Metabolic Syndrome Following Transplant for Leukemia

白血病移植后的代谢综合征

• 批准号: 7276060
• 负责人: KEVIN S BAKER
• 金额: $ 42.08万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-15 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7276060
• 关键词: Acute leukemia; Address; Adolescent; Adult; Adverse effects; Age; Allogenic; Autologous; Behavioral; Blood Pressure; Blood Vessels; Body mass index; Cardiovascular Diseases; Cardiovascular Physiology; Cardiovascular system; Cell Transplants; Central obesity; Child; Childhood; Cholesterol; Chronic; Clinical; Controlled Study; Cranial Irradiation; Data; Development; Diet; Dietary intake; Disease; Dose; Dyslipidemias; Electromagnetic Energy; Exposure to; Fasting; Frequencies; Funding; Gender; Glucocorticoids; Glucose; Glucose Intolerance; Growth; Hematologic Neoplasms; Hematopoietic; High Dose Chemotherapy; Hypertension; Impairment; Incidence; Individual; Inflammatory; Insulin; Insulin Resistance; Interleukin-6; Intervention; Late Effects; Length; Leptin; Lipids; Malignant - descriptor; Malignant Childhood Neoplasm; Measurement; Measures; Mediating; Mediator of activation protein; Mentored Clinical Oncology Award; Mentored Clinical Scientist Award; Mentored Patient-Oriented Research Career Development Award; Metabolic syndrome; Modality; Neuraxis; Non-Insulin-Dependent Diabetes Mellitus; Non-Malignant; Obesity; Participant; Pattern; Pharmacotherapy; Physical activity; Prevention; Proteins; Radiation; Research; Research Personnel; Risk; Risk Factors; Scanning; Serum; Survivors; Therapeutic; Thick; Time; Transplantation; Treatment Protocols; Tumor Necrosis Factor-alpha; Tumor Necrosis Factors; Vasodilation; Whole-Body Irradiation; adipokines; adiponectin; cancer therapy; cardiovascular risk factor; chemotherapy; cysteine rich protein; cytokine; day; design; follow-up; graft vs host disease; growth hormone deficiency; human TNF protein; intima media; leukemia; low density lipoprotein triglyceride; mortality; normal aging; programs; radiation effect; sex; young adult

DESCRIPTION (provided by applicant): Adult survivors of acute leukemia in childhood have a higher than expected frequency of obesity early mortality from cardiovascular disease, and an increased risk for the metabolic syndrome (MS), and this may be more common in individuals who received hematopoietic cell transplant (HCT) as part of their therapy. The major objective of this research is to evaluate the relationship between HCT specific treatment exposures and the development of insulin resistance and the MS in adolescent and young adult survivors after HCT for treatment of hematologic malignancies in childhood, and this application is the result of the successful progression of Dr. Baker's recent K23 award, funded to study late effects in survivors after HCT. The specific aims of this proposal are: 1) to measure insulin resistance (IR, euglycemic insulin clamp) serum insulin, glucose, and lipids; to obtain blood pressure, and anthropometric measurements; and DEXA scans in 190 survivors of HCT and 190 controls; 2) evaluate the association of specific HCT treatments exposures with the development of the MS; 3) to measure cytokines, CRP and adipokines; 4) to measure early signs of impaired endothelial function and sub-clinical cardiovascular disease; and 5) to obtain measures of dietary intake and physical activity in HCT survivors and controls. These data will address the hypotheses that a) HCT survivors will be more IR, and that IR will increase independent of age with longer follow-up after HCT, b) specific HCT treatment exposures will be associated with growth hormone deficiency and higher degrees of IR, c) allogeneic HCT will be associated with higher levels of inflammatory mediators associated with IR, d) vascular measurements of sub-clinical cardiovascular changes will be higher in survivors with MS and will be associated with total body irradiation exposure (TBI), e) HCT survivors will be less physically active and this will be correlated with exposure to TBI and with having had graft vs. host disease. This research offers a significant and exciting opportunity to explore a potentially modifiable late effect of childhood cancer treatment, the MS and the associated heightened risk for premature cardiovascular disease and type 2 diabetes. Since HCT is a widely applied therapeutic modality for leukemia as well as many other malignant and non-malignant diseases in children and adults with thousands of individuals worldwide every year becoming survivors, it is an increasingly important group to study.

描述（由申请人提供）：儿童期急性白血病的成年幸存者因心血管疾病而早期死亡的肥胖频率高于预期，并且代谢综合征 (MS) 的风险增加，这在接受造血细胞移植 (HCT) 作为治疗一部分的个体中可能更为常见。这项研究的主要目的是评估 HCT 特异性治疗暴露与青少年和年轻成人幸存者在 HCT 治疗儿童期血液恶性肿瘤后胰岛素抵抗和 MS 的发展之间的关系，这项申请是 Baker 博士最近 K23 奖成功进展的结果，该奖项资助研究 HCT 后幸存者的后期影响。该提案的具体目标是：1）测量胰岛素抵抗（IR，正常血糖胰岛素钳）血清胰岛素、葡萄糖和血脂；获取血压和人体测量值；对 190 名 HCT 幸存者和 190 名对照者进行 DEXA 扫描； 2) 评估特定 HCT 治疗暴露与 MS 发展的关联； 3) 测量细胞因子、CRP和脂肪因子； 4) 测量内皮功能受损和亚临床心血管疾病的早期迹象； 5) 获取 HCT 幸存者和对照者的饮食摄入和体力活动测量结果。这些数据将提出以下假设：a) HCT 幸存者的 IR 会更高，并且随着 HCT 后随访时间的延长，IR 的增加将与年龄无关，b) 特定的 HCT 治疗暴露将与生长激素缺乏和更高程度的 IR 相关，c) 异基因 HCT 将与与 IR 相关的炎症介质水平升高相关，d) MS 幸存者的亚临床心血管变化的血管测量值将更高 并且与全身辐射暴露（TBI）相关，e) HCT 幸存者的体力活动较少，这将与 TBI 暴露以及患有移植物抗宿主病相关。这项研究提供了一个重要且令人兴奋的机会来探索儿童癌症治疗的潜在可改变的晚期效应、MS 以及相关的早发心血管疾病和 2 型糖尿病风险增加。由于 HCT 是一种广泛应用于儿童和成人白血病以及许多其他恶性和非恶性疾病的治疗方式，全世界每年有数千人成为幸存者，因此它是一个越来越重要的研究群体。