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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 目的：评估胰岛素依赖性葡萄糖摄取减少对非糖尿病范围内空腹高血糖升高的影响。 研究计划：将采用两步高血糖钳直接测量胰岛素依赖性葡萄糖摄取，并在三组受试者之间进行比较：（i）20 名患有 NFG 和 NGT 的受试者； (ii) 20名患有孤立性IGT的受试者； (iii) 根据 ADA 标准，20 名 IFG 受试者。 方法：使用氚化葡萄糖的两步高血糖钳夹测量不依赖于胰岛素的葡萄糖摄取。 在整个研究过程中将注入氚化葡萄糖以测量肝葡萄糖的产生。 将注射生长抑素以实现胰腺钳夹。 基础胰岛素和胰高血糖素将被替换。 血浆葡萄糖将分两步升高，每步 90 分钟（例如从约 100 到 225，然后 350）。 不依赖于胰岛素的葡萄糖摄取将计算为葡萄糖输注速率和内源性葡萄糖产量的总和。 临床相关性：T2DM 是一种常见的代谢性疾病，与高发病率和死亡率相关。 高血糖是微血管并发症（例如失明、肾衰竭和神经病变）的主要危险因素。 空腹高血糖是 2 型糖尿病患者血糖负荷的主要原因。 更好地了解导致空腹高血糖的机制将有助于开发纠正潜在致病紊乱的疗法，从而预防糖尿病并发症。 重要的是，患有孤立性 IFG 的受试者患 T2DM 的风险增加。 针对空腹高血糖的有效疗法可有效预防 IFG 向 T2DM 的转化。