IS NON-DIABETIC FASTING HYPERGLYCEMIA EXPLAINED BY IMPAIRED GLUCOSE UPTAKE

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者的研究机构。 目的：评估非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贡献。 研究报告：将采用两步高血糖钳夹直接测量胰岛素非依赖性葡萄糖摄取，并根据ADA标准在三组受试者中进行比较：（i）20例NFG和NGT受试者;（ii）20例单纯IGT受试者;（iii）20例IFG受试者。 方法：胰岛素非依赖性葡萄糖摄取将用氚标记葡萄糖的两步高血糖钳夹法测量。 整个研究期间将输注氚化葡萄糖，以测量肝葡萄糖生成。 将输注生长抑素以实现胰腺钳夹。 将替换基础胰岛素和胰高血糖素。 血糖将分两步升高，每步90分钟（例如，从~100到225，然后是350）。 胰岛素非依赖性葡萄糖摄取将计算为葡萄糖输注速率和内源性葡萄糖产生的总和。 临床相关性：T2 DM是一种常见的代谢性疾病，与高发病率和死亡率相关。 高血压是微血管并发症（例如失明、肾衰竭和神经病）的主要风险因素。 空腹高血糖是2型糖尿病患者血糖负荷的主要因素。 更好地了解导致空腹高血糖的机制将有助于开发纠正潜在致病性紊乱的治疗方法，从而预防糖尿病并发症。 重要的是，患有孤立性IFG的受试者发生T2 DM的风险增加。 针对空腹高血糖的有效治疗可有效预防IFG向T2 DM的转化。

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.