Effect of moderate exercise on insulin sensitivity and substrate metabolism during post‐exercise recovery in cirrhosis

We examined whether a single bout of moderate exercise has a beneficial effect on insulin sensitivity and fuel homeostasis in cirrhosis. Clinically stable cirrhotic patients and age‐, sex‐, and weight‐matched controls participated in insulin clamp studies (either euglycemic hyperinsulinemic or hyperglycemic hyperinsulinemic) in combination with indirect calorimetry and [6,6‐2H2]glucose. Three to seven days later, studies were repeated following a single bout of exercise (30 minutes of treadmill exercise at 60% of maximal aerobic capacity). After an overnight fast, following exercise, both cirrhotic and control individuals showed a shift in fuel utilization to enhanced lipid oxidation, decreased glucose oxidation, and increased nonoxidative glucose disposal rates (i.e., glycogen synthesis in muscle) when compared with pre‐exercise rates but differences were statistically significant only in the patient group. During euglycemic hyperinsulinemia, insulin‐mediated glucose disposal was significantly reduced in cirrhotic patients (3.43 ± 0.26 vs. 7.36 ± 0.48 mg/kg/min, P < .01). Following exercise, glucose uptake increased significantly in cirrhotic patients when compared with pre‐exercise levels (P < .05) but remained unchanged in the control group. The increase in total body glucose disposal in cirrhotic patients was entirely accounted for by an increase in nonoxidative glucose disposal (0.81 ± 0.20 vs. 0.51 ± 0.15 mg/kg/min, P < .05). During combined hyperglycemia/hyperinsulinemia, however, insulin sensitivity was unaffected by exercise in both patients and control individuals. In summary, in cirrhotic patients, a single bout of moderate exercise 1) causes a shift in substrate utilization with an increase in lipid oxidation in the postexercise period that is significantly more pronounced than in controls, and 2) increases insulin sensitivity only during euglycemia but not during the more physiological condition of hyperglycemia. Single bouts of moderate exercise therefore may not have a beneficial effect on the metabolic status of patients with chronic liver disease.