Better understanding and new insight of genetic risk loci for gestational diabetes mellitus.

Abstract

Gestational diabetes mellitus (GDM) is one of the most common complications of pregnancy, and women with GDM are at increased risk for type 2 diabetes mellitus1. Uncomplicated pregnancy is characterized by insulin resistance and enhanced insulin secretion as a compensatory mechanism to maintain normal glucose tolerance (NGT). However, previous studies showed that in women with GDM during pregnancy, the decreased sensitivity of insulin is at a similar level to NGT, but with more pronounced insulin resistance than NGT. These phenomena might contribute to hyperglycemia in addition to defective insulin release2. Furthermore, women with a history of GDM have been considered a high‐risk group for diabetes mellitus. A study reported from Korea showed that Korean women with a history of GDM have a four‐ to fivefold greater risk of developing postpartum diabetes than the general population (Figure 1). The incidence of type 2 diabetes mellitus within 30 years), prepregnant body mass index (>23 kg/m2), family history of type 2 diabetes mellitus, fasting glucose level at the time of GDM diagnosis (>5.8 mmol/L) and early diagnosis of GDM during pregnancy (<26 weeks)3. In contrast, the putative risk factors for type 2 diabetes mellitus in the Korean population include (but are not limited to) old age, urban living, female sex, obesity, smoking, family history of diabetes, impaired liver function, metabolic syndrome, elevated blood pressure and increased triglycerides4. Although all the risk factors have yet to be identified, the aforementioned variables are the key risk factors for diabetes mellitus in Koreans. Most of these risk factors have also been identified as key risk factors in other places including Europe, South America, North America and Africa. As previously mentioned, some of the risk factors, such as family history of diabetes, lipid profile, high blood pressure and obesity, are common risk factors of both type 2 diabetes mellitus and GDM. Thus, one could question whether GDM is another type of diabetes mellitus or a simple identification of existing type 2 diabetes mellitus during pregnancy when physical, metabolic and psychological changes occur dramatically. It was very difficult to answer the question until the advancement of the Genome‐Wide Association Study (GWAS), which enabled the investigation of genetic background. The genome‐wide association (GWA) approach is an emerging methodology that allows us to identify genetic variants with specific loci that predispose individuals to complex traits and/or diseases.