Glucose turnover in chronic uremia: increased recycling with diminished oxidation of glucose.

The effects of chronic renal failure and hemodialysis on the glucose turnover rate, glucose carbon recycling, and glucose oxidation were evaluated in eight chronically uremic subjects. Six normal subjects served as controls. The studies were repeated in seven uremic subjects after they had been established on hemodialysis for 3 to 18 months. Glucose 13C (ul) was administered by a prime-constant-rate infusion, and the isotopic enrichment of the whole glucose molecule (m + 6), ie, all six carbon atoms of glucose labeled with 13C and that of the C1 atom of glucose in the plasma were measured by mass spectrometry. It was assumed that the C1 atom of the glucose molecule represented the 13C enrichment of the individual glucose carbons. The “true” rate of glucose production was estimated from the dilution of the glucose 13C (ul) mass (m + 6) in the plasma. In contrast to the whole glucose molecule (m + 6), recycling of tracer carbon resulted in an increased 13C enrichment of the C1 atom of the glucose molecule and an underestimation of glucose turnover (“apparent”). Glucose carbon recycling was estimated from the difference between the “true” and “apparent” rates of glucose turnover. The contribution of glucose to respiratory CO2 was quantified by comparing the 13C enrichment of expired CO2 with that of the plasma glucose carbon. The plasma glucose concentration after an overnight fast was similar in the uremic and control subjects (72.3 ± 9.5 and 79.0 ± 9.5 mg/dL, respectively; mean ± SD). The “apparent” rate of glucose production, as measured by the reversible tracer 13C enrichment of the C1 atom of the plasma glucose molecule, was decreased in the uremic subjects, while the “true” rates of glucose production were similar in both groups (normal: 2.02 ± 0.19 mg/kg · min; uremic: 2.19 ± 0.53 mg/kg · min). Glucose carbon recycling contributed between 3.3% and 26.2% to the total glucose production in the controls. In seven out of eight uremic subjects, glucose carbon recycling ranged between 28.6% and 41.7% of glucose turnover. Glucose carbon recycling was 4.7% of glucose turnover in the eighth uremic subject. The contribution of glucose to respiratory CO2 was significantly reduced in the chronically uremic subjects (P < 0.02) and correlated with the rate of glucose turnover (r = 0.51, P = 0.05). Chronic hemodialysis had no effect on glucose kinetics in the uremic subjects. It caused a decrease (not statistically significant) in the volume of distribution of glucose and a corresponding increase in the glucose concentration, so that the glucose pool size remained unchanged in the uremic subjects. In three additional subjects, the acute effects of hemodialysis were examined by measuring glucose kinetics at 24 and 48 hours after hemodialysis. No significant effect of hemodialysis on glucose production and utilization was observed. The plasma insulin concentration was significantly increased in all uremic subjects compared with the normal subjects. We conclude that in chronic uremia in humans, after an overnight fast (1) the glucose production rate is unchanged; (2) glucose carbon recycling is increased, while glucose oxidation is decreased; and (3) hemodialysis has no effect on these variables. As the insulin concentration was increased in all uremic subjects, these data further reflect decreased insulin action, possibly at the level of pyruvate dehydrogenase.