LIPID-METABOLISM AND SUBSTRATE OXIDATION DURING INTRAVENOUS FRUCTOSE ADMINISTRATION IN CIRRHOSIS

We used isotope dilution techniques (constant intravenous [IV] infusio n of 2-H-3-glycerol and 1-C-14-palmitate) and indirect calorimetry to measure lipid kinetics and substrate oxidation rates during IV fructos e administration at 200 and then 500 mg/kg/h in eight cirrhotic patien ts and seven normal control subjects. Pasting plasma glucose, glycerol . and glycerol appearance rate (R,) were similar in both groups, but i nsulin levels were fourfold higher in cirrhotics (P < .01). Fasting se rum nonesterified fatty acid (NEFA) levels (cirrhotics, 869 +/- 124, c ontrols, 717 +/- 90 mu mol/L) and NEFA R(a) (7.1 +/- 0.8 v 5.5 +/- 0.9 mu mol/min/kg) were higher in cirrhotics, but the differences were no t significant. Plasma fructose was similar in both groups at both fruc tose infusion rates. Fructose appeared to stimulate insulin secretion. With IV fructose, serum NEFA levels decreased, reaching similar low l evels when 500 mg/kg/h was infused, due to a reduction in NEFA R(a) an d an increase in the NEFA metabolic clearance rate (MCR). Glycerol lev els showed little change. As glycerol R(a) decreased by less than 20% in both groups, the decrease in serum NEFA was primarily due to enhanc ed reesterification of fatty acids both within adipose tissue (prevent ing their release) and in other tissues (enhancing their removal from plasma). Although total fructose utilization was normal in cirrhotics, they oxidized more of the infused fructose; nonoxidative disposal was reduced (first step, 242 +/- 12 v 318 +/- 16 mg/kg in 2 hours, P < .0 02; second step, 657 +/- 32 v 786 +/- 21 mg/kg in 2 hours, P < .005). Although tissue fructose uptake is insulin-independent, insulin resist ance in cirrhosis may influence the intracellular metabolism of fructo se. Copyright (C) 1994 by W.B. Saunders Company