American Diabetes Association
DC22-1385 Online_material.docx (49.09 kB)

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



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


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. 


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.


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. 


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


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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