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:
- 金额:$ 31.18万
- 依托单位:
- 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:
- 关键词:2,4-thiazolidinedioneAdrenal Cortex HormonesAffectAgeAgonistAnimal ModelAnimalsArthritisAtherosclerosisAttentionBlood GlucoseBody mass indexC-reactive proteinCardiovascular DiseasesCardiovascular systemCentral obesityChronicClinical ResearchCoronary ArteriosclerosisCoronary arteryDataDevelopmentDiabetes MellitusDiseaseDyslipidemiasEmployee StrikesEvaluationGeneral PopulationHumanHyperinsulinismHypertensionIL6 geneIndividualInflammationInflammation MediatorsInflammation ProcessInflammatoryInsulinInsulin ResistanceInterleukin-6JointsLigandsMeasuresMetabolic syndromeModelingMorbidity - disease rateMyocardial IschemiaNuclearOutcomePatientsPeroxisome Proliferator-Activated ReceptorsPharmaceutical PreparationsPioglitazonePlacebosPopulationPrevalenceRaceRandomizedRheumatoid ArthritisSeveritiesTNF geneTestingThiazolidinedionescardiovascular risk factorimprovedin vivoindexinginflammatory markerinsulin sensitivityinsulin sensitizing drugsmanmortalitymultidisciplinarynovel strategiespremature atherosclerosispreventsextooltranscription factortranslational 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
项目成果
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{{ truncateString('C M STEIN', 18)}}的其他基金
Inflammation and Insulin Resistance in Rheumatoid Arthritis
类风湿关节炎的炎症和胰岛素抵抗
- 批准号:
8327307 - 财政年份:2011
- 资助金额:
$ 31.18万 - 项目类别:
Clinical Effects of Genetic Variability in Adrenergic Receptors
肾上腺素能受体遗传变异的临床影响
- 批准号:
7252845 - 财政年份:2007
- 资助金额:
$ 31.18万 - 项目类别:
Inflammation and Insulin Resistance in Rheumatoid Arthritis
类风湿关节炎的炎症和胰岛素抵抗
- 批准号:
8132287 - 财政年份:
- 资助金额:
$ 31.18万 - 项目类别:
Inflammation and Insulin Resistance in Rheumatoid Arthritis
类风湿关节炎的炎症和胰岛素抵抗
- 批准号:
7912914 - 财政年份:
- 资助金额:
$ 31.18万 - 项目类别: