C-peptide in Precision Diabetes Care and Beyond: A Comprehensive Review

Impaired pancreatic β-cell function is a key feature in the pathophysiology of both type 1 and long-standing type 2 diabetes. C-peptide, produced in 1:1 ratio along with insulin, is secreted at a relatively steady rate over long duration, making it an effective biomarker for endogenous insulin secretion. Given the heterogeneity and complex pathophysiology of diabetes, C-peptide estimation plays an important role in the accurate classification of diabetes and in guiding treatment decisions, particularly for patients needing insulin therapy. In autoimmune diabetes, especially adult-onset forms, C-peptide has gained importance as a biomarker. However, its greatest utility is often observed 3 to 5 years post-diagnosis, when detectable C-peptide levels may help differentiate between MODY (Maturity-onset Diabetes of the Young) and type 2 diabetes. The clinical applications of C-peptide extend beyond diagnosis, including risk stratification for diabetes-related vascular complications, determining pharmacotherapy choices, evaluating hypoglycemia, and even in the context of bariatric surgery. Despite its usefulness, the role of C-peptide in type 2 diabetes remains limited, primarily due to insulin resistance, which may elevate C-peptide levels. Estimating C-peptide is a cost-effective and reliable method, but there is still considerable variation in its application. Factors such as sample collection, timing in relation to meals, and the lack of standardization in assay techniques raise issues regarding the consistency and repeatability of results among various laboratories. This review aims to explore the current evidence surrounding C-peptide estimation in diabetes care, as well as the limitations and uncertainties that continue to challenge its clinical application.