Effects of insulin and amino acids on glucose and leucine metabolism in CAPD patients

This study investigates the basal and insulin-stimulated glucose metabolism, substrate utilization, and protein turnover in eight patients maintained on continuous ambulatory peritoneal dialysis (CAPD) (mean age 39 +/- 5 yr, body mass index [BMI] 108 +/- 6) and 14 control subjects (mean age 33 +/- 4 pr, BMI 103 +/- 3), Euglycemic insulin clamp studies (180 min) were performed in combination with continuous indirect calorimetry and 1-C-14 leucine infusion (study I), Postabsorptive glucose oxidation was higher (1.75 +/- 0.18 versus 1.42 +/- 0.14 mg/kg per min) and lipid oxidation was lower (0.43 +/- 0.09 versus 0.61 +/- 0.12 mg/kg per min in CAPD patients than in control subjects (P < 0.05 versus control subjects). During the last 60 min of euglycemic hyperinsulinemia, the total rate of glucose metabolism was similar in CAPD and control subjects (6.33 +/- 0.51 versus 6.54 +/- 0.62 mg/kg per min). Both insulin-stimulated glucose oxidation (2.53 +/- 0.27 versus 2.64 +/- 0.37 mg/kg per min) and glucose storage (3.70 +/- 0.48 versus 3.90 +/- 0.58 mg/kg per min) were similar in CAPD and control subjects. Basal leucine flux tan index of endogenous proteolysis) was significantly lower in CAPD patients than in control subjects (1.21 +/- 0.15 versus 1.65 +/- 0.07 mu mol/kg per min). Leucine oxidation (0.13 +/- 0.02 versus 0.26 +/- 0.02 mu mol/kg per min) and nonoxidative leucine disposal tan index of protein synthesis) (1.09 +/- 0.16 versus 1.35 +/- 0.05 mu mol/kg per min) were also reduced in CAPD compared with control subjects (P < 0.01 versus control subjects). In response to insulin (study Ij, endogenous leucine flux decreased to 0.83 +/- 0.08 and 1.05 +/- 0.05 mu mol/kg per min in CAPD and control subjects, respectively (all P < 0.01 versus basal). Leucine oxidation declined to 0.06 +/- 0.01 and to 0.19 +/- 0.02 mu mol/kg per min in CAPD and control subjects, respectively (P < 0.01 versus basal), A second insulin clamp was performed in combination with an intravenous amino acid infusion (study II). During insulin plus amino acid administration, nonoxidative leucine disposal rose to 1.23 +/- 0.17 and 1.42 +/- 0.09 mu mol/kg per min in CAPD and control subjects, respectively (both P < 0.05 versus basal. P = NS versus control subjects), and leucine balance, an index of the net amino acid flux into protein, become positive in both groups (0.30 +/- 0.05 versus 0.40 +/- 0.07 mu mol/kg per min in CAPD and control subjects, respectively) (both P < 0.01 versus basal, P = NS versus control subjects), In summary, in CAPD patients: (1) basal glucose oxidation is increased, (2) basal lipid oxidation is decreased; (3) insulin-mediated glucose oxidation and storage are normal, (4) basal leucine flux is reduced, (5) the antiproteolitic action of insulin is normal, and (6) the anabolic response to insulin plus amino acid administration is normal. Uremic patients maintained on CAPD treatment show a preferential utilization of glucose as postabsorptive energy substrate; however, their anabolic response to substrate administration and the sensitivity to insulin are normal.