Psoriasis and the risk of diabetes

牛皮癣和糖尿病的风险

基本信息

批准号：
8828569
负责人：
JOEL M GELFAND
金额：
$ 18.19万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-04-01 至 2016-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8828569
关键词：
Address Affect Age of Onset American Anatomy Animals Apolipoproteins B Atherosclerosis Biological Markers Body Surface Area Body mass index CD4 Positive T Lymphocytes Cardiovascular Diseases Cardiovascular system Caring Cessation of life Characteristics Chronic Clinic Clinical Clinical Research Clinical effectiveness Cohort Studies Cross-Sectional Studies Data Dermatology Development Diabetes Mellitus Diabetes prevention Disease Emotional Environment Epidemiologic Studies Epidemiology Event Ferritin Funding Future Genetic Health Helper-Inducer T-Lymphocyte Human Impairment Inflammation Inflammatory Insulin Resistance Interleukin 2 Receptor Interleukin-18 Knowledge Maintenance Mediating Medical Electronics Medicine Mentors Metabolic Modeling Myocardial Infarction Obesity Outcome Pain Pathway interactions Patients Pattern Phenotype Phototherapy Physicians Placebos Prevention Preventive Intervention Psoriasis Public Health Randomized Controlled Trials Recommendation Research Research Personnel Risk Risk Factors Scientist Severities Site Skin Stroke Susceptibility Gene System TNF gene Testing Thick Training Translational Research United Kingdom United States United States National Institutes of Health adalimumab adipokines alpha-Fetoproteins arm base cardiovascular risk factor clinical practice cohort comparative effectiveness design diabetes risk effectiveness research follow-up high risk immunoregulation improved inhibitor/antagonist innovation lipid metabolism man mortality novel patient oriented research population based premature prevent prospective randomized placebo controlled trial skills skin disorder skin lesion standard of care targeted treatment ultraviolet vascular inflammation

项目摘要

DESCRIPTION (provided by applicant): Psoriasis and the risk of diabetes Psoriasis affects over 7 million people in the US (125 million people worldwide) and is the most common helper T-cell (Th)-1 and Th-17 mediated inflammatory disease in humans. Epidemiological studies indicate that psoriasis is associated with an increased risk for major cardiovascular (CV) events and premature death due to CV disease independent of traditional risk factors. Emerging data suggest that patients with psoriasis may also be at increased risk for developing diabetes as well. The chronic inflammatory pathways involved in the maintenance of psoriasis have been shown to promote insulin resistance in animal and human models of diabetes. Furthermore, psoriasis and diabetes share susceptibility genes (such as CDKAL1). These shared genetic and inflammatory pathways suggest biologic plausibility for an increased risk of diabetes in patients with psoriasis. However, it is not known how clinical aspects of psoriasis (such as body surface area of involvement, anatomic sites of involvement, etc) impact diabetes risk nor is it known if successful treatment of psoriasis will lower the risk of diabetes. We will address these key knowledge gaps by conducting new aims to ongoing NIH funded projects. First, we will determine the risk of diabetes in a large population-based cohort of 9000 patients with psoriasis called the incident health outcomes and psoriasis events (iHOPE) study, established by R01 HL089744. Second we will determine how clinical aspects of psoriasis are associated with prevalent diabetes in a United States multi-centered clinic-based cohort of 1800 extensively phenotyped patients with psoriasis, 200 of whom have prevalent diabetes. This cohort was derived from the Dermatology Clinical Effectiveness Research Network (DCERN) established by RC1 AR058204. Third, we will determine if treatment of psoriasis with a systemic TNF-inhibitor (adalimumab) improves novel biomarkers which predict future development of diabetes compared to skin targeted treatment (ultraviolet B phototherapy) or placebo. This new aim will be investigated in the ongoing Vascular Inflammation in Psoriasis (VIP) trial funded by R01 HL111293, which is designed to evaluate vascular inflammation and lipid metabolism outcomes. These projects leverage existing studies conducted by the applicant to develop highly significant and innovative aims which will: 1) provide added value to ongoing studies while aiding the applicant to develop new skills in epidemiological and translational research focusing on diabetes; 2) address an important problem by determining which patients with psoriasis are at highest risk for developing diabetes thus warranting preventive interventions already proven to reduce the risk of diabetes; 3) determine if a class of medicines (i.e., TNF inhibitors) which are commonly used across multiple inflammatory disease indications hold promise for diabetes prevention through the study of innovative biomarkers in a rigorous randomized controlled trial which may yield new clinical practice paradigms; and, 4) provide a diverse clinical research platform in which to mentor young physician scientists in patient oriented research and promote their successful transition to independence.

描述（由申请人提供）：牛皮癣和糖尿病的风险牛皮癣会影响美国超过700万人（全球1.25亿人），是人类中最常见的最常见的助手T-CELL（TH）-1和TH-17介导的炎症性疾病。流行病学研究表明，牛皮癣与由于CV疾病而与传统危险因素无关的CV疾病引起的主要心血管（CV）事件的风险增加。新兴数据表明，牛皮癣患者也可能患有糖尿病的风险增加。已经证明参与牛皮癣维持的慢性炎症途径可在糖尿病的动物和人类模型中促进胰岛素抵抗。此外，牛皮癣和糖尿病具有敏感性基因（例如CDKAL1）。这些共有的遗传和炎症途径表明，牛皮癣患者患糖尿病风险的生物学合理性。然而，尚不清楚牛皮癣的临床方面（例如受累的身体表面积，参与的解剖部位等）会影响糖尿病的风险，也不知道成功治疗牛皮癣是否会降低糖尿病的风险。我们将通过实现正在进行的NIH资助项目的新目标来解决这些关键知识差距。首先，我们将确定由R01 HL089744建立的9000例牛皮癣患者（IHOPE）研究（IHOPE）研究的9000例牛皮癣患者的糖尿病风险。其次，我们将确定牛皮癣的临床方面如何与美国多中心诊所的普遍糖尿病有关，该糖尿病是1800种广泛表型牛皮癣患者的临床研究，其中200例患有普遍存在的糖尿病。该队列源自RC1 AR058204建立的皮肤病学临床有效性研究网络（DCERN）。第三，我们将确定使用全身性TNF抑制剂（Adalimumab）治疗牛皮癣是否可以改善新型生物标志物，这些新型生物标志物可以预测与皮肤靶向治疗（紫外线B光疗）或安慰剂相比的未来糖尿病发展。这一新目标将在由R01 HL111293资助的牛皮癣（VIP）试验中正在进行的血管炎症中进行研究，该试验旨在评估血管炎症和脂质代谢结果。这些项目利用申请人进行的现有研究，以开发出非常重要和创新的目标：1）为正在进行的研究提供额外的价值，同时帮助申请人开发针对糖尿病的流行病学和转化研究的新技能； 2）通过确定哪些牛皮癣患者患糖尿病的风险最高，从而解决一个重要的预防干预措施，以降低糖尿病的风险，解决了一个重要的问题； 3）确定在多种炎症性疾病指示中通常使用的一类药物（即TNF抑制剂）是否通过研究创新的生物标志物在一项严格的随机对照试验中预防糖尿病有望预防糖尿病，该试验可能会产生新的临床实践范式；，4）提供了一个多样化的临床研究平台，在该平台中指导年轻的医师科学家以患者为导向的研究并促进他们成功过渡到独立性。