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Bidirectional relationship between type 2 diabetes mellitus and coronary artery disease: Prospective cohort study and genetic analyses.
Zhang, Wenqiang; Zhang, Li; Xiao, Chenghan; Wu, Xueyao; Cui, Huijie; Yang, Chao; Yan, Peijing; Tang, Mingshuang; Wang, Yutong; Chen, Lin; Liu, Yunjie; Zou, Yanqiu; Zhang, Ling; Yang, Chunxia; Yao, Yuqin; Li, Jiayuan; Liu, Zhenmi; Jiang, Xia; Zhang, Ben.
Affiliation
  • Zhang W; 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, Sichuan 610041, China.
  • Zhang L; 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, Sichuan 610041, China.
  • Xiao C; 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, Sichuan 610041, China.
  • Wu X; Department of Maternal, Child and Adolescent Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
  • Cui H; 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, Sichuan 610041, China.
  • Yang C; 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, Sichuan 610041, China.
  • Yan P; 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, Sichuan 610041, China.
  • Tang M; 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, Sichuan 610041, China.
  • Wang Y; 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, Sichuan 610041, China.
  • Chen L; 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, Sichuan 610041, China.
  • Liu Y; 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, Sichuan 610041, China.
  • Zou Y; 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, Sichuan 610041, China.
  • Zhang L; 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, Sichuan 610041, China.
  • Yang C; 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, Sichuan 610041, China.
  • Yao Y; Department of Iatrical Polymer Material and Artificial Apparatus, School of Polymer Science and Engineering, Sichuan University, Chengdu, Sichuan 610041, China.
  • Li J; 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, Sichuan 610041, China.
  • Liu Z; 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, Sichuan 610041, China.
  • Jiang X; Department of Occupational and Environmental Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
  • Zhang B; 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, Sichuan 610041, China.
Chin Med J (Engl) ; 137(5): 577-587, 2024 Mar 05.
Article in En | MEDLINE | ID: mdl-38062574
ABSTRACT

BACKGROUND:

While type 2 diabetes mellitus (T2DM) is considered a putative causal risk factor for coronary artery disease (CAD), the intrinsic link underlying T2DM and CAD is not fully understood. We aimed to highlight the importance of integrated care targeting both diseases by investigating the phenotypic and genetic relationships between T2DM and CAD.

METHODS:

We evaluated phenotypic associations using data from the United Kingdom Biobank ( N = 472,050). We investigated genetic relationships by leveraging genomic data conducted in European ancestry for T2DM, with and without adjustment for body mass index (BMI) (T2DM Ncase / Ncontrol = 74,124/824,006; T2DM adjusted for BMI [T2DM adj BMI] Ncase / Ncontrol = 50,409/523,897) and for CAD ( Ncase / Ncontrol = 181,522/984,168). We performed additional analyses using genomic data conducted in multiancestry individuals for T2DM ( Ncase / Ncontrol = 180,834/1,159,055).

RESULTS:

Observational analysis suggested a bidirectional relationship between T2DM and CAD (T2DM→CAD hazard ratio [HR] = 2.12, 95% confidence interval [CI] 2.01-2.24; CAD→T2DM HR = 1.72, 95% CI 1.63-1.81). A positive overall genetic correlation between T2DM and CAD was observed ( rg = 0.39, P = 1.43 × 10 -75 ), which was largely independent of BMI (T2DM adj BMI-CAD rg = 0.31, P = 1.20 × 10 -36 ). This was corroborated by six local signals, among which 9p21.3 showed the strongest genetic correlation. Cross-trait meta-analysis replicated 101 previously reported loci and discovered six novel pleiotropic loci. Mendelian randomization analysis supported a bidirectional causal relationship (T2DM→CAD odds ratio [OR] = 1.13, 95% CI 1.11-1.16; CAD→T2DM OR = 1.12, 95% CI 1.07-1.18), which was confirmed in multiancestry individuals (T2DM→CAD OR = 1.13, 95% CI 1.10-1.16; CAD→T2DM OR = 1.08, 95% CI 1.04-1.13). This bidirectional relationship was significantly mediated by systolic blood pressure and intake of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, with mediation proportions of 54.1% (95% CI 24.9-83.4%) and 90.4% (95% CI 29.3-151.5%), respectively.

CONCLUSION:

Our observational and genetic analyses demonstrated an intrinsic bidirectional relationship between T2DM and CAD and clarified the biological mechanisms underlying this relationship.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Coronary Artery Disease / Diabetes Mellitus, Type 2 Limits: Humans Language: En Journal: Chin Med J (Engl) Year: 2024 Type: Article Affiliation country: China
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Coronary Artery Disease / Diabetes Mellitus, Type 2 Limits: Humans Language: En Journal: Chin Med J (Engl) Year: 2024 Type: Article Affiliation country: China