During insulin secretion, C-peptide is enzymatically cleaved off and cosecreted in equimolar proportion with mature insulin molecules. In most disease conditions associated with abnormal serum insulin levels, the changes in serum C-peptide levels parallel insulin-related alterations (insulin to C-peptide molar ratio < or =1). Both serum C-peptide and serum insulin levels are elevated in renal failure and in disease states that lead to augmented primary endogenous insulin secretion (eg, insulinoma, sulfonylurea intoxication). Discordant serum insulin and serum C-peptide abnormalities are mainly observed in 2 situations: exogenous insulin administration and the presence of anti-insulin autoantibodies.