Genetic determinants of glycemic traits and the risk of gestational diabetes mellitus

Camille E. Powe*, Michael Nodzenski, Octavious Talbot, Catherine Allard, Catherine Briggs, Marysa V. Leya, Patrice Perron, Luigi Bouchard, Jose C. Florez, Denise M. Scholtens, William L. Lowe, Marie France Hivert

*Corresponding author for this work

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2703-2709
Number of pages7
JournalDiabetes
Volume67
Issue number12
DOIs
StatePublished - Dec 1 2018

Fingerprint

Gestational Diabetes
Fasting
Insulin
Type 2 Diabetes Mellitus
Pregnancy
Pregnancy Outcome
Glucose
Hyperglycemia
Insulin Resistance
C-Peptide
Genetic Polymorphisms
Glucose Tolerance Test

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Powe, C. E., Nodzenski, M., Talbot, O., Allard, C., Briggs, C., Leya, M. V., ... Hivert, M. F. (2018). Genetic determinants of glycemic traits and the risk of gestational diabetes mellitus. Diabetes, 67(12), 2703-2709. https://doi.org/10.2337/db18-0203
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. In: Diabetes. 2018 ; Vol. 67, No. 12. pp. 2703-2709.
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Powe, CE, Nodzenski, M, Talbot, O, Allard, C, Briggs, C, Leya, MV, Perron, P, Bouchard, L, Florez, JC, Scholtens, DM, Lowe, WL & Hivert, MF 2018, 'Genetic determinants of glycemic traits and the risk of gestational diabetes mellitus', Diabetes, vol. 67, no. 12, pp. 2703-2709. https://doi.org/10.2337/db18-0203

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.

In: Diabetes, Vol. 67, No. 12, 01.12.2018, p. 2703-2709.

Research output: Contribution to journalArticle

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AU - Powe, Camille E.

AU - Nodzenski, Michael

AU - Talbot, Octavious

AU - Allard, Catherine

AU - Briggs, Catherine

AU - Leya, Marysa V.

AU - Perron, Patrice

AU - Bouchard, Luigi

AU - Florez, Jose C.

AU - Scholtens, Denise M.

AU - Lowe, William L.

AU - Hivert, Marie France

PY - 2018/12/1

Y1 - 2018/12/1

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Powe CE, Nodzenski M, Talbot O, Allard C, Briggs C, Leya MV et al. Genetic determinants of glycemic traits and the risk of gestational diabetes mellitus. Diabetes. 2018 Dec 1;67(12):2703-2709. https://doi.org/10.2337/db18-0203