C‐peptide and Proinsulin after Oral Glucose

ABSTRACT. Radioimmunoassays (RIA) for C‐peptide and proinsulin have been developed and their sources of error investigated. Immunoreactive insulin (IRI), C‐peptide and proinsulin were determined prior and up to 3 hours after glucose load in 13 non‐diabetics. Fasting proinsulin constituted 35% of the IRI (μU/μU), but the proportion of proinsulin increased at 2 and 3 hours to about 47 % and 70%. Since this percent depends on the reactivity of proinsulin in the insulin RIA an improved method of expressing the relationship between proinsulin and insulin was used. The insulin concentration (IRI μU/ ml—proinsulin μU/ml) was determined and the molar ratio between proinsulin: insulin calculated. It was 0.83±0.45 at fasting and 0.28±0.14 at 15 min. At 1.5 hours the ratio was 1.30±0.78 and continued to rise in most persons. Proinsulin: C‐peptide was 0.051 at fasting, not changing much during the first hour, after which the ratio increased to 0.113 and 0.141 at 2 and 3 hours, respectively. Thus proinsulin may be secreted in increasing quantities as compared to insulin and C‐peptide in the late phase of a heavy oral glucose load. The B‐cell activity in insulin treated diabetics may be evaluated by C‐peptide determinations. In serum with insulin antibodies, bound proinsulin has to be removed prior to C‐peptide determination to avoid falsely high C‐peptide estimates. The most simple method is a PEG precipitation of the antibody complexes. C‐peptide is then estimated in the 12.5% PEG‐containing supernatant. It was found to be important to prepare the standards in 12.5% PEG to obtain correct results.