title: Type 2 diabetes, obesity, and sex difference affect the fate of glucose in the human heart.
abstract: Type 2 diabetes, obesity, and sex difference affect myocardial glucose uptake and utilization. However, their effect on the intramyocellular fate of glucose in humans has been unknown. How the heart uses glucose is important, because it affects energy production and oxygen efficiency, which in turn affect heart function and adaptability. We hypothesized that type 2 diabetes, sex difference, and obesity affect myocardial glucose oxidation, glycolysis, and glycogen production. In a first-in-human study, we measured intramyocardiocellular glucose metabolism from time-activity curves generated from previously obtained positron emission tomography scans of 110 subjects in 3 groups: nonobese, obese, and diabetes. Group and sex difference interacted in the prediction of all glucose uptake, utilization, and metabolism rates. Group independently predicted fractional glucose uptake and its components: glycolysis, glycogen deposition, and glucose oxidation rates. Sex difference predicted glycolysis rates. However, there were fewer differences in glucose metabolism between diabetic patients and others when plasma glucose levels were included in the modeling. The potentially detrimental effects of obesity and diabetes on myocardial glucose metabolism are more pronounced in men than women. This sex difference dimorphism needs to be taken into account in the design, trials, and application of metabolic modulator therapy. Slightly higher plasma glucose levels improve depressed glucose oxidation and glycogen deposition rates in diabetic patients.
authors.affiliation: Cardiovascular Division, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri;
authors.forename: Linda R
authors.initials: LR
authors.lastname: Peterson
authors.affiliation: Division of Radiological Sciences, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri; and.
authors.forename: Pilar
authors.initials: P
authors.lastname: Herrero
authors.affiliation: Division of Radiological Sciences, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri; and.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Coggan
authors.affiliation: Division of Radiological Sciences, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri; and.
authors.forename: Zulia
authors.initials: Z
authors.lastname: Kisrieva-Ware
authors.affiliation: Cardiovascular Division, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri;
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Saeed
authors.affiliation: Cardiovascular Division, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri;
authors.forename: Carmen
authors.initials: C
authors.lastname: Dence
authors.affiliation: Division of Radiological Sciences, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri; and.
authors.forename: Deborah
authors.initials: D
authors.lastname: Koudelis
authors.affiliation: Endocrinology Division, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Janet B
authors.initials: JB
authors.lastname: McGill
authors.affiliation: Cardiovascular Division, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri;
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Lyons
authors.affiliation: Cardiovascular Division, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri;
authors.forename: Eric
authors.initials: E
authors.lastname: Novak
authors.affiliation: Cardiovascular Division, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri;
authors.forename: Víctor G
authors.initials: VG
authors.lastname: Dávila-Román
authors.affiliation: Cardiovascular Division, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri;
authors.forename: Alan D
authors.initials: AD
authors.lastname: Waggoner
authors.affiliation: Division of Radiological Sciences, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri; and Groplerr@mir.wustl.edu.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Gropler
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D004734:Energy Metabolism; D005260:Female; D006003:Glycogen / Q000378:metabolism; D006019:Glycolysis; D006439:Hemodynamics; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D009765:Obesity / Q000097:blood / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D010084:Oxidation-Reduction; D049268:Positron-Emission Tomography; D012737:Sex Factors; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D006003:Glycogen
keywords: glucose metabolism; glucose oxidation; myocardium; obesity; sex difference; type 2 diabetes