Vitamin D and Vascular Function in Obese Children

肥胖儿童的维生素 D 和血管功能

• 批准号: 8436909
• 负责人: KUMARAVEL RAJAKUMAR
• 金额: $ 70.71万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-02-01 至 2018-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8436909
• 关键词: 18 year old; 19 year old; 25-hydroxyvitamin D; Adult; Affect; Blood Glucose; Blood Pressure; Blood Vessels; Body fat; Calcium; Cardiovascular Diseases; Cardiovascular system; Child; Childhood; Cholecalciferol; Clinical; Counseling; Diet; Dose; Down-Regulation; Dual-Energy X-Ray Absorptiometry; Exhibits; Fasting; Functional disorder; Health; High Density Lipoprotein Cholesterol; High Prevalence; Homeostasis; Hyperglycemia; Hypertension; Hypertriglyceridemia; Immune; Inflammation; Inflammation Mediators; Inflammatory; Insulin; Insulin Resistance; Intake; Interleukin-6; Leptin; Life; Life Style; Masks; Measures; Mediating; Metabolic; Metabolic syndrome; Metabolism; Modeling; Monitor; Nitric Oxide; Nutritional; Obesity; Outcome; Outcome Measure; Overweight; Participant; Physiologic pulse; Population; Prevention strategy; Primary Prevention; Process; Public Health; Randomized; Risk; Risk Factors; Safety; Serum; Supplementation; TNF gene; Testing; Time; Triglycerides; Tumor Necrosis Factor-alpha; United States; Vasodilation; Vitamin D; Vitamin D Deficiency; Vitamin Deficiency; Work; adipokines; adiponectin; aged; arterial stiffness; atherogenesis; attenuation; brachial artery; cardiovascular disorder risk; double-blind placebo controlled trial; efficacy testing; fasting glucose; high risk; human TNF protein; improved; inflammatory marker; innovation; insight; insulin sensitivity; obesity in children; primary outcome; prognostic; public health relevance; response; waist circumference

DESCRIPTION (provided by applicant): Vitamin D deficiency is emerging as an independent risk factor for subclinical vascular dysfunction, metabolic syndrome, and later cardiovascular disease (CVD) in children. Obese children (BMI 95th percentile) and overweight children (BMI 85th-94th percentile) exhibit CVD risk factors and a relatively high prevalence of hypovitaminosis D, and their atherogenic risks track from childhood to adulthood. Therefore, vitamin D replenishment in vitamin D-deficient obese and overweight children has the potential to improve their cardiometabolic health and reduce their risk of CVD later in life. In this proposa, we will test the central hypothesis that enhancement of vitamin D status in such children will improve their vascular health and their CVD and metabolic syndrome risk profile. Our primary objective is to determine, in obese and overweight children aged 10 to 18 years with vitamin D deficiency (defined as serum 25-hydroxyvitamin D <20 ng/mL), the efficacy of enhanced vitamin D3 supplementation in improving vascular endothelial function, arterial stiffness, insulin sensitivity, and metabolic syndrome risk status; and to assess whether these effects are dose- dependent. As a secondary objective, we will examine the vitamin D supplementation-induced effect on adipokines and inflammatory markers relevant to CVD risk. In a double-masked, controlled trial, we will randomize 252 eligible children to receive either 600 IU (conventional supplementation), or 1000 IU or 2000 IU (enhanced supplementation) of vitamin D3 daily for 6 months. Study outcome measures, assessed at baseline, 3 and 6 months, will include (1) brachial artery flow-mediated dilation (FMD) as a measure of vascular endothelial function; (2) pulse wave velocity as a measure of arterial stiffness; (3) surrogate estimates of insulin sensitivity (fasting glucose/fasting insulin ratio or Homeostasis Model of Assessment - Insulin Resistance [HOMA-IR]); (4) metabolic syndrome risk factors (blood pressure, waist circumference, HDL cholesterol, triglycerides, and fasting blood glucose); (5) inflammatory markers (e.g. CRP, IL-6, TNF-alpha); (6) adipokines (leptin and adiponectin); and (7) nitric oxide metabolites. Brachial FMD at 6 months will be the primary outcome measure. We will assess the safety of enhanced vitamin D3 supplementation by measuring serum calcium at the 3- and 6-month-follow-ups. Total body fat will be ascertained by Dual-energy X-ray Absorptiometry to examine the confounding effects of adiposity on outcome measures. Innovative aspects of this proposal include (1) characterizing the temporal changes in vascular health and cardiometabolic risk outcomes in response to enhancement of vitamin D status in a population of children at high-risk for vascular dysfunction and cardiometabolic risks; and (2) delineating the vitamin D effects on inflammatory markers and adipokines relevant to CVD risk. Establishing the protective benefits of vitamin D would have major public health importance, since optimization of vitamin D status would be an inexpensive primary prevention strategy for improving cardiometabolic health during childhood and for reducing CVD risk during adulthood.

描述（由申请人提供）：维生素D缺乏正在成为亚临床血管功能障碍、代谢综合征和儿童心血管疾病（CVD）的独立风险因素。肥胖儿童（BMI第95百分位数）和超重儿童（BMI第85 - 94百分位数）表现出CVD危险因素和相对较高的维生素D缺乏症患病率，其致动脉粥样硬化的风险从儿童期到成年期一直存在。因此，维生素D缺乏的肥胖和超重儿童补充维生素D有可能改善他们的心脏代谢健康，并降低他们以后患CVD的风险。在本提案中，我们将检验中心假设，即增强这些儿童的维生素D状态将改善他们的血管健康及其CVD和代谢综合征风险状况。我们的主要目的是确定在患有维生素D缺乏症（定义为血清25-羟基维生素D <20 ng/mL）的10至18岁肥胖和超重儿童中，增强维生素D3补充剂在改善血管内皮功能、动脉僵硬度、胰岛素敏感性和代谢综合征风险状态方面的疗效;并评估这些效果是否具有剂量依赖性。作为次要目的，我们将研究维生素D摄入对脂肪因子和与CVD风险相关的炎症标志物的影响。在一项双盲对照试验中，我们将252名符合条件的儿童随机接受600 IU（常规补充剂）或1000 IU或2000 IU（增强补充剂）的维生素D3每日6个月。在基线、3个月和6个月时评估的研究结局指标将包括（1）肱动脉血流介导的扩张（FMD），作为血管内皮功能的指标;（2）脉搏波速度，作为动脉僵硬度的指标;（3）胰岛素敏感性的替代估计值（空腹血糖/空腹胰岛素比值或稳态评估模型-胰岛素抵抗[HOMA-IR]）;（4）代谢综合征危险因素（血压、腰围、HDL胆固醇、甘油三酯和空腹血糖）;（5）炎症标志物（例如CRP、IL-6、TNF-α）;（6）脂肪因子（瘦素和脂联素）;和（7）一氧化氮代谢物。6个月时的肱FMD将是主要结局指标。我们将通过在3个月和6个月随访时测量血清钙来评估增强维生素D3补充剂的安全性。将通过双能X线吸收测定法确定总体脂，以检查肥胖对结局指标的混杂影响。该提案的创新方面包括：（1）表征血管健康和心脏代谢风险结果的时间变化，以响应血管功能障碍和心脏代谢风险高风险儿童人群中维生素D状态的增强;（2）描述维生素D对与CVD风险相关的炎症标志物和脂肪因子的影响。确定维生素D的保护性益处将具有重大的公共卫生重要性，因为维生素D状况的优化将是一种廉价的初级预防策略，可改善儿童期的心脏代谢健康，并降低成年期的CVD风险。