Low-Protein Diet Improves Muscle Energy Metabolism in Chronic Renal Failure

Tissue sensitivity to insulin was examined with the euglycemic insulin clamp technique in 17 chronically uremic and 36 control subjects. The plasma insulin concentration was raised by approximately 100 microU/ml and the plasma glucose concentration was maintained at the basal level with a variable glucose infusion. Under these steady-state conditions of euglycemia, the glucose infusion rate is a measure of the amount of glucose taken up by the entire body. In uremic subjects insulin-mediated glucose metabolism was reduced by 47% compared with controls (3.71 +/- 0.20 vs. 7.38 +/- 0.26 mg/kg . min; P less than 0.001). Basal hepatic glucose production (measured with [3H]-3-glucose) was normal in uremic subjects (2.17 +/- 0.04 mg/kg . min) and suppressed normally by 94 +/- 2% following insulin administration. In six uremic and six control subjects, net splanchnic glucose balance was also measured directly by the hepatic venous catheterization technique. In the postabsorptive state splanchnic glucose production was similar in uremics (1.57 +/- 0.03 mg/kg . min) and controls (1.79 +/- 0.20 mg/kg . min). After 90 min of sustained hyperinsulinemia, splanchnic glucose balance reverted to a net uptake which was similar in uremics (0.42 +/- 0.11 mg/kg . min) and controls (0.53 +/- 0.12 mg/kg . min). In contrast, glucose uptake by the leg was reduced by 60% in the uremic group (21 +/- 1 vs. 52 +/- 8 mumol/min . kg of leg wt; P less than 0.005) and this decrease closely paralleled the decrease in total glucose metabolism by the entire body. These results indicate that: (a) suppression of hepatic glucose production by physiologic hyperinsulinemia is not impaired by uremia, (b) insulin-mediated glucose uptake by the liver is normal in uremic subjects, and (c) tissue insensitivity to insulin is the primary cause of insulin resistance in uremia.

Dietary energy requirements were evaluated during 16 studies that were carried out in six clinically stable nondialyzed chronically uremic patients who lived in a clinical research center and were fed diets providing 45, 35, 25 or 15 kcal/kg/day. Each diet was fed for 23.7 +/- 5.7 SD days and provided about 0.55 to 0.60 g protein/kg/day. Nitrogen balance after equilibration and adjusted for changes in body urea nitrogen, and change in body weight each correlated directly with energy intake. Correcting for estimated unmeasured nitrogen losses of about 0.58 g/day, nitrogen balance was negative in one of four patients fed 45 kcal/kg/day, one of five patients receiving 35 kcal/kg/day, three of five patients ingesting 25 kcal/kg/day and both patients fed 15 kcal/kg/day. The urea nitrogen appearance (UNA), the UNA divided by nitrogen intake, and several plasma amino acids, determined after an overnight fast, each correlated inversely with dietary energy intake. Resting energy expenditure measured by indirect calorimetry did not differ from normal and averaged 0.012 +/- 0.0033 kcal/kg/min with the different diets. These observations suggest that although some clinically stable nondialyzed chronically uremic patients ingesting 0.55 to 0.60 g protein/kg/day may maintain nitrogen balance with energy intakes below 30 kcal/kg/day, a dietary intake providing approximately 35 kcal/kg/day may be more likely to maintain neutral or positive nitrogen balance, maintain or increase body mass, and reduce net urea generation.

Prolonged fasting (for days or weeks) decreases glucose production and oxidation. The effects of short-term starvation (ie, less than 24 hours) on glucose metabolism are not known. To evaluate this issue, glucose oxidation and glucose turnover were measured after 16-hour and subsequently after 22-hour fasting. Glucose oxidation was calculated by indirect calorimetry in 12 healthy men (age 22 to 44 years); glucose turnover was measured by primed, continuous infusion of 3-3H-glucose in eight of these 12 volunteers. After 16-hour fasting net glucose oxidation was 0.59 +/- 0.17 mg x kg-1 x min-1 and glucose tissue uptake 2.34 +/- 0.12 mg x kg-1 x min-1. No correlation was found between net glucose oxidation and glucose tissue uptake. Prolonging fasting with an additional 6 hours resulted in decreases of respiratory quotient (0.77 +/- 0.01 v 0.72 +/- 0.01) (P less than .005), plasma glucose concentration (4.7 +/- 0.1 v 4.6 +/- 0.1 mmol/L) (P less than .05), glucose tissue uptake (2.10 +/- 0.12 mg x kg-1 x min-1) (P less than .05), net glucose oxidation (0.09 +/- 0.04 mg x kg-1 x min-1) (P less than .005), and plasma insulin concentration (8 +/- 1 v6 +/- 1 mU/L) (P less than .005). Net glucose oxidation expressed as a percentage of glucose tissue uptake decreased from 22% +/- 8% to 2% +/- 1% (P less than .05). There was no net glucose oxidation in seven of 12 controls after 22-hour fasting.(ABSTRACT TRUNCATED AT 250 WORDS)