IMMUNORADIOMETRIC ASSAY OF HUMAN INTACT PROINSULIN APPLIED TO PATIENTS WITH TYPE-2 DIABETES, IMPAIRED GLUCOSE-TOLERANCE, AND HYPERANDROGENISM

We describe an immunoradiometric assay for human intact proinsulin in serum. In this method, one monoclonal antibody, coated onto polyacryla mide beads, cross-reacts with proinsulins and insulin. A sandwich is f ormed with intact proinsulin, split (65-66) proinsulin, and des (64-65 ) proinsulin binding with an I-125-labeled monoclonal antibody specifi c for an epitope at the intact B-C junction of proinsulin. Because spl it (65-66) and des (64-65) proinsulin concentrations are very low in s erum, this assay essentially measures intact proinsulin. When we used 1-mL serum samples, the mean detection limit was 0.4 pmol/L. Mean proi nsulin concentrations (pmol/L) were 3.4 (range 1-9.1) in healthy fasti ng subjects, 28.5 (9.7-101) in patients with type 2 diabetes (treated with metformin and sulfonylureas), 5.0 (1.6-9.3) in women with hyperan drogenism and normal insulinemia, 10.3 (2.6-36) in women with hyperand rogenism and hyperinsulinemia, and 8.5 (4.8-21.3) in patients with imp aired glucose tolerance.