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Diabetes mellitus, metformin's target gene AMPK, and inflammatory bowel disease: A Mendelian randomization study

Wei Wu1, Huomu Tong2, Yunsheng Li1

  • 1Department of Geriatrics, Chun'an First People's Hospital (Chun'an Branch of Zhejiang Provincial People's Hospital), Hangzhou, Zhejiang Province, China.

Medicine
|February 17, 2025
PubMed

Insights

Inflammatory bowel disease (IBD) and type 1 diabetes mellitus (T1DM) show a bidirectional link, with Crohn disease increasing T1DM risk. AMP-activated protein kinase (AMPK) did not significantly impact IBD risk.

Area of Science:

  • Gastroenterology and Endocrinology
  • Genetics and Epidemiology

Background:

  • The relationship between inflammatory bowel disease (IBD) and diabetes mellitus is not well understood.
  • Investigating potential causal links and the role of AMP-activated protein kinase (AMPK), a metformin target, in IBD development is crucial.

Purpose of the Study:

  • To examine the bidirectional causal relationship between IBD (ulcerative colitis, Crohn disease) and diabetes mellitus (type 1 and type 2).
  • To investigate the association between AMPK and IBD risk, using AMPK-related variants linked to HbA1c as instrumental variables.

Main Methods:

  • Bidirectional two-sample Mendelian randomization analysis was employed.
  • The inverse variance weighted method was the primary analytical approach.
  • Genetic variants associated with HbA1c were used as proxies for the metformin target gene AMPK.

Main Results:

  • A suggestive bidirectional association was found between IBD and type 1 diabetes mellitus (T1DM).
  • Crohn disease (CD) showed an increased risk of T1DM, and T1DM increased the risk of IBD.
  • No significant causal relationship was observed between IBD and type 2 diabetes mellitus (T2DM).
  • AMP-activated protein kinase (AMPK) did not demonstrate a significant effect on IBD risk.

Conclusions:

  • This study suggests a bidirectional association between IBD and T1DM, with CD potentially contributing to T1DM development.
  • No causal link was established between IBD and T2DM.
  • The metformin target gene AMPK was not found to significantly influence the onset of IBD.

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