Metabolic Syndrome--Prepubertal African Amer./Caucasian

代谢综合症——青春期前的非洲裔美国人/白种人

• 批准号: 6875955
• 负责人: MELINDA S SOTHERN
• 金额: $ 39.79万
• 依托单位: LSU HEALTH SCIENCES CENTER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-16 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6875955
• 关键词: African American; adipose tissue; bioenergetics; biomarker; blood pressure; body composition; calorimetry; cardiovascular disorder risk; caucasian American; clinical research; diabetes risk; glucose tolerance test; human birth weight; human puberty; insulin sensitivity /resistance; liver; metabolic syndrome; middle childhood (6-11); noninsulin dependent diabetes mellitus; nuclear magnetic resonance spectroscopy; racial /ethnic difference; striated muscles; triglycerides

DESCRIPTION (provided by applicant): Recent research indicates that the metabolic syndrome develops during childhood and is associated with several early risk factors including low (<= 10th percentile body mass index [BMI-USCDC]) or high (>= 90th percentile [BMI-USCDC]) birth weight. However, markers that precede the syndrome and mechanisms that explain these relationships have yet to be identified. These mechanisms may originate in the intrauterine environment, be exacerbated in susceptible populations, such as African Americans and, be further promoted by an early "obesigenic" environment. Thus, we propose that young African American children with low or high birth weight may be predisposed genetically and behaviorally to the early manifestation of subtle, non-symptomatic metabolic abnormalities that work synergistically to create a metabolic syndrome phenotype. The metabolic abnormalities increasing the propensity to type 2 diabetes may originate earlier than previously proposed. In adults insulin sensitivity is correlated negatively with lipid depots in the skeletal muscle (intramyocellular lipids = IMCL) and in the liver long before the development of diabetes. Noninvasive techniques for examining the relationship of skeletal muscle and liver lipids to insulin sensitivity have not been applied to prepubertal African American youth. How early and to what extent metabolic abnormalities occur in children and whether it is more prevalent in African American vs. Caucasian children are unknown. We therefore propose to: 1) Explore the potential markers and mechanisms of impaired insulin sensitivity in pre-pubertal (7-9 years) African American and Caucasian children with low or high birth weight. 2) Determine the relationship of birth weight and ethnicity to insulin sensitivity in these youth. We aim to explore potential markers and mechanisms of the impaired insulin sensitivity observed in 7-9 y prepubertal children by examining the relationships between insulin sensitivity and ectopic fat deposition i.e. triglyceride content in skeletal muscle and liver, abdominal fat (independent of ectopic fat), resting energy metabolism (REE and respiratory quotient [RQ] [fat oxidation] and cardiovascular disease risk factors lipid profiles and blood pressure). Insulin Sensitivity will be measured by Frequently Sampled Intravenous Glucose Tolerance Test (FSIGTT), triglyceride contents in skeletal muscle and liver by Nuclear Magnetic Resonance pectroscopy (ill-MRS) and energy metabolism by ventilated hood indirect calorimetry. A secondary aim is to examine he relationship of birth weight and ethnicity (African American vs. Caucasian) to insulin sensitivity in children, 7-9 years (with and without adjusting for total body fat and/or ectopic fat).

描述(由申请人提供)：最近的研究表明，代谢综合征在儿童时期发展，并与几个早期风险因素有关，包括低(=10%体重指数[BMI-USCDC])或高(&gt；=第90%[BMI-USCDC])出生体重。然而，先于综合征的标志物和解释这些关系的机制尚未确定。这些机制可能起源于宫内环境，在易感人群中加剧，如非裔美国人，并被早期的“顺从”环境进一步促进。因此，我们认为，出生体重低或高的年轻非裔美国儿童可能在基因和行为上倾向于早期表现出微妙的、无症状的代谢异常，这些异常协同作用产生代谢综合征表型。增加2型糖尿病倾向的代谢异常可能比先前提出的更早开始。在成人中，胰岛素敏感性与骨骼肌(肌细胞内脂肪=IMCL)和肝脏中的脂类储存量呈负相关，而远在糖尿病发生之前。检查骨骼肌和肝脏脂肪与胰岛素敏感性关系的非侵入性技术尚未应用于青春期前的非裔美国青年。新陈代谢异常在儿童中发生的时间有多早，程度有多大，是否在非裔美国人儿童中比白人儿童中更普遍，目前尚不清楚。因此，我们建议：1)探索青春期前(7-9岁)出生体重低或高的非裔美国人和高加索儿童胰岛素敏感性受损的潜在标志物和机制。2)确定这些青年的出生体重和种族与胰岛素敏感性的关系。我们旨在通过研究胰岛素敏感性与异位脂肪沉积的关系，即骨骼肌和肝脏中的甘油三酯含量、腹部脂肪(与异位脂肪无关)、静息能量代谢(REE和呼吸商[RQ][脂肪氧化]以及心血管疾病危险因素脂谱和血压)之间的关系，来探索7-9岁青春期前儿童胰岛素敏感性受损的潜在标志和机制。胰岛素敏感性测定采用频繁静脉葡萄糖耐量试验(FSIGTT)，骨骼肌和肝脏甘油三酯含量测定采用核磁共振波谱分析(ILL-MRS)，能量代谢测定采用通风罩间接量热法。第二个目标是研究出生体重和种族(非裔美国人与高加索人)与7-9岁儿童胰岛素敏感性的关系(调整和不调整身体总脂肪和/或异位脂肪)。