Diabetes, Vol 38, Issue 6 764-772, Copyright © 1989 by American Diabetes Association
Effects of interrupted insulin treatment on fetal outcome of pregnant diabetic rats
RS Eriksson, L Thunberg and UJ Eriksson
Department of Medical Cell Biology, University of Uppsala, Sweden.
Streptozocin-induced diabetic female rats became normoglycemic after
subcutaneous insertion of insulin-releasing osmotic minipumps. These female
rats were mated with normal males from the same Sprague-Dawley substrain.
In this substrain, the offspring of diabetic rats show a markedly increased
congenital malformation rate compared with fetuses of nondiabetic rats. The
pregnant diabetic rats were subjected to removal and insertion of pumps at
defined gestational days that marked the beginning or end of a 2- or 4-day
period of insulin withdrawal. Evaluation of the offspring on day 20 of
pregnancy included fetal/placental weights, estimated number of implants,
resorptions, and morphological assessment of congenital malformations.
Resorptions occurred in all interruption groups, but malformations were
found only in animals with insulin withdrawal on gestational days 4-8, 6-8,
6-10, 8-10, and 8-12. The highest resorption (42%) and malformation (17%)
rates were found in the rats subjected to insulin withdrawal during
gestational days 6-10. Because manifestly diabetic rats with no insulin
treatment showed similar resorption (39%) and malformation (17%) rates,
this study suggests that a teratogenic period in diabetic rat pregnancy
occurs during gestational days 6-10, a period corresponding to
postconceptional wk 2-4 in human pregnancy. Interruption of insulin
treatment induced similar maternal weight loss and similar maternal serum
concentrations of D-glucose, cholesterol, urea, and creatinine in rats with
and without malformed offspring.(ABSTRACT TRUNCATED AT 250 WORDS)