Impact of Two Standardized Clinical Care Protocols on Pregnancy Outcomes in Women With Monogenic Diabetes MODY2
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 46
- 试验地点
- 1
- 主要终点
- Birth weight for gestational age
研究概览
简要总结
Maturity-onset diabetes of youth (MODY) are the most frequent monogenic diabetes with autosomic dominant inheritance (2% of diabetes). The MODY2 diabetes is related to a defect in the glucokinase (GCK) enzyme, the first limiting step of insulin secretion. An abnormal GCK leads to a delayed insulin secretion. Patients with GCK mutations have only mild raised fasting plasma glucose. Treatment is usually unnecessary since hyperglycemia is stable and MODY2 patients have no microvascular complications of diabetes. In contrast, pregnancy in MODY2 women is a challenging situation. A non-mutated fetus will produce excess insulin in response to raised maternal blood glucose leading to an accelerated growth and a higher risk of macrosomia. The mother of non-mutated fetus should therefore be treated to normalize her blood glucose levels. On contrary, a mutated fetus will produce a delayed insulin secretion (as his MODY2 mother) in response to maternal hyperglycemia. Consequently insulin therapy during pregnancy would reduce fetal insulin secretion and result in a low birth weight.
Moreover, insulin therapy exposes pregnant women to more labor induction, prematurity and cesarean deliveries. In these MODY2 women whose glucose set point is physiologically higher, glycemic goals are difficult to achieve while often requiring extensive insulin therapy. An optimal situation would consist in initiating insulin therapy only for women with non-mutated offsprings. Unfortunately no antenatal diagnosis of the GCK mutation on fetal cells is available yet. In literature, birth weight differences between mutated and non-mutated neonates may reach up to 700g. In clinical practice, two strategies are used but without standardized protocol on glycemic targets, delay and doses of insulin : 1) insulin at diagnosis of pregnancy 2) treatment based on fetal abdominal circumference and fetal weight measurements by ultrasonography (US) and initiated if fetal biometry is greater than the 75th percentile.
The purpose of the study is to evaluate for the first time these two management strategies through a prospective and standardized study. Hypothesis: US assessment would be sufficient to identify fetuses at risk of macrosomia and to initiate insulin treatment in mothers.
详细描述
Study design The investigators propose to conduct a national multicenter prospective study on the clinical management of pregnancy in women with GCK mutations.
Medical management of the pregnancy After obtaining written informed consent, each investigator of the Diabetes Departments will include MODY2 women, at the time of gestation planning or at the first prenatal appointment. Pre-gestational maternal parameters (maternal age, pre-gestational weight, blood glucose, mean blood glucose levels before and 2 hours post prandial over one week when available, HbA1c, parity, medical history of macrosomia) will be collected.
Antenatal care will be provided according to the local routine protocol for MODY2. All women will receive dietary and physical activity counselling according to current recommendations for pregnant women with pregestational diabetes. Vitamin B9, 0.4 or 5 mg/day, according to local habits, will be prescribed as usual care from pregestational appointment until the end of first trimester.
- Women with a pregestational HbA1c ≥ 6.5 % will be systematically treated with insulin because of a potential increase in the malformation rate as documented in women with type 1 diabetes (Bell, Glinianaia et al. 2012).
- In women with pregestational HbA1c < 6.5%, insulin therapy will be initiated either according to capillary maternal blood glucose target values or according to fetal growth assessed by ultrasonography, according to each Diabetes Department habits.
In both groups, care will be standardized as follows:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Women diagnosed with a GCK mutation before pregnancy
- •Aged ≥ 18 years old
- •Pre-gestational BMI < 30kg/m²
- •Term of pregnancy < 14 WG , if delay overdue, to be validated by investigators
- •Written informed consent
排除标准
- •Twin pregnancy
- •Not able to understand and sign written informed consent
- •Not affiliated to the French Social Security
研究组 & 干预措施
Insulin therapy from the beginning of pregnancy
Insulin therapy (Glargine/Lantus®, Détémir/Levemir® , Insulatard® , Umuline NPH® , Lispro/Humalog® , Asparte/Novorapid® or Actrapid ®) administered from the beginning of pregnancy according to maternal blood glucose (if fasting blood glucose > 0.95g/l or post-prandial blood glucose > 1.20g/l) as recommended by the national guidelines for gestational diabetes mellitus.
Insulin administered to patients either by subcutaneous injections or by pump.
干预措施: insulin therapy (Other)
Insulin therapy initiated according to fetal growth
Insulin therapy (Glargine/Lantus®, Détémir/Levemir® , Insulatard® , Umuline NPH® , Lispro/Humalog® , Asparte/Novorapid® or Actrapid ®) initiated according to fetal growth evaluated by ultrasonography measurements. MODY2 women will not be treated with insulin until delivery, except when the fetal abdominal circumference exceeds ≥ the 75 percentile on one US or maternal fasting capillary blood glucose is ≥ 1,20 g/L or maternal post-prandial capillary blood glucose is ≥ 2,00 g/L.
Insulin administered to patients either by subcutaneous injections or by pump.
干预措施: insulin therapy (Other)
结局指标
主要结局
Birth weight for gestational age
时间窗: at birth
this end point will sustain two derived criteria: birth weight for gestational age as a quantitative criterion and birth weight considered as small (below the 10th percentile), normal, or large (above the 90th percentile).
次要结局
- Neonatal leptin level(at birth)
- Number of neonatal hypoglycaemia(at birth)
- Number of hyperinsulinemia(at birth)
- Weight gain during pregnancy(at 38 weeks of pregnancy)
- Number of fetal and neonatal complications(at birth)
- Composite obstetrical outcome(at birth)
- Mean blood glucose levels(before and 2 hours post prandial over one week, at weeks 36-38 of pregnancy)
- Post-prandial hyperglycaemic peak (level and delay)(at 32 weeks of pregnancy)
- HbA1c level(pre-gestational and monthly during pregnancy)
- Fructosamine level(monthly during pregnancy)
- Number of women requiring insulin treatment(at 38 weeks of pregnancy)
- Term of insulin therapy(at 38 weeks of pregnancy)
- Type of insulin(at 38 weeks of pregnancy)
- Number of injections(at 38 weeks of pregnancy)
- Number of units/kg.day of insulin(over one week at weeks 14/16, 25/27 and 36/38)
- Number of pregnancy induced hypertension(at delivery)
- Number of preeclampsia(at delivery)
- Number of medical appointments(at delivery)
- Duration of hospital stay(at delivery)
- depression (Edinburgh Postnatal Depression Scale.(at delivery)
- Quality of Life (SF-36 questionary)(at delivery)
- Anxiety score (short form of the Spielberger State - Trait Anxiety Inventory(at delivery)
- Mean blood glucose levels(before and 2 hours post prandial over one week, before pregnancy)
- Mean blood glucose levels(before and 2 hours post prandial over one week, at weeks 14-16 of pregnancy)
- Mean blood glucose levels(before and 2 hours post prandial over one week, at weeks 25-27 of pregnancy)
- Post-prandial hyperglycaemic peak (level and delay)(at 22 weeks of pregnancy)