TY - JOUR

T1 - Muscle glycogen synthesis and breakdown are both impaired in glycogenin-1 deficiency

AU - Stemmerik, Mads Godtfeldt

AU - Madsen, Karen Lindhardt

AU - Laforêt, Pascal

AU - Buch, Astrid Emilie

AU - Vissing, John

N1 - © 2017 American Academy of Neurology.

PY - 2017/12/12

Y1 - 2017/12/12

N2 - OBJECTIVE: To study fat and carbohydrate metabolism during exercise in patients with glycogenin-1 (GYG1) deficiency, and to study whether IV glucose supplementation can alleviate exercise intolerance in these patients.METHODS: This is a case-control study with 4 patients with GYG1 deficiency and 4 healthy controls. Patients performed 1 hour of cycling at 50% of their maximal workload capacity, while controls cycled at the same absolute workloads as patients. Heart rate was measured continuously, and production and utilization of fat and glucose was assessed by stable isotope technique. The following day, patients repeated the exercise, this time receiving an IV 10% glucose supplement.RESULTS: Glucose utilization during exercise was similar in patients and controls, while palmitate utilization was greater in patients compared to controls. However, exercise-induced increases in lactate were attenuated to about half normal in patients. This was also the case during a handgrip exercise test. Glucose infusion improved exercise tolerance in patients, and lowered heart rate by on average 11 beats per minute during exercise.CONCLUSIONS: The findings suggest that patients with GYG1 deficiency not only have abnormal formation of glycogen, but also have impaired muscle glycogenolysis, as suggested by impaired lactate production during exercise and improved exercise tolerance with glucose infusion.

AB - OBJECTIVE: To study fat and carbohydrate metabolism during exercise in patients with glycogenin-1 (GYG1) deficiency, and to study whether IV glucose supplementation can alleviate exercise intolerance in these patients.METHODS: This is a case-control study with 4 patients with GYG1 deficiency and 4 healthy controls. Patients performed 1 hour of cycling at 50% of their maximal workload capacity, while controls cycled at the same absolute workloads as patients. Heart rate was measured continuously, and production and utilization of fat and glucose was assessed by stable isotope technique. The following day, patients repeated the exercise, this time receiving an IV 10% glucose supplement.RESULTS: Glucose utilization during exercise was similar in patients and controls, while palmitate utilization was greater in patients compared to controls. However, exercise-induced increases in lactate were attenuated to about half normal in patients. This was also the case during a handgrip exercise test. Glucose infusion improved exercise tolerance in patients, and lowered heart rate by on average 11 beats per minute during exercise.CONCLUSIONS: The findings suggest that patients with GYG1 deficiency not only have abnormal formation of glycogen, but also have impaired muscle glycogenolysis, as suggested by impaired lactate production during exercise and improved exercise tolerance with glucose infusion.

KW - Administration, Intravenous

KW - Adult

KW - Aged

KW - Carbohydrate Metabolism

KW - Case-Control Studies

KW - Exercise

KW - Exercise Tolerance

KW - Female

KW - Glucose/metabolism

KW - Glucosyltransferases/deficiency

KW - Glycogen/biosynthesis

KW - Glycogenolysis

KW - Glycoproteins/deficiency

KW - Heart Rate

KW - Humans

KW - Lactic Acid/metabolism

KW - Lipid Metabolism

KW - Male

KW - Middle Aged

KW - Muscle, Skeletal/metabolism

KW - Palmitates/metabolism

U2 - 10.1212/WNL.0000000000004752

DO - 10.1212/WNL.0000000000004752

M3 - Journal article

C2 - 29142088

VL - 89

SP - 2491

EP - 2494

JO - Neurology

JF - Neurology

SN - 0028-3878

IS - 24

ER -