Insulin Sensitivity in Children with low Birth Weight

描述(申请人提供)：低出生体重与晚年胰岛素敏感性受损有关。这种关系可能是由于宫内发育迟缓，导致代谢紊乱，并最终促进糖尿病，特别是在遗传脆弱的人。然而，这种关系，如果存在的话，在非裔美国人中并没有很好地建立起来。只有一项研究试图研究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(肥胖症在7-9岁反弹)期间进行的。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，并被有利于肥胖的早期环境进一步促进。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容易出现微妙的、无症状的代谢异常的早期表现，这些异常协同作用创造了儿童肥胖症的表型。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出生体重较低的青春期前非裔美国人或高加索青年。在这项研究中，我们建议研究7-9岁的非裔美国人和高加索儿童的出生体重(低体重和正常体重)和种族(非裔美国人和高加索人)与胰岛素敏感性的关系(调整和不调整全身脂肪)。我们将通过研究胰岛素敏感性与异位脂肪沉积(骨骼肌和肝脏中的甘油三酯含量)、腹部脂肪、静息能量代谢(REE和呼吸商[RQ])以及心血管疾病危险因素(血脂和血压)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(1H-MRS)，能量代谢测定采用通风式间接热量法。

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.