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

<p>  </p> <p><strong>OBJECTIVE</strong></p> <p>We conducted a Mendelian randomization (MR) study to examine the associations of type 2 diabetes and glycemic traits with gastrointestinal diseases (GDs). </p> <p><strong>RESEARCH DESIGN & METHODS</strong></p> <p>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. </p> <p><strong>RESULTS</strong></p> <p>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.</p> <p><strong>CONCLUSIONS</strong></p> <p>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. </p>