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

基本信息

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
项目类别：
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

项目摘要

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）在美国影响140万人，其发病率每年增加3-5％。尽管正在研究许多有前途的治疗方式，但目前尚无治愈方法，患者过早地屈服于长期并发症，尤其是冠状动脉疾病（CAD）。在非DM个体和2型糖尿病患者中发现的传统危险因素并未完全解释T1D中观察到的CAD的过多风险。高血糖，高血压，血脂异常，蛋白尿，肥胖，炎症和低脂联素水平显然起作用。胰岛素抵抗可能是上述危险因素的主要问题，但在T1D受试者中更难量化。在此应用中，我提出了一系列研究，其总体双重目标是获得高级研究技能，同时将T1D成人CAD发病机理的发现和调查方法转化为糖尿病儿童，这是初级预防的最终目标人群。这项培训赠款的目标是追求以下特定旨在在1型糖尿病（CACTI）研究中发展冠状动脉钙化框架内的研究技能（CACTI）研究，以测试该应用特定的假设：1）散布相互关联的相互关系，使高血糖，肾脏功能，高血压和胰岛素的抑制作用（肾小管降低）的依据（肾脏均应降低）（抑制性征症）（使用基线和仙人掌队列的后续数据开发过早CAD； 2）在仙人掌中的年轻人中进行电子高糖性高胰岛素夹具研究，以基于易于衡量T1D受试者的传统和新颖标记的胰岛素敏感性的准确估计； 3）建立与T1D（n = 60）和非DM（n = 60）的120名青少年（12-19岁）组成的队列。在芭芭拉·戴维斯（Barbara Davis）儿童糖尿病中心，该队列中心血管危险因素的形成和分析将为未来的R01应用提供试验数据。已经确定了这些目标是将T1D中CVD的研究从年轻人转化为青少年。尽管建立了成人CVD危险因素的指南，但对T1D的青少年进行筛查和干预是不存在的，要么是基于从成人数据中推断出来的。这项研究的总体假设是，在具有T1D的青年和筛查和治疗阈值中，CVD危险因素大大升高。