Genetic and Epigenetic Mechanisms of Developing Gestational Diabetes Mellitus and Its Effects on the Fetus

Study Overview
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Brief Summary
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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 trialr, open-label.

Detailed Description
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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.

Official Title
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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

Conditions
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Gestational Diabetes Mellitus

Intervention / Treatment
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* Other: Life-style modification, insulin therapy if needed
* Other: Life-style modification, insulin therapy if needed


Participation Criteria
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Eligibility Criteria
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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.
Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Women with GDM are randomised to 2 treatment groups: group 1 - treatment group with very tight glycemic targets (<5.1 mmol / L fasting glucose and <7.0 mmol / l hour after a meal) and group 2 - treatment group with tight-moderate glycemic targets (<5.3 mmol / L fasting glucose and <7.8 mmol / l in an hour after a meal).
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: very tight glycemic targets<br> | Other: Life-style modification, insulin therapy if needed<br>* 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<br>Other: Life-style modification, insulin therapy if needed<br>* 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<br>|
| Active Comparator: tight-moderate glycemic targets<br> | Other: Life-style modification, insulin therapy if needed<br>* 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<br>Other: Life-style modification, insulin therapy if needed<br>* 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<br>|
| No Intervention: Control group<br>Only observation in women with normal glucose tolerance | |

What is the study measuring?
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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 |
| --- | --- | --- |
| 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 |