Insulin resistance in liver cirrhosis. Positron-emission tomography scan analysis of skeletal muscle glucose metabolism.
BACKGROUND
Insulin resistance and glucose intolerance are a major feature of patients with liver cirrhosis. However, site and mechanism of insulin resistance in cirrhosis are unknown. We investigated insulin-induced glucose metabolism of skeletal muscle by positron-emission tomography to identify possible defects of muscle glucose metabolism in these patients.


METHODS
Whole body glucose disposal and oxidation were determined by the combined use of the euglycemic-hyperinsulinemic clamp technique (insulin infusion rate: 1 mU/kg body wt per min) and indirect calorimetry in seven patients with biopsy-proven liver cirrhosis (Child: 1A, 5B, and 1C) and five healthy volunteers. Muscle glucose uptake of the thighs was measured simultaneously by dynamic [18F]fluorodeoxyglucose positron-emission tomography scan.


RESULTS
Both whole body and nonoxidative glucose disposal were significantly reduced in patients with liver cirrhosis (by 48%, P < 0.001, and 79%, P < 0.0001, respectively), whereas glucose oxidation and the increase in plasma lactate were normal. Concomitantly, skeletal muscle glucose uptake was reduced by 69% in liver cirrhosis (P < 0.003) and explained 55 or 92% of whole body glucose disposal in cirrhotics and controls, respectively. Analysis of kinetic constants using a three-compartment model further indicated reduced glucose transport (P < 0.05) but unchanged phosphorylation of glucose in patients with liver cirrhosis.


CONCLUSIONS
Patients with liver cirrhosis show significant insulin resistance that is characterized by both decreased glucose transport and decreased nonoxidative glucose metabolism in skeletal muscle.
Selberg
O
O
Abteilung Gastroenterologie und Hepatologie, Medizinische Hochschule Hannover, Germany.
Burchert
W
W
vd Hoff
J
J
Meyer
G J
GJ
Hundeshagen
H
H
Radoch
E
E
Balks
H J
HJ
Müller
M J
MJ
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D003847:Deoxyglucose / Q000031:analogs & derivatives / Q000378:metabolism; D005260:Female; D005462:Fluorine Radioisotopes; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007333:Insulin Resistance; D007700:Kinetics; D008103:Liver Cirrhosis / Q000000981:diagnostic imaging / Q000378:metabolism*; D008297:Male; D009132:Muscles / Q000000981:diagnostic imaging / Q000378:metabolism*; D010101:Oxygen Consumption; D012016:Reference Values; D014055:Tomography, Emission-Computed / Q000379:methods
D001786:Blood Glucose; D005462:Fluorine Radioisotopes; D019788:Fluorodeoxyglucose F18; D003847:Deoxyglucose; D005947:Glucose