Type 1 Diabetes mellitus (T1D) is one of the leading chronic diseases of childhood, affecting 1.54 per 1,000 youth in the United States. Despite the increasing body of evidence indicating the importance of premature atherosclerosis as a major contributor to increased morbidity and mortality in patients with T1D, the risk factors for premature CVD and the progression from preclinical to advanced disease have not been studied systematically. The overall goal of this proposal is to understand the contribution of metabolic, behavioral and diabetes-specific risk factors to the development of cardiovascular sub-clinical abnormalities in adolescents and young adults with T1D, as compared to non-diabetic controls. The proposed work is an ancillary study to the CDC/DDT and NIH/NIDDK funded SEARCH for Diabetes in Youth project, The current proposal (SEARCH CVD) will integrate all relevant information provided by SEARCH, will recruit non-diabetic controls, and will collect data on CVD sub-clinical outcomes among 800 10-25 year old adolescents and young adults from Colorado and Ohio. Using case-control and within case longitudinal designs, SEARCH CVD will address specific hypotheses related to the presence of, and risk factors for, preclinical CVD in youth with and without T1D.
The specific aims of this proposal are:
Aim 1 : To describe the presence and determinants of sub-clinical abnormalities in cardiovascular (CVD) structure and function among 400 adolescents and young adults with T1D and 400 non-diabetic controls. a. Structure: increased left ventricular mass (LV mass), increased carotid intimal-medial thickness (cIMT) b. Function: decreased cardiac function, increased arterial stiffness and endothelial dysfunction Aim 2: To explore the 6-year rate of change and risk factors for changes in pulse wave velocity, augmentation index and brachial distensibility in youth with T1D and prior measures of arterial stiffness. Diabetes-specific, metabolic and behavioral risk factors will be explored. Public Health Relevance: Little is known about the development and progression of preclinical CVD in young patients with T1D. If the progression is similar to that in adults, there is a major public health concern in that they may experience adverse CVD outcomes as early as their late 20's to early 30's. This study will advance our understanding of the natural history of early CVD in youth, and will provide insights into the mechanisms from which strategies to prevent or limit vascular disease in individuals with T1D can be developed.
Little is known about the development and progression of preclinical CVD in young patients with T1D. If the progression is similar to that in adults, there is a major public health concern in that they may experience adverse CVD outcomes as early as their late 20's to early 30's. This study will advance our understanding of the natural history of early CVD in youth, and will provide insights into the mechanisms from which strategies to prevent or limit vascular disease in individuals with T1D can be developed.
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