Identification and Validation of Transcription Factor Variants in Gestational Diabetes

Gestational diabetes mellitus (GDM), is a form of diabetes diagnosed during the second or third trimester of pregnancy in women without previous diabetes and is diagnosed using the oral glucose tolerance test (OGTT)1. Hormonal change that occurs during pregnancy may lead to insulin resistance affecting the ability of the body to use insulin effectively. While this is expected during pregnancy, in some cases the insulin resistance becomes so pronounce leading to GDM. Overweight, obesity, maternal age, and family history of diabetes are risk factors for the development of GDM2. GDM effects both the mother and fetus, mothers with GDM are at risk of developing T2D and cardiovascular diseases in the long-term2. Also, GDM can cause fetal overgrowth (macrosomia) increasing the risk of birth complications. In the long-term, children born of GDM pregnancies are at higher risk of developing obesity and T2D2. Beta-cell dysfunction and chronic insulin resistance are believed to be the main underlaying mechanisms for GDM2. Neuro-hormonal dysfunction and inflammation of adipose tissues play a role in the pathophysiology of GDM2,3. In addition, it’s believed that certain genetic variants are associated with an increased risk in the development of GDM and the interaction between these genetic predispositions and environmental factors such as obesity plays an important role in the development of GDM. Some genetic variants have been identified in association with GDM such as TCF7L24–7, MTNR1B7–10, and GCK7,11. And in a more recent study more variants were identified such as CDKAL1 and CDKN2B7. According to the International Diabetes Federation, in 2021, approximately 21.1 million live births (16.7%) were affected by hyperglycemia (high blood glucose) during pregnancy. And in Qatar, it has been reported that the prevalence of GDM in 2017 was 24.25% 12,13. For that in this study we aim to identify and validate transcription factor variants associated to GDM in a Qatari-based cohort.

Hamad Bin Khalifa University (HBKU)