Effects of High-dose Folic Acid Supplementation on Maternal/Child Health Outcomes: Gestational Diabetes Mellitus in Pregnancy and Insulin Resistance in Offspring

Published:October 27, 2022DOI:



      The purpose of this study was to evaluate the effects of maternal high folic acid (FA) supplementation during pregnancy on glucose intolerance in dams and insulin resistance in offspring.


      Wistar female rats (n=18) were mated and randomly divided into 3 groups: a control group and 2 experimental groups. Three different feeding protocols were administered during pregnancy: control group-2 mg/kg FA (recommended level FA supplementation); experimental 1 group-5 mg/kg FA (tolerable upper intake level of FA supplementation [ULFolS]); and experimental 2 group-40 mg/kg FA (high FA supplementation [HfolS]). All dams were fed the same FA content diet (2 mg/kg FA) during the lactation period. An oral glucose tolerance test was performed on day 16th of pregnancy. After the lactation period, body weight and food intake of 36 pups were monitored. Dams were euthanized at the end of the lactation period and half of the pups were euthanized at the end of week 7 and the others at the end of week 12. Serum FA, homocysteine, vitamin B12, insulin, glucose, interleukin-6, tumour necrosis factor-alpha, glycated hemoglobin (A1C) and adiponectin levels of mothers and pups were evaluated. The homeostatic model of insulin resistance (HOMA-IR) was used to determine insulin resistance in dams and offspring.


      According to glucose tolerance test results of dams, blood glucose values at minutes 0, 60, 90 and 120 for the HFolS group were significantly higher compared with the control group (p<0.05). The glycated hemoglobin A1C level in HFolS dams was significantly higher than in the control group (p<0.05). The mean birthweight of the pups in the HFolS group was significantly higher than that of control pups (p<0.05). HOMA-IR values for control and HFolS offspring were similar at weeks 7 and 12 and higher than in ULFolS offspring (p>0.05).


      In this study, it was determined that the effects of high doses of FA exposure during pregnancy on glucose intolerance in dams and insulin resistance in offspring.



      Dans la présente étude, nous avons évalué les effets d’une supplémentation à forte teneur en acide folique (AF) de la mère pendant la gestation sur l’intolérance au glucose chez les mères et la résistance à l’insuline de leurs ratons.


      Des rates Wistar (n = 18) ont été accouplées et réparties de façon aléatoire en 3 groupes : 1 groupe témoin et 2 groupes expérimentaux. Trois protocoles d’alimentation différents ont été suivis pendant la gestation : groupe témoin, 2 mg/kg d’AF (apport recommandé en AF); groupe expérimental 1, 5 mg/kg d’AF (apport maximal tolérable en AF [AMTAF)]); groupe expérimental 2, 40 mg/kg d’AF (apport élevé en AF [AEAF]). Les mères ont été nourries avec une diète qui avait la même teneur en AF (2 mg/kg d’AF) pendant la période de lactation. Une épreuve d’hyperglycémie provoquée par voie orale a été réalisée au 16e jour de la gestation. Après la période de lactation, le poids corporel et l’apport alimentaire de 36 ratons ont été surveillés. Les mères ont été euthanasiées à la fin de la période de lactation, la moitié des ratons ont été euthanasiés à la fin de la 7e semaine, et les autres à la fin de la 12e semaine. Les concentrations sériques d’AF, d’homocystéine, de vitamine B12, d’insuline, de glucose, d’interleukine-6, du facteur onconécrosant alpha, de l’hémoglobine glyquée (A1c) et de l’adiponectine des mères et des bébés ont été évaluées. Le modèle homéostasique de la résistance à l’insuline (HOMA-IR, de l’anglais Homeostasis Model Assessment of Insulin Resistance) a été utilisé pour déterminer la résistance à l’insuline chez les mères et leurs ratons.


      Selon les résultats de l’épreuve d’hyperglycémie provoquée des mères, les valeurs de la glycémie à 0, 60, 90 et 130 minutes du groupe AEAF étaient significativement plus élevées que les valeurs de la glycémie du groupe témoin (p < 0,05). Les concentrations de l’A1c des mères du groupe AEAF étaient significativement plus élevées que les concentrations de l’A1c des mères du groupe témoin (p < 0,05). Le poids moyen des ratons du groupe AEAF à la naissance était significativement plus élevé que celui des ratons témoins (p < 0,05). Les valeurs HOMA-IR des témoins et des ratons du groupe AEAF étaient similaires à la 7e semaine et à la 12e semaine, et plus élevées que les ratons du groupe AMTAF (p > 0,05).


      Ces travaux nous ont permis de déterminer les effets de l’exposition à des doses élevées d’AF pendant la gestation sur l’intolérance au glucose des mères et la résistance à l’insuline de leurs ratons.


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