The genetic interface between gestational diabetes and type 2 diabetes

Abstract

Objective: Although the Western diet and lifestyle has contributed to an increase in the prevalence of gestational diabetes (GDM) worldwide, genetic predisposition also plays an important role. This article reviews the current state of knowledge regarding the genetic interface between type 2 diabetes (T2D) and GDM. Methods: Review of the current literature on genetics of T2D and GDM. Results: Maturity Onset Diabetes of the Young (MODY) due to glucokinase mutations may account for as much as 5% of GDM patients. Knowledge of both maternal and fetal genotypes may be useful for individualizing glycemic goals during pregnancy in families harboring these mutations. Of the 38 common T2D susceptibility variants identified to date, several are also associated with GDM. Presumably, these mutations increase GDM risk through decreased ability of β-cells to compensate for the insulin resistance associated with pregnancy. The effect of these alleles on risk for GDM is modest (odds ratios (odds ratio (OR)~1.1–1.6); thus, they individually are poorly predictive. Conclusions: Future studies must concentrate on understanding the biological underpinnings of known T2D risk alleles and the discovery of new alleles for both GDM and T2D. These insights may lead to more effective strategies for preventing and treating GDM.

Keywords::

• Genomics
• genome-wide association study
• SNPs
• MODY
• personalized medicine
• macrosomia

Declaration of interest: This work was supported, in part by the Mid-Atlantic Nutrition and Obesity Center (NIH P30 DK072488) and the Geriatric Research and Education Clinical Center, Veterans Administration Medical Center, Baltimore, MD. The authors have no declarations of interest to report.