# Dissecting the bidirectional associations between the progression of gastrointestinal and endocrine diseases

**Authors:** Hongyan Liu, Shucheng Si, Hua Zhang, Siyan Zhan

PMC · DOI: 10.3389/fendo.2025.1538603 · 2025-05-06

## TL;DR

This study finds strong two-way links between gastrointestinal and endocrine diseases, showing each increases the risk of the other.

## Contribution

The study reveals extensive bidirectional associations between specific gastrointestinal and endocrine diseases using a large prospective cohort.

## Key findings

- Gastrointestinal diseases increase the risk of endocrine diseases (HR 1.22), and vice versa (HR 1.48).
- Type 2 diabetes shows bidirectional links with six gastrointestinal diseases like gastritis and irritable bowel syndrome.
- Risk increases with more comorbidities: each additional comorbidity raises disease risk further.

## Abstract

The widespread intrinsic link between gastrointestinal and endocrine diseases was poorly understood. We aimed to dissect the bidirectional association in the progression of gastrointestinal with endocrine diseases, either the overall, individual, or comorbidities with each other.

A bidirectional-designed prospective cohort included 481841 and 452858 participants free of gastrointestinal and endocrine diseases at baseline in the UK Biobank. Multivariable Cox proportional hazard models were used to estimate the hazard ratios (HRs) and 95% confidence interval (CI) for incident endocrine diseases according to gastrointestinal disease status or the number of gastrointestinal comorbidities, and vice versa.

Overall gastrointestinal disease was associated with an increased risk of incident endocrine diseases (HR, 1.22; 95% CI, 1.19-1.25), and conversely, overall endocrine disease also increased the risk of total gastrointestinal diseases (HR, 1.48; 95% CI, 1.44-1.53). For specific diseases, extensive bidirectional associations were observed between type 2 diabetes and six gastrointestinal diseases (gastritis and duodenitis, irritable bowel syndrome, gastrointestinal hemorrhage, dyspepsia, duodenal ulcer, and gastric ulcer), thyroid disorders, and five gastrointestinal diseases (gastritis and duodenitis, irritable bowel syndrome, dyspepsia, malabsorption, and ulcerative colitis), hyperparathyroidism and three gastrointestinal diseases (gastritis and duodenitis, gastrointestinal hemorrhage, and duodenal ulcer), etc. The risk of overall endocrine (HR, 1.14; 95% CI, 1.12-1.16) and gastrointestinal diseases (HR, 1.50; 95% CI, 1.46-1.55) increased with per-comorbidity increasing. This trend was similarly observed for most individual diseases.

We observed an extensive bidirectional association in overall, specific, and number of comorbidities between gastrointestinal and endocrine diseases.

## Linked entities

- **Diseases:** type 2 diabetes (MONDO:0005148), irritable bowel syndrome (MONDO:0005052), dyspepsia (MONDO:0002268), duodenal ulcer (MONDO:0005412), gastric ulcer (MONDO:0001126), malabsorption (MONDO:0020598), ulcerative colitis (MONDO:0005101), hyperparathyroidism (MONDO:0001741)

## Full-text entities

- **Diseases:** endocrine disease (MESH:D004700), thyroid disorders (MESH:D013959), gastrointestinal (MESH:D005767), hyperparathyroidism (MESH:D006961), ulcerative colitis (MESH:D003093), gastrointestinal hemorrhage (MESH:D006471), gastritis (MESH:D005756), duodenal ulcer (MESH:D004381), malabsorption (MESH:D008286), duodenitis (MESH:D004382), type 2 diabetes (MESH:D003924), irritable bowel syndrome (MESH:D043183), gastric ulcer (MESH:D013276), dyspepsia (MESH:D004415)

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12088960/full.md

---
Source: https://tomesphere.com/paper/PMC12088960