PMID- 38062574
OWN - NLM
STAT- MEDLINE
DCOM- 20240313
LR  - 20240314
IS  - 2542-5641 (Electronic)
IS  - 0366-6999 (Print)
IS  - 0366-6999 (Linking)
VI  - 137
IP  - 5
DP  - 2024 Mar 5
TI  - Bidirectional relationship between type 2 diabetes mellitus and coronary artery 
      disease: Prospective cohort study and genetic analyses.
PG  - 577-587
LID - 10.1097/CM9.0000000000002894 [doi]
AB  - 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 x 10 -75 ), 
      which was largely independent of BMI (T2DM adj BMI-CAD: rg = 0.31, P = 1.20 x 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.
CI  - Copyright (c) 2024 The Chinese Medical Association, produced by Wolters Kluwer, 
      Inc. under the CC-BY-NC-ND license.
FAU - Zhang, Wenqiang
AU  - Zhang W
AD  - 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.
FAU - Zhang, Li
AU  - Zhang L
AD  - 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.
FAU - Xiao, Chenghan
AU  - Xiao C
AD  - 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.
AD  - Department of Maternal, Child and Adolescent Health, West China School of Public 
      Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan 
      610041, China.
FAU - Wu, Xueyao
AU  - Wu X
AD  - 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.
FAU - Cui, Huijie
AU  - Cui H
AD  - 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.
FAU - Yang, Chao
AU  - Yang C
AD  - 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.
FAU - Yan, Peijing
AU  - Yan P
AD  - 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.
FAU - Tang, Mingshuang
AU  - Tang M
AD  - 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.
FAU - Wang, Yutong
AU  - Wang Y
AD  - 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.
FAU - Chen, Lin
AU  - Chen L
AD  - 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.
FAU - Liu, Yunjie
AU  - Liu Y
AD  - 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.
FAU - Zou, Yanqiu
AU  - Zou Y
AD  - 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.
FAU - Zhang, Ling
AU  - Zhang L
AD  - 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.
AD  - Department of Iatrical Polymer Material and Artificial Apparatus, School of 
      Polymer Science and Engineering, Sichuan University, Chengdu, Sichuan 610041, 
      China.
FAU - Yang, Chunxia
AU  - Yang C
AD  - 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.
FAU - Yao, Yuqin
AU  - Yao Y
AD  - 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.
AD  - Department of Occupational and Environmental Health, West China School of Public 
      Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan 
      610041, China.
FAU - Li, Jiayuan
AU  - Li J
AD  - 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.
FAU - Liu, Zhenmi
AU  - Liu Z
AD  - 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.
AD  - Department of Maternal, Child and Adolescent Health, West China School of Public 
      Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan 
      610041, China.
FAU - Jiang, Xia
AU  - Jiang X
AD  - 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.
AD  - Department of Nutrition and Food Hygiene, West China School of Public Health and 
      West China Fourth Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
AD  - Department of Clinical Neuroscience, Karolinska Institutet, Stockholm 17177, 
      Sweden.
FAU - Zhang, Ben
AU  - Zhang B
AD  - 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.
AD  - Department of Occupational and Environmental Health, West China School of Public 
      Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan 
      610041, China.
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
DEP - 20231208
PL  - China
TA  - Chin Med J (Engl)
JT  - Chinese medical journal
JID - 7513795
SB  - IM
MH  - Humans
MH  - *Coronary Artery Disease/genetics
MH  - *Diabetes Mellitus, Type 2/genetics
MH  - Prospective Studies
MH  - Risk Factors
MH  - Phenotype
MH  - Genome-Wide Association Study
MH  - Polymorphism, Single Nucleotide/genetics
PMC - PMC10932529
COIS- None.
EDAT- 2023/12/08 06:41
MHDA- 2024/03/13 06:47
PMCR- 2024/03/05
CRDT- 2023/12/08 00:05
PHST- 2023/09/18 00:00 [received]
PHST- 2024/03/13 06:47 [medline]
PHST- 2023/12/08 06:41 [pubmed]
PHST- 2023/12/08 00:05 [entrez]
PHST- 2024/03/05 00:00 [pmc-release]
AID - 00029330-990000000-00887 [pii]
AID - CMJ-2023-1642 [pii]
AID - 10.1097/CM9.0000000000002894 [doi]
PST - ppublish
SO  - Chin Med J (Engl). 2024 Mar 5;137(5):577-587. doi: 10.1097/CM9.0000000000002894. 
      Epub 2023 Dec 8.