The purpose of this study was to determine whether or not in rats with experimentally induced diabetes there is an increased frequency of congenital malformations; data in the literature are not consistent on this point. Virgin CD females rats were injected with 40-50 mg/kg streptozotocin (Stz) before mating (SIBM group) or on the first day of pregnancy (SI1). Both SIBM and SI1 females were divided into two groups according to their blood glucose levels: severely diabetic (SD, greater than 300 mg%) and mildly diabetic (MD, 120-250 mg%). Food and water consumption by the control and MD groups were the same, but the SD females developed polyphagia, polyuria, and polydypsia, which continued to increase throughout pregnancy, as did the blood glucose levels. All the MD females mated and carried to term. In SD females both frequency of mating and fertility were only slightly lower than in the controls. All the females were killed on the 21st day of pregnancy. Pre- and postimplantation losses were the same for diabetic and control rats, but SIBM-SD females ovulated less than other groups. Weights of fetuses of SD dams were lower and blood sugar levels higher than those of the other groups. The placentas of SD rats were significantly heavier and there was cystic degeneration of spongiosa. The incidence of major malformations was minimal (approximately 2%) in fetuses of SD females and there were none at all in controls or MD females. In conclusion, our data are in agreement with those of other investigators who have found that rats with experimentally induced diabetes have smaller fetuses and increased placental weight.(ABSTRACT TRUNCATED AT 250 WORDS)
Beginning in 1963 we have administered fast-acting insulin in three daily injections up to the maximal tolerated dose (M.T.D.), which can be defined as the highest quantity that can be given without bringing about hypoglycemic disturbances. This therapeutic criteria was applied both to gestational (280 pregnant women) and clinical (199 pregnant women) diabetes. M.T.D. was established on first admission to hospital and afterward controlled weekly in the outpatient clinic and during short periods of hospitalization (average of 53 days per patient). The average increase of the M.T.D. was 38 IU from 15 wk until delivery. As regards maternal blood sugar, at the M.T.D. average values at fasting and over the 24-h period were very close to the corresponding values of the control group (normal pregnancy). Total perinatal mortality (P.M.) was 2.9%; in the gestational diabetes group it was 2%. The incidence of congenital malformations (CM.) (2.4%) increased with the severity of diabetes. No congenital defects were observed in 96 infants of patients treated before the 15th wk. Labor started spontaneously in 90.4% of the cases. The incidence of cesarean section was 21% in patients in White's Classes Al and A2 (as recently redefined by Freinkel and Metzger 8 ) and 28% in other classes and that of forceps and vacuum extraction was 1% and 6%, respectively. The incidence of small-for-dates and overweight newborns from mothers with gestational and clinical diabetes without vascular complications is consistent with normal figures (macrosomia 3.4%). Small-for-dates newborns from pregnant diabetic women with vascular complications had a significant incidence. Respiratory distress syndrome (RDS) was 0.6% and hypoglycemia was 13.4%. No case of death was due to these two causes. Clinical results are discussed, DIABETES CARE3.- 489-494, MAY-JUNE 1980.
k Fifty years have elapsed since the discovery of insulin; however, pregnancy is still far from being sufficiently safe in diabetic women. The most convincing proof is given by the high perinatal mortality ranging from 10 to 15% in specialized departments [16], which would be even higher if therapeutic abortion was not performed in numerous cases of severe maternal disease [3,11,23], On the other hand, äs far äs the mother is concerned, insulin therapy has deeply changed the prognosis of pregnant diabetic patients compared with the preinsulin era. However, severe complications such äs toxemia, urinary tract infections, aggravation of vascular diseases and so forth contribute to maintain the death rate at about 1% [16, 23], The problem of metabolic balanceIn an extensive review of the problem it has already been emphasized, many years ago [10], that unfavourable development of pregnancy and high perinatal mortality are associated specially with pregnant women lacking a good metabolic balance. These findings were subsequently confirmed [16,23] so that one may wonder whether in cases, considered to have been compensated for but still showing a high perinatal mortality rate, an actual optimal compensation had been obtained or whether its further improvement might have ameliorated fetal prognosis. As a matter of fact, the treatment of pregnant or non-pregnant diabetic patients is carried out everywhere by regulating the inCürriculum vitae GIAN sulin dosage on the basis of glycemia and glycosuria. The difficulties found in establishing the degree of metabolic compensation by means of these indices caused a considerable discrepancy of opinion äs to the optimal values for the best therapeutical approach [6,16,19,23,35,37]. On the other hand, it may be debatable whether such a criterion represents an "optimum" for the feto-placental unit in considering that the features of newborns of diabetic mothers frequently appear even in newborns of prediabetic mothers, where blood sugar levels show little or no alteration; interesting results were obtained by insulin therapy in these cases [14,22,25,41]. On the basis of the aforesaid considerations we began our investigations for a stricter control of diabetes mellitus in pregnancy in 1963. There-J. Perinat. Med. l (1973)
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