The prevalence of type 2 diabetes mellitus has increased dramatically in adolescents. This appears to be a direct result of the increase in prevalence and severity of obesity in the pediatric population. In adults with type 2 diabetes, it is well known that the risk for cardiovascular disease (CVD) is quite high. This has led to current clinical recommendation that adults with diabetes be considered equivalent in risk to those adults who already have existing coronary artery disease. It is not known if adolescents with type 2 diabetes have an equivalent high level of risk of CVD as the adult population. If they do then it would be expected that they would develop clinical CVD in their late 20's or 30's. This would have important clinical implications and would suggest the need for very aggressive management of CVD risk factors and diabetes. The proposed study is a cross-sectional evaluation of cardiac and vascular structure and function in a population of adolescents with type 2 diabetes compared to a group with similar age, sex, race and BMI with obesity alone and a non obese group with similar age, sex and race. 300 subjects with type 2 diabetes, 300 subjects with obesity and 300 non obese subjects will be studied. Assessment of CVD development will be accomplished using novel non invasive imaging methods for subclinical atherosclerosis including echocardiographic measurement of cardiac structure and function, ultrasound evaluation of carotid intimalmedial thickness, and evaluation of endothelial function by brachial artery reactivity. The primary hypothesis is that adolescents with type 2 diabetes will have greater abnormality in cardiac and vascular structure and function compared to controls with obesity. Subjects with obesity alone will have greater abnormality in cardiac and vascular structure and function compared to controls who are not obese. Correlates of cardiac and vascular abnormalities including markers of inflammation, adiponectin, diet and physical activity will also be evaluated. The results of the proposed study will fill an important gap in knowledge, will serve as the baseline for future longitudinal studies and may provide the basis for clinical strategies to prevent the development of CVD in young patients with type 2 diabetes and those with obesity.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL076269-02
Application #
7067543
Study Section
Special Emphasis Panel (ZRG1-HOP-N (02))
Program Officer
Harman, Jane
Project Start
2005-06-01
Project End
2009-05-31
Budget Start
2006-06-01
Budget End
2007-05-31
Support Year
2
Fiscal Year
2006
Total Cost
$671,817
Indirect Cost
Name
Children's Hospital Med Ctr (Cincinnati)
Department
Type
DUNS #
071284913
City
Cincinnati
State
OH
Country
United States
Zip Code
45229
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Shah, Amy S; Davidson, W Sean; Gao, Zhiqian et al. (2016) Superiority of lipoprotein particle number to detect associations with arterial thickness and stiffness in obese youth with and without prediabetes. J Clin Lipidol 10:610-8
Shah, Amy S; Dolan, Lawrence M; Khoury, Philip R et al. (2015) Severe Obesity in Adolescents and Young Adults Is Associated With Subclinical Cardiac and Vascular Changes. J Clin Endocrinol Metab 100:2751-7
Totaro, Silvia; Khoury, Philip R; Kimball, Thomas R et al. (2015) Arterial stiffness is increased in young normotensive subjects with high central blood pressure. J Am Soc Hypertens 9:285-92
Urbina, Elaine M; Khoury, Philip R; McCoy, Connie E et al. (2015) Comparison of mercury sphygmomanometry blood pressure readings with oscillometric and central blood pressure in predicting target organ damage in youth. Blood Press Monit 20:150-6
Jha, Pranati; Dolan, Lawrence M; Khoury, Philip R et al. (2015) Low Serum Vitamin D Levels Are Associated With Increased Arterial Stiffness in Youth With Type 2 Diabetes. Diabetes Care 38:1551-7
Shah, Amy S; Gao, Zhiqian; Urbina, Elaine M et al. (2014) Prediabetes: the effects on arterial thickness and stiffness in obese youth. J Clin Endocrinol Metab 99:1037-43
Shah, Amy S; Urbina, Elaine M; Khoury, Philip R et al. (2013) Lipids and lipoprotein ratios: contribution to carotid intima media thickness in adolescents and young adults with type 2 diabetes mellitus. J Clin Lipidol 7:441-5
Urbina, Elaine M; Khoury, Philip R; McCoy, Connie E et al. (2013) Triglyceride to HDL-C ratio and increased arterial stiffness in children, adolescents, and young adults. Pediatrics 131:e1082-90
Edwards, Nicholas M; Daniels, Stephen R; Claytor, Randall P et al. (2012) Physical activity is independently associated with multiple measures of arterial stiffness in adolescents and young adults. Metabolism 61:869-72

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