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，接受过临床流行病学硕士学位培训，一直致力于以患者为导向的研究领域的学术事业。她现在计划扩大对儿科肥胖和 2 型糖尿病 (T2DM) 的研究兴趣，将其心血管并发症纳入其中。那里 目前缺乏关于青少年最佳血脂水平以及哪些青少年心血管疾病 (CVD) 风险最高的科学证据。 Magge 博士计划在宾夕法尼亚大学心脏病学部的 Daniel Rader 博士和共同导师 Drs.查尔斯·斯坦利和埃米尔·莫勒。该提案的研究计划是一项针对 4 组 12-17 岁青春期青少年的观察性队列研究：瘦对照 (LC)、肥胖胰岛素敏感 (OIS)、肥胖胰岛素抵抗 (OIR) 和肥胖 T2DM (OT2)。这些小组将有助于区分肥胖、胰岛素抵抗和导致高血糖的胰岛素分泌缺陷的影响。该研究的主要目的（横断面）是：1. 比较 4 组的血脂状况，并描绘血脂异常与胰岛素抵抗之间的关系（通过静脉内葡萄糖耐量试验测量），2. 比较所测量的亚临床动脉粥样硬化3. 通过 CIMT 测量，其次通过臂反应性 (FMD) 测量 4 组内皮功能障碍，以确定哪些炎症介质和/或脂肪细胞因子与这些青少年早期动脉粥样硬化（CIMT）的存在相关。次要目标（前瞻性）是一个探索性目标，旨在调查 a.) CIMT 和 FMD 在各组中是否在 2 年内取得进展，以及 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（ CIMT 的变化）。很少有儿科研究使用这些技术，也没有报告肥胖和 T2DM 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、炎症标志物以及非侵入性成像在该人群中的应用方面的专业知识。她的目标是找出那些心血管疾病风险最高的青少年，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 博士成为一名独立、以患者为中心的研究人员。公共卫生相关性：目前儿童肥胖的流行导致了 T2DM 和儿童期代谢综合征，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、T2DM 和血脂异常，他们很可能比现在的成年人早几十年成为罹患 CVD 的危险人群。这将造成巨大的人员伤亡和公共卫生负担。儿科医生在儿童时期学会应对这种风险至关重要。