Unraveling the syndrome of diabetic embryopathy: From cell signaling to clinical care
E. Albert Reece, MD, PhD, MBA, is the Vice President for Medical Affairs, University of Maryland; the John Z. and Akiko K. Bowers Distinguished Professor, and Dean of the School of Medicine. He is also professor in the departments of Obstetrics and Gynecology, Medicine, and Biochemistry & Molecular Biology. He is a member of the prestigious Institute of Medicine (IOM) of the National Academy of Sciences.
Successful fetal and maternal outcomes in the context of maternal pregestational diabetes (type 1 or type 2) largely depend on how well glycemic control is maintained, especially prior to conception and in the first trimester of pregnancy. Stringent metabolic control and monitoring, and nutritional management via supplements and antioxidants significantly reduce the risk for or can eliminate poor outcomes due to hyperglycemia on both the maternal and fetal side.
Experiments in animal models have shown that hyperglycemia induces oxidative stress within the developing cells and tissues of the fetus. As maternal glucose concentration increases, so does the concentration of reactive oxygen species (ROS) within the fetus. When ROS concentration increases, the natural antioxidant capacity of fetal cells decreases, which leads to at least three biomolecular events causing birth defects: membrane alterations; mitochondrial dysfunction; and initiation of apoptosis.
Studies using mice that are genetically modified to overexpress the human antioxidant superoxide dismutase have shown that combating oxidative stress in a diabetic pregnant mouse model is possible, and that antioxidants can reduce the rate of hyperglycemia-induced malformations. In addition, blocking cell-death pathways, by inhibiting pro-apoptotic signaling proteins, can prevent birth defects. More recent work has explored the use of naturally-occurring proteins and compounds to reduce maternal diabetes-induced oxidative stress. Although epidemiological studies examining the benefits of these interventions are needed, the push to translate basic-science findings into preclinical and rigorous clinical studies has made more effective interventions and prevention strategies for diabetes and its complications very close to becoming clinical practice realities.
The page was last updated on Saturday, April 25, 2015 - 3:04pm