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

• 批准号: 7299340
• 负责人: SHEELA NATESH MAGGE
• 金额: $ 15.81万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-15 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7299340
• 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; Inflammatory; Injury; Insulin; Insulin Resistance; Invasive; LDL Cholesterol Lipoproteins; Learning; Lipids; Low-Density Lipoproteins; Master' s Degree; Measures; Mediating; Mediator of activation protein; 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; Today; Training; Triglycerides; Universities; adipokines; brachial artery; cardiovascular disorder risk; career; clinical epidemiology; comparison group; cytokine; experience; insulin sensitivity; interest; intima media; intravenous glucose tolerance test; non-diabetic; patient oriented; patient oriented research; pediatrician; prospective; treatment trial

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博士是一名儿科内分泌学家，接受了临床流行病学硕士学位培训，他表现出对以患者为导向的研究的学术事业的持续承诺。她现在计划扩大对小儿肥胖症和2型糖尿病（T2DM）的研究兴趣，以包括其心血管并发症。那里 目前缺乏关于青少年最佳脂质水平的科学证据，哪些青少年处于最高的心血管疾病（CVD）风险。 Magge博士计划在儿童肥胖症和2型糖尿病的血脂异常和CVD风险领域中获得专业知识，在宾夕法尼亚大学心脏病学系的Daniel Rader博士的指导下，以及院长Drs。查尔斯·斯坦利（Charles Stanley）和埃米尔·莫勒（Emile Mohler）。该提案的研究计划是对4组青少年的观察队列研究，年龄在12-17岁之间：精益控制（LC），肥胖的胰岛素敏感（OIS），肥胖的胰岛素抵抗（OIR）和肥胖，肥胖（OT2）。这些组将有助于区分肥胖，胰岛素抵抗和引起高血糖的胰岛素分泌缺陷的影响。研究的主要目的（横截面）是：1。比较4组的脂质谱并描绘血脂异常和胰岛素抵抗之间的关系（通过静脉葡萄糖耐受性测试测量），2。进行测量的亚级动脉粥样硬化。通过CIMT，其次是通过臂反应性（FMD）测量的内皮功能障碍，在4组中，3。确定这些青少年在这些青少年中与早期动脉粥样硬化（CIMT）的存在相关的炎性介质和/或脂肪细胞因子。次要目的（前瞻性）是研究a。）CIMT和FMD在两年内以及b。）是否进展，b。）哪些脂质水平，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（更改CIMT）。很少有儿科研究使用这些技术，并且没有人报告肥胖和T2DM儿童的纵向CIMT数据。玛格博士还在颁奖期间制定了一项全面的教育计划，以获得血脂异常，炎症标记和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CVD风险最高的青少年，他们将从未来的管理和治疗试验中受益。拟议的项目将培训Magge博士的职业生涯，是一名独立的，以患者为导向的研究人员。公共卫生相关性：当前的小儿肥胖症流行，导致T2DM和童年时期的代谢综合症，使血脂异常以及未来CVD对儿科的严重关注的风险。随着越来越多的儿童患肥胖症，T2DM和血脂异常，他们可能会比今天的成年人更早地患有CVD数十年的人群。这将代表着巨大的人类损失和公共卫生负担。儿科医生学会在童年时期解决这种风险至关重要。