C-peptide is associated with NAFLD inflammatory and fibrotic progression in type 2 diabetes

Background: A higher prevalence of nonalcoholic steatohepatitis (NASH) and advanced stages of fibrosis was observed in type 2 diabetes. We aim to investigate whether C-peptide is associated with nonalcoholic fatty liver disease (NAFLD) progression in type 2 diabetic adults. Methods: A total of 4937 diabetic participants were enrolled from China in 2018. Liver steatosis was detected by ultrasound. Subjects with NAFLD were categorized into simple NAFLD and probable NASH by the concurrent presence of metabolic syndrome. NAFLD fibrosis score was used to identify patients with probable advanced fibrosis. Results: Individuals with a longer history of type 2 diabetes had a lower C-peptide level and a lower prevalence of probable NASH but a higher prevalence of advanced fibrosis. C-peptide was positively associated with simple NAFLD and probable NASH, with odds ratios (ORs) of 4.55 [95% confidence interval (CI) 3.16, 6.55] and 5.28 (95% CI 3.94, 7.09), respectively, comparing quartile 4 with quartile 1 (both p for trend <0.001). However, C-peptide quartiles were negatively associated with the probable presence of advanced fibrosis (Q4 vs. Q1, OR 0.59, 95% CI 0.36, 0.97, p for trend <0.05). A 1-SD increment of ln(C-peptide) was also significantly associated with inflammatory and fibrotic progression (OR 1.34, 95% CI 1.27, 1.41; OR 0.88, 95% CI 0.79, 0.98, respectively). Conclusions: Significant but opposite associations between C-peptide and inflammatory and fibrotic progression of NAFLD were observed. Understanding islet hormone changes during type 2 diabetes and differentiating the stage of NAFLD may help to personalize treatment strategies for NAFLD patients with type 2 diabetes.