Prevention of Gestational Diabetes

Study Overview
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Brief Summary
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Pregnancy is a vulnerable period for both a mother and her developing child. The investigator hypothesizes that diet-induced glucose excursions in the pregnant mother are a key contributor to unfavourable brain development and epigenetic marks in the developing child. It is long known that metabolic conditions are influenced by maternal nutrition and that this can impact the unborn infant. The most prominent example is gestational diabetes (GDM). It is unclear at what point unfavourable changes in brain development occur during pregnancy. Unlike many previous trials, we plan to introduce healthy diet early in the first trimester. Comparative analyses of DNA methylation patterns in the offspring of women with or without GDM revealed preferentially methylated genes, particularly in pathways linked to metabolic diseases. NuPreGDM is a randomized, controlled, open label intervention trail. The investigator aims to assess the effect of individual diet counselling combined with CGM compared to regular diet on glucose levels and postprandial glycemic excursions during an OGTT in pregnancy. The investigator wants to assess the effect of dietary counselling combined with continuous glucose monitoring on GDM risk, glycaemia and pregnancy outcome, starting in the first trimester. The investigator further hypothesizes that improved glucose levels by a healthy diet will affect brain activity of the infant and prevent unfavourable epigenetic modifications. The investigator plans to include 50 pregnant women within gestational week 4 and 14 after the last menstruation, with elevated risk for development of (GDM). Participants will be randomized 1:1 to either diet modification group (intervention) or to standard diet group (control). In the current trial, the investigator aims to modulate maternal metabolism with periodic personalized diet counselling on the basis of continuous glucose monitoring (CGM) compared to regular diet throughout pregnancy. The investigator propose that a reduction in glucose excursions in the mother will lead to a healthy environment for the developing child and prevent altered brain activity in utero, which will be assessed by fMEG (fetal magnetoencephalography) during a 75g OGTT in gestational week 28. The investigator further planned to examine child's leucocytes from cord blood to assess whether a healthy diet of the mother prevented epigenetic alterations due to improved maternal glycaemia, as exploratory endpoint. The development of blood sugar levels of the mother postpartum will be assessed by an further OGTT 6-12 weeks postpartum.

Official Title
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Nutritional Prevention of Gestational Diabetes Mellitus

Conditions
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Gestational Diabetes

Intervention / Treatment
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* Behavioral: Diet Modification Group
* Other: Regular Diet Group


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pregnant women between gestational week 4 and 14 after the last menstruation (proof of b-human choriongonadotropin in urine or proof of pregnancy via ultrasound.) Pre-pregnancy overweight (pregravid BMI > = 27) or positive family history of type 2 diabetes or GDM in first-degree relatives or GDM in previous pregnancy or previous macrosomia (baby with birth weight > 4000 g) or advanced maternal age > = 40 years Ability to understand and voluntarily sign an informed consent document prior to any study related procedures. Exclusion Criteria: Age < 18 years Multiple pregnancy Pre-pregnancy Diabetes mellitus Intake of medication that interferes with glucose-metabolism, such as glucose lowering or increasing drugs at inclusion visit (e.g. Steroids, Antidiabetics, Insulin, Metformin) Treatment with drugs with central nervous actions Chronic alcohol disease and drug abuse Pre-existing cardiac condition Mental disorder Weight loss >10% in the previous 6 months GFR < 60 ml/min/1.73 m2 2-fold increased transaminase levels in reference to the upper standard Any other (clinical) condition that would endanger participant's safety or question scientific success according to a physician's opinion.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Diet Modification Group<br> | Behavioral: Diet Modification Group<br>* The diet modification group will receive diet counselling by an experienced dietician at least every four weeks throughout pregnancy starting in the first trimester. The dietary counselling will be guided by the individual glucose profiles obtained through flash glucose monitoring.<br>|
| Other: Regular Diet Group<br> | Other: Regular Diet Group<br>* Participants of the standard diet will receive general diet counselling on one occasion at the onset of the study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glycaemic excursion during an oral glucose tolerance test | The effect of a diet modification on glucose levels and postprandial glycemic excursions (AUC) during a 75g oral glucose tolerance test (OGTT) will be measured. | gestational week (GW) 24 - 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucose variability | The effect of diet modification during pregnancy on 24h glucose profiles and postprandial glycemic excursions (AUC) will be measured by flash glucose monitoring. | Gestational week 14,20, 28, 34 and one week postpartum | 
| Maternal weight gain during pregnancy | Body weight will be measured regularly during pregnancy. | Gestational week 14,20, 28, 34 | 
| Maternal insulin sensitivity | Whole body insulin sensitivity will be quantified from 5 point 75g oral glucose tolerance test. | gestational week (GW) 24 - 28 and 6-12 weeks postpartum | 
| Maternal insulin secretion | Insulin secretion will be quantified from 5 point 75g oral glucose tolerance test. | gestational week (GW) 24 - 28 and 6-12 weeks postpartum | 
| Fetal brain activity | Fetal brain activity will be assessed by fMEG (fetal magnetoencephalography). | Gestational week 28 | 
| Fetal heart rate variability | Fetal heart rate variability will be assessed by fMCG (fetal magnetocardiography). | Gestational week 28 | 
| Offsprings APGAR Score | APGAR of the newborn will be recorded at time of birth | Delivery | 
| Offsprings body weight | Body weight of the newborn will be recorded at time of birth | Delivery | 
| Offsprings body length | Length of the newborn will be recorded at time of birth | Delivery | 
| Offsprings head circumference | Head circumference of the newborn will be recorded at time of birth | Delivery | 
| Way of delivery | Way of delivery (cesarean section or vaginal delivery) will be documented | Delivery | 
| Time of delivery | Time of delivery will be recorded as gestational week | Delivery |