Does insulin administration contribute to immune complex formation in diabetes?

The effect of insulin administration on immune complex (IC) formation in diabetic patients was analysed in vivo and in vitro. Firstly, serial studies of IC status were performed over a mean period of 18 months in 44 diabetic patients, 37 of whom were receiving standard insulin therapy. Thirty patients changed to monocomponent (MC) insulin while seven commenced MC insulin after tablet failure. The other seven patients remained on standard insulin throughout the study. Secondly, nine patients had serial measurements of IC over a 6-8 h period following a routine morning dose of MC insulin; eight control subjects were similarly studied. The insulin content of IC in insulin treated patients was assessed in vitro by examining, (a) the selective precipitation of antibody bound insulin by 3% polyethylene glycol (PEG) and (b) the insulin specificity of antisera raised against PEG precipitates of IC positive sera. The longitudinal study of circulating IC showed no significant changes apart from an isolated fall in IgA containing IC at 6 months after changing therapy (P less than 0.05). No short term change in IC was observed after MC insulin administration. The precipitability of antibody bound insulin in insulin treated patients was not significantly different to that seen in non-insulin treated patients or normal sera. Antisera to PEG precipitates of diabetic sera showed no significant specificity for insulin, although they showed marked reactivity with other plasma components (such as immunoglobulins and complement components). It is concluded that administered insulin plays little or no role in IC formation in insulin treated diabetic patients.