MULTIFACTORIAL BASIS OF THE SYNDROME OF DIABETIC EMBRYOPATHY

Objective: The aim of the current paper is to explore the multifactori al basis of diabetes-induced embryopathy. Method: A review of the lite rature regarding congenital malformations was undertaken to elucidate new advances in our understanding of diabetic embryopathy. Data from b oth clinical and experimental studies were collected and analyzed.Resu lts: Numerous investigators have demonstrated that hyperglycemia and o ther meta belie fuels produce teratogenic effects during organogenesis . However, the exact mechanism(s) involved have not been completely el ucidated. We and others have shown that aberrant metabolic fuels inclu ding hyperglycemia and hyperketonemia are teratogenic and that these e ffects occur via the yolk sac which appears to be the target site of i njury. Other proposed etiologic factors include nutrient deficient sta tes in membrane lipids such as arachidonic acid and myo-inositol as we ll as the generation of excess free oxygen radicals. This review highl ights 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 i n the diabetic pregnancy is multifactorial, it may operate via a commo n pathway. Prevention of malformations in offspring of diabetic rats i s achieved by glycemic control during organogenesis. Similar results m ay be obtained in a hyperglycemic state, provided there is restoration of essential fatty acid/phospholipid deficiency state and normalizati on of excess free radicals which may be achieved through dietary suppl ementation of polyunsaturated fatty acids, myoinositol, or antioxidant s. The latter approach offers great promise as an adjunct to periconce ptional glycemic control and as a dietary prophylaxis against the synd rome of diabetic embryopathy. (C) 1997 Wiley-Liss, Inc.