The objective of the present study was to investigate the predictive value of islet cell antibodies (ICA) and insulin autoantibodies (IAA) for development of diabetes in women with previous gestational diabetes (GDM). Two hundred and forty-one previous diet-treated GDM patients and 57 women without previous GDM were examined 2-11 years after the index pregnancy. In subgroups, plasma from the diagnostic OGTT during index pregnancy was analysed for ICA and IAA. Among the previous GDM patients, 3.7% had developed Type 1 diabetes and 13.7% Type 2 diabetes. Four (2.9%) of the 139 GDM patients tested for ICA were ICA-positive and three of these had Type 1 diabetes at follow-up, as well as three ICA-negative patients. The sensitivity, specificity, and predictive value of ICA-positivity for later development of diabetes were 50%, 99%, and 75%, respectively. None of the women was IAA-positive during pregnancy. In conclusion, the majority of the patients with GDM did not show evidence of ongoing autoimmune destruction of the beta cells during the index pregnancy. However, ICA-positive GDM patients had a high risk of developing Type 1 diabetes later in life.

Increased secretory demand from obesity-associated insulin resistance cannot explain elevated intact proinsulin and disproportionate hyperproinsulinemia in type 2 diabetes. This abnormality may be an integrated part of pancreatic beta-cell dysfunction in this disease.

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Human sera were tested for insulin antibodies by fluid and solid phase assays. Radioimmune titres determined with 125-I Tyr A14 insulin were not correlated with those obtained using insulin coated microplates and enzyme linked immunodetection (n = 60). Several reasons for this lack of correlation were found. Iodine substitution on the A14 residue of insulin may significantly alter the avidity of some insulin antibodies for their ligand; hence, disclosing a heretofore unsuspected pitfall for antibody determination by radioimmunoassay. Specificity for bovine insulin was easily demonstrable in fluid phase by comparing the binding of monoiodinated bovine, porcine and human insulin. By contrast, in solid phase assay, titres obtained with microplates coated with bovine or human insulin were almost equal, regardless of the serum specificity for bovine insulin. This lack of specificity of the solid phase assay is not due to denaturation or unavailability of the bovine specific epitope because: bovine specificity could be demonstrated by competitive assay, after preincubation of the serum with insulin of the different species; and, coating with crosslinked insulin dimers or oligomers instead of monomers did not unmask bovine specificity. It is concluded that radioimmune methods are best suited to study specificity but may be biased by the presence of the radioiodine label whereas solid phase assay detects low avidity antibodies with great efficiency but is less appropriate to study specificity.

[123I]Insulin was injected intravenously into rats and the distribution and kinetics of radioactivity were analyzed by external detection with a scintillation camera connected to a computer. When injected alone, [123I]insulin was rapidly taken up by the liver and to a smaller extent by the kidneys. After reaching a maximum at 3 to 5 minutes after injection, liver radioactivity rapidly declined and free iodide appeared in the plasma. After previous saturation of the insulin receptor compartment, [123I]insulin was concentrated by the kidneys only and the rate of appearance of free iodide was markedly decreased. The results demonstrate the potential usefulness of this noninvasive technique to visualize insulin interaction with the liver and kidneys and to study the rate of insulin degradation by each organ in vivo. Preliminary experiments in man demonstrate its feasibility and low radiotoxicity.