This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Background: Treatment for children with Acute Lymphocytic Leukemia (ALL) is known to induce hyperglycemia which has identified as a predictor of adverse outcomes such as infectious complications, relapse, and death. The etiology of hyperglycemia remains unknown. Based on survival data on obesity in survivors of childhood cancer, we hypothesize that insulin resistance exists prior to the diagnosis of ALL and worsens during therapy. Furthermore, we speculate that the children with the highest levels of insulin resistance will develop hyperglycemia during induction therapy. Methods: We plan to conduct a prospective clinical study at Texas Children s Cancer Center on 40 newly diagnosed children with low risk ALL treated on or according to protocol AALLO331. Fasting blood samples will be collected at three time points during induction: pretreatment (day 1), 2 weeks into induction therapy (day 15), and at the end of induction therapy (day 30). The blood sample includes: glucose, c-peptide, HbA1C, insulin, Diabetes antibodies (ICA 512 and GAD 65), and inflammatory markers (CRP, TNF-alpha, and IL-6). We will calculate insulin resistance, as measured by HOMA-IR, and compare results over time. Additionally, patients will be divided into a hyperglycemia (2 or more blood glucose concentrations >140 mg/dL) or euglycemia group for comparison based on glucose monitoring done during the first 4 days of treatment. Data will be analyzed using a Students t-test to compare the difference in insulin resistance between the 2 groups at the three time points. We will use ANOVA for repeated measures to compare the degree of change in each individual patient s insulin resistance from diagnosis to the end of induction. Results/Conclusions: Based on our preliminary data, we expect that 50% of the patients will fall into the hyperglycemia group. With the sample size we calculated, we expect to detect a difference of 1 SD for HOMA-IR between our two groups. We predict that patients who develop hyperglycemia have higher starting HOMA-IR values which continue to rise during the course of treatment. We hope that our inflammatory markers mimic the rise in HOMA-IR and offer an explanation for the underlying pathophysiology of hyperglycemia s effect on adverse outcomes. Treatment for children with Acute Lymphoblastic Leukemia is known to induce hyperglycemia. Multiple studies, including those of our own, have shown that hyperglycemia during the first month of chemotherapy, known as induction, predicts adverse outcomes such as infections, hospitalizations, relapse, and death [1-3]. Our retrospective preliminary data reveals that 55% of patients (n= 135) developed hyperglycemia, defined as 2 or more blood glucose concentrations >140mg/dL, within the first month of therapy. While the exact etiology of hyperglycemia remains unknown, it is theorized that hyperglycemia results from either a state of insulin resistance due to steroid use, failure of insulin secretion due to beta cell damage from chemotherapeutic agents such as L-asparaginase, or a combination of insulin resistance and beta cell damage. We believe that insulin resistance may play the greater role as survivors of childhood ALL are found to have greater rates of obesity, insulin resistance, and metabolic syndrome in adulthood compared to the general population [4, 5]. What remains unanswered is whether insulin resistance is already present during induction therapy. We hope to show that insulin resistance plays a prominent role in the development of hyperglycemia

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
General Clinical Research Centers Program (M01)
Project #
5M01RR000188-46
Application #
8166720
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Project Start
2009-12-01
Project End
2010-11-30
Budget Start
2009-12-01
Budget End
2010-11-30
Support Year
46
Fiscal Year
2010
Total Cost
$24,798
Indirect Cost
Name
Baylor College of Medicine
Department
Pediatrics
Type
Schools of Medicine
DUNS #
051113330
City
Houston
State
TX
Country
United States
Zip Code
77030
Hunsaker, Sanita L; Garland, Beth H; Rofey, Dana et al. (2018) A Multisite 2-Year Follow Up of Psychopathology Prevalence, Predictors, and Correlates Among Adolescents Who Did or Did Not Undergo Weight Loss Surgery. J Adolesc Health 63:142-150
Lanzieri, Tatiana M; Chung, Winnie; Leung, Jessica et al. (2018) Hearing Trajectory in Children with Congenital Cytomegalovirus Infection. Otolaryngol Head Neck Surg 158:736-744
Bollard, Catherine M; Tripic, Tamara; Cruz, Conrad Russell et al. (2018) Tumor-Specific T-Cells Engineered to Overcome Tumor Immune Evasion Induce Clinical Responses in Patients With Relapsed Hodgkin Lymphoma. J Clin Oncol 36:1128-1139
Michalsky, Marc P; Inge, Thomas H; Jenkins, Todd M et al. (2018) Cardiovascular Risk Factors After Adolescent Bariatric Surgery. Pediatrics 141:
Lau, Chantal (2018) Breastfeeding Challenges and the Preterm Mother-Infant Dyad: A Conceptual Model. Breastfeed Med 13:8-17
Wattacheril, Julia; Lavine, Joel E; Chalasani, Naga P et al. (2017) Genome-Wide Associations Related to Hepatic Histology in Nonalcoholic Fatty Liver Disease in Hispanic Boys. J Pediatr 190:100-107.e2
El-Hattab, Ayman W; Almannai, Mohammed; Scaglia, Fernando (2017) Arginine and citrulline for the treatment of MELAS syndrome. J Inborn Errors Metab Screen 5:
Lanzieri, Tatiana M; Chung, Winnie; Flores, Marily et al. (2017) Hearing Loss in Children With Asymptomatic Congenital Cytomegalovirus Infection. Pediatrics 139:
Thakur, Neeta; Barcelo, Nicolas E; Borrell, Luisa N et al. (2017) Perceived Discrimination Associated With Asthma and Related Outcomes in Minority Youth: The GALA II and SAGE II Studies. Chest 151:804-812
Gururangan, Sridharan; Reap, Elizabeth; Schmittling, Robert et al. (2017) Regulatory T cell subsets in patients with medulloblastoma at diagnosis and during standard irradiation and chemotherapy (PBTC N-11). Cancer Immunol Immunother 66:1589-1595

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