Myocardial glucose uptake in patients with the m.3243A > G mutation in mitochondrial DNA

• Published in: Journal of inherited metabolic disease Vol. 39; no. 1; pp. 67 - 74
• Main Authors: Lindroos, Markus M., Pärkkä, Jussi P., Taittonen, Markku T., Iozzo, Patricia, Kärppä, Mikko, Hassinen, Ilmo E., Knuuti, Juhani, Nuutila, Pirjo, Majamaa, Kari
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.01.2016; Blackwell Publishing Ltd
• Subjects: Biochemistry; Blood Glucose - metabolism; Case-Control Studies; Diabetes Mellitus - genetics; Diabetes Mellitus - metabolism; DNA, Mitochondrial - genetics; Epithelium - metabolism; Female; Glucose - metabolism; Glucose Tolerance Test - methods; Human Genetics; Humans; Internal Medicine; Male; Medicine; Medicine & Public Health; Metabolic Diseases; Middle Aged; Mitochondria - genetics; Muscle, Skeletal - metabolism; Mutation - genetics; Myocardium - metabolism; Original Article; Pediatrics; Mutation Load; Rate Pressure Product; Positron Emission Tomography; Glucose Uptake; Free Fatty Acid Concentration
• ISSN: 0141-8955; 1573-2665
• DOI: 10.1007/s10545-015-9865-1

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.