Measurement of serum C-peptide immunoreactivity by radioimmunoassay in insulin-dependent diabetics

A radioimmunoassay for C-peptide utilizing synthetic C-peptide as an antigen and tyrosylated synthetic C-peptide for iodination was evaluated for its clinical use. Mean fasting C-peptide levels in 24 normal subjects was 2.6 +/- 0.8 ng/ml. During the oral glucose tolerance test, baseline C-peptide in five normal subjects was 1.5 +/- 0.8 ng/ml, and at 60 min was 5.6 +/- 1.6 ng/ml. For two insulin-dependent diabetic patients, diagnoses of factitious hypoglycemia were documented on the basis of simultaneous free insulin and C-peptide determinations. Sera from 24 insulin-dependent diabetics were analyzed for free and total immunoreactive C-peptide and insulin levels. For 20% of juvenile and 64% of maturity-onset diabetics, the presence of proinsulin-like material bound to insulin antibodies was demonstrated by measurement in unextracted serum. This accounted for 20% to 100% of total C-peptide immunoreactivity in these patients. Simple polyethylene glycol precipitation of immune complexes and the measurement of free immunoreactive C-peptide in the supernatant demonstrated subnormal levels (less than 0.5 ng/ml) in all juvenile diabetics and normal levels (1.8 +/- 1.3 ng/ml) in 70% of maturity-onset diabetics.