Exploration of the Lipid Metabolism During the Diabetic Pregnancies

Overview

Justification: Intrauterine exposure to type 1 or type 2 diabetes increase the risk of macrosomia (35 % to 50 % versus 10 % in general population) despite a good glycemic control. The consequences are : shoulder's dystocia, lung immaturity, caesarean section, neonatal hypoglycaemia and a high frequency of obesity and metabolic disorders in adults. The mechanisms of macrosomia are unclear; chronic hyperglycemia and subsequent hyperinsulinaemia observed during the diabetic pregnancy might explain only partially the fetal weight. Considerable interest has been generated over the last decade on the lipids and fatty acids alterations in diabetes pregnancies. Change in lipoproteins metabolism have been described associated with macrosomia. Maternal nutrition before and during pregnancy plays an important role in fetal growth and subsequent development of an increased susceptibility to obesity and diabetes in later life. Main objective: Looking for an association between maternal and fetal blood lipid parameters and birth weight and body fat in a context of type 1 or type 2 diabetes. Secondary objectives: * Identify lipid markers associated with fetal macrosomia. * Analyze the placenta by measuring the expression of genes implicated in the storage and the transfer of fatty acids. * Analyze and compare the expression level of placental genes subjected to parental imprinting and validated in animal models.

Plan of study: Longitudinal study on 3 groups: 70 type 1 diabetic women, 70 type 2 diabetic women and 70 women with normal glucose tolerance during pregnancy. Recruitment in the department of Diabetology and Obstetrics of CHRU of Amiens and Lille. Nutritional survey and sampling of blood in the 1st, 2nd and 3rd trimester of pregnancy and at 6 weeks post partum. Collection of cord blood and placental tissues. Histological and molecular analysis of placenta will be realized both in the departments of Anatomopathology of Lille and Amiens and in Biochemistry Molecular Biology of CHRU of Lille. Homocysteine and folate assays on cord blood will be centralized in Paris (Hospital St Louis). Main criteria of judgment Fetal weight corrected by the gestational age. Expected results: * An inverse correlation between maternal and fetal blood fatty acids ratios (polyunsaturated fatty acids/ monounsaturated fatty acids + saturated) and birth weight in the diabetic groups. * Differences of distribution of fatty acids of maternal and foetal erythrocytic phospholipids correlated with the fetal weight. * Qualitative and quantitative variations of expression of placental genes such as lipases and genes submitted to parental imprinting. The biologic parameters will be confronted with the data of the nutritional survey and with glycemic control during pregnancy.