Risk Assessment for Gastrointestinal Diseases via Clinical Dimension and Genome-Wide Polygenic Risk Scores of Type 2 Diabetes: A Population-Based Cohort Study

Abstract

OBJECTIVE We aimed to evaluate whether individuals with type 2 diabetes (T2D) were at higher risk of developing a wide range of gastrointestinal diseases based on a population-based cohort study. RESEARCH DESIGN AND METHODS This study included 374,125 participants free of gastrointestinal disorders at baseline; of them, 19,719 (5.27%) with T2D were followed-up by linking to multiple medical records to record gastrointestinal disease diagnoses. Multivariable Cox models were used to estimate the hazard ratios (HRs) and CIs. Logistic models were used to examine the associations between polygenic risk scores (PRS) and clinical gastrointestinal phenotypes. RESULTS During a median follow-up of 12.0 years, we observed the new onset of 15 gastrointestinal diseases. Compared with nondiabetes, participants with T2D had an increased risk of gastritis and duodenitis (HR 1.58, 95% CI 1.51–1.65), peptic ulcer (HR 1.56, 95% CI 1.43–1.71), diverticular disease (HR 1.19, 95% CI 1.14–1.24), pancreatitis (HR 1.45, 95% CI 1.24–1.71), nonalcoholic fatty liver disease (HR 2.46, 95% CI 2.25–2.69), liver cirrhosis (HR 2.92, 95% CI 2.58–3.30), biliary disease (HR 1.18, 95% CI 1.10–1.26), gastrointestinal tract cancers (HR 1.28, 95% CI 1.17–1.40), and hepatobiliary and pancreatic cancer (HR 2.32, 95% CI 2.01–2.67). Positive associations of PRS of T2D with gastritis, duodenitis, and nonalcoholic fatty liver disease were also observed. CONCLUSIONS In this large cohort study, we found that T2D was associated with increased risks of a wide range of gastrointestinal outcomes. We suggest the importance of early detection and prevention of gastrointestinal disorders among patients with T2D.