No abstract

A constant infusion of 14 C-cortisol and 3 H-cortisone for 4 hr was given to six pregnant women, at term, at the time of elective cesarean section. Radioactive and nonradioactive cortisol (F) and cortisone (E) concentrations were determined in maternal and cord plasma at the time when the concentration of the radioactive steroids had reached a plateau. Metabolic clearance rates (MCR), plasma levels of endogenous F and E, blood production rates (BP), conversion ratios (Cr), and transfer constants ([p] BB values) were calculated and compared with those obtained in eight nonpregnant women, half of whom took contraceptive medication (subjects taking "the pill") and half of whom did not (control subjects).The MCR (F) of women near term, control subjects, and women receiving contraceptive treatment were (mean db SD) 133 ± 47, 141 ± 37, and 62 db 24 liters/24 hr, respectively. The latter was significantly lower than the other two. The MCR (E) were similar in all three groups of subjects and 4-7 times greater than MCR (F).The ratio of the endogenous F/E for control subjects was significantly lower (4.8 ± 0.6) than that for women on the pill (9.0 ± 1.6) or for pregnant women (7.5 ± 1.7). In contrast to their mothers, the neonates had an F/E ratio of 0.85 ± 0.34 with a mother /cord ratio for F of 4.9 ± 2.5 and for E of 0.50 ± 0.15.In eight fetuses of 3-6 months of gestational age, plasma concentrations of F (2.1 ± 1.2 jug/100 ml) and E (4.7 ± 3.3 jug/100 ml) were lower than those of six neonates (6.3 db 2.9 for F and 7.2 ± 1.2 /ig/100 ml for E).For control subjects, the Cr F^E was significantly higher and the Cr E^F significantly lower than these ratios for pregnant women and for women on contraceptive medication. From the values of BP (F) for each subject and the corresponding transfer constant [P]BB E it was estimated that all the BP (E) for the subjects studied arose from BP (F), which suggested that, within the limits of error of the methods used, there was no E secretion. SpeculationFrom previous studies in sheep, it was demonstrated that cortisol crossed the placenta from the mother to the fetus but that the fetus near term was also able to secrete cor-509 510 BEITINS ET AL.tisol. In this study of pregnant women we were able to calculate the maternal contribution to the fetal cortisol and cortisone concentration and to show that the fetus secretes three-fourths of its cortisol but that its cortisone was mainly maternal in origin. We were also able to show that cortisol and cortisone concentrations, similar to those at term, existed in utero as early as the 3rd month. We therefore speculate that the human fetal adrenal is capable of corticosteroid secretion early in pregnancy.

Objective: To examine the persistence of the original treatment effects 10 years after the Diabetes Control and Complications Trial (DCCT) in the follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study. In the DCCT, intensive therapy aimed at nearnormal glycemia reduced the risk of microvascular complications of type 1 diabetes mellitus compared with conventional therapy.Methods: Retinopathy was evaluated by fundus photography in 1211 subjects at EDIC year 10. Further 3-step progression on the Early Treatment Diabetic Retinopathy Study scale from DCCT closeout was the primary outcome.Results: After 10 years of EDIC follow-up, there was no significant difference in mean glycated hemoglobin levels (8.07% vs 7.98%) between the original treatment groups. Nevertheless, compared with the former conven-tional treatment group, the former intensive group had significantly lower incidences from DCCT close of further retinopathy progression and proliferative retinopathy or worse (hazard reductions, 53%-56%; PϽ.001). The risk (hazard) reductions at 10 years of EDIC were attenuated compared with the 70% to 71% over the first 4 years of EDIC (PϽ.001). The persistent beneficial effects of former intensive therapy were largely explained by the difference in glycated hemoglobin levels during DCCT. Conclusion:The persistent difference in diabetic retinopathy between former intensive and conventional therapy ("metabolic memory") continues for at least 10 years but may be waning.

No abstract

No abstract

The hyperinsulinemia of obesity could result from a decrease in the metabolic clearance rate of insulin (MCR-I), an increase in the secretory rate of insulin (SR-I), or a combination of both these processes. Because C-peptide and insulin are secreted in an equimolar ratio, the plasma concentrations of C-peptide (C) and insulin (I) are inversely proportional to their rates of metabolic clearance (C/I = MCR-I/MCR-C). We obtained 24-h integrated concentrations (IC) of insulin (IC-I) and C-peptide (IC-C) in 23 obese and 45 nonobese subjects over a period of normal activity and food intake. The IC-I was 69% higher in the obese subjects (P less than 0.0001). A 13% increase in the IC-C (P = 0.04), with a constant rate of C-peptide clearance, indicates a proportionate increase in SR-I. A 33% decrease in the IC-C/IC-I in the obese group (P less than 0.005) reflects a decrease in MCR-I; hence, 75% of the hyperinsulinemia is due to a decrease in the clearance of insulin. Because peripheral MCR-I (pMCR-I) is similar in obese and nonobese subjects, the decrease in MCR-I may be due to a decrease in the hepatic clearance of insulin. This conclusion was supported by our comparison of 24-h IC-C/IC-I ratios in the obese and nonobese subjects. Whereas the 24-h IC-C/IC-I of the nonobese resembled the fasting state, the 24-h IC-C/IC-I of the obese resembled the postprandial state, when insulin removal by the liver is known to be suppressed. These data are consistent with a decreased 24-h hepatic MCR-I (hMCR-I) as the cause of the hyperinsulinemia of obesity.

No abstract

The purpose of this study was to compare the reproducibility of two approaches to the evaluation of GH secretion: the integrated concentration of GH (IC-GH), a physiological test of GH secretion, and pharmacological stimulation tests. IC-GH was determined in 40 poorly growing children twice within 4 weeks. The first and second IC-GH were highly correlated r = 0.859, P less than 0.001. One hundred and thirteen poorly growing children underwent pharmacological GH stimulation tests twice within 6 weeks. A moderate correlation was found between the first and second pharmacological test r = 0.524, P less than 0.01. Among the three pharmacological stimuli studied, clonidine (n = 81) had the highest reproducibility followed by arginine (n = 20), and insulin (n = 12). We conclude that IC-GH is more consistently reproducible than the GH response to repeated pharmacological stimulation.