title: Impact of sex on the heart's metabolic and functional responses to diabetic therapies.
abstract: Increased myocardial lipid delivery is a determinant of myocardial substrate metabolism and function in animal models of type 2 diabetes (T2DM). Sex also has major effects on myocardial metabolism in the human heart. Our aims were to determine whether 1) sex affects the myocardial metabolic response to lipid lowering in T2DM, 2) altering lipid [fatty acid (FA) or triglyceride] delivery to the heart would lower the elevated myocardial lipid metabolism associated with T2DM, and 3) decreasing lipid delivery improves diastolic dysfunction in T2DM. To this end, we studied 78 T2DM patients (43 women) with positron emission tomography, echocardiography, and whole body tracer studies before and 3 mo after randomization to metformin (MET), metformin + rosiglitazone (ROSI), or metformin + Lovaza (LOV). No treatment main effects were found for myocardial substrate metabolism, partly because men and women often had different responses to a given treatment. In men, MET decreased FA clearance, which was linked to increased plasma FA levels, myocardial FA utilization and oxidation, and lower myocardial glucose utilization. In women, ROSI increased FA clearance, thereby decreasing plasma FA levels and myocardial FA utilization. Although LOV did not change triglyceride levels, it improved diastolic function, particularly in men. Group and sex also interacted in determining myocardial glucose uptake. Thus, in T2DM, different therapeutic regimens impact myocardial metabolism and diastolic function in a sex-specific manner. This suggests that sex should be taken into account when designing a patient's diabetes treatment.
authors.affiliation: Cardiovascular Division, Washington University School of Medicine, St. Louis, Missouri;
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Lyons
authors.forename: Linda R
authors.initials: LR
authors.lastname: Peterson
authors.forename: Janet B
authors.initials: JB
authors.lastname: McGill
authors.forename: Pilar
authors.initials: P
authors.lastname: Herrero
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Coggan
authors.forename: Ibrahim M
authors.initials: IM
authors.lastname: Saeed
authors.forename: Carol
authors.initials: C
authors.lastname: Recklein
authors.forename: Kenneth B
authors.initials: KB
authors.lastname: Schechtman
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Gropler
mesh_terms: D000704:Analysis of Variance; D016009:Chi-Square Distribution; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D003971:Diastole / Q000187:drug effects; D019587:Dietary Supplements; D004281:Docosahexaenoic Acids / Q000627:therapeutic use*; D004311:Double-Blind Method; D004338:Drug Combinations; D015150:Echocardiography, Doppler; D015118:Eicosapentaenoic Acid / Q000627:therapeutic use*; D004734:Energy Metabolism / Q000187:drug effects*; D005227:Fatty Acids / Q000378:metabolism; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use*; D005260:Female; D054624:Health Status Disparities; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D008923:Missouri; D009206:Myocardium / Q000378:metabolism*; D049268:Positron-Emission Tomography; D020127:Recovery of Function; D012737:Sex Factors; D013318:Stroke Volume / Q000187:drug effects; D013844:Thiazoles / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D014280:Triglycerides / Q000378:metabolism; D016277:Ventricular Function, Left / Q000187:drug effects*; D017725:Ventricular Pressure / Q000187:drug effects
chemical_list: D004338:Drug Combinations; D005227:Fatty Acids; D015525:Fatty Acids, Omega-3; D007004:Hypoglycemic Agents; D013844:Thiazoles; D014280:Triglycerides; C471074:rosiglitazone-metformin combination; D004281:Docosahexaenoic Acids; D008687:Metformin; D015118:Eicosapentaenoic Acid; C405603:Omacor
keywords: Lovaza; metformin; myocardial metabolism; rosiglitazone; sex; type 2 diabetes
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