title: Sex and type 2 diabetes: obesity-independent effects on left ventricular substrate metabolism and relaxation in humans.
abstract: Patients with type 2 diabetes (T2DM), particularly women, are at risk for heart failure. Myocardial substrate metabolism derangements contribute to cardiac dysfunction in diabetic animal models. The purpose of this study was to determine the effects of diabetes and sex on myocardial metabolism and diastolic function in humans, separate from those of obesity. Thirty-six diabetic subjects (22 women) and 36 nondiabetic, BMI-matched subjects (21 women) underwent positron emission tomography (myocardial metabolism) and echocardiography (structure, function). Myocardial blood flow and oxygen consumption (MVO(2)) were higher in women than men (P = 0.003 and <0.0001, respectively). Plasma fatty acid (FA) levels were higher in diabetics (vs. obese, P < 0.003) and sex and diabetes status interacted in its prediction (P = 0.03). Myocardial FA utilization, oxidation, and esterification were higher and percent FA oxidation lower in diabetics (vs. obese, P = 0.0004, P = 0.007, P = 0.002, P = 0.02). FA utilization and esterification were higher and percent FA oxidation lower in women (vs. men, P = 0.03, P = 0.01, P = 0.03). Diabetes and sex did not affect myocardial glucose utilization, but myocardial glucose uptake/plasma insulin was lower in the diabetics (P = 0.04). Left ventricular relaxation was lower in diabetics (P < 0.0001) and in men (P = 0.001), and diabetes and sex interacted in its prediction (P = 0.03). Sex, T2DM, or their interaction affect myocardial blood flow, MVO(2), FA metabolism, and relaxation separate from obesity's effects. Sexually dimorphic myocardial metabolic and relaxation responses to diabetes may play a role in the known cardiovascular differences between men and women with diabetes.
authors.affiliation: Division of Cardiovascular Diseases, Department of Medicine, Washington University School of Medicine, St Louis, Missouri, USA.
authors.forename: Linda R
authors.initials: LR
authors.lastname: Peterson
authors.forename: Ibrahim M
authors.initials: IM
authors.lastname: Saeed
authors.forename: Janet B
authors.initials: JB
authors.lastname: McGill
authors.forename: Pilar
authors.initials: P
authors.lastname: Herrero
authors.forename: Kenneth B
authors.initials: KB
authors.lastname: Schechtman
authors.forename: Ratnasiri
authors.initials: R
authors.lastname: Gunawardena
authors.forename: Carol L
authors.initials: CL
authors.lastname: Recklein
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Coggan
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: DeMoss
authors.forename: Carmen S
authors.initials: CS
authors.lastname: Dence
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Gropler
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology; D004452:Echocardiography; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D009126:Muscle Relaxation; D009206:Myocardium / Q000378:metabolism*; D009765:Obesity / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology; D010101:Oxygen Consumption; D049268:Positron-Emission Tomography; D012737:Sex Factors; D018487:Ventricular Dysfunction, Left / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D001786:Blood Glucose; D005227:Fatty Acids