title: Metabolic handling of orally administered glucose in cirrhosis.
abstract: We used a dual-isotope method (oral [1-14C]glucose and intravenous [6-3H]glucose) to examine whether the oral glucose intolerance of cirrhosis is due to (a) a greater input of glucose into the systemic circulation (owing to a lower first-pass hepatic uptake of ingested glucose, or to impaired inhibition of hepatic glucose output), (b) a lower rate of glucose removal, or (c) a combination of these mechanisms. Indirect calorimetry was used to measure oxidative and nonoxidative metabolism. Basal plasma glucose levels (cirrhotics, 5.6 +/- 0.4[SE], controls, 5.1 +/- 0.2 mmol/liter), and rates of glucose appearance (Ra) and disappearance (Rd) were similar in the two groups. After 75 g of oral glucose, plasma glucose levels were higher in cirrhotics than controls, the curves diverging for 80 min despite markedly higher insulin levels in cirrhotics. During the first 20 min, there was very little change in glucose Rd and the greater initial increase in plasma glucose in cirrhotics resulted from a higher Ra of ingested [1-14C]glucose into the systemic circulation, suggesting a reduced first-pass hepatic uptake of portal venous glucose. The continuing divergence of the plasma glucose curves was due to a lower glucose Rd between 30 and 80 min (cirrhotics 236 +/- 17 mg/kg in 50 min, controls 280 +/- 17 mg/kg in 50 min, P < 0.05, one-tailed test). Glucose metabolic clearance rate rose more slowly in cirrhotics and was significantly lower than in controls during the first 2 h after glucose ingestion (2.24 +/- 0.17 vs 3.30 +/- 0.23 ml/kg per min, P < 0.005), in keeping with their known insulin insensitivity. Despite the higher initial glucose Ra in cirrhotics, during the entire 4-h period the quantity of total glucose and of ingested glucose (cirrhotics 54 +/- 2 g [72% of oral load], controls 54 +/- 3 g) appearing in the systemic circulation were similar. Overall glucose Rd (cirrhotics 72.5 +/- 3.8 g/4 h, controls 77.2 +/- 2.2 g/4h) and percent suppression of hepatic glucose output over 4 h (cirrhotics, 53 +/- 10%, controls 49 +/- 8%) were also similar. After glucose ingestion much of the extra glucose utilized was oxidized to provide energy that in the basal state was derived from lipid fuels. Glucose oxidation after glucose ingestion was similar in both groups and accounted for approximately two-thirds of glucose Rd. The reduction in overall nonoxidative glucose disposal did not reach significance (21 +/- 5 vs. 29 +/- 3 g/4 h, 0.05 < P < 0.1). Although our data would be compatible with an impairment of tissue glycogen deposition after oral glucose, glucose storage as glycogen probably plays a small part part in overall glucose disposal. Our results suggest that the higher glucose levels seen in cirrhotics after oral glucose are due initially to an increase in the amount of ingested glucose appearing in the systemic circulation, and subsequently to an impairment in glucose uptake by tissues due to insulin insensitivity. Impaired suppression of hepatic glucose output does not contribute to oral glucose intolerance.
authors.affiliation: University Department of Medicine, Royal Free Hospital School of Medicine, London, United Kingdom.
authors.forename: Y T
authors.initials: YT
authors.lastname: Kruszynska
authors.forename: A
authors.initials: A
authors.lastname: Meyer-Alber
authors.forename: F
authors.initials: F
authors.lastname: Darakhshan
authors.forename: P D
authors.initials: PD
authors.lastname: Home
authors.forename: N
authors.initials: N
authors.lastname: McIntyre
mesh_terms: D000284:Administration, Oral; D001786:Blood Glucose / Q000378:metabolism*; D002250:Carbon Radioisotopes; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism*; D006019:Glycolysis; D006801:Humans; D007328:Insulin / Q000097:blood; D007700:Kinetics; D008104:Liver Cirrhosis, Alcoholic / Q000097:blood / Q000378:metabolism*; D008875:Middle Aged; D011865:Radioisotope Dilution Technique; D012016:Reference Values; D013997:Time Factors; D014316:Tritium
chemical_list: D001786:Blood Glucose; D002250:Carbon Radioisotopes; D007328:Insulin; D014316:Tritium; D005947:Glucose