TRAINING CORE

训练核心

• 批准号: 7305079
• 负责人: Joseph NEIL HENDERSON
• 金额: $ 8.69万
• 依托单位: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-10-01 至 2012-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7305079
• 关键词: Affect; American; American Indians; Bone Density; Caucasians; Caucasoid Race; Complication; Connective Tissue Diseases; Data; Development; Diabetes Mellitus; Disease; Double-Blind Method; European; Future; Glucocorticoids; Glucose Intolerance; Hypertension; Incidence; Individual; Inflammatory; Insulin Resistance; Metformin; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Osteoporosis; Pathogenesis; Patients; Persons; Pharmaceutical Preparations; Population; Predisposing Factor; Randomized; Rate; Rheumatism; Rheumatoid Arthritis; Risk; Risk Factors; Systemic Lupus Erythematosus; Testing; Training; improved; insulin sensitivity

Specific Aims The American Indian population is differentially affected by inflammatory connective tissue diseases such as rheumatoid arthritis and systemic lupus erythematosus. In addition, obesity, insulin resistance, and type 2 diabetes mellitus as well as hypertension are much more common in American Indians than in Americans of European ancestry. Inflammatory connective tissue diseases are frequently treated with glucocorticoids, but these drugs have a high rate of serious complications that mirror the diseases listed above that are found in excess among American Indians; namely, obesity, insulin resistance, type 2 diabetes and hypertension. There are very little data concerning risk factors that predispose individuals to these complications. We hypothesize that a major predisposing factor is insulin resistance. Thus, a corollary hypothesis is that American Indians will be at increased risk of complications from glucocorticoids. Meanwhile, osteoporosis is also a common complication of glucocorticoid therapy; however, the pathogenesis of altered bone mineral density with glucocorticoids likely does not involve insulin resistance. Thus, we hypothesize that this complication will not be increased in American Indians. Agents that increase insulin sensitivity such as metformin are known to reduce future diabetes onset in persons with insulin resistance. We hypothesize that metformin will lower the incidence of obesity, diabetes and hypertension among American Indians treated with glucocorticoids. These hypotheses will be tested by studying American Indians with inflammatory connective tissue diseases who are being treated with glucocorticoids in the following specific aims - 1. Pre-existing insulin resistance will be assessed as a risk factor for development of obesity, hypertension, glucose intolerance and type 2 diabetes among American Indian and Caucasian rheumatic disease patients receiving glucocorticoid therapy. Hypothesis: American Indians are at high risk of these complications from glucocorticoid therapy because of a high rate of insulin resistance. 2. Pre-existing insulin resistance will be assessed as a risk factor for development of osteoporosis among American Indians and Caucasian rheumatic disease patients receiving glucocorticoid therapy. Hypothesis: Osteoporosis as a complication of glucocorticoid therapy is not related to insulin resistance and will not be found more commonly among American Indians than Caucasians. 3. Determine whether metformin reduces obesity, hypertension, glucose intolerance and/or type 2 diabetes in American Indians receiving glucocorticoid therapy for inflammatory rheumatic diseases in randomized, double blinded trial. Hypothesis: By virtue of improving insulin resistance metformin will reduce complications of glucocorticoid therapy that are known to be associated with insulin resistance.

具体目标 美洲印第安人受炎性结缔组织的影响不同 风湿性关节炎和系统性红斑狼疮等疾病。此外，肥胖、胰岛素 耐药，2型糖尿病和高血压在美国更常见 印第安人多于欧洲血统的美国人。炎性结缔组织病有 经常使用糖皮质激素治疗，但这些药物严重并发症的发生率很高 与上面列出的在美洲印第安人中发现过多的疾病类似，即肥胖， 胰岛素抵抗、2型糖尿病和高血压。有关风险因素的数据很少。 使个体更容易受到这些并发症的影响。我们假设一个主要的诱因是 就是胰岛素抵抗。因此，一个必然的假设是，美国印第安人将面临更高的风险 糖皮质激素的并发症。同时，骨质疏松也是一种常见的并发症 糖皮质激素治疗；然而，骨密度改变的发病机制与 糖皮质激素可能不会引起胰岛素抵抗。因此，我们假设这一复杂情况 不会在美国印第安人中增加。增加胰岛素敏感性的药物，如二甲双胍 已知可减少胰岛素抵抗患者未来的糖尿病发病。我们假设 二甲双胍将降低美国印第安人肥胖、糖尿病和高血压的发病率 用糖皮质激素治疗。这些假设将通过对美国印第安人的研究来检验 以下患者正在使用糖皮质激素治疗炎性结缔组织病 具体目标-- 1.先前存在的胰岛素抵抗将被评估为肥胖的风险因素， 美洲印第安人和高加索人中的高血压、糖耐量减低和2型糖尿病 风湿病患者接受糖皮质激素治疗。 假设：美洲印第安人在糖皮质激素治疗中发生这些并发症的风险很高 因为胰岛素抵抗的比率很高。 2.先前存在的胰岛素抵抗将被评估为发展为骨质疏松症的风险因素 在接受糖皮质激素治疗的美洲印第安人和高加索风湿病患者中。 假设：作为糖皮质激素治疗并发症的骨质疏松症与胰岛素无关 而且在美洲印第安人中不会比高加索人中更常见。 3.确定二甲双胍是否能降低肥胖、高血压、糖耐量低减和/或2型 年接受糖皮质激素治疗炎症性风湿病的美国印第安人中的糖尿病 随机、双盲试验。 假设：通过改善胰岛素抵抗，二甲双胍将减少高血压并发症 糖皮质激素治疗，已知与胰岛素抵抗有关。