Genetics in Gestational Diabetes Mellitus: Association with Incidence, Severity, Pregnancy Outcome and Response to Treatment

Abstract

Constant advances in gene mapping technology have allowed research to focus from rare monogenic disorders on common complex diseases involving multiple susceptibility genes-environment interactions. Gestational diabetes mellitus (GDM) is a heterogeneous pathogenic condition affecting 2-5% of all pregnant women during pregnancy. GDM is considered to result when genetic predisposition is triggered by increased insulin resistance during pregnancy leading to what seems to be one of the primary characteristics of GDM, the pancreatic b-cell impairment. Genetic predisposition to GDM has been suggested given the occurrence of the disease within family members. Furthermore, GDM is reported to be often present in women with maturity onset diabetes of the young (MODY) gene mutations. In addition, candidate susceptibility gene variants have been suggested to increase the risk of GDM. These genes include glucokinase (GCK), HLA antigens, insulin receptor (INSR), insulin-like growth factor-2 (IGF2), HNF4A, insulin gene (INS-VNTR), plasminogen activator inhibitor 1 (PAI-1), potassium inwardly rectifying channel subfamily J, member 11 (KCNJ11), hepatocyte nuclear factor-4a (HNF4A). Identification of the possible underlying genetic factors of GDM would eventually enrich our knowledge on the pathophysiologic mechanism of the disease and contribute to the individualization of both prevention and treatment of complications for the mother and fetus. However, so far, little is known about the genetic basis of GDM and its potential clinical significance. This review focuses on possible gestational diabetes mellitus susceptibility genes and their association with the disease incidence and severity as well as the pregnancy outcome and the response to treatment.

Glutathione S-Transferase M1 and T1 Gene Polymorphisms are not Associated with Increased Risk of Gestational Diabetes Mellitus Development

“…If both parents are diabetic, this ratio increases up to 60-75%. In GDM, in which there is an insulin resistance in target tissues, a familial predisposition is also present (26,27). In our GDM group, the family history of DM was more common than in the control group (26% and 10%, respectively), but the difference did not reach statistical significance.…”

The Impact of Polycystic Ovarian Syndrome on Gestational Diabetes

“…In women with familial partial lipodystrophy due to LMNA (lamin A/C) mutations, a rare disorder characterized by a selective loss of adipose www.intechopen.com tissue and insulin resistance, the prevalence of PCOS and gestational diabetes was found to be higher than in the general population (Vantyghem et al, 2008). Moreover, mutations of the VNTR (variable number of tandem repeats) locus, upstream of the insulin gene (INS) where insulin expression is regulated, have been found in both women who suffer from PCOS and in women with GDM (Waterworth et al, 1997) (Lambrinoudaki et al, 2010).…”

Gestational Diabetes Induces Pancreatic Beta-Cells Apoptosis in Adult Rat Offspring

“…GDM is a condition affecting approximately 2-10 % of all pregnancies in the United States and Europe (Landon & Gabbe, 2011). Diabetes in pregnant women leads to adverse short-term and long-term metabolic disease states in both the mother and offspring (Lambrinoudaki et al, 2010& Vrachnis et al, 2012. Children born to mothers diagnosed with GDM are more susceptible to complex diseases, including obesity, type 2 diabetes and cardiovascular complications during adulthood.…”