Resting energy expenditure and the thermic effect of adrenaline in patients with liver cirrhosis.

1. Resting energy expenditure and the metabolic responses to adrenaline (infusion rate: 0.03 micrograms min-1 kg-1 fat-free mass for 1 h) were investigated in 25 patients with liver cirrhosis. The patient group was heterogeneous and varied with respect to the aetiology of cirrhosis, the clinical condition (i.e. Child A or B), the nutritional status and the degree of hyperinsulinaemia. 2. When compared with 10 healthy control subjects the basal plasma adrenaline and noradrenaline concentrations were both increased in cirrhosis and remained elevated during adrenaline infusion (+39% and +31%, respectively; P < 0.05). Concomitantly, the peripheral plasma insulin concentration and the molar C-peptide/insulin ratio were increased in liver cirrhosis (+96% and +30%, respectively; P < 0.05). Hyperinsulinaemia was more pronounced in patients with ethanol-induced liver cirrhosis. 3. When expressed per kg fat-free mass, resting energy expenditure was enhanced in liver cirrhosis (+21%; P < 0.05) and was more pronounced (i.e. resting energy expenditures of +35% to +49% above estimated values) in patients with ethanol-induced cirrhosis, at advanced stages of the disease and in association with decreased body cell mass. 4. Infusion of adrenaline increased heart rate, O2 consumption and the plasma concentrations of glucose, lactate, free fatty acids, glycerol and 3-hydroxybutyrate, and similar transient increases and subsequent decreases in the respiratory quotient were observed in both groups. However, the lipolytic, ketogenic and thermic responses were reduced in cirrhotic patients. Reduced metabolic responses were more pronounced in hyperinsulinaemic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanism of insulin resistance associated with liver cirrhosis.

Insulin-induced glucose metabolism was investigated in 26 patients with biopsy-proven liver cirrhosis and 10 control subjects. Two glucose clamp protocols together with continuous indirect calorimetry were performed to examine whether reduced rates of glucose oxidation and/or nonoxidative glucose metabolism explain insulin resistance in liver cirrhosis. Using a 4-hour, two-step protocol (0-2 hours, plasma glucose 5.2 mmol/L, plasma insulin 92 mU/L to test the half-maximum response; 2-4 hours, hyperglycemia 10.0 mmol/L, plasma insulin 442 mU/L to test the maximum cellular glucose disposal) liver cirrhosis reduced glucose disposal to 45% and 60% of control values, respectively. Simultaneously, insulin-induced increases in glucose oxidation, plasma lactate levels, and lipogenesis were normal, whereas nonoxidative glucose metabolism was reduced (-82% and -47% of controls, respectively). To determine whether reduced nonoxidative glucose metabolism was caused by reduced glucose disposal, glucose disposal was "matched" to normal values in a subgroup of cirrhotic patients. Nonoxidative glucose metabolism values were normal, but plasma lactate concentrations disproportionally increased (+96%) after "matching" glucose disposal. Insulin resistance was independent of the etiology of the cirrhosis, the biochemical parameters of parenchymal cell damage and liver function, and the clinical and nutritional state of the patients. It is concluded that liver cirrhosis impairs insulin sensitivity and maximum cellular glucose disposal. Reduced glucose disposal is caused by defective glucose storage. Insulin resistance is independent of the etiology of liver cirrhosis and of the clinical and nutritional state of the patient.

Energy expenditure and substrate metabolism in ethanol-induced liver cirrhosis.

Energy expenditure and substrate metabolism were investigated in 10 patients with alcoholic liver cirrhosis (EtOH-Ci) and 10 healthy controls (C). Resting metabolic rate (RMR) varied from 1,269 to 2,467 kcal/day in C and from 1,228 to 2,098 kcal/day in EtOH-Ci. RMR was significantly related to fat-free mass (FFM) in both groups, but EtOH-Ci decreased FFM and increased RMR when expressed per kilogram FFM (+33%). Glucose intolerance, hyperinsulinemia, and a decreased C-peptide-to-insulin ratio were observed in EtOH-Ci after a test meal. Concomitantly, nonoxidative glucose metabolism was reduced in association with normal increases in glucose oxidation. EtOH-Ci reduced insulin sensitivity (-59%) and maximal insulin-dependent glucose disposal (-40%) during a sequential two-step glucose clamp protocol (phase 1: 1 mU.kg body wt-1.min-1 insulin infusion rate + euglycemia; phase 2: 4 mU.kg body wt-1.min-1 insulin infusion rate + 165 mg/dl plasma glucose concentration). This was explained by reduced glucose storage (-99%, -51%) in association with normal responses in glucose oxidation rate, plasma lactate concentration, lipid oxidation rate, and rate of lipogenesis. Defective glucose storage was independent of reduced FFM. EtOH-Ci increased glucose-induced thermogenesis by 57%. We conclude that increased resting metabolic rate, enhanced thermogenesis, defective glucose storage, and normal glucose oxidation together result in increased energy needs and favor negative energy balance in patients with alcoholic cirrhosis.