Déterminants de l’hypoglycémie néonatale et maternelle chez les femmes ayant un diabète gestationnel traité par glyburide

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.Le diabète gestationnel (DG), dont la prévalence était de 10,8% en 2016 en France, est associée à une morbidité maternelle et néonatale. Actuellement, le traitement de référence est l’insulinothérapie. Le glyburide est efficace notamment sur le contrôle de l’équilibre glycémique par rapport à l'insuline. Cependant, il serait associé à une augmentation du risque d’hypoglycémie maternelle et néonatale en comparaison à l’insulinothérapie.L’objectif général de cette thèse était de mieux comprendre les déterminants de l’hypoglycémie maternelle et de l’hypoglycémie néonatale à partir d’analyses ancillaires et secondaires issues de l’essai randomisé national INDAO, publié en 2018.Les objectifs spécifiques étaient d’étudier 1-le passage transplacentaire de glyburide à l'accouchement, 2-l'association entre les mesures anthropométriques néonatales (rapport poids-taille (RPT) et poids de naissance) et l'hypoglycémie néonatale chez les femmes bénéficiant d’un traitement médicamenteux du DG, 3-l'association entre l’hypoglycémie maternelle et les variants à fonction diminuée CYP2C9*2 et les variants perte de fonction CYP2C9*3 et OATP1B3*4, puis l'association entre la dose quotidienne de glyburide et les porteurs de variants perte et diminution de fonction.Nous avons montré qu’il existait un passage placentaire du glyburide avec un rapport de la concentration de glyburide fœtus/mère de 0,62 (IC 95% : 0,50-0,74). Le risque d'hypoglycémie néonatale augmentait de manière significative avec l’augmentation de la concentration de glyburide dans le cordon ombilical, indépendamment de la macrosomie néonatale. Ensuite, nous avons montré que le risque accru d'hypoglycémie néonatale est associé de manière indépendante à des valeurs extrêmes du RPT, pour un faible Z-score du RPT (inférieur à -1,28), et un Z-score du RPT élevé (supérieur à 1,28), indépendamment du traitement maternel. Enfin, nous avons constaté un taux augmenté d'hypoglycémie maternelle au début du traitement par glyburide dans le groupe variant comprenant les porteuses de l’allèle CYP2C9*3 et/ou d'OATP1B*4 à l’état homozygote, associé à une augmentation moindre de la dose de glyburide et à une dose plus faible de glyburide atteinte en fin de traitement.Ces travaux apportent de nouvelles connaissances concernant le mécanisme d’action du glyburide chez les femmes enceintes, permettant une meilleure utilisation dans le traitement du DG. Demeurent cependant pour l’enfant les conséquences potentielles à long terme de l’exposition prolongée in utero au glyburide

Déterminants de l’hypoglycémie néonatale et maternelle chez les femmes ayant un diabète gestationnel traité par glyburide

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.Le diabète gestationnel (DG), dont la prévalence était de 10,8% en 2016 en France, est associée à une morbidité maternelle et néonatale. Actuellement, le traitement de référence est l’insulinothérapie. Le glyburide est efficace notamment sur le contrôle de l’équilibre glycémique par rapport à l'insuline. Cependant, il serait associé à une augmentation du risque d’hypoglycémie maternelle et néonatale en comparaison à l’insulinothérapie.L’objectif général de cette thèse était de mieux comprendre les déterminants de l’hypoglycémie maternelle et de l’hypoglycémie néonatale à partir d’analyses ancillaires et secondaires issues de l’essai randomisé national INDAO, publié en 2018.Les objectifs spécifiques étaient d’étudier 1-le passage transplacentaire de glyburide à l'accouchement, 2-l'association entre les mesures anthropométriques néonatales (rapport poids-taille (RPT) et poids de naissance) et l'hypoglycémie néonatale chez les femmes bénéficiant d’un traitement médicamenteux du DG, 3-l'association entre l’hypoglycémie maternelle et les variants à fonction diminuée CYP2C9*2 et les variants perte de fonction CYP2C9*3 et OATP1B3*4, puis l'association entre la dose quotidienne de glyburide et les porteurs de variants perte et diminution de fonction.Nous avons montré qu’il existait un passage placentaire du glyburide avec un rapport de la concentration de glyburide fœtus/mère de 0,62 (IC 95% : 0,50-0,74). Le risque d'hypoglycémie néonatale augmentait de manière significative avec l’augmentation de la concentration de glyburide dans le cordon ombilical, indépendamment de la macrosomie néonatale. Ensuite, nous avons montré que le risque accru d'hypoglycémie néonatale est associé de manière indépendante à des valeurs extrêmes du RPT, pour un faible Z-score du RPT (inférieur à -1,28), et un Z-score du RPT élevé (supérieur à 1,28), indépendamment du traitement maternel. Enfin, nous avons constaté un taux augmenté d'hypoglycémie maternelle au début du traitement par glyburide dans le groupe variant comprenant les porteuses de l’allèle CYP2C9*3 et/ou d'OATP1B*4 à l’état homozygote, associé à une augmentation moindre de la dose de glyburide et à une dose plus faible de glyburide atteinte en fin de traitement.Ces travaux apportent de nouvelles connaissances concernant le mécanisme d’action du glyburide chez les femmes enceintes, permettant une meilleure utilisation dans le traitement du DG. Demeurent cependant pour l’enfant les conséquences potentielles à long terme de l’exposition prolongée in utero au glyburide

Determinants of neonatal and maternal hypoglycemia in women with gestational diabetes treated with glyburide

Le diabète gestationnel (DG), dont la prévalence était de 10,8% en 2016 en France, est associée à une morbidité maternelle et néonatale. Actuellement, le traitement de référence est l’insulinothérapie. Le glyburide est efficace notamment sur le contrôle de l’équilibre glycémique par rapport à l'insuline. Cependant, il serait associé à une augmentation du risque d’hypoglycémie maternelle et néonatale en comparaison à l’insulinothérapie.L’objectif général de cette thèse était de mieux comprendre les déterminants de l’hypoglycémie maternelle et de l’hypoglycémie néonatale à partir d’analyses ancillaires et secondaires issues de l’essai randomisé national INDAO, publié en 2018.Les objectifs spécifiques étaient d’étudier 1-le passage transplacentaire de glyburide à l'accouchement, 2-l'association entre les mesures anthropométriques néonatales (rapport poids-taille (RPT) et poids de naissance) et l'hypoglycémie néonatale chez les femmes bénéficiant d’un traitement médicamenteux du DG, 3-l'association entre l’hypoglycémie maternelle et les variants à fonction diminuée CYP2C9*2 et les variants perte de fonction CYP2C9*3 et OATP1B3*4, puis l'association entre la dose quotidienne de glyburide et les porteurs de variants perte et diminution de fonction.Nous avons montré qu’il existait un passage placentaire du glyburide avec un rapport de la concentration de glyburide fœtus/mère de 0,62 (IC 95% : 0,50-0,74). Le risque d'hypoglycémie néonatale augmentait de manière significative avec l’augmentation de la concentration de glyburide dans le cordon ombilical, indépendamment de la macrosomie néonatale. Ensuite, nous avons montré que le risque accru d'hypoglycémie néonatale est associé de manière indépendante à des valeurs extrêmes du RPT, pour un faible Z-score du RPT (inférieur à -1,28), et un Z-score du RPT élevé (supérieur à 1,28), indépendamment du traitement maternel. Enfin, nous avons constaté un taux augmenté d'hypoglycémie maternelle au début du traitement par glyburide dans le groupe variant comprenant les porteuses de l’allèle CYP2C9*3 et/ou d'OATP1B*4 à l’état homozygote, associé à une augmentation moindre de la dose de glyburide et à une dose plus faible de glyburide atteinte en fin de traitement.Ces travaux apportent de nouvelles connaissances concernant le mécanisme d’action du glyburide chez les femmes enceintes, permettant une meilleure utilisation dans le traitement du DG. Demeurent cependant pour l’enfant les conséquences potentielles à long terme de l’exposition prolongée in utero au glyburide.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

Déterminants de l’hypoglycémie néonatale et maternelle chez les femmes ayant un diabète gestationnel traité par glyburide

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.Le diabète gestationnel (DG), dont la prévalence était de 10,8% en 2016 en France, est associée à une morbidité maternelle et néonatale. Actuellement, le traitement de référence est l’insulinothérapie. Le glyburide est efficace notamment sur le contrôle de l’équilibre glycémique par rapport à l'insuline. Cependant, il serait associé à une augmentation du risque d’hypoglycémie maternelle et néonatale en comparaison à l’insulinothérapie.L’objectif général de cette thèse était de mieux comprendre les déterminants de l’hypoglycémie maternelle et de l’hypoglycémie néonatale à partir d’analyses ancillaires et secondaires issues de l’essai randomisé national INDAO, publié en 2018.Les objectifs spécifiques étaient d’étudier 1-le passage transplacentaire de glyburide à l'accouchement, 2-l'association entre les mesures anthropométriques néonatales (rapport poids-taille (RPT) et poids de naissance) et l'hypoglycémie néonatale chez les femmes bénéficiant d’un traitement médicamenteux du DG, 3-l'association entre l’hypoglycémie maternelle et les variants à fonction diminuée CYP2C9*2 et les variants perte de fonction CYP2C9*3 et OATP1B3*4, puis l'association entre la dose quotidienne de glyburide et les porteurs de variants perte et diminution de fonction.Nous avons montré qu’il existait un passage placentaire du glyburide avec un rapport de la concentration de glyburide fœtus/mère de 0,62 (IC 95% : 0,50-0,74). Le risque d'hypoglycémie néonatale augmentait de manière significative avec l’augmentation de la concentration de glyburide dans le cordon ombilical, indépendamment de la macrosomie néonatale. Ensuite, nous avons montré que le risque accru d'hypoglycémie néonatale est associé de manière indépendante à des valeurs extrêmes du RPT, pour un faible Z-score du RPT (inférieur à -1,28), et un Z-score du RPT élevé (supérieur à 1,28), indépendamment du traitement maternel. Enfin, nous avons constaté un taux augmenté d'hypoglycémie maternelle au début du traitement par glyburide dans le groupe variant comprenant les porteuses de l’allèle CYP2C9*3 et/ou d'OATP1B*4 à l’état homozygote, associé à une augmentation moindre de la dose de glyburide et à une dose plus faible de glyburide atteinte en fin de traitement.Ces travaux apportent de nouvelles connaissances concernant le mécanisme d’action du glyburide chez les femmes enceintes, permettant une meilleure utilisation dans le traitement du DG. Demeurent cependant pour l’enfant les conséquences potentielles à long terme de l’exposition prolongée in utero au glyburide

Does socioeconomic status have any influence on success at the national ranking exam?, a prospective survey

International audienceBackground: The weight of social inequalities during education is a reality. Students of lower socioeconomic status may have less chance of success in higher education, particularly in medical studies. However, the role of students’ socioeconomic factors, such as their parents’ profession, in their success in the national ranking exam (NRE) has not been studied. Our aim was to investigate the association between socioeconomic factors and success in the national ranking exam among sixth year medical students at the Paris-Sud Faculty of Medicine. Methods: This was a prospective survey of all sixth-year medical students at the Paris-Sud Faculty of Medicine, using a questionnaire on socioeconomic factors, which were compared according to NRE rank. Results: Of 172 sixth year medical students, 110 completed the questionnaire. Their ranking ranged from 20 to 7695, with a median of 2815 (interquartile range: 1029–4581). The factors associated with the NRE rank were a high school diploma (baccalauréat) A or B grade, success at the first attempt in the first-year medical examination, and enrollment in the NRE preparatory lectures during the sixth year of medical training (linear regression, p < 0.001). The educational status and socio-professional category of the parents were not associated with the NRE rank (linear regression, p = 0.92). Conclusion: At the Paris-Sud Faculty of Medicine, there was no association between parental socioeconomic status and sixth year students’ success in the NRE

Transplacental transfer of glyburide in women with gestational diabetes and neonatal hypoglycemia risk

International audienceBackground: In pregnant women with gestational diabetes, glyburide can be an alternative to insulin despite concerns about its transplacental transfer. However, transplacental transfer of glyburide is poorly quantified and the relationship between cord blood glyburide concentration and hypoglycemia has not been studied. Our objective was to quantify the transplacental transfer of glyburide at delivery and to study the association between the cord blood glyburide concentration and the risk of neonatal hypoglycemia in patients with gestational diabetes treated with glyburide.Methods and findings: INDAO was a multicenter, noninferiority, randomized trial conducted between May 2012 and November 2016 in 914 women with singleton pregnancies and gestational diabetes. An ancillary study was conducted in the 87 patients of the Bicêtre University Hospital Center. The sample consisted of 46 patients with utilizable assays at delivery. The relationships between glyburide concentration and the time since the last intake of glyburide and between fetal glyburide concentration and neonatal hypoglycemia were modeled with linear or logistic regressions using fractional polynomials. There was placental transfer of glyburide at a fetal to maternal ratio of 62% (95% CI [50; 74]). Umbilical cord blood glyburide concentration decreased steeply after the last maternal glyburide intake. After 24 hours, the mean umbilical cord blood concentration was less than 5 ng/mL. Neonatal hypoglycemia risk was increased with an odds ratio of hypoglycemia equal to 3.70 [1.40-9.77] for each 10 ng/mL increase in the cord blood glyburide concentration. However, no newborns were admitted to the NICU because of clinical signs of hypoglycemia or for treatment of hypoglycemia.Conclusion: Considering that neonatal glyburide exposure may be limited by stopping treatment a sufficient time before labor, there may still be a place for glyburide in the management of gestational diabetes

Jama Surg

IMPORTANCE The stereotype that men perform surgery better than women is ancient. Surgeons have long been mainly men, but in recent decades an inversion has begun; the number of women surgeons is increasing, especially in obstetrics and gynecology. Studies outside obstetrics suggest that postoperative morbidity and mortality may be lower after surgery by women.OBJECTIVE To evaluate the association between surgeons' gender and the risks of maternal morbidity and postpartum hemorrhage (PPH) after cesarean deliveries. DESIGN, SETTING, AND PARTICIPANTS This prospective cohort study was based on data from the Tranexamic Acid for Preventing Postpartum Hemorrhage after Cesarean Delivery (TRAAP2) trial, a multicenter, randomized, placebo-controlled trial that took place from March 2018 through January 2020 (23 months). It aimed to investigate whether the administration of tranexamic acid plus a prophylactic uterotonic agent decreased PPH incidence after cesarean delivery compared with a uterotonic agent alone. Women having a cesarean delivery before or during labor at or after 34 weeks' gestation were recruited from 27 French maternity hospitals.EXPOSURES Self-reported gender (man or woman), assessed by a questionnaire immediately after delivery.MAIN OUTCOMES AND MEASURES The primary end point was the incidence of a composite maternal morbidity variable, and the secondary end point was the incidence of PPH (the primary outcome of the TRAAP2 trial), defined by a calculated estimated blood loss exceeding 1000 mL or transfusion by day 2.RESULTS Among 4244 women included, men surgeons performed 943 cesarean deliveries (22.2%) and women surgeons performed 3301(77.8%). The rate of attending obstetricians was higher among men (441 of 929 [47.5%]) than women (687 of 3239 [21.2%]). The risk of maternal morbidity did not differ for men and women surgeons: 119 of 837 (14.2%) vs 476 of 2928 (16.3%) (adjusted risk ratio, 0.92 [95% CI, 0.77-1.13]). Interaction between surgeon gender and level of experience on the risk of maternal morbidity was not statistically significant. Similarly, the groups did not differ for PPH risk (adjusted risk ratio, 0.98 [95% CI, 0.85-1.13]).CONCLUSIONS AND RELEVANCE Risks of postoperative maternal morbidity and of PPH exceeding 1000 mL or requiring transfusion by day 2 did not differ by the surgeon's gender

Hypoglycemia and Glycemic Control With Glyburide in Women With Gestational Diabetes and Genetic Variants of Cytochrome P450 2C9 and/or OATP1B3

International audienceGlyburide is mainly metabolized by the cytochrome P450 2C9 (CYP2C9) enzyme and enters the liver via the transporter OATP1B3. The variants OATP1B3*4 (699 G>A; rs7311358) and CYP2C9*2 and *3 are known to have a significant influence on the hepatic uptake and metabolism of glyburide, with lower clearance than in the wild type. In an ancillary study of the INDAO trial, we selected 117 pregnant women with gestational diabetes treated by glyburide and assessed the role of the combined CYP2C9 and OATP1B3 genetic polymorphisms in hypoglycemia and glycemic control. Three groups were constituted: (1) the wild-type genotype group (wild-type allele genotype for both CYP2C9*1 and OATP1B3*1 (699G)), (2) the intermediate group (carriers of CYP2C9*2 allele or OATP1B3*4 (699G>A) heterozygous), and (3) the variant group (carriers of CYP2C9*3 allele and/or OATP1B3*4 (699G>A) homozygous variant). We found that the risk of hypoglycemia was significantly higher in the variant genotype at the second week of treatment: 20.0% (4/20) vs. 8.1% (3/37) in the intermediate group and 4.1% (2/49) in the wild-type genotype group (P = 0.03). The last daily dose of glyburide during pregnancy was lower for patients in the variant genotype group: 4.7 mg (SD 3.5) vs. 8.7 mg (SD 5.7) in the wild-type group and 5.7 mg (SD 3.7) in the intermediate group (P < 0.01). In conclusion, the no-function variants CYP2C9*3 and OATP1B3*4 are associated with a higher risk of hypoglycemia and a lower dose of glyburide in women with gestational diabetes treated with glyburide, which is consistent with the pharmacokinetic roles of both CYP2C9 and OATP1B3