Splanchnic tissues play a crucial role in uremic glucose intolerance.

Objective: Determine the mechanism of glucose intolerance in chronically uremic subjects.

Design: Comparison of doubly labeled oral glucose tolerance tests.

Subjects: Seven nondialyzed chronically uremic subjects (creatinine, 420 +/- 104 micromol/L) and 7 healthy subjects, matched for age and body mass index.

Intervention: Plasma glucose was labeled by an infusion of dideuterated glucose started 120 minutes before ingestion of 1 g/kg of naturally 13C-enriched corn starch glucose. Glucose levels and oxidation were monitored for 330 minutes after glucose ingestion.

Results: Uremic subjects had normal fasting plasma glucose levels and impaired glucose tolerance with high plasma insulin (P <.001 versus controls). Glucose tolerance was impaired because of an increased total rate of appearance of glucose (cumulated on 330 minutes: uremic, 1,231 +/- 42 mg/kg/330 min, controls, 1,031 +/- 64; P <.05). Peripheral glucose uptake was increased (P <.05) because of an increased nonoxidative disposal (P =.051).

Conclusions: Although peripheral glucose uptake resisted the stimulatory effect of the high insulin levels, glucose tolerance was impaired through splanchnic metabolic disturbances: reduced splanchnic glucose uptake and increased endogenous glucose production. The respective contribution of these abnormalities remains to be determined.