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Dyslipidemia and CV Risk Factors in Pediatric Obesity and Type 2 Diabetes

儿童肥胖和 2 型糖尿病中的血脂异常和心血管危险因素

基本信息

批准号：
7857956
负责人：
SHEELA NATESH MAGGE
金额：
$ 15.67万
依托单位：
CHILDREN'S HOSP OF PHILADELPHIA
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-15 至 2012-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7857956
关键词：
Address Adolescence Adolescent Adult Adverse effects Age Area Atherosclerosis Award Cardiology Cardiovascular Diseases Cardiovascular system Carotid Atherosclerotic Disease Cell Adhesion Cell Adhesion Molecules Child Childhood Cohort Studies Cross-Sectional Studies Data Defect Disease Dyslipidemias Endocrinologist Epidemic Fasting Functional disorder Future Goals High Density Lipoprotein Cholesterol Human Hyperglycemia Hypertriglyceridemia Image Imaging Techniques Individual Inflammation Mediators Inflammatory Injury Insulin Insulin Resistance LDL Cholesterol Lipoproteins Learning Lipids Low-Density Lipoproteins Master&apos s Degree Measures Mediating Mentors Mentorship Metabolic Metabolic syndrome Methods Non-Insulin-Dependent Diabetes Mellitus Obesity Pattern Pediatrics Pennsylvania Physiological Plasma Population Population Study Populations at Risk Process Production Puberty Public Health Relative (related person)Reporting Research Research Personnel Research Proposals Risk Risk Factors Sampling Staging Surrogate Markers Techniques Thick Training Triglycerides Universities adipokines brachial artery cardiovascular disorder risk career clinical epidemiology comparison group cytokine experience inflammatory marker insulin sensitivity interest intima media intravenous glucose tolerance test non-diabetic obesity in children patient oriented patient oriented research pediatrician prospective public health relevance treatment trial

项目摘要

DESCRIPTION (provided by applicant): Dr. Sheela N. Magge is a pediatric endocrinologist with Masters degree training in Clinical Epidemiology, who has shown a sustained commitment to an academic career in patient-oriented research. She now plans to extend her research interests in pediatric obesity and type 2 diabetes (T2DM) to include their cardiovascular complications. There is a current dearth of scientific evidence as to what optimal lipid levels are in adolescents, and which adolescents are at the highest cardiovascular disease (CVD) risk. Dr. Magge plans to gain expertise in the area of dyslipidemia and CVD risk in childhood obesity and type 2 diabetes, under the mentorship of Dr. Daniel Rader of the Division of Cardiology at the University of Pennsylvania, and co-mentors, Drs. Charles Stanley and Emile Mohler. The proposal's research plan is an observational cohort study of 4 groups of pubertal adolescents, ages 12-17 years: lean controls (LC), obese insulin sensitive (OIS), obese insulin resistant (OIR), and obese with T2DM (OT2). These groups will help to differentiate between the effects of obesity, insulin resistance, and insulin secretory defects causing hyperglycemia. The primary aims (cross-sectional) of the study are: 1. to compare the lipid profiles of the 4 groups and delineate the relationship between dyslipidemia and insulin resistance (measured by intravenous glucose tolerance test), 2. to compare subclinical atherosclerosis as measured by CIMT, and secondarily, endothelial dysfunction as measured by brachial reactivity (FMD), in the 4 groups, 3. to identify which inflammatory mediators and/or adipocytokines correlate with the presence of early atherosclerosis (CIMT) in these adolescents. The secondary aim (prospective) is an exploratory aim to investigate a.) whether CIMT and FMD progress over 2 years in the groups, and b.) which lipid levels, inflammatory mediators, and/or adipokines best predict the progression of early atherosclerosis (change in CIMT). Few pediatric studies have used these techniques, and none have reported longitudinal CIMT data in obese and T2DM children. Dr. Magge has also developed a comprehensive educational plan during the award period, to gain expertise in dyslipidemia, inflammatory markers, and the use of non-invasive imaging in this population. Her goal is to identify those adolescents at the highest CVD risk, who would benefit from future management and treatment trials. The proposed project will train Dr. Magge for a career as an independent, patient-oriented researcher. Public health relevance: The current epidemic of pediatric obesity, leading to T2DM and the metabolic syndrome during childhood, have made dyslipidemia and the risk of future CVD serious concerns in pediatrics. As more children develop obesity, T2DM, and dyslipidemia, they are likely to become a population at risk for developing CVD decades earlier than adults today. This will represent a tremendous human toll and public health burden. It is vital that pediatricians learn to address this risk during childhood.

描述（由申请人提供）：Sheela N. Magge是一名儿科内分泌学家，拥有临床流行病学硕士学位，他一直致力于以患者为导向的研究。她现在计划扩大她在儿童肥胖和2型糖尿病（T2 DM）的研究兴趣，包括他们的心血管并发症。那里目前缺乏科学证据来确定青少年的最佳血脂水平，以及哪些青少年处于最高的心血管疾病（CVD）风险中。Magge博士计划在宾夕法尼亚大学心脏病科的丹尼尔雷德博士和共同导师查尔斯·斯坦利博士和埃米尔·莫勒博士的指导下，获得儿童肥胖和2型糖尿病中血脂异常和心血管疾病风险领域的专业知识。该提案的研究计划是一项观察性队列研究，包括4组12-17岁的青春期青少年：瘦对照组（LC）、肥胖胰岛素敏感组（OIS）、肥胖胰岛素抵抗组（OIR）和肥胖伴T2 DM组（OT 2）。这些小组将有助于区分肥胖、胰岛素抵抗和胰岛素分泌缺陷引起的高血糖症。本研究的主要目的（横截面）是：1。比较4组血脂水平，并探讨血脂异常与胰岛素抵抗（静脉葡萄糖耐量试验）的关系.比较4组中CIMT测量的亚临床动脉粥样硬化，其次是肱动脉反应性（FMD）测量的内皮功能障碍，3.以确定哪些炎症介质和/或脂肪细胞因子与这些青少年的早期动脉粥样硬化（CIMT）的存在相关。次要目的（前瞻性）是研究a的探索性目的。）各组中CIMT和FMD是否在2年内进展，以及B.）哪种脂质水平、炎症介质和/或脂肪因子最能预测早期动脉粥样硬化的进展（CIMT的变化）。很少有儿科研究使用这些技术，没有报告肥胖和T2 DM儿童的纵向CIMT数据。Magge博士还在获奖期间制定了一项全面的教育计划，以获得血脂异常，炎症标志物以及在该人群中使用非侵入性成像的专业知识。她的目标是确定那些处于最高CVD风险的青少年，他们将从未来的管理和治疗试验中受益。该项目将培养Magge博士成为一名独立的、以患者为导向的研究人员。公共卫生相关性：目前儿童肥胖症的流行，导致儿童时期的T2 DM和代谢综合征，使血脂异常和未来CVD的风险成为儿科的严重问题。随着越来越多的儿童患上肥胖症、T2 DM和血脂异常，他们可能比今天的成年人早几十年成为患CVD的风险人群。这将造成巨大的人员伤亡和公共卫生负担。至关重要的是，儿科医生学会在儿童时期解决这种风险。