ROLE OF THE SPLANCHNIC TISSUES IN THE PATHOGENESIS OF ALTERED CARBOHYDRATE-METABOLISM IN PATIENTS WITH CHRONIC-RENAL-FAILURE

To evaluate the contribution of the splanchnic area to the carbohydrate abnormalities associated with chronic uremia, the splanchnic exchange of glucose and gluconeogenic substrates was quantitated basally and after an iv glucose load in nine uremic patients with impaired glucose tolerance and seven control subjects. In the basal state, blood glucose and splanchnic glucose production were similar in the two groups. During glucose infusion (33 μmol/kg·min for 90 min), blood glucose reached significantly higher levels in the uremic patients than in controls (P < 0.02). Plasma insulin increased slightly more in uremic patients than in controls (P < 0.05 at 15 min). Both basal and postglucose glucagon levels were 2- to 3-fold higher in uremic patients than in normal subjects (P < 0.05–0.02). In both groups, splanchnic glucose balance switched from net output in the basal state (-9.4 ± 0.5 and -8.0 ± 1.1 μmol/kg·min in normals and uremics, respectively) to net uptake with glucose infusion. However, this response was less marked in the uremic patients than in normal subjects (P < 0.05–0.02 at 30 and 90 min). The cumulative net splanchnic glucose balance over the 90-min study period was 538 ± 55 μmol/kg in normal subjects and 279 ± 89 in uremic subjects (P < 0.05). A net splanchnic lactate uptake was present in the basal state in normal (4.2 ± 0.5 μmol/kg·min) and uremic subjects (3.4 ± 0.5). During glucose infusion, in normal subjects splanchnic lactate exchange switched to a net output (-4.0 ± 1.6 μmol/kg·min), whereas in the uremic group it remained as a net uptake (1.1 ± 0.7) throughout the study period. Splanchnic gluconeogenic amino acid uptake was similar in the two groups in the basal state (1.8 ± 0.1 μmol/kg·min and 2.2 ± 0.2 in normal and uremic subjects, respectively). Glucose infusion caused a marked fall in amino acid uptake by liver in normal subjects, whereas no change was observed in the uremic group (0.9 ± 0.3 and 1.9 ± 0.2 μmol/kg·min, respectively). Splanchnic glycerol uptake was not different in the two groups in the basal state (0.75 ± 0.2 and 1.1 ± 0.2 μmol/kg·min) and decreased to a similar extent during glucose infusion. We conclude the following. 1) In uremic patients with glucose intolerance but normal fasting glycemia, the splanchnic metabolism of glucose and gluconeogenic substrates is normal in the postabsorptive state. 2) After glucose administration, splanchnic glucose disposal is impaired in uremic subjects despite relative hyperinsulinemia, whereas the splanchnic uptake of most gluconeogenic precursors is less suppressed than that in normal subjects. The data indicate that besides the well documented peripheral insulin resistance, an important splanchnic defect is present in the initial stages of chronic uremia that contributes to the carbohydrate abnormality associated with this disease. © 1990 by The Endocrine Society.