Heterogeneous Impact of Type 2 Diabetes Mellitus-Related Genetic Variants on Gestational Glycemic Traits: Review and Future Research Needs

Mol Genet Genomics. 2019 Aug;294(4):811-847. doi: 10.1007/s00438-019-01552-0. Epub 2019 Apr 3.


Gestational glucose homeostasis influences mother's metabolic health, pregnancy outcomes, fetal development and offspring growth. To understand the genetic roles in pregnant glucose metabolism and genetic predisposition for gestational diabetes (GDM), we reviewed the recent literature up to Jan, 2018 and evaluated the influence of T2DM-related genetic variants on gestational glycemic traits and glucose tolerance. A total of 140 variants of 89 genes were integrated. Their associations with glycemic traits in and outside pregnancy were compared. The genetic circumstances underlying glucose metabolism exhibit a similarity between pregnant and non-pregnant populations. While, not all of the T2DM-associated genetic variants are related to pregnant glucose tolerance, such as genes involved in fasting insulin/C-peptide regulation. Some genetic variants may have distinct effects on gestational glucose homeostasis. And certain genes may be particularly involved in this process via specific mechanisms, such as HKDC1, MTNR1B, BACE2, genes encoding cell cycle regulators, adipocyte regulators, inflammatory factors and hepatic factors related to gestational glucose sensing and insulin signaling. However, it is currently difficult to evaluate these associations with quantitative synthesis due to inadequate data, different analytical methods, varied measurements for glycemic traits, controversies in diagnosis of GDM, and unknown ethnicity- and/or sex-related influences on pregnant maternal metabolism. In conclusion, different genetic associations with glycemic traits may exist between pregnant and non-pregnant conditions. Comprehensive research on specific genetic regulation in gestation is necessary.

Keywords: Genetic association; Genetic variants; Gestational diabetes mellitus; Gestational glycemic traits; Glucose tolerance; Type 2 diabetes mellitus.

Publication types

  • Review

MeSH terms

  • Amyloid Precursor Protein Secretases / genetics
  • Aspartic Acid Endopeptidases / genetics
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes, Gestational / genetics*
  • Female
  • Gene Regulatory Networks*
  • Genetic Predisposition to Disease
  • Genetic Variation*
  • Hexokinase / genetics
  • Humans
  • Pregnancy
  • Receptor, Melatonin, MT2 / genetics


  • MTNR1B protein, human
  • Receptor, Melatonin, MT2
  • Hexokinase
  • hexokinase domain containing 1 protein, human
  • Amyloid Precursor Protein Secretases
  • Aspartic Acid Endopeptidases
  • BACE2 protein, human