Twenty‐four‐hour urine insulin as a measure of hyperinsulinaemia/insulin resistance before onset of pre‐eclampsia and gestational hypertension

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Abstract
Objective  To evaluate levels of 24‐hour urine insulin excretion before the onset of pre‐eclampsia and gestational hypertension.Design  Nested case–control study within the Calcium for Preeclampsia Prevention (CPEP) study cohort.Setting  Five university medical centres in the United States.Sample  Cases had developed pre‐eclampsia (n= 70) or gestational hypertension (n= 142) in the absence of gestational diabetes. Controls (n= 429) had remained normotensive without gestational diabetes.Methods  Subjects were required to have had an adequate baseline 24‐hour urine collection prior to CPEP enrolment at 13–21 weeks. Controls were matched to cases by enrolment site and specimen storage time, without regard to gestational age or CPEP treatment. Adjusted mean 24‐hour urine insulin excretion was, however, calculated using analysis of covariance, with adjustment models for pre‐eclampsia considering body mass index, race and smoking status; and for gestational hypertension, gestational age at specimen collection, height, body mass index and smoking. Urine insulin was measured by radio‐immunoassay.Main outcome measures  Twenty‐four‐hour urine insulin excretion.Results  Adjusted 24‐hour urine insulin excretion at baseline (mean 17 weeks of gestation) was greater in women who developed pre‐eclampsia than in normotensive controls (mean [SE]: 15.6 [1.5] vs 13.1 [1.2] × 103μIU/24 hour, P= 0.06), but not in women who developed gestational hypertension (14.7 [0.9] vs 15.0 [0.6] × 103μIU/24 hour, P= 0.79, in cases vs controls). Among women who developed pre‐eclampsia, adjusted urine insulin excretion was greater than controls only in women with mild pre‐eclampsia and not in severe pre‐eclampsia (mild pre‐eclampsia vs controls: 17.3 [2.0] vs 13.7 [1.6] × 103μIU/24 hour, P= 0.04; severe pre‐eclampsia vs controls: 12.3 [2.2] vs 11.5 [1.2], P= 0.69).Conclusion  The data suggest that early hyperinsulinaemia, a marker of insulin resistance, may predispose to mild pre‐eclampsia.