Markers of normoglycemic remission in obese diabetics

肥胖糖尿病患者血糖正常缓解的标志物

• 批准号: 7124624
• 负责人: Guillermo E Umpierrez
• 金额: $ 11.36万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-30 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7124624
• 关键词: African American; apoptosis; autoantibody; biological signal transduction; biomarker; biopsy; clinical research; diabetes mellitus therapy; diabetic acidosis; disease /therapy duration; gene expression; human subject; hyperglycemia; immunogenetics; insulin sensitivity /resistance; longitudinal human study; muscle metabolism; muscle proteins; obesity; pancreatic islet function; patient oriented research; phosphorylation; remission /regression; striated muscles

DESCRIPTION (provided by applicant): Obesity in African-Americans (AA) presents a unique model to help identify the markers and mechanisms of associated metabolic disorders. Over half of newly diagnosed AA presenting with severe hyperglycemia and/or unprovoked diabetic ketoacidosis (DKA) display metabolic and immunogenetic features of type 2 diabetes. This variant of type 2 diabetes is referred to as atypical diabetes, Flatbush diabetes, and more recently as ketosis-prone diabetes (KPDM). We have shown that patients with KPDM have markedly decreased insulin secretion and impaired insulin sensitivity, but aggressive management can result in improvement in (-cell function and insulin sensitivity to allow discontinuation of insulin therapy. We also showed that distinctive markers of remission in skeletal muscle are improved expression and insulin-stimulated phosphorylation of Akt2 Ser474 and other key signal transduction kinases and phosphatases. We hypothesize that the correlation between measures of beta-cell function, muscle insulin-stimulated signal transduction and protein expression will identify specific markers indicative of short- and long-term near-normoglycemic remission and/or risk for continued hyperglycemia. The first aim is to identify clinical, metabolic, and immunogenetic markers predictive of short- and long-term near-normoglycemic remission or lack thereof in obese AA with KPDM. Beta-cell function and insulin sensitivity will be measured at initial presentation and again at either near-normoglycemic remission or 12 weeks of insulin therapy. The second aim is to measure insulin-stimulated protein phosphorylation and signal transduction protein expression in the muscle biopsies obtained at presentation and at follow-up. Response to treatment (near-normoglycemic remission or lack thereof) will be correlated with measurements of beta-cell function, insulin sensitivity, muscle insulin-stimulated signaling and protein expression. Because of their unique clinical characteristics, patients with KPDM represent an ideal population in which to identify markers indicative of short- and long-term remission and/or risk for continued hyperglycemia. Identifying such markers will facilitate and guide future therapeutic interventions and may identify patients at risk to develop chronic complications of diabetes

描述（由申请人提供）： 非裔美国人（AA）的肥胖症提出了一个独特的模型，以帮助识别相关代谢疾病的标记和机制。超过一半的新诊断AA表现出严重的高血糖和/或无端的糖尿病性酮症酸中毒（DKA）表现出2型糖尿病的代谢和免疫遗传特征。这种2型糖尿病的变体被称为非典型糖尿病，Flatbush糖尿病，而最近也称为容易发生糖尿病（KPDM）。 We have shown that patients with KPDM have markedly decreased insulin secretion and impaired insulin sensitivity, but aggressive management can result in improvement in (-cell function and insulin sensitivity to allow discontinuation of insulin therapy. We also showed that distinctive markers of remission in skeletal muscle are improved expression and insulin-stimulated phosphorylation of Akt2 Ser474 and other key signal transduction kinases磷酸酶。我们假设β-细胞功能的度量，肌肉胰岛素刺激的信号转导和蛋白质表达之间的相关性将确定特定的标志物，表明短期和长期的近距离囊性缓解和/或持续的高血糖量的临床，近距离预测的近距离疾病。在具有KPDM的肥胖AA中，将在初始介绍中测量β-细胞功能和胰岛素敏感性，并在近糖类缓解或12周的胰岛素治疗中再次测量。第二个目的是测量胰岛素刺激的蛋白质磷酸化和信号转导蛋白表达在介绍和随访时获得的肌肉活检中。对治疗的反应（接近糖症的缓解或缺乏治疗）将与测量β细胞功能，胰岛素敏感性，肌肉胰岛素刺激的信号传导和蛋白质表达相关。由于其独特的临床特征，KPDM患者代表了理想的人群，在该人群中，可以识别表明短期和/或持续高血糖的风险的标志物。识别此类标记将有助于并指导未来的治疗干预措施，并可能确定有风险的患者患糖尿病的慢性并发症