Gestational Diabetes Mellitus
Conditions
Brief summary
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.
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).
Interventions
OTHERVery 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
OTHERTight-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
Sponsors
Federal State Budgetary Institution, V. A. Almazov Federal North-West Medical Research Centre, of the Ministry of Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention 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).
Eligibility
Sex/Gender
FEMALE
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| NR3C1 | within 24 hours after delivery | Level of expression of NR3C1 gene |
| ANGPTL4 | within 24 hours after delivery | Level of expression of ANGPTL4 gene |
| ADIPOQ | within 24 hours after delivery | Level of expression of ADIPOQ gene |
| LEP | within 24 hours after delivery | Level of expression of LEP gene |
| LGA newborns | within 24 hours after delivery | Number (%) of large for gestational age (LGA) newborns |
| TRIB1 | within 24 hours after delivery | Level of expression of TRIB1 gene |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| SGA newborns | within 24 hours after delivery | Number (%) of small for gestationa age (SGA) newborns |
| Methylation of candidate genes | within 24 hours after delivery | Levels of methylation (%) of candidate genes with confirmed differences in the expression in HUVECs isolated within 24 hours after delivery |
| rate of macrosomia | delivery | birth weight ≥4000 g |
| birthweight | delivery | birth weight (g) |
| length at birth | delivery | length at birth (cm) |
| rate of stillbirth | > 20 weeks | Foetal death in utero \> 20 weeks |
| rate of neonatal death | 1 month after delivery | death \<1 months after delivery |
| rate of shoulder dystocia | delivery | 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 |
| rate of birth trauma | delivery | bone fracture, damage to nerves |
| rate of preterm birth | delivery | babies born at \<37 weeks gestational age |
| gestational age | delivery | gestational age at delivery |
| rate of neonatal hypoglycemia | first 48 hours of age | plasma glucose level below 2.6 mmol/L within the first 48 hours of age |
| rate of neonatal respiratory distress syndrome | delivery | respiratory failure or distress |
| rate of jaundice | delivery | jaundice necessitating phototherapy and/or exchange transfusion |
| Rate of neonates with Apgar score <7 at 5 minutes | delivery | 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. |
| rate of NICU admission | within 72 hours postpartum | neonatal intensive care unit (NICU) admission |
| length of stay of infants admitted to neonatal intensive care unit | up to 30 days after delivery | length of stay of infants admitted to neonatal intensive care unit, days |
| cord blood C-peptide | delivery | cord blood C-peptide levels |
| rate of composite neonatal outcome | delivery | infant death, shoulder dystocia, bone fracture, and nerve palsy |
| rate of maternal death | within 42 days of termination of pregnancy | death of a woman while pregnant or within 42 days of termination of pregnancy |
| rate of eclampsia | from 20 weeks to delivery | generalized convulsions and/or coma |
| rate of placental abruption | before delivery | premature separation of the placenta from the uterine wall before delivery |
| rate of postpartum hemorrhage | delivery | requiring or offered blood transfusion or an operative procedure |
| rate of preeclampsia | from 20 weeks to delivery | onset of new hypertension and proteinuria and/or end-organ dysfunction after 20 weeks of gestation |
| rate of gestational hypertension | from 20 weeks to delivery | new-onset hypertension (140/90 mmHg or higher), without proteinuria after 20 weeks of gestation |
| rate of induction of labor | delivery | the use of medications or other methods to bring on (induce) labour |
| rate of perineal trauma | delivery | perineal or deep vaginal laceration |
| rate of operative vaginal delivery (vacuum extraction) | delivery | application of vacuum to the foetal head |
| gestational weight gain | delivery | Weight from preconception until last weight measured within 4 weeks before delivery. |
| blood pressure at admission to the birth unit | at admission to the birth unit | blood pressure at admission to the birth unit, mm Hg |
| rate of maternal hypoglycemia | during pregnancy | typical symptoms with capillary glucose \<3.9 mmol/L, or, if asymptomatic, by capillary glucose \<3.3 mmol/L |
| insulin therapy requirements | from 12 weeks to delivery | Prescription of insulin treatment |
| rate of stroke | during pregnancy or within 42 days after delivery | Maternal sudden loss of brain function due to blocked or burst blood vessels during pregnancy or postpartum. |
| rate of acute pulmonary oedema | During pregnancy of within 42 days after delivery | Maternal acute pulmonary oedema |
| rate of cardiac arrest | During pregnancy or within 42 days after delivery | Maternal cardiac arrest |
| 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 | — |
| Cesarian sections | within 24 hours after delivery | Number (%) of deliveries by Cesarian sections |
Other
| Measure | Time frame | Description |
|---|---|---|
| HbA1c | 36 week | HbA1c level, % |
| glycaemic control parameters | from 12 weeks to delivery | mean fasting and postprandial capillary glucose, adherence to target ranges via self-monitoring |
| lipid profile | 36 week | levels of serum total cholesterol, low density lipoproteins, high density lipoproteins , triglycerides, mmol/L |
| fasting glucose | 36 week | fasting plasma glucose level, mmol/L |
Countries
Russia
Outcome results
None listed