Cardiovascular disease in Type 1 melitus: Young adults to adolescents

1 型糖尿病中的心血管疾病：年轻人到青少年

• 批准号: 7406752
• 负责人: David Matthew Maahs
• 金额: $ 13.34万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7406752
• 关键词: Adolescent; Adult; Affect; Age; Albumins; Albuminuria; Atherosclerosis; Blood Pressure; Blood Vessels; Cardiovascular Diseases; Central obesity; Child; Childhood; Chronic; Clinical Research; Cohort Studies; Complex; Coronary Arteriosclerosis; Creatinine; Cross-Sectional Studies; Cystatins; Data; Data Analyses; Development; Diabetes Mellitus; Diagnosis; Dose; Dyslipidemias; Electron Beam Tomography; Excretory function; Filtration; Foundations; Functional disorder; Future; Genetic; Glycosylated hemoglobin A; Goals; Grant; Guidelines; Hyperglycemia; Hypertension; Impaired Renal Function; Incidence; Individual; Inflammation; Insulin; Insulin Resistance; Insulin-Dependent Diabetes Mellitus; Intervention; Investigation; Lipoproteins; Low-Density Lipoproteins; Measurement; Measures; Methods; Modality; Modeling; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Participant; Pathogenesis; Patients; Plasma; Play; Population; Primary Prevention; Protocols documentation; Rate; Renal function; Research; Research Personnel; Risk; Risk Factors; Role; Screening procedure; Series; Serum; Staging; Stress; Syndrome; System; Target Populations; Testing; Therapeutic; Training; Translating; Visit; Work; Youth; adiponectin; analytical tool; base; calcification; cardiovascular disorder risk; cardiovascular risk factor; cohort; coronary artery calcification; diabetic; follow-up; indexing; insulin sensitivity; novel; particle; post gamma-globulins; programs; prospective; response; skills; urinary; waist circumference; young adult

DESCRIPTION (provided by applicant): Type 1 Diabetes Mellitus (T1D) affects 1.4 million people in the U.S. and its incidence is increasing by 3- 5% annually. While numerous promising therapeutic modalities are being investigated, currently no cure exists and the patients succumb prematurely to long-term complications, especially coronary artery disease (CAD). Excess risk of CAD seen in T1D is not fully explained by traditional risk factors identified in non-DM individuals and those with type 2 diabetes. Hyperglycemia, hypertension, dyslipidemia, albuminuria, obesity, inflammation, and low adiponectin levels clearly play a role. Insulin resistance may be the primary problem, underlying the above risk factors, but is more difficult to quantify in T1D subjects. In this application, I am proposing a series of studies with the overarching dual goal of acquiring advanced research skills while translating findings and methods of investigation of the pathogenesis of CAD in T1D adults to diabetic children -the ultimate target population for primary prevention. The goal of this training grant is to pursue the following specific aims to develop research skills within the framework of the Coronary Artery Calcification in Type 1 Diabetes (CACTI) Study to test hypotheses specific to this application: 1) to disentangle the inter-relationship between hyperglycemia, kidney function, hypertension, and insulin resistance (defined by visceral obesity, low adiponectin levels and dyslipidemia) in the development of premature CAD using the baseline and follow-up data from the CACTI cohort; 2) To perform euglycemic hyperinsulinemic clamp studies in young adults in CACTI to develop an accurate estimate of insulin sensitivity based on easy to measure traditional and novel markers in T1D subjects; and 3) To establish a cohort of 120 adolescents (ages 12-19) with T1D (n=60) and non-DM (n=60). Formation and analysis of cardiovascular risk factors in this cohort at the Barbara Davis Center for Childhood Diabetes will provide pilot data for a future R01 application. These goals have been identified to translate research on CVD in T1D from young adults to adolescents. Although guidelines for CVD risk factors in adults are established, screening and intervention in adolescents with T1D are either absent or based on extrapolation from adult data. The general hypothesis for this research is that greatly elevated CVD risk factors are present in youth with T1D and screening and treatment thresholds need to be determined.

描述（由申请人提供）： 1 型糖尿病 (T1D) 影响着美国 140 万人，其发病率每年增加 3-5%。尽管正在研究许多有希望的治疗方法，但目前尚无治愈方法，并且患者会过早死于长期并发症，尤其是冠状动脉疾病（CAD）。在非糖尿病个体和 2 型糖尿病患者中发现的传统危险因素并不能完全解释 1 型糖尿病中出现的 CAD 风险过高。高血糖、高血压、血脂异常、蛋白尿、肥胖、炎症和脂联素水平低显然起着一定的作用。胰岛素抵抗可能是导致上述风险因素的首要问题，但在 T1D 受试者中更难以量化。在本申请中，我提出了一系列研究，其总体双重目标是获得先进的研究技能，同时将 T1D 成人 CAD 发病机制的调查结果和方法转化为糖尿病儿童（一级预防的最终目标人群）。该培训补助金的目标是追求以下具体目标，以在 1 型糖尿病冠状动脉钙化 (CACTI) 研究框架内培养研究技能，以测试特定于该应用的假设：1) 理清之间的相互关系使用基线和随访观察高血糖、肾功能、高血压和胰岛素抵抗（由内脏肥胖、脂联素水平低和血脂异常定义）在早发 CAD 发展中的作用来自 CACTI 队列的数据； 2) 在 CACTI 中对年轻人进行正常血糖高胰岛素钳夹研究，以根据 T1D 受试者易于测量的传统和新型标记物准确估计胰岛素敏感性； 3) 建立一个由 120 名患有 T1D (n=60) 和非糖尿病 (n=60) 的青少年（12-19 岁）组成的队列。芭芭拉戴维斯儿童糖尿病中心对该队列中心血管危险因素的形成和分析将为未来的 R01 应用提供试点数据。这些目标已确定为将 T1D CVD 研究从年轻人转向青少年。尽管针对成人 CVD 危险因素的指南已经制定，但对青少年 T1D 的筛查和干预要么缺乏，要么基于成人数据的推断。这项研究的一般假设是，患有 T1D 的青少年中存在大大升高的 CVD 危险因素，需要确定筛查和治疗阈值。