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: 7017187
• 负责人: Guillermo E Umpierrez
• 金额: $ 12.36万
• 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 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7017187
• 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）：