Association of serum C-peptide with all- cause and cardiovascular disease mortality in ultrasound-defined nonalcoholic fatty liver disease

Objective: To determine the prognostic value of C-peptide in long-term nonalcoholic fatty liver disease (NAFLD) mortality.Methods: A total of 4670 participants with NAFLD were enrolled in this study. Multivariable Cox regression models evaluated the links between C-peptide levels and all-cause and cardiovascular disease (CVD) mortality risk using adjusted hazard ratios (aHR). In addition, a two-piecewise Cox model with penalized splines was adapted to investigate the nonlinear relationships between C -peptide and mortality.Results: After a mean follow-up period of 20 years, 1714 deaths from all causes were recorded. In an adjusted Cox regression analysis, using the low C-peptide group as the reference (quartile 1), higher C-peptide (quartile 4) was notably associated with increased all-cause mortality (aHR =1.39; 95% CI: 1.18-1.65) and CVD death (aHR = 1.97; 95% CI: 1.41-2.76). Spline analyses dem-onstrated that the association between C-peptide levels and all-cause mortality was U-shaped, with a threshold value of 0.41 nmol/L. Below the threshold, every one-unit increment in C -pep-tide had a 70% reduced risk of all-cause death (aHR = 0.30, 95% CI: 0.1-0.7). Above the thresh-old, the C-peptide levels were associated with a higher probability of all-cause death (aHR = 1. 3, 95% CI:1.2-1.4).Conclusions: In the US NAFLD population defined by ultrasound, a U-shaped association was detected between baseline serum C-peptide level and all-cause mortality.(c) 2022 Elsevier Masson SAS. All rights reserved.