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Evaluation of sFlt-1 and PlGF for predicting preeclampsia in pregnant women with diabetes mellitus

AIM: The aim of this study was to evaluate soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) levels in the blood of women with various types of diabetes mellitus, depending on the correction method applied, and to determine the prognostic significance of the sFlt-1 / PlGF ratio for predicting the development of preeclampsia in this patient population. 
MATERIALS AND METHODS: We examined 140 pregnant women who were included in six main study groups: type 1 diabetes mellitus (with or without pregravid preparation), type 2 diabetes mellitus (diet therapy or insulin therapy), and gestational diabetes mellitus (diet therapy or insulin therapy). The comparison groups consisted of pregnant women with preeclampsia and patients without complications of pregnancy. Using electrochemiluminescence analysis, PlGF and sFlt-1 levels in the blood serum were determined twice, at 11+013+6 and 30+033+6 weeks of gestation. Statistical data processing was performed using the IBM SPSS Statistics version 23 and GraphPad Prism version 8.0 software packages. 
RESULTS: In the blood serum of pregnant women with diabetes mellitus in the first and third trimesters of pregnancy, we found an increase in sFlt-1 level and a decrease in PlGF level, as well as an increase in the sFlt-1 / PlGF ratio. These changes were most pronounced in individuals with type 1 diabetes mellitus without pregravid preparation and with type 2 diabetes mellitus on insulin therapy. In patients with pregestational types of diabetes mellitus, the sFlt-1 / PlGF ratio was a predictor of preeclampsia already in the early stages of pregnancy. Analysis of the ROC curve showed that the threshold sFlt-1 / PlGF ratio for predicting preeclampsia in pregnant women with diabetes mellitus in the first trimester was 32.5 (sensitivity 92.9%, specificity 50.0%) and in the third trimester 71.8 (sensitivity 85.7%, specificity 82.3%) with AUC 0.78 (95% CI 0.680.88) and 0.89 (95% CI 0.830.95), respectively. In the first trimester, the positive and negative predictive values of the sFlt-1 / PlGF ratio as a predictor of preeclampsia in pregnant women with diabetes mellitus were 63.3% and 97.6%, respectively; in the third trimester, 38.9% and 93.6%, respectively. 
CONCLUSIONS: Blood level alterations of PlGF and sFlt-1 are characteristic of patients with diabetes mellitus in the first and third trimesters of pregnancy. An increase in the sFlt-1 / PlGF ratio is associated with a higher incidence of unfavorable perinatal outcomes in women with impaired carbohydrate metabolism. Determination of the sFlt-1 / PlGF ratio is a valid method for predicting the development or absence of preeclampsia in women with diabetes mellitus.