This K01 application proposes a 5-year mentored training and research plan to develop expertise in measurement, analysis and interpretation of, and interventions for, myocardial substrate metabolism and ventricular function abnormalities in HIV-infected people with metabolic complications (i.e. impaired glucose tolerance, fat redistribution). Didactic training will include coursework in cardiovascular diseases, nuclear medicine, and cardiac sonography. The primary aim of this proposal is to test the effects of two insulin sensitizing interventions, a cardiorespiratory exercise training (GET) program and a thiazolidinedione (TZD), on peripheral and myocardial substrate metabolism and left ventricular function in HIV-infected individuals with impaired glucose tolerance (HIV+IGT). In HIV-IGT, it is hypothesized that reduced peripheral and myocardial glucose utilization and elevated peripheral and myocardial FFA oxidation is associated with left ventricular dysfunction. Furthermore, both GET and TZD treatment will improve ventricular function through an increase of myocardial glucose utilization. Lastly, due to an additive effect of increased myocardial blood flow following GET, GET will provide a greater improvement in LV function than TZD treatment. Results from this proposal are projected to demonstrate the efficacy of GET and TZD for the treatment of metabolically induced LVD in HIV-infected people. Hypotheses for this proposal will be tested through randomized, closely supervised, our-month treatments of either GET or TZD. Myocardial substrate metabolism, blood flow and ventricular function and peripheral substrate metabolism will be measured before and immediately following completion of each intervention. Myocardial substrate metabolism and blood flow will be measured by radioisotope tracer methodology and Positron Emission Tomography (PET) imaging, ventricular function by standard 2-D and Doppler echocardiography, and peripheral substrate metabolism by stable-isotope tracer methodology and mass spectrometry. The candidate will receive specific training and guidance by exemplary mentors and a faculty advisory committee and will receive the full support of Washington University's outstanding research environment. This award will assist in accomplishing the candidate's long-term career goal of becoming an independent research scientist in the field of peripheral and myocardial metabolic and mechanical function complications in HIV.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Scientist Development Award - Research & Training (K01)
Project #
Application #
Study Section
Special Emphasis Panel (ZDK1-GRB-B (J2))
Program Officer
Hyde, James F
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Washington University
Internal Medicine/Medicine
Schools of Medicine
Saint Louis
United States
Zip Code
Cade, W Todd; Singh, Gautam K; Holland, Mark R et al. (2015) Maternal post-absorptive leucine kinetics during late pregnancy in US women with HIV taking antiretroviral therapy: a cross-sectional pilot study. Clin Nutr ESPEN 10:e140-e146
Cade, William Todd; Overton, Edgar Turner; Mondy, Kristin et al. (2013) Relationships among HIV infection, metabolic risk factors, and left ventricular structure and function. AIDS Res Hum Retroviruses 29:1151-60
Cade, W Todd; Reeds, Dominic N; Overton, E Turner et al. (2013) Pilot study of pioglitazone and exercise training effects on basal myocardial substrate metabolism and left ventricular function in HIV-positive individuals with metabolic complications. HIV Clin Trials 14:303-12
Cade, W Todd; Spencer, Carolyn T; Reeds, Dominic N et al. (2013) Substrate metabolism during basal and hyperinsulinemic conditions in adolescents and young-adults with Barth syndrome. J Inherit Metab Dis 36:91-101
Cade, W Todd; Reeds, Dominic N; Overton, E Turner et al. (2011) Effects of human immunodeficiency virus and metabolic complications on myocardial nutrient metabolism, blood flow, and oxygen consumption: a cross-sectional analysis. Cardiovasc Diabetol 10:111
Tuttle, Lori J; Sinacore, David R; Cade, W Todd et al. (2011) Lower physical activity is associated with higher intermuscular adipose tissue in people with type 2 diabetes and peripheral neuropathy. Phys Ther 91:923-30
Yarasheski, Kevin E; Cade, W Todd; Overton, E Turner et al. (2011) Exercise training augments the peripheral insulin-sensitizing effects of pioglitazone in HIV-infected adults with insulin resistance and central adiposity. Am J Physiol Endocrinol Metab 300:E243-51
Cade, W T; Reeds, D N; Mondy, K E et al. (2010) Yoga lifestyle intervention reduces blood pressure in HIV-infected adults with cardiovascular disease risk factors. HIV Med 11:379-88
O'Connor, Robert D; Bashir, Adil; Todd Cade, W et al. (2009) 1H-magnetic resonance spectroscopy for quantifying myocardial lipid content in humans with the cardiometabolic syndrome. J Clin Hypertens (Greenwich) 11:528-32
Carper, Michael J; Cade, W Todd; Cam, Margaret et al. (2008) HIV-protease inhibitors induce expression of suppressor of cytokine signaling-1 in insulin-sensitive tissues and promote insulin resistance and type 2 diabetes mellitus. Am J Physiol Endocrinol Metab 294:E558-67

Showing the most recent 10 out of 11 publications