Early Gestational Diabetes Mellitus

Study Overview
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Brief Summary
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In 2010, the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) panel published consensus-based recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Cognizant that milder degrees of hyperglycemia would also be detected by early pregnancy testing, the IADPSG recommended that fasting plasma glucose (FPG) in the range of 5.1-6.9 mmol/l should be considered diagnostic of early Gestational Diabetes Mellitus (GDM) even if the level of proof for this recommendation is very low regarding to prognosis. This threshold was extrapolated from the FPG value used between 24 and 28 weeks. In France, a FPG is proposed at the first prenatal visit for women with risk factors of GDM. Early GDM is diagnosed if FPG is ≥ 5.1 mmol/l, leading to an intensive metabolic management. Data have shown that GDM prevalence increased rapidly from 5.9% in 2009 to 9.3% in 2014. 26.9% of women with hyperglycemia during their pregnancy but without known diabetes are treated before 22 weeks' gestation (WG). More recent data from Italy and China, where IADPSG diagnosis criteria were applied, have strongly challenged this recommendation, and showed that early FPG ≥ 5.1mmo/L is poorly predictive of later GDM. No prior studies have demonstrated benefits to early screening and management. In 2016, the IADPSG members have suggested that the use of the FPG threshold ≥5.1 mmol/l for the identification of GDM in early pregnancy is not justified by current evidence

Official Title
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Late Versus Early Management of Gestational Diabetes Mellitus: a Non Inferiority Randomized Multicenter Trial

Conditions
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Gestational Diabetes

Intervention / Treatment
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* Other: late management strategy
* Other: early management strategy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pregnant woman Singleton pregnancy Early GDM defined by a fasting plasma glucose between 5.1 mmol/l and 6.1 mmol/ with at least one risk factor (age ≥35 years and/or BMI ≥ 25 kg/m2 and/or familial history of diabetes and/or personal history of GDM and/or personal history of macrosomia). First prenatal visit prior 20 weeks of gestation at the time of randomization. Signed informed consent Exclusion Criteria: Diabetic follow-up started at time of inclusion Pre-existing diabetes in pregnancy Renal impairment Hepatic insufficiency History of bariatric surgery Long time corticosteroids treatment Insufficient understanding Language difficulties Lack of social Insurance Person in emergency situation Person under the protection of justice (tutelage/ curatorship) Persons deprived of their liberty

Ages Eligible for Study
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Minimum Age: 18 Years

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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Early management GDM group<br>defined as no intervention until GDM screening at 24-28 weeks' gestation. If there is a diagnosis of GDM at 24-28 according to the IADPSG criteria), intensive metabolic treatment until delivery | Other: early management strategy<br>* early management of GDM defined as intensive metabolic treatment. Intensive treatment involved the following multidisciplinary approach: lifestyle defined by diet and exercise intervention according to the French guidelines<br>|
| Experimental: Late management GDM group<br>early management of GDM defined as intensive metabolic treatment (diet, physical activity self-blood glucose monitoring according and/or insulin therapy according to the French guidelines). This intensive treatment will begin after the randomization until delivery. | Other: late management strategy<br>* late management strategy of GDM defined as no intervention until GDM screening at 24-28 weeks. Between 24-28 weeks gestation, a 75-g OGTT will be done<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The occurrence of materno-fetal complications | Composite endpoint defined by Large for Gestational Age (LGA) (defined by birth weight ≥90th percentile, adjusted for gestational age, sex, maternal BMI, parity, ethnicity) and/or neonatal hypoglycemia and/or shoulder dystocia and/or birth traumatisms | at delivery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation between composite endpoint (defined in the outcome 1) and the 5 risk factors of GDM | Correlation between composite endpoint (defined in the outcome 1) and the 5 risk factors of GDM (age more or equal to 35 years, BMI more or equal to 25 kg/m2, familial history of diabetes, personal history of GDM, personal history of macrosomia) | at delivery | 
| Need for insulin during pregnancy | After at least 10 days of dietary and lifestyles measures, if the target are not achieved, women will receive insulin therapy. fastin glucose target <5.1 mmol/ and/or a 2 hour post prandial capillary glucose < 6.6 mmol/l at each 10 days a contact with the diabetologist or the nurses for the transmission of the capillary glycaemia either by phone or by the platform 'myDiabby | at each 10 days until delivery | 
| Metabolic data: Fasting plasma glucose | Change of value of fasting plasma glucose | at inclusion (because <20 weeks') and an average at 24 28 weeks of gestation | 
| Metabolic data: HbA1c | Change of value of HbA1c | at inclusion (because <20 weeks') and an average at 24 28 weeks of gestation | 
| Oral Glucose Tolerance Test (OGTT) |  | an average at 24 28 weeks of gestation | 
| Percent of GDM women in the late GDM management group according to the IADPSG criteria. | IADPSG criteria(fasting glucose more or equal to 5.1 mmol/l and/or 1h more or equal to 10.0 mmol/l and /or 2h more or equal to 8.5 mmol/l | an average at 24 28 weeks of gestation | 
| Number of complications in each subgroup of the late GDM management group | Maternal and neonatal complication | at delivery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Early gestational diabetes, pregnancy, fasting plasma glucose, diagnosis, prognosis