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Inflammation and Insulin Resistance in Rheumatoid Arthritis

类风湿关节炎的炎症和胰岛素抵抗

基本信息

批准号：
8381910
负责人：
C M STEIN
金额：
$ 31.18万
依托单位：
VANDERBILT UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-08-01 至 2015-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8381910
关键词：
2,4-thiazolidinedione Adrenal Cortex Hormones Affect Age Agonist Animal Model Animals Arthritis Atherosclerosis Attention Blood Glucose Body mass index C-reactive protein Cardiovascular Diseases Cardiovascular system Central obesity Chronic Clinical Research Coronary Arteriosclerosis Coronary artery Data Development Diabetes Mellitus Disease Dyslipidemias Employee Strikes Evaluation General Population Human Hyperinsulinism Hypertension IL6 gene Individual Inflammation Inflammation Mediators Inflammation Process Inflammatory Insulin Insulin Resistance Interleukin-6 Joints Ligands Measures Metabolic syndrome Modeling Morbidity - disease rate Myocardial Ischemia Nuclear Outcome Patients Peroxisome Proliferator-Activated Receptors Pharmaceutical Preparations Pioglitazone Placebos Population Prevalence Race Randomized Rheumatoid Arthritis Severities TNF gene Testing Thiazolidinediones cardiovascular risk factor improved in vivo indexing inflammatory marker insulin sensitivity insulin sensitizing drugs man mortality multidisciplinary novel strategies premature atherosclerosis prevent sex tool transcription factor translational study

项目摘要

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.

类风湿关节炎的炎症和胰岛素抵抗