This research application will use an already established cohort to investigate the early development of obesity, insulin resistance, and their interaction with associated cardiovascular (CV) risk factors in a cross- generational study between parents (generation 1), on whom we have long-term repeated observations from age 7 to 40, and their children (generation 2). The underlying hypotheses are that early adiposity and insulin resistance drive the development of CV risk and that children, by sharing genetic and environmental factors with their parents, exhibit a similar risk profile for development of type 2 diabetes and atherosclerotic CV disease. Our access to a cohort of individuals who were initially recruited in early childhood, followed through adolescence and young adulthood and currently have children equivalent in age to their own age when they were first recruited, offers a unique opportunity to test this hypothesis. The major objective of this application is to relate individual CV risk factors (hyperinsulinemia, blood pressure, obesity, lipids), lifestyle behaviors, visceral fat (abdominal CT), measures of inflammation, adipocytokines, oxidative stress, vascular studies, and specific measures of insulin resistance (euglycemic hyperinsulinemic clamps) between generations by comparing findings in the parents (generation 1, when they were children and at their current adult age) with their children (generation 2). Overt cardiovascular disease is rare in children, but the factors associated with its development are present early in life. Thus, this study will document the importance, in this current era of epidemic obesity and type 2 diabetes mellitus (T2DM), of identifying high-risk families and children in order to introduce effective intervention strategies prior to disease development. Delineation of similarities in the elements of CV risk between parents and their children and identification of markers that predict which children are at risk for metabolic and cardiovascular complications are the initial steps to achieve this clinical scientific goal. ? ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK072124-02
Application #
7426842
Study Section
Kidney, Nutrition, Obesity and Diabetes (KNOD)
Program Officer
Staten, Myrlene A
Project Start
2007-07-01
Project End
2012-06-30
Budget Start
2008-07-01
Budget End
2009-06-30
Support Year
2
Fiscal Year
2008
Total Cost
$588,474
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Pediatrics
Type
Schools of Medicine
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Harbin, Michelle M; Zavala, Hanan; Ryder, Justin R et al. (2018) Associations of sex, age and adiposity in endothelium-independent dilation in children. Physiol Meas 39:045002
Gooty, Vasu D; Sinaiko, Alan R; Ryder, Justin R et al. (2018) Association Between Carotid Intima Media Thickness, Age, and Cardiovascular Risk Factors in Children and Adolescents. Metab Syndr Relat Disord 16:122-126
Wang, Raymond Y; Rudser, Kyle D; Dengel, Donald R et al. (2017) The Carotid Intima-Media Thickness and Arterial Stiffness of Pediatric Mucopolysaccharidosis Patients Are Increased Compared to Both Pediatric and Adult Controls. Int J Mol Sci 18:
Ryder, Justin R; Pankratz, Nathan D; Dengel, Donald R et al. (2017) Heritability of Vascular Structure and Function: A Parent-Child Study. J Am Heart Assoc 6:
Ostrem, Joseph D; Evanoff, Nicholas G; Ryder, Justin R et al. (2017) High-flow-mediated constriction in adults is not influenced by biomarkers of cardiovascular and metabolic risk. J Clin Ultrasound 45:35-42
Ryder, Justin R; Dengel, Donald R; Jacobs Jr, David R et al. (2016) Relations among Adiposity and Insulin Resistance with Flow-Mediated Dilation, Carotid Intima-Media Thickness, and Arterial Stiffness in Children. J Pediatr 168:205-11
Evanoff, Nicholas G; Kelly, Aaron S; Steinberger, Julia et al. (2016) Peak shear and peak flow mediated dilation: a time-course relationship. J Clin Ultrasound 44:182-7
Armenian, Saro H; Hudson, Melissa M; Mulder, Renee L et al. (2015) Recommendations for cardiomyopathy surveillance for survivors of childhood cancer: a report from the International Late Effects of Childhood Cancer Guideline Harmonization Group. Lancet Oncol 16:e123-36
Knowles, Joshua W; Xie, Weijia; Zhang, Zhongyang et al. (2015) Identification and validation of N-acetyltransferase 2 as an insulin sensitivity gene. J Clin Invest 125:1739-51
Bosch, T A; Dengel, D R; Kelly, A S et al. (2015) Visceral adipose tissue measured by DXA correlates with measurement by CT and is associated with cardiometabolic risk factors in children. Pediatr Obes 10:172-9

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