Inflammation and Insulin Resistance in RA Rheumatoid arthritis (RA), affects approximately 1% of the population and is associated with an increased prevalence of ischemic heart disease. We have shown that the prevalence of coronary artery atherosclerosis is increased markedly in patients with RA, but the underlying mechanisms are not known. In preliminary studies we found that insulin concentrations are more than 2-fold higher in patients with RA than controls and are correlated with inflammatory markers such as IL6, TNF and CRP, and with coronary atherosclerosis. Thus, related processes, inflammation and hyperinsulinemia, contribute mechanistically to increased cardiovascular morbidity in RA. The relationship between hyperinsulinemia and inflammation is bi-directional - inflammation facilitates insulin resistance, and insulin resistance promotes chronic inflammation. Thiazolidinediones, selective PPARy agonists, are insulin sensitizers even in individuals without diabetes and are a powerful tool to understand the mechanisms underlying the realtionship between inflammation and insulin resistance. Thiazolidinediones, not only improve insulin sensitivity, but also decrease inflammation, including arthritis in animal models. Thus, in a proof-of-concept translational study, we will randomize patients with RA to receive pioglitazone or placebo for 6 months to test the hypotheses that treatment with a PPARy agonist will decrease inflammation (Specific Aim 1), improve insulin sensitivity (Specific Aim 2) and improve augmentation index (Specific Aim 3) in patients with RA. The proposed studies will provide mechanistic information regarding the relationship between inflammation and hyperinsulinemia, and will identify novel strategies for potentially reversing or preventing the long term damage to joints and the vasculature in RA, and perhaps other inflammatory diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Comprehensive Center (P60)
Project #
5P60AR056116-03
Application #
8132287
Study Section
Special Emphasis Panel (ZAR1)
Project Start
Project End
Budget Start
2010-08-01
Budget End
2011-07-31
Support Year
3
Fiscal Year
2010
Total Cost
$308,725
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Type
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
Bradham, William; Ormseth, Michelle J; Elumogo, Comfort et al. (2018) Absence of Fibrosis and Inflammation by Cardiac Magnetic Resonance Imaging in Rheumatoid Arthritis Patients with Low to Moderate Disease Activity. J Rheumatol 45:1078-1084
Carranza-Leon, Daniel; Octaria, Rany; Ormseth, Michelle J et al. (2018) Association between urinary sodium and potassium excretion and blood pressure and inflammation in patients with rheumatoid arthritis. Clin Rheumatol 37:895-900
Byram, Kevin W; Oeser, Annette M; Linton, MacRae F et al. (2018) Exercise is Associated With Increased Small HDL Particle Concentration and Decreased Vascular Stiffness in Rheumatoid Arthritis. J Clin Rheumatol 24:417-421
Ferraz-Amaro, Iván; Winchester, Robert; Gregersen, Peter K et al. (2017) Coronary Artery Calcification and Rheumatoid Arthritis: Lack of Relationship to Risk Alleles for Coronary Artery Disease in the General Population. Arthritis Rheumatol 69:529-541
Chung, C P; Ormseth, M J; Connelly, M A et al. (2016) GlycA, a novel marker of inflammation, is elevated in systemic lupus erythematosus. Lupus 25:296-300
Ormseth, Michelle J; Yancey, Patricia G; Solus, Joseph F et al. (2016) Effect of Drug Therapy on Net Cholesterol Efflux Capacity of High-Density Lipoprotein-Enriched Serum in Rheumatoid Arthritis. Arthritis Rheumatol 68:2099-105
Ormseth, Michelle J; Yancey, Patricia G; Yamamoto, Suguru et al. (2016) Net cholesterol efflux capacity of HDL enriched serum and coronary atherosclerosis in rheumatoid arthritis. IJC Metab Endocr 13:6-11
Wiese, Andrew D; Griffin, Marie R; Stein, C Michael et al. (2016) Opioid Analgesics and the Risk of Serious Infections Among Patients With Rheumatoid Arthritis: A Self-Controlled Case Series Study. Arthritis Rheumatol 68:323-31
Ormseth, Michelle J; Solus, Joseph F; Oeser, Annette M et al. (2016) Telomere Length and Coronary Atherosclerosis in Rheumatoid Arthritis. J Rheumatol 43:1469-74
Barnado, A; Oeser, A; Zhang, Y et al. (2016) Association of estimated sodium and potassium intake with blood pressure in patients with systemic lupus erythematosus. Lupus 25:1463-1469

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