Observational and genetic analyses clarify the relationship between type 2 diabetes mellitus and gallstone disease.
Front Endocrinol (Lausanne)
; 14: 1337071, 2023.
Article
em 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 (GSDâT2DM 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 (T2DMâGSD odds ratio (OR)=1.08, P=4.6×10-8; GSDâT2DM 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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cálculos Biliares
/
Diabetes Mellitus Tipo 2
Tipo de estudo:
Clinical_trials
/
Observational_studies
/
Systematic_reviews
Limite:
Humans
Idioma:
En
Revista:
Front Endocrinol (Lausanne)
Ano de publicação:
2023
Tipo de documento:
Article