Measurement of deuterium-labeled glucose flux in newborn infants by the continuous isotope infusion technique

Although hypoglycemia is a frequent neonatal problem, direct estimates of glucose turnover in newborn infants have not been possible before the advent of practical, stable isotope microtechniques. Using the well-established constant isotopic infusion procedure, glucose flux has been measured in newborn infants for the first time with the metabolically non-recycling tracer, glucose-6,6-d2. Nineteen infants from 650 to 4330 grams (25 to 44 weeks gestation) were studied at various times during the first week of postnatal life. 100 to 200 microliter capillary blood samples, obtained at appropriate intervals during the course of a 150 to 240 minute infusion of dideuterioglucose, were processed by rapid ion exchange purification and the glucose converted to the 6-0-acetyl-1,2 : 3,5-di-O-(n-butane-boronyl)-α-D-glucofuranose derivative for subsequent measurement of isotopic enrichment by combined GC-MS with selected ion recording using an AVA:Voltage Sweeping circuit. Glucose flux rates were calculated by steady-state equations, where appropriate, or by non steady-state approximations when blood glucose concentration and/or glucose isotopic enrichment changed during the course of the investigation. Total glucose flux ranged from 3 to 43 mg/min (3.7 to 11.1 mg/kg.min) and was directly correlated with body weight, estimated brain weight, and average blood sugar concentration during the course of the study. These data agree closely with previous indirect estimates of glucose metabolism in the newborn period and represent the first direct measurements of new glucose production and utilization in the human neonate