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Observational and genetic analyses clarify the relationship between type 2 diabetes mellitus and gallstone disease.
Yan, Peijing; Zhang, Li; Yang, Chao; Zhang, Wenqiang; Wang, Yutong; Zhang, Min; Cui, Huijie; Tang, Mingshuang; Chen, Lin; Wu, Xueyao; Zhao, Xunying; Zou, Yanqiu; Xiao, Jinyu; Liu, Yunjie; Xiao, Chenghan; Yang, Yanfang; Zhang, Ling; Yao, Yuqin; Li, Jiayuan; Liu, Zhenmi; Yang, Chunxia; Jiang, Xia; Zhang, Ben.
Affiliation
  • Yan P; Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, and West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China.
  • Zhang L; Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, and West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China.
  • Yang C; Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, and West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China.
  • Zhang W; School of Public Health, Southwest Medical University, Luzhou, Sichuan, China.
  • Wang Y; Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, and West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China.
  • Zhang M; Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, and West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China.
  • Cui H; Clinical Research Center, Women and Children's Hospital of Chongqing Medical University, Chongqing, China.
  • Tang M; Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, and West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China.
  • Chen L; Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, and West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China.
  • Wu X; Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, and West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China.
  • Zhao X; Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, and West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China.
  • Zou Y; Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, and West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China.
  • Xiao J; Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, and West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China.
  • Liu Y; Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, and West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China.
  • Xiao C; Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, and West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China.
  • Yang Y; Department of Maternal, Child and Adolescent Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.
  • Zhang L; Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, and West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China.
  • Yao Y; Department of Iatrical Polymer Material and Artificial Apparatus, School of Polymer Science and Engineering, Sichuan University, Chengdu, China.
  • Li J; Department of Occupational and Environmental Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.
  • Liu Z; Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, and West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China.
  • Yang C; Department of Maternal, Child and Adolescent Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.
  • Jiang X; Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, and West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China.
  • Zhang B; Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, and West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China.
Front Endocrinol (Lausanne) ; 14: 1337071, 2023.
Article in En | MEDLINE | ID: mdl-38356679
ABSTRACT

Background:

The relationship between type 2 diabetes mellitus (T2DM) and gallstone disease (GSD) have been incompletely understood. We aimed to investigate their phenotypic and genetic associations and evaluate the biological mechanisms underlying these associations.

Methods:

We first evaluated the phenotypic association between T2DM and GSD using data from the UK Biobank (n>450,000) using a prospective observational design. We then conducted genetic analyses using summary statistics from a meta-analysis of genome-wide association studies of T2DM, with and without adjusting for body mass index (BMI) (Ncase=74,124, Ncontrol=824,006; T2DMadjBMI Ncase=50,409, Ncontrol=523,897) and GSD (Ncase=43,639, Ncontrol=506,798).

Results:

A unidirectional phenotypic association was observed, where individuals with T2DM exhibited a higher GSD risk (hazard ratio (HR)=1.39, P<0.001), but not in the reverse direction (GSD→T2DM HR=1.00, P=0.912). The positive T2DM-GSD genetic correlation (rg=0.35, P=7.71×10-23) remained even after adjusting for BMI (T2DMadjBMI rg=0.22, P=4.48×10-10). Mendelian randomization analyses provided evidence of a unidirectional causal relationship (T2DM→GSD odds ratio (OR)=1.08, P=4.6×10-8; GSD→T2DM OR=1.02, P=0.48), even after adjusting for important metabolic confounders (OR=1.02, P=0.02). This association was further corroborated through a comprehensive functional analysis reflected by 23 pleiotropic single nucleotide polymorphisms, as well as multiple neural and motor-enriched tissues.

Conclusion:

Through comprehensive observational and genetic analyses, our study clarified the causal relationship between T2DM and GSD, but not in the reverse direction. These findings might provide new insights into prevention and treatment strategies for T2DM and GSD.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Gallstones / Diabetes Mellitus, Type 2 Type of study: Clinical_trials / Observational_studies / Systematic_reviews Limits: Humans Language: En Journal: Front Endocrinol (Lausanne) Year: 2023 Type: Article Affiliation country: China
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Gallstones / Diabetes Mellitus, Type 2 Type of study: Clinical_trials / Observational_studies / Systematic_reviews Limits: Humans Language: En Journal: Front Endocrinol (Lausanne) Year: 2023 Type: Article Affiliation country: China