Genetic and Epigenetic Mechanisms of Developing Gestational Diabetes Mellitus and Its Effects on the Fetus (GEM GDM)

Genetic and Epigenetic Mechanisms of Developing Gestational Diabetes Mellitus and Its Effects on the Fetus: a Randomised Controlled Trial of Different Glycemic Targets During Pregnancy

This is a randomized controlled trial of different glycemic targets during tratment of women with GDM with assessement of epygenetic aspects of their effects on the fetus and pregnancy outcomes. This study is interventional, randomised controlled trial, open-label.

Study Overview

• Status: Completed
• Conditions: Gestational Diabetes Mellitus
• Intervention / Treatment: Other: Very tight glycemic targets, life-style modification, insulin therapy if needed; Other: Tight-moderate glycemic targets, life-style modification, insulin therapy if needed

Detailed Description

The study aims to clarify the effect of hyperglycemia and its correction, the level of physical activity and consumption of major macro- and micronutrients by women during pregnancy on DNA methylation and expression of genes involved in neuroendocrine regulation and development of metabolic diseases in offspring, as well as functional characteristics of human umbilical vein endothelial cells (HUVECs). For the purpose of the study women with GDM are randomised to 2 treatment groups per glycemic targets ( very tight and tight-moderate glycemic targets). Data on glycenmic levels during the study and consumption of major macro- and micronutrients will be collected using a mobile application with electronic dairies report forms.

This clinical trial record primarily describes the overarching observational cohort study "Genetic and Epigenetic Mechanisms of Developing Gestational Diabetes Mellitus and Its Effects on the Fetus" including women with GDM and healthy pregnant women.

Substudy Protocol: A key predefined component of this larger study is an interventional, randomized controlled substudy entitled "Tight versus less tight glycaemic targets for women with gestational diabetes mellitus: a randomised controlled trial" (also known as the GEM GDM Trial).

The GEM GDM Trial is an open-label, randomized controlled trial (RCT) that compares the effects of tight (very tight) versus less tight (tight-moderate) glycemic control on maternal and neonatal outcomes in women diagnosed with Gestational Diabetes Mellitus (GDM). Participants from the main GEM cohort who are diagnosed with GDM according to International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria are eligible for screening and subsequent randomization into this substudy.

The substudy aims to enroll 650 pregnant women with a singleton pregnancy and GDM, randomly assigning them in a 1:1 ratio to one of two glycemic target groups.

• Tight Target Group: Fasting capillary glucose <5.1 mmol/L (<92 mg/dL); 1-hour postprandial glucose <7.0 mmol/L (<126 mg/dL).
• Less Tight Target Group: Fasting capillary glucose <5.3 mmol/L (<95 mg/dL); 1-hour postprandial glucose <7.8 mmol/L (<140 mg/dL).

• Study Type: Interventional
• Enrollment (Actual): 850
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Russia
  • Saint Petersburg, Russia, 197341
    • Almazov NMRC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Pregnant women with GDM diagnosed according to the Russian national consensus and the recommendations of the International Association of Diabetes and Pregnancy Study Groups (fasting glucose of ≥5.1 mmol/L, and/or ≥10.0 mmol/L after 1 h, and/or ≥8.5 mmol/L after 2 h in oral glucose tolerance test (OGTT) with 75 g of glucose).
• Gestational age at the time of inclusion in the study 12 weeks 0 days - 31 weeks 6 days
• For control group: pregnant women with normal glucose tolerance confirmed by OGTT at 24-31 weeks of gestation.

Exclusion Criteria:

• Diabetes mellitus type 1 and tipe 2
• Other deseases that affect methabolism of carbohydrates
• Use of drugs that affect methabolism of carbohydrates
• Malformations of the fetus identifired prior to inclusion to the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: very tight glycemic targets	Other: Very tight glycemic targets, life-style modification, insulin therapy if needed; All patients are assigned to life-style modification (diet and physical exercise). If target glucose levels (<5.1 mmol/L fasting and <7.0 mmol/L postprandial) are not achieved insulin therapy is started; Other Names: Tight glycemic targets
Active Comparator: tight-moderate glycemic targets; Less tight glycemic targets	Other: Tight-moderate glycemic targets, life-style modification, insulin therapy if needed; All patients are assigned to life-style modification (diet and physical exercise). If target glucose levels (<5.3 mmol/L fasting and <7.8 mmol/L postprandial) are not achieved insulin therapy is started
No Intervention: Control group; Only observation in women with normal glucose tolerance

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
LGA newborns	Number (%) of large for gestational age (LGA) newborns	within 24 hours after delivery
TRIB1	Level of expression of TRIB1 gene	within 24 hours after delivery
LEP	Level of expression of LEP gene	within 24 hours after delivery
ADIPOQ	Level of expression of ADIPOQ gene	within 24 hours after delivery
ANGPTL4	Level of expression of ANGPTL4 gene	within 24 hours after delivery
NR3C1	Level of expression of NR3C1 gene	within 24 hours after delivery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
rate of preeclampsia	onset of new hypertension and proteinuria and/or end-organ dysfunction after 20 weeks of gestation	from 20 weeks to delivery
rate of eclampsia	generalized convulsions and/or coma	from 20 weeks to delivery
rate of neonatal death	death <1 months after delivery	1 month after delivery
Cesarian sections	Number (%) of deliveries by Cesarian sections	within 24 hours after delivery
SGA newborns	Number (%) of small for gestationa age (SGA) newborns	within 24 hours after delivery
Methylation of candidate genes	Levels of methylation (%) of candidate genes with confirmed differences in the expression in HUVECs isolated within 24 hours after delivery	within 24 hours after delivery
rate of macrosomia	birth weight ≥4000 g	delivery
birthweight	birth weight (g)	delivery
length at birth	length at birth (cm)	delivery
rate of stillbirth	Foetal death in utero > 20 weeks	> 20 weeks
rate of shoulder dystocia	vaginal cephalic delivery in which, after the head is delivered and gentle traction proves unsuccessful, additional obstetric maneuvers are required to complete the delivery of the fetus	delivery
rate of birth trauma	bone fracture, damage to nerves	delivery
rate of preterm birth	babies born at <37 weeks gestational age	delivery
gestational age	gestational age at delivery	delivery
rate of neonatal hypoglycemia	plasma glucose level below 2.6 mmol/L within the first 48 hours of age	first 48 hours of age
rate of neonatal respiratory distress syndrome	respiratory failure or distress	delivery
rate of jaundice	jaundice necessitating phototherapy and/or exchange transfusion	delivery
rate of NICU admission	neonatal intensive care unit (NICU) admission	within 72 hours postpartum
length of stay of infants admitted to neonatal intensive care unit	length of stay of infants admitted to neonatal intensive care unit, days	up to 30 days after delivery
cord blood C-peptide	cord blood C-peptide levels	delivery
rate of composite neonatal outcome	infant death, shoulder dystocia, bone fracture, and nerve palsy	delivery
rate of maternal death	death of a woman while pregnant or within 42 days of termination of pregnancy	within 42 days of termination of pregnancy
rate of placental abruption	premature separation of the placenta from the uterine wall before delivery	before delivery
rate of postpartum hemorrhage	requiring or offered blood transfusion or an operative procedure	delivery
rate of gestational hypertension	new-onset hypertension (140/90 mmHg or higher), without proteinuria after 20 weeks of gestation	from 20 weeks to delivery
rate of induction of labor	the use of medications or other methods to bring on (induce) labour	delivery
rate of perineal trauma	perineal or deep vaginal laceration	delivery
rate of operative vaginal delivery (vacuum extraction)	application of vacuum to the foetal head	delivery
gestational weight gain	Weight from preconception until last weight measured within 4 weeks before delivery.	delivery
blood pressure at admission to the birth unit	blood pressure at admission to the birth unit, mm Hg	at admission to the birth unit
rate of maternal hypoglycemia	typical symptoms with capillary glucose <3.9 mmol/L, or, if asymptomatic, by capillary glucose <3.3 mmol/L	during pregnancy
insulin therapy requirements	Prescription of insulin treatment	from 12 weeks to delivery
rate of stroke	Maternal sudden loss of brain function due to blocked or burst blood vessels during pregnancy or postpartum.	during pregnancy or within 42 days after delivery
rate of acute pulmonary oedema	Maternal acute pulmonary oedema	During pregnancy of within 42 days after delivery
rate of cardiac arrest	Maternal cardiac arrest	During pregnancy or within 42 days after delivery
rate of maternal respiratory arrest		During pregnancy or within 42 days after delivery
rate of maternal respiratory distress syndrome		During pregnancy or within 42 days after delivery
rate of maternal deep vein thrombosis or pulmonary embolus requiring anticoagulant therapy		During pregnancy or within 42 days after delivery
rate of maternal haemolysis		During pregnancy or within 42 days after delivery
Rate of neonates with Apgar score <7 at 5 minutes	A measure of the health of a newborn infant done at 5 min. The newborn is given points (0, 1, 2) for heart rate, respiratory effort, muscle tone, response to stimulation and skin coloration. A score of 10 points indicates excellent health.	delivery

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
HbA1c	HbA1c level, %	36 week
fasting glucose	fasting plasma glucose level, mmol/L	36 week
lipid profile	levels of serum total cholesterol, low density lipoproteins, high density lipoproteins , triglycerides, mmol/L	36 week
glycaemic control parameters	mean fasting and postprandial capillary glucose, adherence to target ranges via self-monitoring	from 12 weeks to delivery

Collaborators and Investigators

• Sponsor: Federal State Budgetary Institution, V. A. Almazov Federal North-West Medical Research Centre, of the Ministry of Health
• Investigators: Study Director: Griniva Elena, MD, PhD, Almazov NMRC

Publications and helpful links

General Publications

• Hofer OJ, Martis R, Alsweiler J, Crowther CA. Different intensities of glycaemic control for women with gestational diabetes mellitus. Cochrane Database Syst Rev. 2023 Oct 10;10(10):CD011624. doi: 10.1002/14651858.CD011624.pub3.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2015
• Primary Completion (Actual): June 10, 2022
• Study Completion (Actual): December 1, 2024

Study Registration Dates

• First Submitted: November 13, 2017
• First Submitted That Met QC Criteria: July 25, 2018
• First Posted (Actual): August 1, 2018

Study Record Updates

• Last Update Posted (Estimated): November 21, 2025
• Last Update Submitted That Met QC Criteria: November 18, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Endocrine System Diseases; Female Urogenital Diseases and Pregnancy Complications; Metabolic Diseases; Pregnancy Complications; Glucose Metabolism Disorders; Diabetes Mellitus; Nutritional and Metabolic Diseases; Diabetes, Gestational; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc
• Other Study ID Numbers: 15-14-30012

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No