Preservation of Beta Cell Function in Prediabetes Early Type 2 Diabetes

糖尿病前期早期 2 型糖尿病中 β 细胞功能的保存

• 批准号: 8334552
• 负责人: Kieren J Mather
• 金额: $ 55.19万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-20 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8334552
• 关键词: 2,4-thiazolidinedione; Agonist; Arginine; Attenuated; Beta Cell; Biological Markers; Biological Preservation; Biology; Blood specimen; Cell physiology; Collaborations; Critiques; Data; Diabetes Mellitus; Diabetes prevention; Disease; Economic Burden; Epidemic; Evaluation; Exhibits; Face; Glucose; Glycosylated hemoglobin A; Hour; Hyperglycemia; Individual; Insulin; Intervention; Measurable; Measurement; Measures; Metformin; Nature; Non-Insulin-Dependent Diabetes Mellitus; OGTT; Obesity; Outcome; Participant; Pathogenesis; Phase; Physiological; Pioglitazone; Population; Positioning Attribute; Prediabetes syndrome; Prevalence; Proteins; Proteomics; Protocols documentation; Published Comment; Randomized; Reading; Recovery; Rest; Risk; Sampling; Site; Study Subject; Testing; Thiazolidinediones; Time; Toxic effect; Treatment Efficacy; Validation; anakinra; cohort; cost; fasting glucose; glargine; glucagon-like peptide 1; glycemic control; health economics; improved; insulin secretion; lifestyle intervention; liquid chromatography mass spectrometry; liraglutide; novel; peer; prevent; response; restoration; therapy design; treatment duration; treatment effect; treatment response; treatment strategy

DESCRIPTION (provided by applicant): This study will be part of a multicenter collaborative effort testing different strategies to achieve durable beta cell preservation in pre-diabetes/early T2D (RFA DK-10-013). The final intervention design and measurement endpoints will be harmonized within the consortium following selection of participating sites. We propose to study subjects with HbA1c 5.7-7.0% and 2 hour glucose >140 mg/dL following an oral glucose tolerance test. Subjects will initially be treated with insulin to achieve fasting glucose readingsof 90-100 mg/dL. Subjects will then be randomized to 6 month's treatment using either a strategy of beta cell support/unloading (using liraglutide plus pioglitazone) or one of beta cell rest/protection (using insulin Glargine plus the IL-1 receptor antagonist Anakinra). We will perform hyperglycemic clamps to measure first phase and second phase glucose-stimulated insulin secretion and use arginine stimulation to measure maximal secretory capacity as a surrogate of beta cell mass. We will also use oral glucose tolerance testing to measure integrated physiologic insulin responses including effects on the 2hr glucose reading. These tests will be performed at baseline (after relief of glucose toxicity) and after 3 and 6 months of randomized treatments. All subjects will transition to metformin monotherapy from months 6 to 24 (end of study), and undergo repeat measurements at 12 and 24 months. The treatment Response (magnitude of improvement in first-phase insulin secretion) and Durability (proportion of subjects maintaining improvements in first phase insulin secretion at 24 months greater than their own baseline at randomization) will be evaluated as coprimary endpoints. We will use baseline blood samples from the high and low responders from each of the above endpoints to undertake a biomarker discovery effort using proteomics. A high-throughput LC/MS/MS approach will be used for unbiased discovery and subsequent identification of circulating proteins that are robustly associated with these outcomes. Samples from local subjects will be used in the discovery phase, and samples from across the consortium will be used in the validation phase.

描述（由申请人提供）：该研究将是一个多中心合作项目的一部分，该项目将测试不同的策略，以实现糖尿病前期/早期持久的β细胞保存