title: Myocardial glucose uptake in patients with the m.3243A > G mutation in mitochondrial DNA.
abstract: Mitochondrial mutations impair glucose oxidation and increase glucose uptake in cell cultures and lead to cardiomyopathy in patients. Here we characterize cardiac glucose uptake in 14 patients with the m.3243A > G mutation in mitochondrial DNA. The 14 patients with m.3243A > G and 13 controls were similar in age, physical activity and body mass index. Ten patients had diabetes. Left ventricular glucose uptake per tissue mass (LVGU) was measured with 2-[(18) F]fluoro-2-deoxyglucose positron emission tomography during euglycemic hyperinsulinemia. Cardiac morphology and function were assessed with magnetic resonance imaging. We found that the LVGU was 25% lower in the patients than that in the controls (P = 0.029). LVGU was inversely correlated with mutation heteroplasmy, glycated haemoglobin and fasting lactate in patients. The seven patients with mutation heteroplasmy ≥ 49% had 44% lower LVGU than the seven patients with heteroplasmy < 49%. This difference remained significant after adjustment for concurrent free fatty acid concentration or glycated haemoglobin or glucose uptake in skeletal muscle or all (p < 0.048 [All]). Patients with m.3243A > G had a lower stroke volume and a higher heart rate than the controls, whereas cardiac output and work were similar. Myocardial glucose uptake is not increased but decreased with a threshold effect pattern in patients with the m.3243A > G mutation. The glucose hypometabolism adds to the impaired cardiac energetics and likely contributes to the progression of the mitochondrial cardiomyopathy.
authors.affiliation: Turku PET Centre, University of Turku, Turku, Finland.
authors.forename: Markus M
authors.initials: MM
authors.lastname: Lindroos
authors.affiliation: Department of Clinical Physiology, Turku University Hospital, Turku, Finland.
authors.forename: Jussi P
authors.initials: JP
authors.lastname: Pärkkä
authors.affiliation: Department of Anaesthesiology, Turku University Hospital, Turku, Finland.
authors.forename: Markku T
authors.initials: MT
authors.lastname: Taittonen
authors.affiliation: Institute of Clinical Physiology, National Research Council (CNR), Pisa, Italy.
authors.forename: Patricia
authors.initials: P
authors.lastname: Iozzo
authors.affiliation: Research Group of Clinical Neuroscience, Neurology, University of Oulu, P.O Box 5000, FIN-90014, Oulu, Finland.|Medical Research Center Oulu, University of Oulu and Oulu University Hospital, Oulu, Finland.
authors.forename: Mikko
authors.initials: M
authors.lastname: Kärppä
authors.affiliation: Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland.
authors.forename: Ilmo E
authors.initials: IE
authors.lastname: Hassinen
authors.affiliation: Turku PET Centre, University of Turku, Turku, Finland.
authors.forename: Juhani
authors.initials: J
authors.lastname: Knuuti
authors.affiliation: Turku PET Centre, University of Turku, Turku, Finland.|Department of Endocrinology, Turku University Hospital, Turku, Finland.
authors.forename: Pirjo
authors.initials: P
authors.lastname: Nuutila
authors.affiliation: Research Group of Clinical Neuroscience, Neurology, University of Oulu, P.O Box 5000, FIN-90014, Oulu, Finland. kari.majamaa@oulu.fi.|Medical Research Center Oulu, University of Oulu and Oulu University Hospital, Oulu, Finland. kari.majamaa@oulu.fi.
authors.forename: Kari
authors.initials: K
authors.lastname: Majamaa
mesh_terms: D001786:Blood Glucose / Q000378:metabolism; D016022:Case-Control Studies; D004272:DNA, Mitochondrial / Q000235:genetics*; D003920:Diabetes Mellitus / Q000235:genetics / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000235:genetics*; D018482:Muscle, Skeletal / Q000378:metabolism; D009154:Mutation / Q000235:genetics*; D009206:Myocardium / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D004272:DNA, Mitochondrial; D005947:Glucose