Lin Chen¹, Yunjie Liu¹, Yanqiu Zou¹, Xueyao Wu¹, Ling Zhang^{1

3}, Chunxia Yang¹, Yuqin Yao^{1

4}, Jiayuan Li¹, Zhenmi Liu^{1

2}, Xia Jiang^{1

5

6}, Ben Zhang^{1

4}

Affiliations

¹ Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, West China-Peking Union Medical College C.C. Chen Institute of Health, West China School of Public Health, and West China Fourth Hospital, Sichuan University, Chengdu.
² Department of Maternal, Child and Adolescent Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.
³ Department of Iatrical Polymer Material and Artificial Apparatus, School of Polymer Science and Engineering, Sichuan University, Chengdu, China.
⁴ Department of Occupational and Environmental Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.
⁵ Department of Nutrition and Food Hygiene, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.
⁶ Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.

PMID: 37552871
DOI: 10.2337/db22-0954

Abstract

While type 2 diabetes mellitus (T2DM) is commonly considered a putative causal risk factor for stroke, the effect of stroke on T2DM remains unclear. The intrinsic link underlying T2DM and stroke has not been thoroughly examined. We aimed to evaluate the phenotypic and genetic relationships underlying T2DM and stroke. We evaluated phenotypic associations using data from the UK Biobank (N = 472,050). We then investigated genetic relationships by leveraging genomic data in European ancestry for T2DM, with and without adjusting (adj) for BMI (T2DM: n = 74,124 case subjects/824,006 control subjects; T2DMadjBMI: n = 50,409 case subjects/523,897 control subjects), and for stroke (n = 73,652 case subjects/1,234,808 control subjects). We performed additional analyses using genomic data in East Asian ancestry for T2DM (n = 77,418 case subjects/356,122 control subjects) and for stroke (n = 27,413 case subjects/237,242 control subjects). Observational analyses suggested a significantly increased hazard of stroke among individuals with T2DM (hazard ratio 2.28 [95% CI 1.97-2.64]), but a slightly increased hazard of T2DM among individuals with stroke (1.22 [1.03-1.45]) which attenuated to 1.14 (0.96-1.36) in sensitivity analysis. A positive global T2DM-stroke genetic correlation was observed (rg = 0.35; P = 1.46 × 10-27), largely independent of BMI (T2DMadjBMI-stroke: rg = 0.27; P = 3.59 × 10-13). This was further corroborated by 38 shared independent loci and 161 shared expression-trait associations. Mendelian randomization analyses suggested a putative causal effect of T2DM on stroke in Europeans (odds ratio 1.07 [95% CI 1.06-1.09]), which remained significant in East Asians (1.03 [1.01-1.06]). Conversely, despite a putative causal effect of stroke on T2DM also observed in Europeans (1.21 [1.07-1.37]), it attenuated to 1.04 (0.91-1.19) in East Asians. Our study provides additional evidence to underscore the significant relationship between T2DM and stroke.

Abstract

Grants and funding