SummaryFive ewes 90-130 days of gestation with chronically indwelling fetal catheters were studied. Blood samples were drawn each morning simultaneously from the maternal femoral artery, fetal femoral artery, and fetal umbilical vein. Total starvation was begun after blood samples had been drawn on the 3rd morning, but water was given ad libitum. The mean maternal arterial plasma glucose concentration before starvation (73.4 2 31.0 (SEM) mg/100 ml plasma HzO) fell to 54.8 f 5.2 mg/100 ml (P < 0.01) after 24 hr of fasting and to 37.5 + 1.6 mg/100 ml (P < 0.001) by 72 hr of fasting. The maternal arterial fructose concentration was low in both the fed (2.9 f 0.4 mg/100 ml) and fasted states (1.8 + 0.5 mg/100 ml, day 3). The maternal arterial insulin concentration fell early in fasting from a mean of 27.9 + 3.9 uU/ml on 2 days before starvation to 12.4 + 1.8 uU/ml after 24 hr of fasting (P < 0.005) and remained low for the duration of the 7-day fasting period. The mean maternal arterial glucagon concentration in the fed state was 112 + 20 pg/ml and did not change significantly throughout the 7 days of maternal fasting.Fetal arterial plasma glucose was much lower than maternal levels (mean 18.4 + 1.1 mg/100 ml plasma Hz0 in the fed state), decreased to 12.1 + 1.4 mg/100 ml after 24 hr of fasting ( P < 0.05) and did not change significantly after the 1st day of fasting.The whole blood fructose concentration in the fetal artery was high in the fed state (71.7 + 11.5 mg/100 ml, mean 2 days before fasting) and fell quickly during starvation (54.2 2 3.4 mg/100 ml after 48 hr). The fructose concentration did not change further for the duration of the fasting period. The fetal arterial insulin concentration was lower than the maternal (19.4 + 1.0 uU/ml in the fed state and did not fall dramatically after fasting as the mother did. After 24 hr of fasting, the fetal insulin was 15.0 + 1.5 uU/ml ( P < 0.005) and remained low throughout the fast. The umbilical venous-arterial differences of insulin were statistically different from 0 in both fed (mean -1.4 f 0.3 u U / d , P < 0.005) and fasted state (mean -1.4 + 0.5 uU/d, P < 0.02), with the fetal artery greater than the umbilical vein in 25 of 28 measurements. The fetal arterial concentration of glucagon was lower than in the ewe (32 f 7 pg/ml) and also did not change significantly during starvation.There was a good correlation of the plasma glucose and insulin concentrations for: both the fetus and the ewe. Analvsis of ~ooled fetal and maternal regression lines for insulin-glucos~relatidnships reveals no difference in the slow (maternal 0.48. fetal 0.48). but a statistically significant differeice'in the y intercept (mateinal -7.70, fetal 8.65, P < 0.005), with the fetal curve shifted to the left.The excellent correlation between plasma glucose and insulin concentration throughout the fed and fasted periods suggests that the decrease in fetal plasma glucose and the decreased utilization of exogenous glucose by the fetus is mediated by fetal insulin level. Although the respons...

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The therapeutic efficacy of human insulin (recombinant DNA) was compared with that of purified porcine insulin (PPI) in seven male subjects with previously treated insulin-dependent diabetes mellitus. In a random crossover design the patients received either PPI or human insulin during one of two consecutive 7-day periods of intensive insulin therapy. Control was evaluated on days 6 and 13. Tissue sensitivity and responsiveness to the study insulins were determined by insulin dose-response studies performed using the euglycemic glucose clamp on days 7 and 14. Insulin dose and all measures of control on days 6 and 13 were not statistically different between treatments. When the insulin dose-response studies during each treatment were compared there were no differences between them. Thus, in previously treated patients with insulin-dependent diabetes, undergoing brief but intensive insulin therapy with continuous subcutaneous insulin infusion, human insulin is as clinically efficacious as PPI. Furthermore, insulin sensitivity and responsiveness, as assessed by dose-response studies during the euglycemic glucose clamp were equivalent for both insulins.