|Grant Number:||5R01CA113930-05 Interpret this number|
|Primary Investigator:||Steinberger, Julia|
|Organization:||University Of Minnesota|
|Project Title:||Metabolic Syndrome in Childhood Cancer Survivors|
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.
The Relative Contributions of the Abdominal Visceral and Subcutaneous Fat Depots to Cardiometabolic Risk in Youth.
Authors: Kelly AS, Dengel DR, Hodges J, Zhang L, Moran A, Chow L, Sinaiko AR, Steinberger J
Source: Clin Obes, 2014 Apr 1;4(2), p. 101-107.
Impact of treatment exposures on cardiovascular risk and insulin resistance in childhood cancer survivors.
Authors: Baker KS, Chow EJ, Goodman PJ, Leisenring WM, Dietz AC, Perkins JL, Chow L, Sinaiko A, Moran A, Petryk A, Steinberger J
Source: Cancer Epidemiol Biomarkers Prev, 2013 Nov;22(11), p. 1954-63.
EPub date: 2013 Sep 5.
Deficits in physical function among young childhood cancer survivors.
Authors: Hoffman MC, Mulrooney DA, Steinberger J, Lee J, Baker KS, Ness KK
Source: J Clin Oncol, 2013 Aug 1;31(22), p. 2799-805.
EPub date: 2013 Jun 24.
Low bone mineral content and challenges in interpretation of dual-energy X-ray absorptiometry in children with mucopolysaccharidosis types I, II, and VI.
Authors: Polgreen LE, Thomas W, Fung E, Viskochil D, Stevenson DA, Steinberger J, Orchard P, Whitley CB, Ensrud KE
Source: J Clin Densitom, 2014 Jan-Mar;17(1), p. 200-6.
EPub date: 2013 Apr 2.
Blunted response to a growth hormone stimulation test is associated with unfavorable cardiovascular risk factor profile in childhood cancer survivors.
Authors: Petryk A, Baker KS, Frohnert B, Moran A, Chow L, Sinaiko AR, Steffen LM, Perkins JL, Zhang L, Hodges JS, Steinberger J
Source: Pediatr Blood Cancer, 2013 Mar;60(3), p. 467-73.
EPub date: 2012 Sep 21.
Modifiable risk factors associated with bone deficits in childhood cancer survivors.
Authors: Polgreen LE, Petryk A, Dietz AC, Sinaiko AR, Leisenring W, Goodman P, Steffen LM, Perkins JL, Dengel DR, Baker KS, Steinberger J
Source: BMC Pediatr, 2012 Mar 28;12, p. 40.
EPub date: 2012 Mar 28.
Hyperleptinemia and hypoadiponectinemia in extreme pediatric obesity.
Authors: Kelly AS, Metzig AM, Schwarzenberg SJ, Norris AL, Fox CK, Steinberger J
Source: Metab Syndr Relat Disord, 2012 Apr;10(2), p. 123-7.
EPub date: 2012 Jan 4.
Cardiovascular risk and insulin resistance in childhood cancer survivors.
Authors: Steinberger J, Sinaiko AR, Kelly AS, Leisenring WM, Steffen LM, Goodman P, Mulrooney DA, Dietz AC, Moran A, Perkins JL, Baker KS
Source: J Pediatr, 2012 Mar;160(3), p. 494-9.
EPub date: 2011 Sep 13.
Circulating oxidized LDL and inflammation in extreme pediatric obesity.
Authors: Norris AL, Steinberger J, Steffen LM, Metzig AM, Schwarzenberg SJ, Kelly AS
Source: Obesity (Silver Spring), 2011 Jul;19(7), p. 1415-9.
EPub date: 2011 Feb 17.