Acute hypoxia reduces exogenous glucose oxidation, glucose turnover, and metabolic clearance rate during steady-state aerobic exercise

Abstract

Background: Exogenous carbohydrate oxidation is lower during steady-state aerobic exercise in native lowlanders sojourning at high altitude (HA) compared to sea level (SL). However, the underlying mechanism contributing to reduction in exogenous carbohydrate oxidation during steady-state aerobic exercise performed at HA has not been explored.

Objective: To determine if alterations in glucose rate of appearance (R_a), disappearance (R_d) and metabolic clearance rate (MCR) at HA provide a mechanism for explaining the observation of lower exogenous carbohydrate oxidation compared to during metabolically-matched, steady-state exercise at SL.

Methods: Using a randomized, crossover design, native lowlanders (n = 8 males, mean ± SD, age: 23 ± 2 yr, body mass: 87 ± 10 kg, and VO_2peak: SL 4.3 ± 0.2 L/min and HA 2.9 ± 0.2 L/min) consumed 145 g (1.8 g/min) of glucose while performing 80-min of metabolically-matched (SL: 1.66 ± 0.14 V̇O₂ L/min 329 ± 28 kcal, HA: 1.59 ± 0.10 V̇O₂ L/min, 320 ± 19 kcal) treadmill exercise in SL (757 mmHg) and HA (460 mmHg) conditions after a 5-h exposure. Substrate oxidation rates (g/min) and glucose turnover (mg/kg/min) during exercise were determined using indirect calorimetry and dual tracer technique (¹³C-glucose oral ingestion and [6,6-²H₂]-glucose primed, continuous infusion).

Results: Total carbohydrate oxidation was higher (P < 0.05) at HA (2.15 ± 0.32) compared to SL (1.39 ± 0.14). Exogenous glucose oxidation rate was lower (P < 0.05) at HA (0.35 ± 0.07) than SL (0.44 ± 0.05). Muscle glycogen oxidation was higher at HA (1.67 ± 0.26) compared to SL (0.83 ± 0.13). Total glucose R_a was lower (P < 0.05) at HA (12.3 ± 1.5) compared to SL (13.8 ± 2.0). Exogenous glucose R_a was lower (P < 0.05) at HA (8.9 ± 1.3) compared to SL (10.9 ± 2.2). Glucose R_d was lower (P < 0.05) at HA (12.7 ± 1.7) compared to SL (14.3 ± 2.0). MCR was lower (P < 0.05) at HA (9.0 ± 1.8) compared to SL (12.1 ± 2.3). Circulating glucose and insulin concentrations were higher in response carbohydrate intake during exercise at HA compared to SL.

Conclusion: Novel results from this investigation suggest that reductions in exogenous carbohydrate oxidation at HA may be multifactorial; however, the apparent insensitivity of peripheral tissue to glucose uptake may be a primary determinate.

Keywords: Glycogenolysis; High altitude sojourn; Insulin resistance; Substrate oxidation.