The influence of metabolic parameters on fetal development weight in women with type 1 diabetes and homozygotic variant in -2548 G/A of leptin gene and its 668 A/G receptor polymorphism

Abstract

Introduction: Leptin, as many other hormones and metabolic factors, may play a role in fetal development in pregnancy complicated by type 1 diabetes. Different genetic variants in leptin gene and leptin gene receptor may have influence on leptin synthesis in the course of pregnancy and metabolic state of the mother. Aim: To assess the possible influence of metabolic factors on fetal weight in type 1 diabetic subjects with homozygotic variants in leptin gene (-2548 G/A) and leptin gene receptor (668 G/A). Methods: 30 diabetic and homozygotic subjects (out of 100 diabetic subjects) were qualified to the study. Genotyping was performed by PCR-RFLP. The following factors were assessed: glycemia, leptin concentration, glycated hemoglobin, lipid profile (total cholesterol, LDL, HDL, triglycerides), maternal body weight. Multiple regression models were developed and ROC curves were used in the analysis. Results: Mean fetal weight in the analyzed group was 3600g. The following parameters were found to have influence on fetal weight: I trimester leptin (R2-0.80741288, p<0.05), I trimester glycemia (R2-0.80741288, p<0.05), III trimester glycemia (R2-0.80741288, p<0.05), I trimester HbA1C (R2-0.80741288, p<0.05), III trimester LDL (R2=0.63192254, p<0.05). Moreover, the influence of LDL and maternal BMI (R2-0.81869348, p<0.05) was found. ROC curve analysis revealed the influence of I trimester leptin - AUC 0.62; sensitivity 0.75; specificity 0.5; cut-off 28.127ng/ml, III trimester HbA1C AUC 0.66; sensitivity 0.23; specificity 0.91; cut-off 7.9%, III trimester mother’s weight AUC 0.63; sensitivity 0.25; specificity 0.93; cut-off 98kg. Conclusion: Apart from well-known metabolic factors influencing fetal weight, I trimester leptin concentration was found to have an impact on fetal growth.