A B S T R A C T The effects of pregnancy and diabetes on systemic glucose production rates and the sources of glucose for the human fetus in utero were evaluated in five normal, four gestationally diabetic, and one insulin-dependent diabetic subject undergoing elective caesarean section at term gestation. Five normal nonpregnant women were studied for comparison. Systemic glucose production rates were measured with stable tracer [1-13C]glucose according to the primeconstant rate infusion technique. Even though the plasma glucose concentration during normal pregnancy had declined as compared with the nonpregnant subjects (P < 0.0005), the systemic glucose production rate was 16% greater, a rate sufficient to provide the glucose requirement of the fetus at term gestation. The decline in glucose concentration could be the result of an increase in apparent volume of distribution of glucose. Systemic glucose production rates in wellcontrolled, gestationally diabetic subjects were similar to those in normal pregnant subjects (2.07±0.53 vs. 2.42±0.51 mg/kg-min). The sources of glucose for the human fetus at term gestation were evaluated by comparing (a) natural variation in 13C:12C ratio of plasma glucose and (b) enriched '3C:'2C ratio ofplasma glucose during [1-13C]glucose infusion in maternal and fetal blood at delivery in both normal and diabetic subjects. These data showed that the fetal glucose pool was in equilibrium with the maternal glucose pool in both normal and diabetic subjects, indicating that a brief A preliminary report of this work has been published as an abstract: Pediatr. Res. 1977.

Although insulin has been demonstrated in human fetal pancreas as early as thirteen weeks of gestation, the controls of insulin secretion in the human fetus and the magnitude of placental insulin transfer to the fetus are unknown. In pregnant women, scheduled for therapeutic abortions by abdominal hysterolomy at fifteen to twenty weeks of gestation, the fetal plasma insulin response to glucose infusion and insulin transfer across the placenta were studied as follows: (1) glucose was infused to eight fetuses in situ, and (2) insulin-I-131 was infused continuously for four to six hours to eight pregnant women via peripheral vein.Insulin was measured radioimmunologically and, following the infusion studies, was precipitated quantitatively by a double antibody method. During fasting, no difference was observed between fetal and maternal plasma glucose or in insulin levels. Although glucose administered to the fetus raised the fetal plasma glucose concentration without changing the maternal level, both fetal and maternal plasma insulin concentrations were unchanged at five and ten minutes. Human insulin-I-131 was not transferred across the placenta and no sequestration of insulin-I-131 occurred in the placenta. Early in human gestation the fetal pancreas appears to be the major source of fetal insulin, and the fetal insulin secretion rate may be relatively unresponsive to acute changes in blood glucose concentration. The placenta acts as a barrier to human insulin-I-131 but does not appear to sequester and catabolize insulin-I-131, as was previously demonstrated in human pregnancies at term. DIABETES 18:409-16, June, 1969.

Treatment with oral prednisone (15 mg every 6 h) for 1 day plus a 4-h glucose infusion at 2.8 mg/min kg body weight to 5 normal, healthy individuals raised their blood glucose to 137 +/- 4.5 mg per 100 ml (mean +/- SEM). In order to evaluate the effects of steroid-induced hyperglycemia on insulin responses, a model for the duplication of blood glucose concentration in serial studies was developed. During glucose infusion at 5.7 mg/min kg body weight, the fractional uptake of glucose at the end of infusion (KG) was 2.08 +/- 0.2%/min and the apparent volume of distribution (V) was 285 +/- 10.5 ml/kg. Further increase in the rate of glucose infusion did not affect KG and V. Based on these parameters, KG and V, the stable blood glucose achieved during the prednisone study (C) was duplicated both after short (4 h) and prolonged (28 h) glucose infusions (138 +/- 4.5 and 146 +/- 4.5 mg/100 ml, respectively) at rates calculated as the product of KG.C.V. The effects of prednisone treatment on insulin secretion were examined (1) during fasting, (2) at identical glucose concentrations during glucose infusions at constant rates, and (3) in response to glucose pulse (0.1 g/kg) during the infusions. During fasting, there was a significant elevation of mean blood glucose with prednisone (99 +/- 1.8 mg/100 ml) compared with that in the control study (88 +/- 1.7 mg/100 ml). The plasma IRI, however, remained unchanged (10 +/- 2.3 vs 10 +/- 1.6 muU/ml). During glucose infusions in the presence of similar blood glucose levels, the IRI was lower after prednisone treatment (18 +/- 1.5 muU/ml) than during the short and prolonged glucose infusions (42 +/- 5.1 and 63 +/- 7.0 muU/ml). The insulin response to the glucose pulse also was significantly lower during steroid treatment. Thus, prednisone apparently has an early inhibitory effect on the insulin response to glucose.