New insights into the pathophysiology of gestational diabetes mellitus: Possible role of human leukocyte antigen-G

SummaryDiabetes can develop in up to 10% of pregnant women who have not previously had the condition. This condition which usually begins in the second half of the pregnancy is called gestational diabetes mellitus (GDM).In most cases, all diabetic symptoms disappear following delivery. However, women with GDM have an increased risk of developing type 2 diabetes mellitus (DM) later in life, especially if they were overweight before the pregnancy.The cause of GDM is unknown. Although hormones present in the pregnancy, especially human placental lactogen, are thought to be responsible for the development of this condition, many questions remain to be answered. It is still not known why GDM develops in a subgroup of pregnant women.It may be possible that events leading to the development of GDM are triggered by an antigenic load which is the fetus itself. Human leukocyte antigen-G (HLA-G) expression that functions to protect the fetus from immune attack by down-regulating cytotoxic T cell responses to fetal trophoblast antigens is postulated to protect the islet cells of the pancreatic tissue also. HLA-G and nuclear factor-κB (NF-κB) interaction is suggested to be central in the events leading to GDM development. An analogy between the development of DM in some transplant patients and GDM development in a proportion of pregnancies is postulated, so that an antigenic load triggers the diabetogenic process.Further support of this hypothesis with new studies may lead to the possibility that recombinant HLA-G can be used for the prevention of diabetes in high risk patients.