Prevention of diabetic embryopathy in offspring of diabetic rats with use of a cocktail of deficient substrates and an antioxidant.
OBJECTIVE
The current study sought to determine whether a dietary cocktail of deficient substrates and antioxidant could reduce the incidence of diabetic embryopathy to the background rate in an in vivo rat model.


METHODS
Sprague-Dawley rats 70 to 90 days old were assigned to one of eight groups: two control groups (groups 1 and 2) and six diabetic groups (groups 3 to 8). One group of controls (group 2) received an oral supplemental cocktail of vitamin E ((alpha-tocopherol, 400 mg/day), safflower oil (arachidonic acid, 1 ml/day), and myo-inositol 0.08 mg per day. Four other diabetic groups (groups 5 to 8) received the cocktail in varying strengths. One diabetic group (group 3) received a normal diet only without insulin or cocktail, whereas another diabetic group (group 4) received insulin but no cocktail supplementation. On day 6 of gestation diabetes was induced in groups 3 to 8 with intravenous streptozotocin (65 mg/kg), and maternal glucose levels were monitored. Animals were killed on day 12; embryos were examined for size, somite number, and evidence of malformations and were biochemically evaluated for vitamin E and myo-inositol levels and superoxide dismutase activity.


RESULTS
The diabetic groups had a significantly higher (p < 0.05) mean blood glucose level than controls did. The insulin-treated group 4 had glucose levels that were comparable to those of controls. The unsupplemented diabetic group 3 had a neural tube defect rate of 23.7% versus 4.04% in controls and 3.55% in insulin-treated diabetics (p < 0.05). The rate of neural tube defects was significantly reduced to the background level in animals receiving half-strength cocktail or stronger doses (groups 6 to 8) compared with the diabetic unsupplemented controls (group 3). Diabetic animals in group 5 receiving only quarter-strength cocktail did not demonstrate a significant reduction in the malformation rate. Serum myo-inositol levels were not significantly different among the groups. However, serum levels of vitamin E were significantly higher in diabetics receiving half-strength cocktail than in nondiabetic controls, diabetics receiving no supplements, and diabetics receiving quarter-strength cocktail. Superoxide dismutase activity was also significantly increased in diabetic animals receiving supplementation versus animals not receiving the same, and the increases in vitamin E and superoxide dismutase were significantly correlated (r = 0.66, p < 0.05).


CONCLUSIONS
These data demonstrate that a cocktail containing deficient substrates and an antioxidant in varying strengths reduces the malformation rate to background in offspring of diabetic rats.
Reece
E A
EA
Department of Obstetrics and Gynecology, and Reproductive Sciences, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Wu
Y K
YK
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D001786:Blood Glucose / Q000032:analysis; D000013:Congenital Abnormalities / Q000517:prevention & control*; D003921:Diabetes Mellitus, Experimental; D004359:Drug Therapy, Combination; D004622:Embryo, Mammalian / Q000187:drug effects; D005260:Female; D007294:Inositol / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000097:blood / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012450:Safflower Oil / Q000627:therapeutic use*; D014810:Vitamin E / Q000627:therapeutic use*
D000975:Antioxidants; D001786:Blood Glucose; D007328:Insulin; D014810:Vitamin E; D007294:Inositol; D012450:Safflower Oil