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

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 mellitus. 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 release. 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 fourto fivefold greater risk of developing postpartum diabetes than the general population (Figure 1). The incidence of type 2 diabetes mellitus within <2 years postpartum is reported to be approximately 10–15% in Korean women. A prospective follow-up study on Korean women with GDM showed that approximately 40% of women with previous GDM were expected to develop diabetes within 5 years postpartum. However, some studies have reported lower incidence rates. This variability might be related to the ethnic variation, lack of uniformity in diagnostic criteria for GDM, diversity in follow-up care, characteristics of women lost to follow up, and differences in statistical management of data. Despite the high rate or an increased risk of type 2 diabetes mellitus after GDM, the putative risk factors are yet to be identified, but many risk factors have been identified among the various ethnic groups. These risk factors include homocysteine level, older age (>30 years), prepregnant body mass index (>23 kg/m), 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). 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 triglycerides. 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. Recently, Kwak et al. published a study covering the genetic risk loci for gestational diabetes in Korean women. A two-stage genome-wide association analysis in Korean women was carried out. In the stage 1 genome scan, 468 women 20