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

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.