Pathogenesis of glucose intolerance and diabetes mellitus in cirrhosis

摘要: Abstract Glucose intolerance and diabetes mellitus are both prevalent in cirrhosis, yet the pathogenesis of impaired glucose metabolism remains unknown. Therefore insulin secretion (hyperglycemic clamp, +125 mg/dl), sensitivity (euglycemic hyperinsulinemic +10 microU/ml +50 microU/ml), whole-body oxidation (indirect calorimetry) turnover ([6,6-2H2]glucose isotope dilution) were evaluated a homogenous group cirrhotic patients with (n = 7) or frank 6). The results compared those obtained control subjects 8). In glucose-intolerant patients, uptake (mainly reflecting utilization by muscle) was significantly during infusions as result decreased stimulation two major intracellular pathways disposal--nonoxidative disposal (i.e., glycogen synthesis) oxidation. Hepatic production normal basal state normally suppressed stepwise infusion (by 65% 85%, respectively, p NS vs. controls). Hyperglycemia-induced increases plasma C-peptide concentrations comparable to controls (p NS). diabetic insulin-mediated reduced, mainly because non-oxidative disposal. appeared be too. increased (3.03 +/- 0.24 2.34 0.10 mg/kg min, < 0.02) (+50 microU/ml: 0.67 0.17 0.13 0.08 0.05) that controls. Both first second phases beta-cell reduced response steady-state hyperglycemia (both 0.01 values). conclusion, cirrhosis from abnormalities occur simultaneously: (a) resistance muscle (b) an inadequate (even when controls) beta-cells appropriately secrete overcome defect action. Diabetes insulin-resistant develops progressive impairment together development hepatic leading fasting tolerance profile.