Genetic Determinants of Glycemic Traits and the Risk of Gestational Diabetes Mellitus

Many common genetic polymorphisms are associated with glycemic traits and type 2 diabetes (T2D), but knowledge about genetic determinants of glycemic traits in pregnancy is limited. We tested genetic variants known to be associated with glycemic traits and T2D in the general population for associati...

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Autores principales: Powe, Camille E., Nodzenski, Michael, Talbot, Octavious, Allard, Catherine, Briggs, Catherine, Leya, Marysa V., Perron, Patrice, Bouchard, Luigi, Florez, Jose C., Scholtens, Denise M., Lowe, William L., Hivert, Marie-France
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6245229/
https://www.ncbi.nlm.nih.gov/pubmed/30257980
http://dx.doi.org/10.2337/db18-0203
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author Powe, Camille E.
Nodzenski, Michael
Talbot, Octavious
Allard, Catherine
Briggs, Catherine
Leya, Marysa V.
Perron, Patrice
Bouchard, Luigi
Florez, Jose C.
Scholtens, Denise M.
Lowe, William L.
Hivert, Marie-France
author_facet Powe, Camille E.
Nodzenski, Michael
Talbot, Octavious
Allard, Catherine
Briggs, Catherine
Leya, Marysa V.
Perron, Patrice
Bouchard, Luigi
Florez, Jose C.
Scholtens, Denise M.
Lowe, William L.
Hivert, Marie-France
author_sort Powe, Camille E.
collection PubMed
description Many common genetic polymorphisms are associated with glycemic traits and type 2 diabetes (T2D), but knowledge about genetic determinants of glycemic traits in pregnancy is limited. We tested genetic variants known to be associated with glycemic traits and T2D in the general population for associations with glycemic traits in pregnancy and gestational diabetes mellitus (GDM). Participants in two cohorts (Genetics of Glucose regulation in Gestation and Growth [Gen3G] and Hyperglycemia and Adverse Pregnancy Outcome [HAPO]) underwent oral glucose tolerance testing at 24–32 weeks’ gestation. We built genetic risk scores (GRSs) for elevated fasting glucose and insulin, reduced insulin secretion and sensitivity, and T2D, using variants discovered in studies of nonpregnant individuals. We tested for associations between these GRSs, glycemic traits in pregnancy, and GDM. In both cohorts, the fasting glucose GRS was strongly associated with fasting glucose. The insulin secretion and sensitivity GRSs were also significantly associated with these traits in Gen3G, where insulin measurements were available. The fasting insulin GRS was weakly associated with fasting insulin (Gen3G) or C-peptide (HAPO). In HAPO (207 GDM case subjects), all five GRSs (T2D, fasting glucose, fasting insulin, insulin secretion, and insulin sensitivity) were significantly associated with GDM. In Gen3G (43 GDM case subjects), both the T2D and insulin secretion GRSs were associated with GDM; effect sizes for the other GRSs were similar to those in HAPO. Thus, despite the profound changes in glycemic physiology during pregnancy, genetic determinants of fasting glucose, fasting insulin, insulin secretion, and insulin sensitivity discovered outside of pregnancy influence GDM risk.
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spelling pubmed-62452292019-12-01 Genetic Determinants of Glycemic Traits and the Risk of Gestational Diabetes Mellitus Powe, Camille E. Nodzenski, Michael Talbot, Octavious Allard, Catherine Briggs, Catherine Leya, Marysa V. Perron, Patrice Bouchard, Luigi Florez, Jose C. Scholtens, Denise M. Lowe, William L. Hivert, Marie-France Diabetes Genetics/Genomes/Proteomics/Metabolomics Many common genetic polymorphisms are associated with glycemic traits and type 2 diabetes (T2D), but knowledge about genetic determinants of glycemic traits in pregnancy is limited. We tested genetic variants known to be associated with glycemic traits and T2D in the general population for associations with glycemic traits in pregnancy and gestational diabetes mellitus (GDM). Participants in two cohorts (Genetics of Glucose regulation in Gestation and Growth [Gen3G] and Hyperglycemia and Adverse Pregnancy Outcome [HAPO]) underwent oral glucose tolerance testing at 24–32 weeks’ gestation. We built genetic risk scores (GRSs) for elevated fasting glucose and insulin, reduced insulin secretion and sensitivity, and T2D, using variants discovered in studies of nonpregnant individuals. We tested for associations between these GRSs, glycemic traits in pregnancy, and GDM. In both cohorts, the fasting glucose GRS was strongly associated with fasting glucose. The insulin secretion and sensitivity GRSs were also significantly associated with these traits in Gen3G, where insulin measurements were available. The fasting insulin GRS was weakly associated with fasting insulin (Gen3G) or C-peptide (HAPO). In HAPO (207 GDM case subjects), all five GRSs (T2D, fasting glucose, fasting insulin, insulin secretion, and insulin sensitivity) were significantly associated with GDM. In Gen3G (43 GDM case subjects), both the T2D and insulin secretion GRSs were associated with GDM; effect sizes for the other GRSs were similar to those in HAPO. Thus, despite the profound changes in glycemic physiology during pregnancy, genetic determinants of fasting glucose, fasting insulin, insulin secretion, and insulin sensitivity discovered outside of pregnancy influence GDM risk. American Diabetes Association 2018-12 2018-09-26 /pmc/articles/PMC6245229/ /pubmed/30257980 http://dx.doi.org/10.2337/db18-0203 Text en © 2018 by the American Diabetes Association. http://www.diabetesjournals.org/content/licenseReaders may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license.
spellingShingle Genetics/Genomes/Proteomics/Metabolomics
Powe, Camille E.
Nodzenski, Michael
Talbot, Octavious
Allard, Catherine
Briggs, Catherine
Leya, Marysa V.
Perron, Patrice
Bouchard, Luigi
Florez, Jose C.
Scholtens, Denise M.
Lowe, William L.
Hivert, Marie-France
Genetic Determinants of Glycemic Traits and the Risk of Gestational Diabetes Mellitus
title Genetic Determinants of Glycemic Traits and the Risk of Gestational Diabetes Mellitus
title_full Genetic Determinants of Glycemic Traits and the Risk of Gestational Diabetes Mellitus
title_fullStr Genetic Determinants of Glycemic Traits and the Risk of Gestational Diabetes Mellitus
title_full_unstemmed Genetic Determinants of Glycemic Traits and the Risk of Gestational Diabetes Mellitus
title_short Genetic Determinants of Glycemic Traits and the Risk of Gestational Diabetes Mellitus
title_sort genetic determinants of glycemic traits and the risk of gestational diabetes mellitus
topic Genetics/Genomes/Proteomics/Metabolomics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6245229/
https://www.ncbi.nlm.nih.gov/pubmed/30257980
http://dx.doi.org/10.2337/db18-0203
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