European journal of gastroenterology & hepatology · 2026
Type 2 diabetes mellitus and liver diseases: a phenome-wide Mendelian randomization atlas and genome-wide genetic correlation study.
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Ding Rong, Zhou Min, Guan Kaile, Xie Liyan, Zhang Yue, Chen Qi, Li Jiaqi, Shan Lei, Lu Huimin
Аннотация
BACKGROUND: The causal relationship between type 2 diabetes mellitus (T2DM) and the various liver disease phenotypes remains uncertain.
RESEARCH DESIGN AND METHODS: Our study provides a comprehensive causal atlas by assessing the causal roles of T2DM across 12 major liver conditions using summary data from genome-wide association studies.
RESULTS: Our study indicated significant genetic correlations between T2DM and five types of liver diseases, with suggestive levels for three additional types. Furthermore, we found evidence of the causal effects of T2DM on seven types of liver diseases. Specifically, T2DM showed significant causality with metabolic dysfunction-associated steatotic liver disease [odds ratio (OR) = 1.49, 95% confidence interval (CI): 1.37-1.62, P = 2.55 × 10-21], cirrhosis of liver (OR = 1.18, 95% CI: 1.05-1.33, P = 3.98 × 10-3), chronic hepatitis (OR = 1.20, 95% CI: 1.06-1.37, P = 3.72 × 10-3), and hepatocellular carcinoma (OR = 1.31, 95% CI: 1.10-1.56, P = 3.02 × 10-3). In addition, suggestive causality was found between T2DM and nonalcoholic steatohepatitis (OR = 1.45, 95% CI: 1.08-1.95, P = 0.012), fibrosis of liver (OR = 1.47, 95% CI: 1.08-2.00, P = 0.015), and malignant liver neoplasm (OR = 1.21, 95% CI: 1.04-1.42, P = 0.013).
CONCLUSION: Our research has comprehensively revealed the clear causal relationship between T2DM and specific liver diseases, emphasizing the importance of preventing such diseases in patients with T2DM. These findings not only confirm and expand the existing knowledge framework regarding the relationship between T2DM and liver diseases but also provide new insights for clinical practice and future research directions.
RESEARCH DESIGN AND METHODS: Our study provides a comprehensive causal atlas by assessing the causal roles of T2DM across 12 major liver conditions using summary data from genome-wide association studies.
RESULTS: Our study indicated significant genetic correlations between T2DM and five types of liver diseases, with suggestive levels for three additional types. Furthermore, we found evidence of the causal effects of T2DM on seven types of liver diseases. Specifically, T2DM showed significant causality with metabolic dysfunction-associated steatotic liver disease [odds ratio (OR) = 1.49, 95% confidence interval (CI): 1.37-1.62, P = 2.55 × 10-21], cirrhosis of liver (OR = 1.18, 95% CI: 1.05-1.33, P = 3.98 × 10-3), chronic hepatitis (OR = 1.20, 95% CI: 1.06-1.37, P = 3.72 × 10-3), and hepatocellular carcinoma (OR = 1.31, 95% CI: 1.10-1.56, P = 3.02 × 10-3). In addition, suggestive causality was found between T2DM and nonalcoholic steatohepatitis (OR = 1.45, 95% CI: 1.08-1.95, P = 0.012), fibrosis of liver (OR = 1.47, 95% CI: 1.08-2.00, P = 0.015), and malignant liver neoplasm (OR = 1.21, 95% CI: 1.04-1.42, P = 0.013).
CONCLUSION: Our research has comprehensively revealed the clear causal relationship between T2DM and specific liver diseases, emphasizing the importance of preventing such diseases in patients with T2DM. These findings not only confirm and expand the existing knowledge framework regarding the relationship between T2DM and liver diseases but also provide new insights for clinical practice and future research directions.