Exercise under hyperinsulinaemic conditions increases whole-body glucose disposal without affecting muscle glycogen utilisation in type 1 diabetes

Aims/hypothesis We examined whole-body and muscle metabolism in patients with type 1 diabetes during moderate exercise at differing circulating insulin concentrations. Methods Eight men (mean ± SEM age 36.4 ± 1.5 years; diabetes duration 11.3 ± 1.4 years; BMI 24.6 ± 0.7 kg/m²; HbA₁c 7.9 ± 0.2% and VO₂ peak 44.5 ± 1.2 ml kg-¹ min-¹) with type 1 diabetes were studied on two occasions at rest (2 h) and during 45 min of cycling at 60% maximum VO₂ with insulin infused at the rate of either 15 (LO study) or 50 (HI) mU m-² min-¹ and blood glucose clamped at 8 mmol/l. Indirect calorimetry, insulin-glucose clamps and thigh muscle biopsies were employed to measure whole-body energy and muscle metabolism. Results Fat oxidation contributed 15 and 23% to total energy expenditure during exercise in the HI and LO studies, respectively. The respective carbohydrate (CHO) oxidation rates were 31.7 ± 2.7 and 27.8 ± 1.9 mg kg-¹ min-¹ (p < 0.05). Exogenous glucose utilisation rate during exercise was substantially greater (p < 0.001) in the HI study (18.4 ± 2.1 mg kg-¹ min-¹) than in the LO study (6.9 ± 1.2 mg kg-¹ min-¹). Muscle glycogen content fell by ~40% during exercise in both trials. Muscle glycogen utilisation, muscle intermediary metabolism, and phosphorylation of protein kinase B/Akt, glycogen synthase kinase 3α/β and extracellular signal-regulated protein kinase 1 and 2 proteins were no different between interventions. Conclusions/interpretation In patients with type 1 diabetes, exercise under peak therapeutic insulin concentrations increases exogenous glucose utilisation but does not spare muscle glycogen utilisation. A disproportionate increase in exogenous glucose utilisation relative to the increase in CHO oxidation suggests an increase in glucose flux through non-oxidative pathways.