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Gastrointestinal Consequences of Type 2 Diabetes Mellitus and Impaired Glycemic Homeostasis: A Mendelian Randomization Study

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posted on 2023-02-17, 20:31 authored by Jie Chen, Shuai Yuan, Tian Fu, Xixian Ruan, Jie Qiao, Xiaoyan Wang, Xue Li, Dipender Gill, Stephen BurgessStephen Burgess, Edward L. Giovannucci, Susanna C. Larsson

  

OBJECTIVE

We conducted a Mendelian randomization (MR) study to examine the associations of type 2 diabetes and glycemic traits with gastrointestinal diseases (GDs). 

RESEARCH DESIGN & METHODS

Uncorrelated genetic variants associated with type 2 diabetes (n=231), fasting insulin (n=38), fasting glucose (n=71), and hemoglobin A1c (n=75) at the genome-wide significance were selected as instrument variables. Genetic associations with 23 common GDs were obtained from the FinnGen and UK Biobank studies, and other large consortia. 

RESULTS

Genetic liability to type 2 diabetes was associated with the risk of 12 GDs. Per one-unit increase in log-transformed odds ratio of type 2 diabetes, the odds ratio was 1.06 (95% confidence interval (CI) 1.03-1.09) for gastroesophageal reflux disease, 1.12 (95% CI 1.07-1.17) for gastric ulcer, 1.11 (95% CI 1.03-1.20) for acute gastritis, 1.07 (95% CI 1.01-1.13) for chronic gastritis, 1.08 (95% CI 1.03-1.12) for irritable bowel syndrome, 1.04 (95% CI 1.01-1.07) for diverticular disease, 1.08 (95% CI 1.02-1.14) for acute pancreatitis, 1.09 (95% CI 1.05-1.12) for cholelithiasis, 1.09 (95% CI 1.05-1.13) for cholelithiasis with cholecystitis, 1.29 (95% CI 1.17-1.43) for non-alcoholic fatty liver disease, 1.12 (95% CI 1.03-1.21) for liver cirrhosis, and 0.93 (95% CI 0.89-0.97) for ulcerative colitis. Genetically predicted higher levels of fasting insulin and glucose were associated with 6 and 1 GDs, respectively.

CONCLUSIONS

This study found associations between genetic liability to type 2 diabetes and an increased risk of a broad range of GDs, highlighting the importance of GD prevention in type 2 diabetes patients. 

Funding

British Heart Foundation Centre of Research x RE/18/4/34215

Cancerfonden

Karolinska Institutet’s Research Foundation Grants x 2020-01842

Key Project of Research and Development Plan of Hunan Province 2019SK2041

National Natural Science Foundation of China 81970494

Natural Science Fund for Distinguished Young Scholars of Zhejiang Province x LR22H260001

Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society x 204623/Z/16/Z

Swedish Heart-Lung Foundation x Hjärt-Lungfonden, 20210351

Swedish Research Council x Vetenskapsrådet; grant no. 2016-01042 and 2019-00

Swedish Research Council for Health, Working Life and Welfare x 2018‐00123

Wellcome 4i Clinical PhD Program x 203928/Z/16/Z

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