Lactate and Energy Metabolism During Exercise in Patients With Blocked Glycogenolysis (McArdle Disease)

TY - JOUR

T1 - Lactate and Energy Metabolism During Exercise in Patients With Blocked Glycogenolysis (McArdle Disease)

AU - Ørngreen, Mette Cathrine

AU - Jeppesen, Tina Dysgaard

AU - Taivassalo, Tanja

AU - Hauerslev, Simon

AU - Preisler, Nicolai

AU - Heinicke, Katja

AU - Haller, Ronald G

AU - Vissing, John

AU - van Hall, Gerrit

PY - 2015/8/1

Y1 - 2015/8/1

N2 - CONTEXT: Patients with blocked muscle glycogen breakdown (McArdle disease) have severely reduced exercise capacity compared to healthy individuals and are not assumed to produce lactate during exercise.OBJECTIVES: The objectives were: 1) to quantify systemic and muscle lactate kinetics and oxidation rates and muscle energy utilization during exercise in patients with McArdle disease; and 2) to elucidate the role of lactate formation in muscle energy production.DESIGN AND SETTING: This was a single trial in a hospital.PARTICIPANTS: Participants were four patients with McArdle disease and seven healthy subjects.INTERVENTION: Patients and healthy controls were studied at rest, which was followed by 40 minutes of cycle-ergometer exercise at 60% of the patients' maximal oxygen uptake (∼35 W).MAIN OUTCOME MEASURES: Main outcome measures were systemic and leg skeletal muscle lactate, alanine, fatty acid, and glucose kinetics.RESULTS: McArdle patients had a marked decrease in plasma lactate concentration at the onset of exercise, and the concentration remained suppressed during exercise. A substantial leg net lactate uptake and subsequent oxidation occurred over the entire exercise period in patients, in contrast to a net lactate release or no exchange in the healthy controls. Despite a net lactate uptake by the active leg, a simultaneous unidirectional lactate release was observed in McArdle patients at rates that were similar to the healthy controls.CONCLUSION: Lactate is an important energy source for contracting skeletal muscle in patients with myophosphorylase deficiency. Although McArdle patients had leg net lactate consumption, a simultaneous release of lactate was observed at rates similar to that found in healthy individuals exercising at the same very low workload, suggesting that lactate formation is mandatory for muscle energy generation during exercise.

AB - CONTEXT: Patients with blocked muscle glycogen breakdown (McArdle disease) have severely reduced exercise capacity compared to healthy individuals and are not assumed to produce lactate during exercise.OBJECTIVES: The objectives were: 1) to quantify systemic and muscle lactate kinetics and oxidation rates and muscle energy utilization during exercise in patients with McArdle disease; and 2) to elucidate the role of lactate formation in muscle energy production.DESIGN AND SETTING: This was a single trial in a hospital.PARTICIPANTS: Participants were four patients with McArdle disease and seven healthy subjects.INTERVENTION: Patients and healthy controls were studied at rest, which was followed by 40 minutes of cycle-ergometer exercise at 60% of the patients' maximal oxygen uptake (∼35 W).MAIN OUTCOME MEASURES: Main outcome measures were systemic and leg skeletal muscle lactate, alanine, fatty acid, and glucose kinetics.RESULTS: McArdle patients had a marked decrease in plasma lactate concentration at the onset of exercise, and the concentration remained suppressed during exercise. A substantial leg net lactate uptake and subsequent oxidation occurred over the entire exercise period in patients, in contrast to a net lactate release or no exchange in the healthy controls. Despite a net lactate uptake by the active leg, a simultaneous unidirectional lactate release was observed in McArdle patients at rates that were similar to the healthy controls.CONCLUSION: Lactate is an important energy source for contracting skeletal muscle in patients with myophosphorylase deficiency. Although McArdle patients had leg net lactate consumption, a simultaneous release of lactate was observed at rates similar to that found in healthy individuals exercising at the same very low workload, suggesting that lactate formation is mandatory for muscle energy generation during exercise.

KW - Adult

KW - Energy Metabolism

KW - Exercise

KW - Exercise Test

KW - Female

KW - Glycogen Storage Disease Type V

KW - Glycogenolysis

KW - Humans

KW - Lactic Acid

KW - Male

KW - Muscle, Skeletal

KW - Oxygen Consumption

KW - Physical Exertion

KW - Young Adult

U2 - 10.1210/jc.2015-1339

DO - 10.1210/jc.2015-1339

M3 - Journal article

C2 - 26030324

SN - 0021-972X

VL - 100

SP - E1096-E1104

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

IS - 8

ER -