Clinica Chimica Acta 284 (1999) 1–13 Dynamic changes in plasma proinsulin / insulin ratio during insulin secretion influence correlation between radioimmunoassay (RIA) and IMX measurements of insulin a, a a * Douglas F. Stickle , Mark A. Reynolds , Martin D. Morris , b Michael J. Quon a Department of Pathology, Brooke Army Medical Center, Fort Sam Houston, TX, USA b National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA Received 30 June 1998; received in revised form 2 September 1998; accepted 1 October 1998 Abstract Because proinsulin and insulin have different circulatory half-lives, the ratio of proinsulin to insulin in plasma depends on the dynamics of insulin secretion. This variation can potentially influence comparison of IMX assays and radioimmunoassays (RIAs) for [insulin], given that the antibody used in the IMX assay has negligible cross-reactivity with proinsulin compared to the 40% cross-reactivity with proinsulin of the antibody used in the RIA. Simulation of a simple mass balance model for insulin and proinsulin concentrations during an oral glucose tolerance test predicts that the ratio (R) of RIA to IMX insulin measurements of [insulin] should transiently decrease, pass through a minimum, increase past the initial value, pass through a maximum and eventually return to the initial value. Using time course specimens from patients, this pattern of variation in R was observed in the majority (12 / 16) of cases studied. The variation in R for time course specimens (CV5 26%) was significantly greater than for other specimens (fasting, random or undesignated; P , 0.05). Thus, when comparing IMX and RIA measurements of [insulin], variation in R for samples from differing states of dynamic insulin secretion contains a component that is attributable to dynamic changes in the ratio of [proinsulin] / [insulin] in plasma. Published by Elsevier Science B.V. Keywords: Insulin; Proinsulin; RIA; IMX *Corresponding author. Tel.: 11-210-295-4332; fax: 11-210-295-4645. E-mail address: douglas.stickle@amedd.army.mil (D.F. Stickle) 0009-8981 / 99 / $ – see front matter Published by Elsevier Science B.V. PII: S0009-8981(99)00072-8