Glucose & Lipid Metabolism in Obese Adolescents

葡萄糖

• 批准号: 6865268
• 负责人: Agneta Lisbeth Sunehag
• 金额: $ 47.38万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6865268
• 关键词: Hispanic Americans; adipose tissue; adolescence (12-20); aerobic exercise; bioenergetics; blood tests; clinical research; clinical trials; diabetes risk; dietary lipid; disease /disorder prevention /control; family genetics; gender difference; genetic markers; genetic screening; gluconeogenesis; human subject; human therapy evaluation; insulin sensitivity /resistance; lipid metabolism; liver metabolism; magnetic resonance imaging; muscle metabolism; noninsulin dependent diabetes mellitus; obesity; photon absorptiometry; stable isotope

DESCRIPTION (provided by applicant): Over the past 30 y the prevalence of overweight children (BMI>95th percentile) (6-19 y) in the USA has increased 3-fold to reach 15% in 2000. Concomitant with the increase in childhood overweight, the incidence of type 2 diabetes in children (0-19 y) has increased 4-fold (to account for ~30% of newly diagnosed diabetes). There is a predominance of both obesity and type 2 diabetes in African American and Hispanic adolescents. The rapid increase in obesity and type 2 diabetes in children and adolescents is a major public health concern necessitating effective strategies for treatment and prevention. Exercise is a potentially valuable tool in this battle. Understanding the physiology of the metabolic effects of obesity and the effects of interventions e.g. exercise on glucose metabolism and insulin sensitivity in obese adolescents is a prerequisite in defining strategies for preventing insulin resistance and impaired glucose metabolism, and the development of type 2 diabetes. In this proposal we will use state of the art stable isotope and MRI techniques to measure insulin sensitivity, gluconeogenesis and intracellular fat content in muscle and liver. We will study 96 adolescents of Hispanic heritage with a balanced distribution with regard to obesity/non-obesity and gender. Genetic admixture will be determined using a panel of 35 markers appropriate to determine the proportion of European vs. Indigenous heritage in a Hispanic population. The subjects will be studied prior to a formalized exercise program and after 12 wks of the program. We will determine whether 1) obesity related decrease in insulin sensitivity and increase in gluconeogenesis are associated with increased intracellular fat accumulation in muscle and liver; 2) a formalized exercise program will improve insulin sensitivity and reduce gluconeogenesis; 3) changes in intramyocellular and/or intrahepatic fat are 1 likely mechanisms for exercise induced metabolic improvements; 4) genetic admixture in itself has an impact on insulin sensitivity and gluconeogenesis when the effects of obesity have been taken into account; 5) plasma concentrations of the fat derived protein adiponectin is a robust marker of intracellular fat in muscle and liver. Thus, the information that can be gained by the proposed studies will increase our understanding of the physiological factors leading to insulin resistance and disturbed glucose metabolism in Hispanic obese adolescents, and the mechanisms for exercise induced metabolic effects. This information is likely to lead to identifying factors and potentially new strategies to prevent and/or delay the onset of type 2 diabetes in adolescents.

DESCRIPTION (provided by applicant): Over the past 30 y the prevalence of overweight children (BMI>95th percentile) (6-19 y) in the USA has increased 3-fold to reach 15% in 2000. Concomitant with the increase in childhood overweight, the incidence of type 2 diabetes in children (0-19 y) has increased 4-fold (to account for ~30% of newly diagnosed diabetes).在非裔美国人和西班牙裔青少年中，肥胖和2型糖尿病都占主导地位。儿童和青少年的肥胖和2型糖尿病的迅速增加是需要有效的治疗和预防策略的主要公共卫生问题。锻炼是这场战斗中潜在的有价值的工具。了解肥胖的代谢作用的生理和干预措施的作用，例如肥胖青少年中葡萄糖代谢和胰岛素敏感性的运动是定义预防胰岛素抵抗和葡萄糖代谢受损的策略的先决条件，以及2型糖尿病的发展。在此提案中，我们将使用最先进的同位素和MRI技术来测量肌肉和肝脏中胰岛素敏感性，糖异生和细胞内脂肪含量。我们将研究96名西班牙裔遗产的青少年，并在肥胖/非肥胖和性别方面具有平衡的分布。遗传混合物将使用适当的35个标记面板确定，以确定西班牙裔人口中欧洲与土著遗产的比例。在制定正式的锻炼计划之前和计划12周之后，将对受试者进行研究。我们将确定1）与肥胖相关的胰岛素敏感性降低和糖异生的增加是否与肌肉和肝脏中细胞内脂肪的积累增加有关； 2）正式的运动计划将提高胰岛素敏感性并减少糖异生； 3）细胞内和/或肝内脂肪的变化是一种运动诱导代谢改善的可能机制； 4）当考虑到肥胖的作用时，遗传混合本身会影响胰岛素敏感性和糖异生； 5）脂肪得出的蛋白脂联素的血浆浓度是肌肉和肝脏细胞内脂肪的强大标记。因此，拟议的研究可以获得的信息将增加我们对西班牙裔肥胖青少年胰岛素耐药性和干扰葡萄糖代谢的生理因素的理解，以及运动诱导的代谢作用的机制。这些信息可能会导致识别因素和潜在的新策略，以预防和/或延迟青少年2型糖尿病的发作。