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

Abstract

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 yr, BMI 103 ± 3). Euglycemic insulin clamp studies (180 min) were performed in combination with continuous indirect calorimetry and 1-14C 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 (an index of endogenous proteolysis) was significantly lower in CAPD patients than in control subjects (1.21 ± 0.15 versus 1.65 ± 0.07 μmol/kg per min). Leucine oxidation (0.13 ± 0.02 versus 0.26 ± 0.02 μmol/kg per min) and nonoxidative leucine disposal (an index of protein synthesis) (1.09 ± 0.16 versus 1.35 ± 0.05 μmol/kg per min) were also reduced in CAPD compared with control subjects (P < 0.01 versus control subjects). In response to insulin (study I), endogenous leucine flux decreased to 0.83 ± 0.08 and 1.05 ± 0.05 μmol/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 μmol/kg per rain 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 μmol/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 μmol/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.