Multifactorial basis of the syndrome of diabetic embryopathy.
OBJECTIVE
The aim of the current paper is to explore the multifactorial basis of diabetes-induced embryopathy.


METHODS
A review of the literature regarding congenital malformations was undertaken to elucidate new advances in our understanding of diabetic embryopathy. Data from both clinical and experimental studies were collected and analyzed.


RESULTS
Numerous investigators have demonstrated that hyperglycemia and other metabolic fuels produce teratogenic effects during organogenesis. However, the exact mechanism(s) involved have not been completely elucidated. We and others have shown that aberrant metabolic fuels including hyperglycemia and hyperketonemia are teratogenic and that these effects occur via the yolk sac which appears to be the target site of injury. Other proposed etiologic factors include nutrient deficient states in membrane lipids such as arachidonic acid and myo-inositol as well as the generation of excess free oxygen radicals. This review highlights the multiple theories that have been proposed and summarizes the experimental and clinical data which support a multifactorial basis.


CONCLUSIONS
Evidence suggests that although the teratogenic process in the diabetic pregnancy is multifactorial, it may operate via a common pathway. Prevention of malformations in offspring of diabetic rats is achieved by glycemic control during organogenesis. Similar results may be obtained in a hyperglycemic state, provided there is restoration of essential fatty acid/phospholipid deficiency state and normalization of excess free radicals which may be achieved through dietary supplementation of polyunsaturated fatty acids, myoinositol, or antioxidants. The latter approach offers great promise as an adjunct to periconceptional glycemic control and as a dietary prophylaxis against the syndrome of diabetic embryopathy.
Reece
E A
EA
Department of Obstetrics, Gynecology and Reproductive Sciences, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
Homko
C J
CJ
Wu
Y K
YK
D000818:Animals; D015984:Causality; D000013:Congenital Abnormalities; D048909:Diabetes Complications; D016640:Diabetes, Gestational; D005260:Female; D005315:Fetal Diseases / Q000453:epidemiology / Q000209:etiology* / Q000517:prevention & control; D006801:Humans; D006943:Hyperglycemia / Q000503:physiopathology; D011247:Pregnancy; D011254:Pregnancy in Diabetics; D051381:Rats; D013577:Syndrome; D015017:Yolk Sac