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

Abstract

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/m 2 ; HbA 1c 7.9±0.2% and VO 2 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 VO 2 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 wholebody 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.

Quantifying the Acute Changes in Glucose with Exercise in Type 1 Diabetes: A Systematic Review and Meta-Analysis

“…Regarding the studies included here, three articles [28,31,33] did not provide experimental data on insulin concentration. In the following three cases, patients exercised at levels lower than both conditions in Chokkalingam et al [52]: Jankovec et al [32] (average insulinemia ~ 80 pmol/L and great inter-subject variability, without statistical differences versus REST); Soo et al [36] (basal 84 ± 18 pmol/L, mean ± SEM; authors reported no significant correlation between basal free insulin and glycemic response); and Yamanouchi et al [37] (pre-prandial trial arm [55.3 ± 21.5 pmol/L, mean ± SD]). Peter et al [34] documented an average plasma insulin of ~ 300 pmol/L during both REST and CONT, without statistical differences between trials in terms of area under the curve for insulinemia (p -0.116).…”

“…However, the amount of muscle glycogen utilized in both situations was similar, and carbohydrate oxidation rates were only around 15 % more in the trial arm with the highest insulinemia. Consequently, the influence of distinct plasma insulin levels in otherwise equivalent exercise conditions remains unclear, as outlined by Chokkalingam et al [52]. Regarding the studies included here, three articles [28,31,33] did not provide experimental data on insulin concentration.…”

“…In a euglycemia clamp experiment (glucose fixed at approximately 8 mmol/L) under two hyperinsulinemic regimens at different levels (plasma insulin at ~ 150 or ~540 pmol/L, corresponding to typical pre-and postprandial concentrations in patients with type 1 diabetes), Chokkalingam et al [52] studied whole-body and muscle metabolism in exercise. Markedly higher exogenous glucose utilization was observed in the trial arm at 540 pmol/L.…”

“…Peter et al [34] documented an average plasma insulin of ~ 300 pmol/L during both REST and CONT, without statistical differences between trials in terms of area under the curve for insulinemia (p -0.116). Physical activity bouts in the remaining studies took place with values comparable to the 150 pmol/L selected in Chokkalingam et al [52]: Rabasa-Lhoret et al [35] (insulin bolus 90 min prior to exercise onset, peak insulinemia at 188.5 ± 28.0 pmol/L, mean ± SD; peak occurring 30 min pre-exercise), Yamanouchi et al [37] (postprandial trial [insulin bolus 90 min prior to exercise onset, peak at 231.9 ± 162.3 pmol/L, mean ± SD]), Guelfi et al [29] (IHE exercise commenced at 198.1 ± 148.0 pmol/L, mean ± SD; no statistical difference with respect to REST), and Guelfi et al [30] (IHE and CONT exercise commenced, respectively, at approximately 160 and 140 pmol/L; no statistical differences in insulinemia profiles at any point of exercise or recovery).…”

Hyperinsulinaemia during exercise does not suppress hepatic glycogen concentrations in patients with type 1 diabetes: a magnetic resonance spectroscopy study

“…The impact of real-life therapeutic insulin concentrations on hepatic glycogen metabolism during exercise in patients with type 1 diabetes is not known. We have recently shown that, in patients with type 1 diabetes, exercise under peak therapeutic insulin concentrations increases exogenous glucose utilisation and that this increase is disproportionate to the relative increase in carbohydrate oxidation, suggesting an increase in glucose flux through non-oxidative pathways, perhaps towards hepatic glycogenesis [25].…”