Insulin Sensitivity in Children with low Birth Weight

描述（由申请人提供）：低出生体重与以后生活中胰岛素敏感性受损有关。这种关系可能是由于宫内生长迟缓，导致代谢紊乱，并最终促进糖尿病，特别是在遗传易感个体中。然而，这种关系即使存在，在非裔美国人中也没有很好地建立起来。只有一项研究试图调查14岁以下儿童低出生体重、种族和胰岛素敏感性之间的关系，但没有一项研究是在肥胖发展的关键时期（7-9岁时肥胖反弹）进行的。更重要的是，低出生体重与胰岛素敏感性受损之间的联系机制尚未确定。这些机制可能起源于宫内环境，在易感人群中加剧，并在有利于肥胖的早期环境中进一步促进。我们认为，低出生体重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，形成儿童肥胖表型。增加肥胖和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非侵入性技术尚未应用于青春期前低出生体重的非洲裔美国人或高加索青年。在本研究中，我们建议检查7-9岁非裔美国人和白种人儿童的出生体重（低与正常）和种族（非裔美国人与白种人）与胰岛素敏感性的关系（有无调整体脂）。我们将通过研究胰岛素敏感性与异位脂肪沉积（骨骼肌和肝脏中甘油三酯含量）、腹部脂肪、静息能量代谢（REE和呼吸商[RQ]）和心血管疾病危险因素（血脂和血压）之间的关系，探讨7-9岁青春期前儿童胰岛素敏感性受损的潜在机制。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波谱（1H-MRS）测量，能量代谢通过通风罩间接量热法测量。

DESCRIPTION (provided by applicant): Low birth weight is associated with impaired insulin sensitivity later in life. The relationship may be due to intrauterine growth retardation, which causes metabolic disorders and ultimately promotes diabetes mellitus, especially in genetically vulnerable individuals. However, the relationship, if present, is not well established in African Americans. Only one study has attempted to examine the relationships between low birth weight, ethnicity and insulin sensitivity in children under 14 years of age but, none during the critical period of obesity development (adiposity rebound at 7-9y). More importantly, mechanisms connecting low birth weight to impaired insulin sensitivity have yet to be identified. These mechanisms may originate in the intrauterine environment, be exacerbated in susceptible populations, and be further promoted by an early environment conducive to obesity. We propose that young African American children with low birth weight may be predisposed genetically and behaviorally to the early manifestation of subtle, nonsymptomatic metabolic abnormalities that work synergistically to create a childhood obesity phenotype. The metabolic abnormalities increasing the propensity to obesity and 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. Non-invasive techniques for examining the relationship of skeletal muscle and liver lipids to insulin sensitivity have not been applied to prepubertal African American or Caucasian youth with low birth weight. In this study we propose to examine the relationship of birth weight (low vs. normal) and ethnicity (African American vs. Caucasian) to insulin sensitivity in 7-9 year old African American and Caucasian children (with and without adjusting for total body fat). We will explore potential mechanisms of the impaired insulin sensitivity observed in 7-9 year old prepubertal children by examining the relationships between insulin sensitivity and ectopic fat deposition (triglyceride content in skeletal muscle and liver), abdominal fat, resting energy metabolism (REE and respiratory quotient [RQ]) 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 Spectroscopy (1H-MRS) and energy metabolism by ventilated hood indirect calorimetry.