Objectives: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in type 2 diabetes, thus crosstalk between islet cells (mainly α and β cells) and liver is suspected. We aim to investigate whether islet dysfunction (evaluated by C-peptide and glucagon) associates with NAFLD progression in Chinese type 2 diabetic adults.

Methods: 4,937 diabetic participants were enrolled from Shanghai, China in 2018. Liver steatosis was detected by ultrasound. Subjects with NAFLD were categorized into simple NAFLD and probable nonalcoholic steatohepatitis (NASH) by the presence of metabolic syndrome. NAFLD fibrosis score was used to identify patients with higher likelihood of bridging fibrosis (stage 3) or cirrhosis (stage 4). Regression analyses were used.

Results: With longer history of type 2 diabetes, individuals were prone to have lower C-peptide, relatively stable glucagon, lower prevalence of probable NASH and higher prevalence of significant fibrosis. C-peptide was positively associated with simple NAFLD and probable NASH, with the ORs of 4.55 (95% CI 3.16, 6.55) and 5.28 (95% CI 3.94, 7.09), comparing quartile 4 with quartile 1 (both P for trend <0.001). Unlike C-peptide, glucagon quartiles were negatively associated with probable NASH (P for trend <0.05). Moreover, 1SD increment of ln(C-peptide/glucagon) was significantly associated with progression ranging from non-NAFLD, simple NAFLD to probable NASH (OR 1.26, 95% CI 1.21, 1.32). Furthermore, 1SD increment of ln(C-peptide), but not glucagon and C-peptide/glucagon ratio, was significantly and negatively associated with fibrotic progression (OR 0.88, 95% CI 0.79, 0.98).

Conclusion: Significant associations were observed among C-peptide, glucagon, C-pepide/glucagon ratio and inflammatory and fibrotic progression of NAFLD. Further understanding the crosstalk among α and β islet cells and liver tissue may help to personalize treatment strategies of NAFLD patients with type 2 diabetes.


N. Wang: None. Y. Wang: None. W. Zhang: None. Y. Chen: None. X. Chen: None. C. Wang: None. Y. Lu: None.


National Natural Science Foundation of China; Science and Technology Commission of Shanghai Municipality; Commission of Health and Family Planning of Pudong District; Shanghai Municipal Commission of Health and Family Planning

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