TRAINING CORE

具体目标 美洲印第安人受炎性结缔组织的影响不同 类风湿性关节炎和系统性红斑狼疮等疾病。此外，肥胖、胰岛素 抵抗力，2型糖尿病以及高血压在美国更常见 印第安人比欧洲血统的美国人。炎症性结缔组织疾病是 经常用糖皮质激素治疗，但这些药物有很高的严重并发症发生率， 反映了上面列出的在美洲印第安人中过度发现的疾病;即，肥胖， 胰岛素抵抗、2型糖尿病和高血压。关于风险因素的数据很少 使个体易患这些并发症。我们假设一个主要的诱发因素 就是胰岛素抵抗因此，一个必然的假设是，美国印第安人将在增加的风险， 糖皮质激素的并发症同时，骨质疏松症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， 糖皮质激素可能不涉及胰岛素抵抗。因此，我们假设这种并发症 在美洲印第安人中不会增加。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研究美洲印第安人来检验， 正在接受糖皮质激素治疗的炎症性结缔组织疾病， 具体目标- 1.既存胰岛素抵抗将被评估为肥胖症发展的风险因素， 美国印第安人和白人中高血压、葡萄糖耐受不良和2型糖尿病 接受糖皮质激素治疗的风湿性疾病患者。 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 因为胰岛素抵抗率很高。 2.既存胰岛素抵抗将被评估为发生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人风湿病患者中。 假设：骨质疏松症作为糖皮质激素治疗的并发症与胰岛素无关 耐药性，并且在美洲印第安人中不会比高加索人更常见。 3.确定二甲双胍是否能减少肥胖、高血压、葡萄糖耐受不良和/或2型糖尿病 接受糖皮质激素治疗炎性风湿性疾病的美洲印第安人的糖尿病 随机双盲试验 假设：由于改善胰岛素抵抗，二甲双胍将减少 糖皮质激素治疗已知与胰岛素抵抗有关。

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.