Mentoring is critical to the success of the patient oriented researcher. Over the prior 5 years, the K-24 has permitted the PI to successfully mentor a number of fellows and trainees in the complex techniques of metabolic and cardiovascular risk assessment in the growing population of HIV patients with metabolic disorders. The goals of the prior grant were achieved, as evidenced by the success of the trainees and their publication record. Importantly, the K-24 has fostered the development of a comprehensive mentoring program, in which motivated trainees are selected, based on their interest in patient oriented research, work habits and ethical standards. A project is selected that is unique and achievable, and significant time is spent by the PI guiding trainees in protocol design, regulatory requirements, acquisition of detailed metabolic techniques, didactic coursework, and funding opportunities. The scientific AIMS of the renewal application are based on a successfully funded R01, investigating: 1) mechanisms of increased CAD risk in HIV patients, and 2) treatment strategies using insulin sensitizing agents and lifestyle modification in this population. In the current proposal it is hypothesized that increased inflammation will contribute to increased carotid intimal medial thickness, and increased coronary calcification in the HIV population. Detailed assessment of body composition, coronary plaques and endothelial disease will be made. Proinflammatory cytokines and indices of inflammation will be measured and related to the development of endothelial dysfunction in longitudinal studies, controlling for traditional risk factors. In the second AIM, a novel lifestyle modification program, based on a highly successful pilot study, will be implemented. HIV-infected subjects with the metabolic syndrome will undergo an intensive lifestyle modification program modeled after the Diabetes Prevention Program. Comparison of lifestyle modification (with a rigorous exercise program) and metformin on fat distribution, inflammatory markers, and carotid IMT will be made. Trainees will be exposed to detailed techniques of body composition assessment and exercise training. Funding for the scientific AIMS has been secured through an NIH R01, and the K-24 is critical to support the Pi's significant time spent in mentoring. The training environment at the Pi's institution is outstanding, in terms of didactic resources and availability of techniques to assess complex metabolic endpoints. Importantly, the PI enjoys the significant support of his Unit and Division Chiefs, who have enthusiastically endorsed his successful mentoring efforts over the prior 5 years of the grant and the plans in the current proposal. Taken together, the proposed K-24 renewal application offers a strong mentoring program in patient oriented research that is based on the teaching of important principles of endocrinology and metabolism. The studies are to be carried out in a population at significantly increased risk for cardiovascular disease and with which the PI has significant expertise.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Midcareer Investigator Award in Patient-Oriented Research (K24)
Project #
5K24DK064545-10
Application #
8204939
Study Section
Special Emphasis Panel (ZDK1-GRB-B (O2))
Program Officer
Hyde, James F
Project Start
2003-03-15
Project End
2013-04-28
Budget Start
2012-03-01
Budget End
2013-04-28
Support Year
10
Fiscal Year
2012
Total Cost
$153,613
Indirect Cost
$11,379
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
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Zanni, Markella V; Fitch, Kathleen V; Feldpausch, Meghan et al. (2014) 2013 American College of Cardiology/American Heart Association and 2004 Adult Treatment Panel III cholesterol guidelines applied to HIV-infected patients with/without subclinical high-risk coronary plaque. AIDS 28:2061-70
Nolte, Julia Eh; Neumann, Till; Manne, Jennifer M et al. (2014) Cost-effectiveness analysis of coronary artery disease screening in HIV-infected men. Eur J Prev Cardiol 21:972-9
Makimura, Hideo; Murphy, Caitlin A; Feldpausch, Meghan N et al. (2014) The effects of tesamorelin on phosphocreatine recovery in obese subjects with reduced GH. J Clin Endocrinol Metab 99:338-43
Zanni, Markella V; Abbara, Suhny; Lo, Janet et al. (2013) Increased coronary atherosclerotic plaque vulnerability by coronary computed tomography angiography in HIV-infected men. AIDS 27:1263-72
McCormack, S E; Shaham, O; McCarthy, M A et al. (2013) Circulating branched-chain amino acid concentrations are associated with obesity and future insulin resistance in children and adolescents. Pediatr Obes 8:52-61
Torriani, Martin; Zanni, Markella V; Fitch, Kathleen et al. (2013) Increased FDG uptake in association with reduced extremity fat in HIV patients. Antivir Ther 18:243-8
Fitch, Kathleen V; Looby, Sara E; Rope, Alison et al. (2013) Effects of aging and smoking on carotid intima-media thickness in HIV-infection. AIDS 27:49-57
Fitch, Kathleen V; Srinivasa, Suman; Abbara, Suhny et al. (2013) Noncalcified coronary atherosclerotic plaque and immune activation in HIV-infected women. J Infect Dis 208:1737-46
Makimura, Hideo; Feldpausch, Meghan N; Stanley, Takara L et al. (2012) Reduced growth hormone secretion in obesity is associated with smaller LDL and HDL particle size. Clin Endocrinol (Oxf) 76:220-7

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