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Metabolomic insights into maternal and neonatal complications in pregnancies affected by type 1 diabetes

AIMS/HYPOTHESIS: Type 1 diabetes in pregnancy is associated with suboptimal pregnancy outcomes, attributed to maternal hyperglycaemia and offspring hyperinsulinism (quantifiable by cord blood C-peptide). We assessed metabolomic patterns associated with risk factors (maternal hyperglycaemia, diet, BM...

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Autores principales: Meek, Claire L., Stewart, Zoe A., Feig, Denice S., Furse, Samuel, Neoh, Sandra L., Koulman, Albert, Murphy, Helen R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10542716/
https://www.ncbi.nlm.nih.gov/pubmed/37615689
http://dx.doi.org/10.1007/s00125-023-05989-2
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author Meek, Claire L.
Stewart, Zoe A.
Feig, Denice S.
Furse, Samuel
Neoh, Sandra L.
Koulman, Albert
Murphy, Helen R.
author_facet Meek, Claire L.
Stewart, Zoe A.
Feig, Denice S.
Furse, Samuel
Neoh, Sandra L.
Koulman, Albert
Murphy, Helen R.
author_sort Meek, Claire L.
collection PubMed
description AIMS/HYPOTHESIS: Type 1 diabetes in pregnancy is associated with suboptimal pregnancy outcomes, attributed to maternal hyperglycaemia and offspring hyperinsulinism (quantifiable by cord blood C-peptide). We assessed metabolomic patterns associated with risk factors (maternal hyperglycaemia, diet, BMI, weight gain) and perinatal complications (pre-eclampsia, large for gestational age [LGA], neonatal hypoglycaemia, hyperinsulinism) in the Continuous Glucose Monitoring in Women with Type 1 Diabetes in Pregnancy Trial (CONCEPTT). METHODS: A total of 174 CONCEPTT participants gave ≥1 non-fasting serum sample for the biorepository at 12 gestational weeks (147 women), 24 weeks (167 women) and 34 weeks (160 women) with cord blood from 93 infants. Results from untargeted metabolite analysis (ultrahigh performance LC-MS) are presented as adjusted logistic/linear regression of maternal and cord blood metabolites, risk factors and perinatal complications using a modified Bonferroni limit of significance for dependent variables. RESULTS: Maternal continuous glucose monitoring time-above-range (but not BMI or excessive gestational weight gain) was associated with increased triacylglycerols in maternal blood and increased carnitines in cord blood. LGA, adiposity, neonatal hypoglycaemia and offspring hyperinsulinism showed distinct metabolite profiles. LGA was associated with increased carnitines, steroid hormones and lipid metabolites, predominantly in the third trimester. However, neonatal hypoglycaemia and offspring hyperinsulinism were both associated with metabolite changes from the first trimester, featuring triacylglycerols or dietary phenols. Pre-eclampsia was associated with increased abundance of phosphatidylethanolamines, a membrane phospholipid, at 24 weeks. CONCLUSIONS/INTERPRETATION: Altered lipid metabolism is a key pathophysiological feature of type 1 diabetes pregnancy. New strategies for optimising maternal diet and insulin dosing from the first trimester are needed to improve pregnancy outcomes in type 1 diabetes. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version of this article (10.1007/s00125-023-05989-2) contains peer-reviewed but unedited supplementary material.
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spelling pubmed-105427162023-10-03 Metabolomic insights into maternal and neonatal complications in pregnancies affected by type 1 diabetes Meek, Claire L. Stewart, Zoe A. Feig, Denice S. Furse, Samuel Neoh, Sandra L. Koulman, Albert Murphy, Helen R. Diabetologia Article AIMS/HYPOTHESIS: Type 1 diabetes in pregnancy is associated with suboptimal pregnancy outcomes, attributed to maternal hyperglycaemia and offspring hyperinsulinism (quantifiable by cord blood C-peptide). We assessed metabolomic patterns associated with risk factors (maternal hyperglycaemia, diet, BMI, weight gain) and perinatal complications (pre-eclampsia, large for gestational age [LGA], neonatal hypoglycaemia, hyperinsulinism) in the Continuous Glucose Monitoring in Women with Type 1 Diabetes in Pregnancy Trial (CONCEPTT). METHODS: A total of 174 CONCEPTT participants gave ≥1 non-fasting serum sample for the biorepository at 12 gestational weeks (147 women), 24 weeks (167 women) and 34 weeks (160 women) with cord blood from 93 infants. Results from untargeted metabolite analysis (ultrahigh performance LC-MS) are presented as adjusted logistic/linear regression of maternal and cord blood metabolites, risk factors and perinatal complications using a modified Bonferroni limit of significance for dependent variables. RESULTS: Maternal continuous glucose monitoring time-above-range (but not BMI or excessive gestational weight gain) was associated with increased triacylglycerols in maternal blood and increased carnitines in cord blood. LGA, adiposity, neonatal hypoglycaemia and offspring hyperinsulinism showed distinct metabolite profiles. LGA was associated with increased carnitines, steroid hormones and lipid metabolites, predominantly in the third trimester. However, neonatal hypoglycaemia and offspring hyperinsulinism were both associated with metabolite changes from the first trimester, featuring triacylglycerols or dietary phenols. Pre-eclampsia was associated with increased abundance of phosphatidylethanolamines, a membrane phospholipid, at 24 weeks. CONCLUSIONS/INTERPRETATION: Altered lipid metabolism is a key pathophysiological feature of type 1 diabetes pregnancy. New strategies for optimising maternal diet and insulin dosing from the first trimester are needed to improve pregnancy outcomes in type 1 diabetes. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version of this article (10.1007/s00125-023-05989-2) contains peer-reviewed but unedited supplementary material. Springer Berlin Heidelberg 2023-08-24 2023 /pmc/articles/PMC10542716/ /pubmed/37615689 http://dx.doi.org/10.1007/s00125-023-05989-2 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Meek, Claire L.
Stewart, Zoe A.
Feig, Denice S.
Furse, Samuel
Neoh, Sandra L.
Koulman, Albert
Murphy, Helen R.
Metabolomic insights into maternal and neonatal complications in pregnancies affected by type 1 diabetes
title Metabolomic insights into maternal and neonatal complications in pregnancies affected by type 1 diabetes
title_full Metabolomic insights into maternal and neonatal complications in pregnancies affected by type 1 diabetes
title_fullStr Metabolomic insights into maternal and neonatal complications in pregnancies affected by type 1 diabetes
title_full_unstemmed Metabolomic insights into maternal and neonatal complications in pregnancies affected by type 1 diabetes
title_short Metabolomic insights into maternal and neonatal complications in pregnancies affected by type 1 diabetes
title_sort metabolomic insights into maternal and neonatal complications in pregnancies affected by type 1 diabetes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10542716/
https://www.ncbi.nlm.nih.gov/pubmed/37615689
http://dx.doi.org/10.1007/s00125-023-05989-2
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