Metabolic Syndrome--Prepubertal African Amer./Caucasian

描述（由申请人提供）：最近的研究表明，代谢综合征发生于儿童期，并与几个早期危险因素相关，包括低（<=第10百分位体重指数[BMI-USCDC]）或高（>=第90百分位[BMI-USCDC]）出生体重。然而，在综合征之前的标记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（如非裔美国人）中加剧，并被早期的“肥胖”环境进一步促进。因此，我们提出，出生体重低或高的年轻非裔美国儿童可能在遗传和行为上倾向于早期表现出微妙的、无症状的代谢异常，这些代谢异常协同作用，形成代谢综合征表型。增加2型糖尿病倾向的代谢异常可能比先前提出的更早发生。成人胰岛素敏感性与骨骼肌（细胞内脂质= IMCL）和肝脏中的脂质储存呈负相关，早在糖尿病发生之前。检查骨骼肌和肝脏脂质与胰岛素敏感性关系的无创技术尚未应用于青春期前的非裔美国青年。代谢异常在儿童中发生的时间和程度，以及在非裔美国儿童和白人儿童中是否更普遍，都是未知的。因此，我们建议：1)探索青春期前（7-9岁）低或高出生体重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)确定这些青少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(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]和心血管疾病危险因素血脂和血压）之间的关系，探索7-9岁青春期前儿童胰岛素敏感性受损的潜在标志物和机制。胰岛素敏感性通过频繁采样静脉葡萄糖耐量试验（FSIGTT）测量，骨骼肌和肝脏甘油三酯含量通过核磁共振（ir - mrs）测量，能量代谢通过通风罩间接量热法测量。第二个目的是检查出生体重和种族（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（无论是否调整总脂肪和/或异位脂肪）。

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).