Effects of diets with different content in protein and fiber on embryotoxicity induced by experimental diabetes in rats.

Three groups of streptozotocin-diabetic rats were maintained during pregnancy on three hyperproteic diets with different protein contents. These differences were compensated by an equal quantity of fiber (group 1: protein 55.0%, fiber 4.5%; group 2: 45.0%, 14.0%; group 3: 35.0%, 24.0%). Three groups of nondiabetic pregnant rats were fed with the same diets and served as control. The differences of the daily protein intake among the diabetic groups were less pronounced than those expected on the basis of the diet composition, and the embryopathic effects (reduced fetal weight, increased in malformation and resorption rate) were not statistically different among the three groups of diabetic animals. The frequency of congenital malformations was higher than that observed in a previous experiment in diabetic rats maintained on a standard diet, but much lower than that observed in animals fed on a purified, fiber-poor, normoproteic diet. When the caloric intake of the diabetic rats in the different groups was determined it was found to be similar for all of them and also similar to the caloric intake of the rats given a standard nonteratogenic diet (in previous experiments), while the rats maintained on a normoproteic, teratogenic diet increased their caloric intake. These results seem to indicate that the diet composition greatly influences the intake of food and calories of pregnant diabetic rats and this may play a role in modulating the embryopathic effect of diabetes.

Damage to the crystalline lens in infants of diabetic mothers: a pathology so far neglected?

Congenital cataract occurs in 90-95% of diabetic rat fetuses. The pathogenetic mechanism is triggered by fetal hyperglycemia and presents the following steps: (1) a high glucose concentration in the lens; (2) reduction of glucose to sorbitol by aldose reductase; (3) accumulation of sorbitol into the fibers of the lens creating a hyperosmotic effect, leading to (4) an infusion of liquid into the fibers, which (5) become hydropic and degenerate (vacuolization). This series of manifestations might also occur in fetuses of pregnant diabetic mothers. Post birth glycemia diminishes rapidly, and this favorable condition which decreases vacuolization is perhaps the reason why such degeneration has not yet been observed. Since the fibers of the lens are permanent cells, damage in the fetal period might later bring about negative consequences. We hope that someone will study whether this ocular pathology occurs in human infants born to diabetic mothers.

Oversized infant of diabetic mother: its cause and prevention.

In this study the birth weights of 431 infants of diabetic mothers of the Milan series have been compared with the birth weights of infants of a control group. The averages and the centile distributions of weights of infants of gestational diabetic mothers (Class A) and of diabetic mothers without vascular complications (Classes B and C) did not differ substantially from those of control newborns (table I, figure 1). This confirms the clinical indication, based on the hyperglycemia-hyperinsulinism theory that fetal macrosomia can be prevented provided maternal metabolism is strictly controlled. In this series insulin was administered at the maximal tolerated dose (MTD), a therapeutic regimen that provides excellent metabolic control of the mother. In multiparae, the birth weights of the infants of the latest pregnancy were drastically lower than the birth weights of the infants in their previous pregnancies (without MTD insulin) (table II). Our results do not confirm the recent hypothesis that pregnant diabetics with strict metabolic control during pregnancy generally give birth to growth retarded infants. The MTD of insulin has also been administered to gestational diabetic mothers, and fetal macrosomia was prevented (table I, figure 1). This confirms the opinion of those who believe that a diet-regimen must be accompanied by insulin administration to correct the slight metabolic abnormality of these patients. As would be expected because of placental insufficiency, infants of patients with vascular complications, including those who have only calcifications of the pelvic vessels (White' Class E), were growth retarded (table I, figure 1). The risk of fetal growth retardation in Class E has not been remarked upon in the literature, since pathology of pelvic vessels is usually disregarded and the patients remain undifferentiated among Classes A-C. The possibility to prevent fetal macrosomia with a strict control of maternal diabetes has been questioned because of the lack of correlation between fetal macrosomia and the degree of maternal hyperglycemia and of fetal hyperinsulinism. We postulate that, if fetal hyperinsulinism causes hypoxia, as it does in experimental animals, the lack of correlation may be due to the fetal hyperinsulinism itself.

Effects of streptozotocin-induced diabetes on fetal development of the rat.

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)

Spontaneous preterm delivery in pregnant diabetics: a high risk hitherto "unrecognized".

Preterm delivery (PD)--before the 259th day from the beginning of the last menstrual period--is very frequent in pregnant diabetics (from 50% to 80% or more, personal investigation in progress). In these patients a policy is generally followed of a systematically controlled early delivery. Therefore, one is inclined to think that the high frequency of PD is mainly the consequence of this policy. However, it has been recently pointed out [5] that spontaneous labor accounts for half or more of PD in pregnant diabetics. Moreover in pregnant women with gestational diabetes PD rate due to spontaneous labor is three times higher than in the general obstetric population [5]. A different result emerges from our case study, 1963-1975. Insulin was administered to the maximal tolerated dose both in case of gestational and clinical diabetes [1, 6, 7, 8, 9, 10, 11, 12]. The incidence of PD due to spontaneous labor is 6.7% (7.1% in gestational and 6.1% in clinical diabetes), i.e. no difference from PD rate in general. Since 1974 M. Chartier, Paris, has been adopting the same therapeutic criteria [2]. His results seem to confirm that the risk of PD due to spontaneous labor drastically reduces in pregnant diabetics strictly controlled.

Recognition and significance of maternogenic fetal acidosis during intensive monitoring of labor.

FHR monitoring and microanalysis of fetal blood are mutually complementary procedures, and optimal knowledge of the fetal state is achieved by making use of both, the former for the preliminary screening of all cases at risk and the latter for the purpose of deciding on obstetric management where pathological changes are evident in the FHR. The major difficulty in obtaining a precise value for the fetal acid-base balance lies in the occurence of "falsely abnormal" cases, i.e. cases in which the fetal pH falls during labor but the clinical condition at birth is good (APGAR greater than or equal to 7). In our own series the incidence of such cases among fetuses at risk was 11.2% (Tab. I). In the majority of these cases the fetal acidosis is thought to be a result of increased metabolic acidosis in the mother (maternogenic fetal metabolic acidosis). The importance of the maternogenic fetal acidosis during labor lies in the fact that unless it is recognised, rapid extraction of the fetus will appear necessary on clinical grounds, although it is in fact unnecessary, since this form of acidosis has no adverse effect on the fetus. Various parameters have been proposed for the differential diagnosis of the maternogenic fetal acidosis. These include the feto-maternal difference in base deficit (F/M deltaBD), the materno-fetal differences in pHqu 40 (M/F deltapHqu 40) the materno-fetal difference actual pH (M/F actual deltapH), and the materno-fetal difference in base deficit of the extra-cellular fluid (M/F deltaBDHb5). A critical analysis of these parameters has been carried out on the results of microtests performed during a 5 year period (1968-1972) at the First Clinic of Obstetrics and Gynecology of Milan University. The cases comprised 59 regarded as normal (normal course of pregnancy, spontaneous commencement of labor at term, clear amniotic fluid, regular FHR, spontaneous birth, APGAR at 90 sec between 8 and 10, weight at birth greater than 2500 g), and 335 considered to be at risk (maternal disease, presence of meconium stained amniotic fluid and/or abnormal changes in FHR). In all of these cases the FHR was recorded by cardiotokography, and the tracings were interpreted according to HON. Microsamples of blood were taken from both mother and fetus during labor and the following determinations were carried out: actual pH, pHqu 40, Hb concentration, hemoglobin oxygen saturation, base deficit Hb5 (BDHb5). The maternofetal differences were then calculated. The same determinations were carried out on samples of maternal blood and of arterial and venous cord blood taken immediately after delivery. The clinical condition of the infant was evaluated by the APGAR score at 90 seconds after birth.