title: Diurnal variation in skeletal muscle and liver glycogen in humans with normal health and Type 2 diabetes.
abstract: In health, food carbohydrate is stored as glycogen in muscle and liver, preventing a deleterious rise in osmotically active plasma glucose after eating. Glycogen concentrations increase sequentially after each meal to peak in the evening, and fall to fasting levels thereafter. Skeletal muscle accounts for the larger part of this diurnal buffering capacity with liver also contributing. The effectiveness of this diurnal mechanism has not been previously studied in Type 2 diabetes. We have quantified the changes in muscle and liver glycogen concentration with 13C magnetic resonance spectroscopy at 3.0 T before and after three meals consumed at 4 h intervals. We studied 40 (25 males; 15 females) well-controlled Type 2 diabetes subjects on metformin only (HbA1c (glycated haemoglobin) 6.4±0.07% or 47±0.8 mmol/mol) and 14 (8 males; 6 females) glucose-tolerant controls matched for age, weight and body mass index (BMI). Muscle glycogen concentration increased by 17% after day-long eating in the control group (68.1±4.8 to 79.7±4.2 mmol/l; P=0.006), and this change inversely correlated with homoeostatic model assessment of insulin resistance [HOMA-IR] (r=-0.56; P=0.02). There was no change in muscle glycogen in the Type 2 diabetes group after day-long eating (68.3±2.6 to 67.1±2.0 mmol/mol; P=0.62). Liver glycogen rose similarly in normal control (325.9±25.0 to 388.1±30.3 mmol/l; P=0.005) and Type 2 diabetes groups (296.1±16.0 to 350.5±6.7 mmol/l; P<0.0001). In early Type 2 diabetes, the major physiological mechanism for skeletal muscle postprandial glycogen storage is completely inactive. This is directly related to insulin resistance, although liver glycogen storage is normal.
authors.affiliation: *Newcastle Magnetic Resonance Centre, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, NE4 5PL, U.K.
authors.forename: Mavin
authors.initials: M
authors.lastname: Macauley
authors.affiliation: *Newcastle Magnetic Resonance Centre, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, NE4 5PL, U.K.
authors.forename: Fiona E
authors.initials: FE
authors.lastname: Smith
authors.affiliation: *Newcastle Magnetic Resonance Centre, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, NE4 5PL, U.K.
authors.forename: Peter E
authors.initials: PE
authors.lastname: Thelwall
authors.affiliation: *Newcastle Magnetic Resonance Centre, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, NE4 5PL, U.K.
authors.forename: Kieren G
authors.initials: KG
authors.lastname: Hollingsworth
authors.affiliation: *Newcastle Magnetic Resonance Centre, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, NE4 5PL, U.K.
authors.forename: Roy
authors.initials: R
authors.lastname: Taylor
mesh_terms: D002247:Carbon Isotopes / Q000378:metabolism; D002940:Circadian Rhythm / Q000502:physiology*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005260:Female; D006003:Glycogen / Q000378:metabolism*; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008099:Liver / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008687:Metformin; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*; D009994:Osmolar Concentration; D010949:Plasma / Q000378:metabolism; D019518:Postprandial Period / Q000502:physiology*; D018709:Statistics, Nonparametric; D014280:Triglycerides / Q000378:metabolism
chemical_list: D002247:Carbon Isotopes; D014280:Triglycerides; D006003:Glycogen; D008687:Metformin