IS NON-DIABETIC FASTING HYPERGLYCEMIA EXPLAINED BY IMPAIRED GLUCOSE UPTAKE

非糖尿病空腹高血糖是由葡萄糖摄取受损解释的吗

• 批准号: 7718703
• 负责人: RALPH A DEFRONZO
• 金额: $ 0.06万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7718703
• 关键词: Blindness; Complications of Diabetes Mellitus; Computer Retrieval of Information on Scientific Projects Database; Diabetic Angiopathies; Fasting; Funding; Glucagon; Glucose; Grant; Hepatic; Hyperglycemia; IFNG gene; Infusion procedures; Institution; Insulin; Kidney Failure; Measures; Metabolic Diseases; Morbidity - disease rate; Neuropathy; Non-Insulin-Dependent Diabetes Mellitus; Pancreas; Plasma; Range; Rate; Research; Research Personnel; Resources; Risk; Risk Factors; Somatostatin; Source; Sum; United States National Institutes of Health; basal insulin; clinically relevant; glucose production; glucose uptake; mortality; non-diabetic; prevent; therapy development

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. OBJECTIVE: To assess the contribution of decrease in insulin independent glucose uptake to the rise in fasting hyperglycemia in the non-diabetic range. RESEARCH PLAN: Insulin independent glucose uptake will be directly measured with two step hyperglycemic clamp and compared among three groups of subjects: (i) 20 subjects with NFG and NGT; (ii) 20 subjects with isolated IGT; and (iii) 20 subjects with IFG, according to ADA criteria. METHODS: Insulin independent glucose uptake will be measured with two step hyperglycemic clamp with tritiated glucose. Tritiated glucose will be infused throughout the study to measure hepatic glucose production. Somatostatin will be infused to achieve pancreatic clamp. Basal insulin and glucagon will be replaced. Plasma glucose will be raised in two steps, 90 minutes each (for eg. from ~100 to 225 and then 350). Insulin independent glucose uptake will be calculated as the sum of glucose infusion rate and endogenous glucose production. CLINICAL RELEVANCE: T2DM is a common metabolic disorder that is associated with high morbidity and mortality. Hyperglycemia is the principal risk factor for microvascular complications (e.g. blindness, kidney failure, and neuropathy). Fasting hyperglycemia is the major contributor to glycemic load in subjects with type 2 diabetes. Better understanding of the mechanisms which contribute to fasting hyperglycemia will aid in the development of therapies which correct the underlying pathogenic disturbance and thereby prevent diabetic complications. Importantly, subjects with isolated IFG are at increased risk for developing T2DM. Effective therapies which target fasting hyperglycemia could be effective in preventing the conversion from IFG to T2DM.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 目的：评估胰岛素独立葡萄糖摄取减少对非糖尿病范围内禁食高血糖的升高的贡献。 研究计划：胰岛素独立的葡萄糖摄取将以两个步骤高血糖夹的直接测量，并在三组受试者中进行比较：（i）20名NFG和NGT的受试者； （ii）20名孤立IGT受试者； （iii）根据ADA标准，有20名IFG受试者。 方法：胰岛素独立的葡萄糖摄取将用两个步骤高血糖夹和triatied葡萄糖进行测量。 在整个研究过程中将注入Trititiated葡萄糖，以测量肝葡萄糖的产生。 生长抑素将被注入以实现胰腺夹。 基础胰岛素和胰高血糖素将被取代。 血浆葡萄糖将以两步升高，每个90分钟（例如，从〜100到225，然后是350）。 胰岛素独立的葡萄糖摄取将计算为葡萄糖输注率和内源性葡萄糖产生的总和。 临床相关性：T2DM是一种常见的代谢疾病，与高发病率和死亡率有关。 高血糖是微血管并发症的主要危险因素（例如失明，肾衰竭和神经病）。 空腹高血糖是2型糖尿病患者血糖负荷的主要因素。 更好地了解有助于禁食高血糖的机制将有助于开发纠正潜在的致病性障碍并防止糖尿病并发症的疗法。 重要的是，具有孤立IFG的受试者患T2DM的风险增加。 靶向禁食高血糖的有效疗法可以有效防止从IFG转化为T2DM。