Obesity, Metabolic Syndrome, Meal-Related Glycemia

肥胖、代谢综合征、膳食相关血糖

• 批准号: 7211658
• 负责人: Barry E. Hurwitz
• 金额: $ 74.93万
• 依托单位: UNIVERSITY OF MIAMI CORAL GABLES
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-02-01 至 2011-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7211658
• 关键词: Adipose tissue; Age; Blood Vessels; Calories; Cardiac; Cardiovascular system; Central obesity; Condition; Coronary heart disease; Data; Development; Devices; Diagnosis; Diagnostic; Elevation; Enrollment; Ethnic Origin; Exercise stress test; Exhibits; Fasting; Fatty acid glycerol esters; Functional disorder; Glucose; Grouping; Hour; Hyperinsulinism; Individual; Insulin; Insulin Resistance; Left Ventricular Mass; Link; Literature; Measures; Mediator of activation protein; Metabolic; Metabolic syndrome; Methodology; Modeling; Nonesterified Fatty Acids; OGTT; Obesity; Overweight; Pathogenesis; Patients; Persons; Plasma; Regulation; Relative (related person); Research; Research Design; Research Personnel; Risk; Role; Stress; Structure; Sum; Technology; Testing; Thick; Time; Vasodilation; Visceral; Visit; Weight; Woman; Work; arterial stiffness; brachial artery; cardiovascular risk factor; cohort; day; design; heart disease risk; high risk men; indexing; insulin sensitivity; reactive hyperemia; sex; subcutaneous; Adipose tissue; Age; Blood Vessels; Calories; Cardiac; Cardiovascular system; Central obesity; Condition; Coronary heart disease; Data; Development; Devices; Diagnosis; Diagnostic; Elevation; Enrollment; Ethnic Origin; Exercise stress test; Exhibits; Fasting; Fatty acid glycerol esters; Functional disorder; Glucose; Grouping; Hour; Hyperinsulinism; Individual; Insulin; Insulin Resistance; Left Ventricular Mass; Link; Literature; Measures; Mediator of activation protein; Metabolic; Metabolic syndrome; Methodology; Modeling; Nonesterified Fatty Acids; OGTT; Obesity; Overweight; Pathogenesis; Patients; Persons; Plasma; Regulation; Relative (related person); Research; Research Design; Research Personnel; Risk; Role; Stress; Structure; Sum; Technology; Testing; Thick; Time; Vasodilation; Visceral; Visit; Weight; Woman; Work; arterial stiffness; brachial artery; cardiovascular risk factor; cohort; day; design; heart disease risk; high risk men; indexing; insulin sensitivity; reactive hyperemia; sex; subcutaneous

DESCRIPTION (provided by applicant): Individuals who are overweight or obese not only constitute a group who are at increased risk for coronary heart disease (CHD) but also display features of Metabolic Syndrome (MSX) and diminished endothelial vasodilatory function many years prior to their normal-weighted counterparts. In our studies of at-risk and healthy cohorts, we have observed that central obesity is a primary predictor of insulin and glucose metabolic dysregulation and is linked with diminished vasodilatory function, an early indicator of CHD risk. The literature has focused more on insulin resistance as the primary deficit in MSX but there is a growing body of evidence that suggests that glycemic dysregulation, as indexed by postprandial indicators, may be independently predictive of GHD risk and vascular dysfunction. Although methodology was previously unavailable, the development of a device to continuously measure glucose levels has now been introduced that would permit assessments of meal-related glycemic regulation over prolonged periods of time and under various conditions. The primary objective of the proposed research is to use this technology, systematically manipulate glucose content of meals over the course of a two-day in-patient visit, and then as function of CHD risk status examine indices of meal-related glycemic functioning and its impact on vascular functioning, in the context of postprandial metabolic mediators i.e., insulinemia, triglyceridemia and free fatty acids. The study will enroll 281 (of 400 screened) persons to obtain complete data on 184 subjects. We will compare 92 high risk men and women who meet MSX diagnostic criteria and have body mass > 25 kg/m2 with 92 low risk age-, sex- and ethnicity-matched individuals who do not have MSX (as per NCEP ATP III criteria) and whose body mass is ¿ 25 kg/m2. Subjects will be screened with an exercise stress test and will have no diagnosed cardiovascular conditions. The study will include two contiguous 24 hour periods of in-patient stay. Subjects will have an oral glucose tolerance test (OGTT) and 4 meals/day of equivalent caloric content but the glucose content will be manipulated such that on one day the glucose content will be 300 calories/meal (as in an OGTT) and the other day the glucose content will be 600 calories/meal. The order of low and high glucose load days will be counterbalanced across subjects. Measures of metabolic mediators will be derived following overnight fasts, OGTTs, and meals for the low and high caloric days. Echocardiographic measures of carotid intimal media thickness and cardiac structure and function will be obtained as well as measures of endothelial-dependent vasodilatory function and arterial stiffness (using the brachial artery reactive hyperemia test before and 1 hour after meals). A measure of insulin sensitivity will be derived using a euglycemic hyperinsulinemia clamp. Measures of central obesity (waist girth, and CT measures of visceral adipose mass, subcutaneous adipose mass) will also be obtained. In sum, the study postulates that high risk overweight and obese persons with MSX relative to low risk controls will exhibit greater meal-related glycemic dysregulation that worsens over the day and worsens with increasing glucose load; more corresponding meal-related decrease in vasodilatory function and enhancement of arterial stiffness will be predicted. This research is an essential step toward understanding in persons with MSX the role of postprandial glycemic regulation in accelerated CHD pathogenesis.

描述（由适用提供）：超重或肥胖的个体不仅构成了一个冠心病风险增加的群体，而且还构成了代谢综合征（MSX）的特征，并且在其正常发球局正常的对抗方面显示了多年来的内皮血管舒张功能。在我们对处于危险和健康队列的研究中，我们观察到中枢性肥胖是胰岛素和葡萄糖代谢失调的主要预测指标，并且与血管舒张功能减少有关，血管舒张功能是CHD风险的早期指标。文献更多地集中于MSX中的胰岛素抵抗，但越来越多的证据表明，如餐后指标所索引的血糖失调可能可以独立地预测GHD风险和血管功能障碍。尽管以前无法使用方法，但现在已经引入了连续测量的葡萄糖水平的设备的开发，该设备将允许在各种条件下的长时间内评估与膳食相关的血糖调节。拟议的研究的主要目的是在为期两天的住院访问过程中使用该技术，系统地操纵餐食的葡萄糖含量，然后作为与餐后代谢中介体的上下文中的CHD风险状态检查指标的功能，以及其对血管功能的影响及其对血管功能的影响。该研究将招募281名（400名筛选）的人，以获取有关184名受试者的完整数据。我们将比较符合MSX诊断标准的92个高风险男性和女性，其体重> 25 kg/m2，其中92个低风险年龄，性别和族裔匹配的人（根据NCEP ATP III标准），其体重为25 kg/m2。受试者将通过运动压力测试对受试者进行筛查，并且不会具有诊断性心血管疾病。该研究将包括两个连续的24小时住院期间。受试者将进行口服葡萄糖耐受性测试（OGTT）和4顿饭/天的同等热量含量，但葡萄糖含量将被操纵，以便有一天，葡萄糖含量将为300卡路里/餐（如OGTT所示），而另一天，葡萄糖含量将为600卡路里的餐/餐。低葡萄糖负载天数的顺序将在受试者之间平衡。在低热量和高热量的日子里，将遵循隔夜禁食，OGTT和餐点的代谢介体的度量。将获得颈动脉内膜培养基厚度和心脏结构和功能的超声心动图测量，以及对内皮依赖性血管舒张功能和动脉僵硬度的测量（使用臂动脉反应性高血症测试和进餐后1小时）。使用葡萄糖高胰岛素血症夹将得出胰岛素敏感性的测量。还将获得中央肥胖症的测量（腰围和内脏脂肪质量的CT测量值，皮下脂肪质量）。总而言之，这项研究假设，相对于低风险控制，具有MSX的高风险超重和肥胖的人会暴露于与膳食相关的血糖失调，这一天会恶化，并且随着葡萄糖负荷的增加而恶化。将预测血管舒张功能和动脉刚度的增强相对相应的相关降低。这项研究是了解与MSX人的重要一步，餐后血糖调节在加速的CHD发病机理中的作用。