The Role of C-peptide in Predicting Diabetes Mellitus after Acute Pancreatitis: A Narrative Review

Abstract

Acute pancreatitis is increasingly recognized as a condition with long-term metabolic consequences, including the development of diabetes mellitus (DM) after recovery. Post-Pancreatitis Diabetes Mellitus (PPDM), a form of diabetes of the exocrine pancreas, arises due to complex interactions between pancreatic inflammation, β-cell injury, insulin resistance, and hormonal dysregulation. Identifying patients at risk for diabetes following acute pancreatitis remains challenging, as conventional glucose-based diagnostic methods detect dysglycemia only after significant endocrine dysfunction has occurred. C-peptide, a by-product of endogenous insulin synthesis, serves as a stable and reliable marker of pancreatic β-cell function and insulin secretory reserve. Unlike insulin, C-peptide is minimally affected by hepatic clearance and has a longer half-life, making it particularly useful for assessing residual endocrine function. This narrative review explores the physiological basis of C-peptide production, its measurement techniques, and its clinical relevance in differentiating insulin resistance from true insulin deficiency. The review also summarizes current evidence supporting the role of C-peptide in risk stratification, disease classification, and prediction of diabetes progression following acute pancreatitis. Incorporating C-peptide assessment into postpancreatitis follow-up protocols may allow earlier identification of high-risk individuals, facilitate personalized management strategies, and improve long-term glycemic outcomes. Further prospective studies are needed to establish standardized timing and clinically relevant cutoff values for C-peptide measurement in this population.