{Reference Type}: Journal Article {Title}: The role of C-peptide in diabetes and its complications: an updated review. {Author}: Chen J;Huang Y;Liu C;Chi J;Wang Y;Xu L; {Journal}: Front Endocrinol (Lausanne) {Volume}: 14 {Issue}: 0 {Year}: 2023 {Factor}: 6.055 {DOI}: 10.3389/fendo.2023.1256093 {Abstract}: Worldwide, diabetes and its complications have seriously affected people's quality of life and become a serious public health problem. C-peptide is not only an indicator of pancreatic β-cell function, but also a biologically active peptide that can bind to cell membrane surface signaling molecules and activate downstream signaling pathways to play antioxidant, anti-apoptotic and inflammatory roles, or regulate cellular transcription through internalization. It is complex how C-peptide is related to diabetic complications. Both deficiencies and overproduction can lead to complications, but their mechanisms of action may be different. C-peptide replacement therapy has shown beneficial effects on diabetic complications in animal models when C-peptide is deficient, but results from clinical trials have been unsatisfactory. The complex pattern of the relationship between C-peptide and diabetic chronic complications has not yet been fully understood. Future basic and clinical studies of C-peptide replacement therapies will need to focus on baseline levels of C-peptide in addition to more attention also needs to be paid to post-treatment C-peptide levels to explore the optimal range of fasting C-peptide and postprandial C-peptide maintenance.