C-peptide microheterogeneity in type 2 diabetes populations

Purpose: The purpose of this study was to investigate naturally occurring C-peptide micro-heterogeneity in healthy and type 2 diabetes (T2D) populations. Experimental design: MS immunoassays capable of simultaneously detecting intact C-peptide and variant forms were applied to plasma samples from 48 healthy individuals and 48 individuals diagnosed with T2D. Results: Common throughout the entire sample set were three previously unreported variations of C-peptide. The relative contribution of one variant, subsequently identified as C-peptide (3-31), was found to be more abundant in the T2D population as compared to the healthy population. Dipeptidyl peptidase IV is suspected to be responsible for this particular cleavage product, which is consistent with the pathophysiology of T2D. Conclusions and clinical relevance: C-peptide does not exist in the human body as a single molecular species. It is qualitatively more heterogeneous than previously thought. These results lay a foundation for future studies devoted to a comprehensive understanding of C-peptide and its variants in healthy and diabetic populations.