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Thesis

French

ID: <

10670/1.4jgl0i

>

Where these data come from
Determinants of neonatal and maternal hypoglycemia in women with gestational diabetes treated with glyburide

Abstract

Gestational diabetes (GD), whose prevalence in France was 10.8% in 2016, is associated with maternal and neonatal morbidity. Currently, the reference treatment is insulin therapy. Glyburide is effective, particularly in achieving glycemic control, compared with insulin. However, according to some studies, it is associated with an increased risk of maternal and neonatal hypoglycemia compared to insulin therapy.The main objective of this thesis was to better understand the determinants of maternal hypoglycemia and neonatal hypoglycemia based on ancillary and secondary analyses from the national randomized INDAO trial, published in 2018. The specific objectives were to investigate 1-the transplacental transfer of glyburide at delivery, 2-the association between neonatal anthropometric measures (weight-for-length ratio [WLR] and birth weight) and neonatal hypoglycemia in women receiving drug therapy for GD, 3-the association between maternal hypoglycemia and CYP2C9*2 reduced-function variants and CYP2C9*3 and OATP1B3*4 loss-of-function variants, and then in a second step to investigate the association between daily glyburide dose and carriers of loss-of-function and reduced-function variants.First, we showed that there was a placental transfer of glyburide with a fetal/maternal glyburide concentration ratio of 0.62 (95% CI 0.50-0.74). The risk of neonatal hypoglycemia increased significantly with increasing umbilical cord blood glyburide concentration, regardless of neonatal macrosomia. Second, we showed that the increased risk of neonatal hypoglycemia was independently associated with extreme values of WLR, for a low WLR Z-score (less than -1.28) and a high WLR Z-score (greater than 1.28), regardless of maternal treatment. Finally, we found an increased rate of maternal hypoglycemia at the beginning of glyburide treatment in the variant group including carriers of the CYP2C9*3 and/or OATP1B*4 allele in a homozygous state, associated with a smaller glyburide dose increment and a lower glyburide dose reached at the end of treatment.This thesis work provides new insights into the mechanism of action of glyburide in pregnant women, allowing for better use in the treatment of GD. However, the potential long-term consequences for the child of prolonged in utero exposure to glyburide remain.

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