As many individuals once treated for childhood cancer progress into adulthood, clinical and epidemiologic research is now focusing on an array of long-term effects from cancer treatment to characterize and understand the """"""""consequences of cure"""""""". There is evidence to indicate that childhood cancer survivors (CCS) are at increased risk for the metabolic syndrome (MS). The syndrome is composed of obesity, insulin resistance, dyslipidemia and hypertension, and is a predictor of type 2 diabetes and cardiovascular disease. In healthy populations obesity has a central role in the development of the MS, however, it is conceivable that in CCS additional mechanisms other than obesity (e.g. endocrine abnormalities, exposure to radiation and antineoplastic agents) may play a critical role in the development of MS. The major objective of this proposal is to evaluate the relation between insulin resistance (by euglycemic insulin clamp), growth hormone deficiency and other mediators of insulin resistance, with the development of MS and cardiovascular risk early in life, before the relations between the components become complex and disease develops. We propose to study a sample of children and adolescents age 9-18 years, who survived childhood cancer for >5 years after diagnosis, and their healthy siblings, who will participate in a 2 day clinical evaluation.
Specific aims are: 1) to determine the prevalence of MS in CCS and compare to healthy controls similar in age and gender distribution, 2) to assess the association of insulin resistance with other components of MS and with early signs of cardiovascular changes, and 3) to assess the relation between obesity and insulin resistance with growth hormone secretion,^adipokines and inflammatory mediators; 4) to evaluate health behaviors related to prevention of cardiovascular disease, diabetes, and obesity. This proposal addresses the need for clinical research focused on newly identified adverse effects of childhood cancer and its treatment, particularly for preventable/modifiable conditions, and will provide new data on potential etiologic factors and avenues for intervention. ? ?

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA113930-01A1
Application #
7031471
Study Section
Epidemiology of Cancer Study Section (EPIC)
Program Officer
Aziz, Noreen M
Project Start
2006-04-01
Project End
2011-02-28
Budget Start
2006-04-01
Budget End
2007-02-28
Support Year
1
Fiscal Year
2006
Total Cost
$492,060
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
Ketterl, Tyler G; Chow, Eric J; Leisenring, Wendy M et al. (2018) Adipokines, Inflammation, and Adiposity in Hematopoietic Cell Transplantation Survivors. Biol Blood Marrow Transplant 24:622-626
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; 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
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
Slater, Megan E; Ross, Julie A; Kelly, Aaron S et al. (2015) Physical activity and cardiovascular risk factors in childhood cancer survivors. Pediatr Blood Cancer 62:305-310
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
Shepard, Charles W; Steinberger, Julia (2015) Premature Atherosclerotic Cardiovascular Disease in Childhood Cancer Survivors. Prog Pediatr Cardiol 39:59-66
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
Petryk, Anna; Polgreen, Lynda E; Barnum, Jessie L et al. (2015) Bone mineral density in children with fanconi anemia after hematopoietic cell transplantation. Biol Blood Marrow Transplant 21:894-9

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