This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Background: Survivors of childhood Acute Lymphocytic Leukemia (ALL) are at increased risk for obesity, insulin resistance, and metabolic syndrome. While it is well established that hyperglycemia during treatment for ALL predicts adverse outcomes such as infections and death, the association with co-morbidities seen in survivors remains unknown. We hypothesize that survivors of childhood ALL with a history of hyperglycemia during induction are at increased risk to develop insulin resistance and metabolic syndrome when compared to euglycemic counterparts. Methods: We plan to conduct a prospective study of 40 survivors of childhood ALL who were diagnosed 1999-2006 and are currently cared for in the Texas Childrens Cancer Center Long-Term Survivor Clinic. Subjects will be divided equally into 2 groups based on presence or absence of hyperglycemia during induction therapy for ALL. Each subject will undergo an oral glucose tolerance test and a DEXA scan for body composition along with measurements of insulin resistance, lipids, and blood pressure. A 2 sample t-test will be used to compare mean insulin resistance between the 2 groups. A chi 2 analysis will be performed for outcomes such as metabolic syndrome, hypertension, dyslipidemia, and obesity. Results/Conclusions: We expect to detect a significant difference in insulin resistance, measured as HOMA, of 2.4 between our two groups. We predict that survivors of ALL with a history of hyperglycemia compared to those who remained euglycemic during induction will be more likely to exhibit insulin resistance. Additionally, we expect to find higher rates of co-morbidities such as impaired glucose tolerance, obesity, hypertension, dyslipidemia, and metabolic syndrome in the hyperglycemia group. If our hypotheses are proven, future studies will be needed to examine the role of hyperglycemia therapy during induction as a means of decreasing co-morbidities in ALL survivors.
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