Harvey M. Rodman

A modern approach to management of pregnant diabetics: a two-year analysis of perinatal outcomes.

Increased understanding of maternal-fetal carbohydrate homeostasis together with modern perinatal technology now provides a more rational basis for obstetric management of the pregnant diabetic patient. These concepts were applied at MacDonald House in the care of 96 diabetic pregnant women over a two-year period. Pregnancy outcomes were compared with prior experiences with the same group of women. The perinatal mortality rate was reduced from 13.5 to 4.2%, and the rate of macrosomia (infants large for gestational age) was reduced from 30.9 to 17.7%. Patients with gestational diabetes, with a prior loss rate of 8.3%, suffered no losses in the current series. Maternal age was not found to correlate with an untoward outcome in this subgroup.

The Newborn of Diabetic Rat. I. Hormonal and Metabolic Changes in the Postnatal Period

Summary: In this study we investigated the effects of streptozotocin-induced maternal diabetes on fetal body weight and alterations in the plasma concentrations of glucose, insulin, glucagon and catecholamines, and in the concentrations of pancreatic insulin and glucagon and of hepatic glycogen and cAMP in newborn rats during the first 6 h of life. Hyperglycemia was regulated in one group of diabetic pregnant rats by administration of insulin twice a day from day 18 of gestation. On day 22 of gestation the body weight of newborns of the insulin-treated diabetic rats was significantly higher than that of normal rats, whereas untreated maternal diabetes caused a reduction in the body weight of the newborns. The newborns of insulin-treated diabetic rats maintained lower concentrations of plasma glucose for a longer period compared to the age-matched neonates of normal rats.At birth and during the first 6 postnatal h of life, plasma insulin was significantly higher in the neonates of both treated and untreated diabetic rats than the age-matched pups of normal rats. There was an increase in the concentration of plasma pancreatic glucagon in the newborns of normal rats within 30 min after birth, in contrast, a gradual reduction or no change in the concentrations of plasma glucagon was observed in the neonates of both groups of diabetic rats during the 6 h postnatal period. The concentrations of plasma epinephrine and norepinephrine were very high at birth in the three groups of newborns, and declined rapidly during the first postnatal h. Significant secondary increases in the concentrations of these two hormones occurred in the three groups of neonates after the plasma glucose concentration had declined to below 2 mM. Changes in the insulin:glucagon molar ratio was associated with a delay in the postnatal increase in hepatic cAMP concentrations and also in the initiation of hepatic glycogenolysis in the neonates of both groups of diabetic rats compared to normal animals. The findings of macrosomia, postnatal hyperinsulinemia, prolonged lowered plasma glucose and attenuated plasma glucagon observed in the newborns of the insulin-treated diabetic rats are similar to the findings reported in the newborn infants of insulin-dependent diabetic women.Speculation: Diabetes during pregnancy in the rats described in this study is reproducible and can be regulated with insulin administration. This experimental model should prove useful in quantifying alterations in hepatic glycogen metabolism and gluconeogenesis, and the mechanism(s) responsible for the attenuated glucagon secretory response in newborns of diabetic mothers.

Stereospecificity of the hydrogen transfer catalyzed by human placental aldose reductase.

Placental aldose reductase (EC 1.1.1.21) was incubated with glucose in the presence of [4A-2H] NADPH prepared in the oxidation of [2-2H] isocitrate by isocitrate dehydrogenase (EC 1.1.1.42) or [4B-2H] NADPH prepared in the oxidation of [1-2H] glucose-6-phosphate dehydrogenase (EC 1.1.1.49). The sorbitol formed from [4A-2H] NADPH contained deuterium and from [4B-2H] NADPH it did not. Therefore, aldose reductase in an A-type enzyme.

Pneumococcal Immunization in Adult Diabetics

The antibody responses of 102 adult insulin-treated diabetics who received 14-va lent pneumococcal polysaccharide vaccine were measured. Grand mean preimmunization antibody levels were similar for diabetics, 255 ng protein N/ml, and controls, 234 ng protein N/ml. Postimmunization, the values in the diabetics, 1009 ng protein N/ml, and 834 ng protein N/ml in 48 healthy controls, were not significantly different. The height of antibody response in the diabetic group did not correlate with age, sex, duration of diabetes, insulin dose, concentration of glycosylated hemoglobin, fasting or 2-h postprandial glucose concentrations, or the presence of retinopathy. Side effects were minimal and occurred in 26%. Antibody response to pneumococcal polysaccharide vaccine is not impaired in adult diabetics. Pneumococcal immunization is safe and may reduce the frequency of pneumonia and its complications in the diabetic population.

Quantitative Vitreous Fluorophotometry in Insulin-treated Cystic Fibrosis Patients

A series of 22 patients with cystic fibrosis (CF) of similar clinical severity (9 with normal carbohydrate tolerance and 13 with insulin-treated fasting hyperglycemia) was examined with quantitative vitreous fluorophotometry. All of the CF patients studied had normal fundi on ophthalmoscopy, fundus photographs, and fluorescein angiography. Mean vitreous fluorescein concentration in the CF patients whose hyperglycemia was treated with insulin (11.79 ng/ml) was significantly higher than in CF patients with normal carbohydrate tolerance (6.98 ng/ml, P < 0.005). Thus, CF patients with fasting hyperglycemia demonstrate a breakdown of the bloodretinal barrier. When CF patients with fasting hyperglycemia were compared with age- and sex-matched type I diabetics, there was no significant difference in mean vitreous fluorescein accumulation. Thus, breakdown of the blood-retinal barrier, one of the earliest detectable functional abnormalities that may be associated with the microangiopathy of diabetes mellitus, also occurs with equal frequency and severity in the diabetes secondary to pancreatic fibrosis associated with CF.

Antibody Response to Pneumococcal Polysaccharides in Insulin-dependent Diabetes Mellitus

Twenty-one insulin-dependent diabetics and 11 healthy control children were immunized with polyvalent pneumococcal polysaccharide vaccine. Serum antibody to pneumococcal polysaccharides was measured by radioimmunoassay before and after immunization. Although there were some differences in type-specific antibody concentrations between diabetic and control subjects, the overall antibody concentrations preimmunization, 3–4 wk postimmunization, and 6–7 wk postimmunization were similar in both populations. In both groups antibody response to immunization correlated strongly with preimmunization antibody concentration. Among the diabetic subjects there was no correlation between antibody responses and duration of disease, insulin dose, or concentration of glycosylated hemoglobin. Insulin-dependent diabetic subjects have a serum antibody response to pneumococcal polysaccharides equivalent to that of controls, and in both populations the magnitude of the antibody response correlates with preimmunization antibody levels.

Glucose metabolism by rat pancreatic islets in vitro

[U-14C]-glucose was incubated with rat islets in a Krebs-Ringer buffer. The uptake of glucose and its oxidation to CO2 were in accord with linear increases over the range of medium concentration of glucose from 0.6–3.0 mg/ml. Uptake was similar at 3.0 and 5.0 mg/ml indicating saturation of uptake in the range of these concentrations. These values are in agreement with reports of insulin release as a function of increasing glucose concentration and hence of insulin release as a function of uptake. Between 62% and 76% of glucose uptake was accounted for in CO2 and lactate. The amount of [14C]-lactate formed was similar to the amount of 14CO2 formed at 0.6 mg/ml, and it was about one-half as much or less at 3.0 and 5.0 mg/ml. Therefore, lactate is not the major product of glucose metabolism by rat islets in vitro. The formation of [3-14C]-lactate from [1-14C]-glucose indicates that lactate formation from glucose proceeds via pyruvate without intermediate randomization of the pyruvate carbons in the Krebs cycle.

Impairment of T-Cell Regulation of the Humoral Immune Response to Type III Pneumococcal Polysaccharide in Diabetic Mice

The peak plaque-forming-cell (PFC) and serum antibody responses of diabetic mice to type III pneumococcal capsular polysaccharide (S3) were delayed compared with normals. Proliferation of PFC precursors was not inhibited in an insulin-deficient environment. The delay in the PFC response to S3 did not occur in diabetic nude mice but was demonstrable in their thymus-bearing heterozygote littermates. Therefore, T-cells appear to mediate the delay in the response of diabetic mice to S3 probably by delaying their differentiation into PFC. Diabetic mice responded normally to the induction of low-dose tolerance to S3, indicating the presence of active suppressor T-cells (Ts) in these mice. However, inactivation of Ts by anti-lymphocyte serum (ALS) required a higher dose in the diabetic mice. Furthermore, inactivation of Ts by ALS totally abolished the delay in peak PFC response. These findings suggest that the delayed PFC response to S3 in diabetic mice was the result of excessive splenic Ts activity. In peripheral blood, diabetic mice appeared to have more amplifier T-cell activity or less suppressor T-cell activity than normals. This response was normalized by insulin treatment.