Placental Barrier to Human Insulin-I¹²⁵in Insulin-Dependent Diabetic Mothers*

Abstract

Although the normal human placenta is impermeable to insulin, the effect of anti-insulin antibodies on this placental barrier in insulindependent diabetic mothers is not known. The placental transfer of human insulin-I 125 was examined in 4 normal and 4 insulin-dependent diabetic mothers. Human insulin-I 125 was infused at a constant rate for 60-90 min prior to delivery and immuno-precipitable insulin-I 125 was measured in the maternal and umbilical venous plasma at delivery. In diabetic patients, insulin-I 125 was separated from circulating endogenous anti-insulin antibodies by acid alcohol extraction prior to immunoprecipitation. In normal mothers insulin-I 125 radioactivity was 683 ±110 cpm/ml (mean ± SEM) in the mater-

Altered diastolic function in infants of mothers with gestational diabetes: No relation to macrosomia

“…When compared to control newborns of similar weight, cardiac hypertrophy was also noted in newborns of mothers with adequately controlled diabetes [10]. No echocardiographic differences were noted in 4 LGA and 36 AGA fetuses of diabetic mothers, suggesting an effect of diabetes rather than fetal size on the heart [12].…”

“…Animal studies have demonstrated that a combination of hyperglycemia and hyperinsulinemia can lead to moderate hypoxia and depressed myocardial function [1,8,13]. Fetal hyperinsulinemia [4] alone may lead to macrosomia and cardiac hypertrophy. Because good metabolic control is known to result in adequate control of the weight, but not of the cardiac alterations, it is intriguing to hypothesize that the effect of fetal hyperinsulinemia (if it is the primary etiologic factor) on the fetal myocardium is different from other organs involved in the process of macrosomia.…”

Ultrastructure of human umbilical arteries. Studies on arteries from newborn children delivered by nonsmoking, white group D, diabetic mothers.

“…On the other hand, antibodies against insulin present in the maternal blood are transferred through the placenta in diabetic women. Labeled insulin has been measured in four diabetic and four nondiabetic patients (the only study in humans), and it was concluded that the placental transfer of insulin was hardly measurable and that the presence of insulin antibodies did not induce insulin transfer (Kalhan et al, 1975).…”

Insulin-related genes expressed in human placenta from normal and diabetic pregnancies.

“…Glucose is used as a major source of metabolic energy in the human fetus (2)(3)(4) and a glucose imbalance, in addition to affecting the growth of embryonic tissue, may well result in developmental abnormalities such as macrosomia, malformations, and increased rate of stillbirths, as is manifested in pregnancies of diabetic women. Insulin, a regulator of glucose metabolism, is an essential growth factor for fast-growing mammalian tissues, including human embryonic tissues (2-4); however maternal insulin does not cross the blood/placental barrier (5)(6)(7)(8). Although it has not been established that insulin or an insulin-like growth factor is necessary for the early development of the human fetus in utero, such a requirement is not unlikely.…”