Exploration of the Lipid Metabolism During the Diabetic Pregnancies (DIAMANT)

Exploration of the Lipid Metabolism During the Diabetic Pregnancies and Research for New Biological Predictors to Nutritional Interventions

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.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus; Pregnancy; Type 1 Diabetes Mellitus; Pregnancy in Diabetes
• Intervention / Treatment: Other: blood tests; Other: diet questionnaire; Other: umbilical cord blood collect; Other: placenta collect

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 186
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Lille, France, 59037
    • CHRU, Lille

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• pregnant women included before 16 amenorrhea weeks

Exclusion Criteria:

• obesity (BMI > 40kg/m2)
• subject became pregnant with medical infertility treatment
• tobacco > 10
• suspected abuse of alcohol

Study Plan

How is the study designed?

Design Details

• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: type 1 diabetic pregnant women	Other: blood tests; 3 measures during pregnancy and 1 at post partum, 1 measure at time of delivery from fetal cord; Other: diet questionnaire; questions about nutrition before and during pregnancy; Other: umbilical cord blood collect; collected at the delivery; Other: placenta collect; collected at the delivery
Other: type 2 diabetic pregnant women	Other: blood tests; 3 measures during pregnancy and 1 at post partum, 1 measure at time of delivery from fetal cord; Other: diet questionnaire; questions about nutrition before and during pregnancy; Other: umbilical cord blood collect; collected at the delivery; Other: placenta collect; collected at the delivery
Other: healthy pregnant women; healthy pregnant women with normal glucose tolerance	Other: blood tests; 3 measures during pregnancy and 1 at post partum, 1 measure at time of delivery from fetal cord; Other: diet questionnaire; questions about nutrition before and during pregnancy; Other: umbilical cord blood collect; collected at the delivery; Other: placenta collect; collected at the delivery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
fetal weight corrected by gestational age	just after delivery

Secondary Outcome Measures

Outcome Measure	Time Frame
cholesterol (total, HDL, LDL)	3 measures during pregnancy and 1 at post partum, 1 measure at time of delivery from fetal cord
triglycerides	3 measures during pregnancy and 1 at post partum, 1 measure at time of delivery from fetal cord
Apolipoprotein A/B rate	3 measures during pregnancy and 1 at post partum, 1 measure at time of delivery from fetal cord
erythrocytary and plasmatic fatty acid distribution	3 measures during pregnancy and 1 at post partum, 1 measure at time of delivery from fetal cord

Collaborators and Investigators

• Sponsor: University Hospital, Lille
• Collaborators: Ministry of Health, France
• Investigators: Study Director: Anne VAMBERGUE, MDPHD, University Hospital, Lille; Principal Investigator: Isabelle FAJARDY, PharmD, Univesity Hospital, Lille; Principal Investigator: Annie MARTIN, PharmD PhD, University Hospital, Lille; Principal Investigator: Gilbert BRIAND, PhD, University Hospital, Lille; Principal Investigator: Jean ROUSSEAUX, MDPhD, University Hospital, Lille; Principal Investigator: Damien SUBTIL, MD, University Hospital, Lille; Principal Investigator: Philippe DUFOUR, MD, University Hospital, Lille; Principal Investigator: Pierre FONTAINE, MDPHD, University Hospital, Lille; Principal Investigator: Philippe DERUELLE, MD, University Hospital, Lille; Principal Investigator: Salha FENDRI, MD, Amiens University Hospital; Principal Investigator: Françoise LE GOUEFF, MD, Centre Hospitalier de Roubaix; Principal Investigator: Delphine VINCENT-DESPLANQUE, MD, Centre Hospitalier de Roubaix; Principal Investigator: Lucie BRESSON, MD, Lille University Hospital; Principal Investigator: Eleonore DELARUE, MD, University Hospital of Lille; Principal Investigator: Odile GAGNEUR, MD, University Hospital of Lille

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (Actual): January 1, 2012
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: March 14, 2008
• First Submitted That Met QC Criteria: March 19, 2008
• First Posted (Estimate): March 20, 2008

Study Record Updates

• Last Update Posted (Estimate): June 1, 2016
• Last Update Submitted That Met QC Criteria: May 31, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: diabetes; pregnancy; placenta; macrosomia; nutritional factors; lipidics markers; umbilical blood cord
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Pregnancy Complications; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diabetes Mellitus, Type 1; Pregnancy in Diabetics
• Other Study ID Numbers: 2007/0714; 2007-A00534-49 (Other Identifier: ID-RCB number, ANSM); PHRC 2007/R1901 (Other Identifier: DHOS); DGS 2007-0340 (Other Identifier: AFSSAPS)