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 #
5R01DK072124-05
Application #
8109215
Study Section
Kidney, Nutrition, Obesity and Diabetes (KNOD)
Program Officer
Staten, Myrlene A
Project Start
2007-07-01
Project End
2013-06-30
Budget Start
2011-07-01
Budget End
2013-06-30
Support Year
5
Fiscal Year
2011
Total Cost
$580,680
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
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
Hopkins, Nicola D; Dengel, Donald R; Stratton, Gareth et al. (2015) Age and sex relationship with flow-mediated dilation in healthy children and adolescents. J Appl Physiol (1985) 119:926-33
Watkins, Ashley N; Kelly, Aaron S; Prineas, Ronald J et al. (2015) Childhood wrist circumference is not a predictor of insulin resistance in adulthood. J Pediatr 166:1085-7
Bosch, Tyler A; Steinberger, Julia; Sinaiko, Alan R et al. (2015) Identification of sex-specific thresholds for accumulation of visceral adipose tissue in adults. Obesity (Silver Spring) 23:375-82
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
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
Halvorsen, Tanya; Moran, Antoinette; Jacobs Jr, David R et al. (2015) Relation of Cardiometabolic Risk Factors between Parents and Children. J Pediatr 167:1049-56.e2
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
Kelly, Aaron S; Marlatt, Kara L; Steinberger, Julia et al. (2014) Younger age is associated with lower reactive hyperemic index but not lower flow-mediated dilation among children and adolescents. Atherosclerosis 234:410-4

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