Metabolic Syndrome in Childhood Cancer Survivors

由于许多曾经接受过儿童癌症治疗的人进入成年期，临床和流行病学研究现在集中在癌症治疗的一系列长期影响上，以描述和理解“治愈的后果”。有证据表明，儿童癌症幸存者（CCS）患代谢综合征（MS）的风险增加。该综合征由肥胖、胰岛素抵抗、血脂异常和高血压组成，是2型糖尿病和心血管疾病的预测因子。在健康人群中，肥胖在MS的发展中具有核心作用，然而，可以想象，在CCS中，除了肥胖之外，还有其他机制。（例如内分泌异常、暴露于辐射和放射性物质）可能在MS的发展中起关键作用。（通过正葡萄糖胰岛素钳夹）、生长激素缺乏和胰岛素抵抗的其他介质，随着MS和心血管风险的发展，在组分之间的关系变得复杂和疾病发展之前。我们建议研究9-18岁的儿童和青少年样本，他们在诊断后存活了超过5年的儿童癌症，以及他们的健康兄弟姐妹，他们将参加为期2天的临床评估。具体目标是：1）确定CCS中MS的患病率，并与年龄和性别分布相似的健康对照进行比较，2）评估胰岛素抵抗与MS的其他组分和与心血管变化的早期体征的关联，和3）评估肥胖和胰岛素抵抗与生长激素分泌、脂肪因子和炎症介质之间的关系; 4）评估与预防心血管疾病、糖尿病和肥胖相关的健康行为。该提案解决了临床研究的需要，重点关注儿童癌症及其治疗的新发现的不良影响，特别是可预防/可改变的疾病，并将提供有关潜在病因因素和干预途径的新数据。

As many individuals once treated for childhood cancer progress into adulthood, clinical and epidemiologic research is now focusing on an array of long-term effects from cancer treatment to characterize and understand the "consequences of cure". There is evidence to indicate that childhood cancer survivors (CCS) are at increased risk for the metabolic syndrome (MS). The syndrome is composed of obesity, insulin resistance, dyslipidemia and hypertension, and is a predictor of type 2 diabetes and cardiovascular disease. In healthy populations obesity has a central role in the development of the MS, however, it is conceivable that in CCS additional mechanisms other than obesity (e.g. endocrine abnormalities, exposure to radiation and antineoplastic agents) may play a critical role in the development of MS. The major objective of this proposal is to evaluate the relation between insulin resistance (by euglycemic insulin clamp), growth hormone deficiency and other mediators of insulin resistance, with the development of MS and cardiovascular risk early in life, before the relations between the components become complex and disease develops. We propose to study a sample of children and adolescents age 9-18 years, who survived childhood cancer for >5 years after diagnosis, and their healthy siblings, who will participate in a 2 day clinical evaluation. Specific aims are: 1) to determine the prevalence of MS in CCS and compare to healthy controls similar in age and gender distribution, 2) to assess the association of insulin resistance with other components of MS and with early signs of cardiovascular changes, and 3) to assess the relation between obesity and insulin resistance with growth hormone secretion,^adipokines and inflammatory mediators; 4) to evaluate health behaviors related to prevention of cardiovascular disease, diabetes, and obesity. This proposal addresses the need for clinical research focused on newly identified adverse effects of childhood cancer and its treatment, particularly for preventable/modifiable conditions, and will provide new data on potential etiologic factors and avenues for intervention.