Challenges in Understanding Diabetic Embryopathy

Perhaps one of the most devastating diabetes complications is diabetic embryopathy, in which the offspring of a mother with diabetes predating pregnancy develops congenital malformations. These malformations can affect multiple organ systems, including the brain and spinal cord, the heart and major vessel, the kidneys, the gut, and skeletal structures (1,2) and result in pre- or postnatal mortality or disability. As malformations are induced during the earliest stages of organogenesis, coinciding with the first recognition of pregnancy (3), it is important to institute rigorous glycemic control before the onset of pregnancy. Nevertheless, recent studies (4,5) have shown that even in planned pregnancies with optimal prepregnancy care, the incidence of malformations in diabetic pregnancies is still at least twice that in nondiabetic pregnancies. As malformations occur in the offspring of women with either type 1 or type 2 diabetes (or offspring of women who are obese at the beginning of pregnancy and may have undiagnosed type 2 diabetes) (2,6–8), and recent evidence indicates that the incidence of diabetes, particularly type 2 diabetes, predating pregnancy is rapidly increasing (9), the burden of this diabetes complication is likely to increase in coming years unless efforts to prevent diabetic embryopathy are improved. However, unlike other diabetes complications, in which the development of pharmacologic interventions offer the hope of treatment or prevention, prevention of …