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.

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK078542-02
Application #
7935192
Study Section
Special Emphasis Panel (ZDK1-GRB-7 (O3))
Program Officer
Jones, Teresa L Z
Project Start
2009-09-22
Project End
2012-08-31
Budget Start
2010-09-01
Budget End
2012-08-31
Support Year
2
Fiscal Year
2010
Total Cost
$740,338
Indirect Cost
Name
University of Colorado Denver
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
041096314
City
Aurora
State
CO
Country
United States
Zip Code
80045
Alman, Amy C; Talton, Jennifer W; Wadwa, R Paul et al. (2018) Inflammation, adiposity, and progression of arterial stiffness in adolescents with type 1 diabetes: The SEARCH CVD Study. J Diabetes Complications 32:995-999
Shah, Amy S; Dabelea, Dana; Fino, Nora F et al. (2016) Predictors of Increased Carotid Intima-Media Thickness in Youth With Type 1 Diabetes: The SEARCH CVD Study. Diabetes Care 39:418-25
Shah, Amy S; Wadwa, R Paul; Dabelea, Dana et al. (2015) Arterial stiffness in adolescents and young adults with and without type 1 diabetes: the SEARCH CVD study. Pediatr Diabetes 16:367-74
Shah, Amy S; Gao, Zhiqian; Dolan, Lawrence M et al. (2015) Assessing endothelial dysfunction in adolescents and young adults with type 1 diabetes mellitus using a non-invasive heat stimulus. Pediatr Diabetes 16:434-40
Shah, Amy S; Black, Sandra; Wadwa, R Paul et al. (2015) Insulin sensitivity and arterial stiffness in youth with type 1 diabetes: the SEARCH CVD study. J Diabetes Complications 29:512-6
Alman, Amy C; Talton, Jennifer W; Wadwa, R Paul et al. (2014) Cardiovascular health in adolescents with type 1 diabetes: the SEARCH CVD study. Pediatr Diabetes 15:502-10
Lamichhane, A P; Liese, A D; Urbina, E M et al. (2014) Associations of dietary intake patterns identified using reduced rank regression with markers of arterial stiffness among youth with type 1 diabetes. Eur J Clin Nutr 68:1327-33
Jaacks, Lindsay M; Crandell, Jamie; Liese, Angela D et al. (2014) No association of dietary fiber intake with inflammation or arterial stiffness in youth with type 1 diabetes. J Diabetes Complications 28:305-10
Shah, Amy S; Dabelea, Dana; Talton, Jennifer W et al. (2014) Smoking and arterial stiffness in youth with type 1 diabetes: the SEARCH Cardiovascular Disease Study. J Pediatr 165:110-6
Urbina, Elaine M; Dabelea, Dana; D'Agostino Jr, Ralph B et al. (2013) Effect of type 1 diabetes on carotid structure and function in adolescents and young adults: the SEARCH CVD study. Diabetes Care 36:2597-9

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