title: Abnormal Glucose Tolerance Is Associated with a Reduced Myocardial Metabolic Flexibility in Patients with Dilated Cardiomyopathy.
abstract: Dilated cardiomyopathy (DCM) is characterized by a metabolic shift from fat to carbohydrates and failure to increase myocardial glucose uptake in response to workload increments. We verified whether this pattern is influenced by an abnormal glucose tolerance (AGT). In 10 patients with DCM, 5 with normal glucose tolerance (DCM-NGT) and 5 with AGT (DCM-AGT), and 5 non-DCM subjects with AGT (N-AGT), we measured coronary blood flow and arteriovenous differences of oxygen and metabolites during Rest, Pacing (at 130 b/min), and Recovery. Myocardial lactate exchange and oleate oxidation were also measured. At Rest, DCM patients showed a reduced nonesterified fatty acids (NEFA) myocardial uptake, while glucose utilization increased only in DCM-AGT. In response to Pacing, glucose uptake promptly rose in N-AGT (from 72 ± 21 to 234 ± 73 nmol/min/g, p < 0.05), did not change in DCM-AGT, and slowly increased in DCM-NGT. DCM-AGT sustained the extra workload by increasing NEFA oxidation (from 1.3 ± 0.2 to 2.9 ± 0.1 μmol/min/gO2 equivalents, p < 0.05), while DCM-NGT showed a delayed increase in glucose uptake. Substrate oxidation rates paralleled the metabolites data. The presence of AGT in patients with DCM exacerbates both the shift from fat to carbohydrates in resting myocardial metabolism and the reduced myocardial metabolic flexibility in response to an increased workload. This trial is registered with ClinicalTrial.gov NCT02440217.
authors.affiliation: Dipartimento di Medicina Clinica e Sperimentale, Via Roma 67, 56126 Pisa, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Tricò
authors.affiliation: Dipartimento di Medicina Clinica e Sperimentale, Via Roma 67, 56126 Pisa, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Baldi
authors.affiliation: Dipartimento di Medicina Clinica e Sperimentale, Via Roma 67, 56126 Pisa, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Frascerra
authors.affiliation: Dipartimento di Medicina Clinica e Sperimentale, Via Roma 67, 56126 Pisa, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Venturi
authors.affiliation: National Research Council, Institute of Clinical Physiology, Pisa, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Marraccini
authors.affiliation: National Research Council, Institute of Clinical Physiology, Pisa, Italy.
authors.forename: Danilo
authors.initials: D
authors.lastname: Neglia
authors.affiliation: Dipartimento di Medicina Clinica e Sperimentale, Via Roma 67, 56126 Pisa, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Natali
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D001783:Blood Flow Velocity; D001786:Blood Glucose / Q000378:metabolism*; D002304:Cardiac Pacing, Artificial; D002311:Cardiomyopathy, Dilated / Q000097:blood / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology; D016022:Case-Control Studies; D003326:Coronary Circulation; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis / Q000378:metabolism*; D004734:Energy Metabolism; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005260:Female; D018149:Glucose Intolerance / Q000097:blood / Q000175:diagnosis / Q000378:metabolism*; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D019301:Oleic Acid / Q000378:metabolism; D010084:Oxidation-Reduction; D010100:Oxygen / Q000097:blood; D016277:Ventricular Function, Left
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D019301:Oleic Acid; D019344:Lactic Acid; D010100:Oxygen