Insulin Resistance and Risk Factors for Cardiovascular Disease in Young Adult Survivors of Childhood Acute Lymphoblastic Leukemia

Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021, USA.
Journal of Clinical Oncology (Impact Factor: 18.43). 07/2009; 27(22):3698-704. DOI: 10.1200/JCO.2008.19.7251
Source: PubMed


To determine the prevalence of insulin resistance and other risk factors for cardiovascular disease (CVD) in young adult survivors of childhood acute lymphoblastic leukemia (ALL).
In this cross-sectional evaluation of 118 survivors of childhood ALL (median age, 23.0 years; range, 18 to 37 years), insulin resistance was estimated using the homeostasis model for assessment of insulin resistance (HOMA-IR). Sex-specific comparisons were made with a cohort of 30- to 37-year-old individuals from the same region participating in the Dallas Heart Study (DHS, N = 782). ALL survivors were stratified by treatment with and without cranial radiotherapy (CRT).
Female ALL survivors had a significantly higher HOMA-IR (CRT, mean 4.6, 95% CI, 3.6 to 5.7; no CRT, mean 3.3, 95% CI, 2.8 to 3.8) in comparison with DHS women (mean 2.4, 95% CI, 2.2 to 2.7). Eighty percent of women treated with CRT had at least three of six CVD risk factors, and they were significantly more likely to have three or more risk factors compared with DHS women (odds ratio [OR], 5.96; 95% CI, 2.15 to 16.47). Male ALL survivors had a significantly higher HOMA-IR (CRT, mean 4.0, 95% CI, 2.8 to 5.6; no CRT, mean 3.4, 95% CI, 2.9 to 3.9) in comparison with DHS men (mean 2.3, 95% CI, 2.1 to 2.6), but were not more likely to have multiple CVD risk factors.
ALL survivors had an increased prevalence of insulin resistance in comparison with a cohort of older individuals from the same community. Importantly, women treated with CRT seem to have an increased prevalence of multiple CVD risk factors, warranting close monitoring and risk-reducing strategies.

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Available from: Beverley Adams-Huet
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    • "As of 2005, there were over 328,000 childhood cancer survivors in the USA, a number that will continue to grow with emerging treatment procedures [1]. Unfortunately, survival from childhood cancer is often accompanied by an increased risk for adverse late effects from treatment [2] [3] [4], including cardiovascular risk [5] [6], insulin resistance [7], and neurologic, musculoskeletal, and pulmonary complications [8]. Furthermore, adult survivors of childhood cancer may be particularly prone to weight-related problems as approximately half report low levels of physical activity [9] [10]. "
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    ABSTRACT: Background. Population-based studies are needed to estimate the prevalence of underweight or overweight/obese childhood cancer survivors. Procedure. Adult survivors (diagnosed ≤20 years) were identified from the linked Utah Cancer Registry and Utah Population Database. We included survivors currently aged ≥20 years and ≥5 years from diagnosis (N = 1060), and a comparison cohort selected on birth year and sex (N = 5410). BMI was calculated from driver license data available from 2000 to 2010. Multivariable generalized linear regression models were used to calculate prevalence relative risks (RR) and 95% confidence intervals (95% CI) of BMI outcomes for survivors and the comparison cohort. Results. Average time since diagnosis was 18.5 years (SD = 7.8), and mean age at BMI for both groups was 30.5 (survivors SD = 7.7, comparison SD = 8.0). Considering all diagnoses, survivors were not at higher risk for being underweight or overweight/obese than the comparison. Male central nervous system tumor survivors were overweight (RR = 1.12, 95% CI 1.01-1.23) more often than the comparison. Female survivors, who were diagnosed at age 10 and under, had a 10% higher risk of being obese than survivors diagnosed at ages 16-20 (P < 0.05). Conclusion. While certain groups of childhood cancer survivors are at risk for being overweight/obese, in general they do not differ from population estimates.
    Full-text · Article · Jan 2014 · Journal of Cancer Epidemiology
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    • "Concerning the lipid panel for the evaluation of cardiovascular disease risk factors, the results of this study showed increased levels of LDL cholesterol in the CRT group, to date with no clinical relevance, which is in accordance with other reports [11,12,36]. Nonetheless, HDL cholesterol, triglyceride concentrations and insulin resistance were not altered, and no influence of CRT was observed, even though these metabolic derangements had been described by various previous studies [11,12,14,36]. Alterations in body fat and metabolic panel are clearly multifactorial, being regulated by gender, host characteristics, therapeutic agents (chemotherapy and exposure to CRT) and hormonal deficiencies. "
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    ABSTRACT: Background Advances in treatment of acute lymphocytic leukemia increased the likelihood of developing late treatment-associated effects, such as abdominal adiposity, increasing the risk of cardiovascular disease in this population. Cranial radiotherapy is one of the factors that might be involved in this process. The aim of this study was to determine the effect of cranial radiotherapy on adiposity indexes in survivors of acute lymphocytic leukemia. Methods A comparative cross-sectional study of 56 acute lymphocytic leukemia survivors, chronological age between 15 and 24 years, assigned into two groups according to the exposure to cranial radiotherapy (25 irradiated and 31 non-irradiated), assessed according to body fat (dual energy X-ray absorptiometry), computed tomography scan-derived abdominal adipose tissue, lipid profile, and insulin resistance. Results Cranial radiotherapy increased body fat and abdominal adipose tissue and altered lipid panel. Yet, lipids showed no clinical relevance so far. There were significantly more obese patients among those who received cranial radiotherapy (52% irradiated versus 22.6% non-irradiated), based on dual energy X-ray absorptiometry body fat measurements. Nonetheless, no association was observed between cranial radiotherapy and body mass index, waist circumference, waist-to-height ratio or insulin resistance. Conclusions Adolescent and young adult survivors of childhood acute lymphocytic leukemia showed an increase in body fat and an alteration of fat distribution, which were related to cranial radiotherapy. Fat compartment modifications possibly indicate a disease of adipose tissue, and cranial radiotherapy imports in this process.
    Full-text · Article · Feb 2013 · Radiation Oncology
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    • "Abnormal body composition is considered a modifiable disorder that may play a role in intervention strategies for treatment-related cardiovascular disease; therefore, we need an understanding of the timing of its development [14]. "
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    ABSTRACT: Evaluation of body mass index (BMI) at final height (FH) and annual BMI increase in adult childhood cancer survivors (CCS) after treatment with anthracyclines, platinum, and/or radiotherapy. BMI (weight/height²) was calculated retrospectively from diagnosis until FH. The prevalence of underweight (BMI < 18.5 kg/m(2)) and overweight (BMI ≥ 25 kg/m(2))/obesity (BMI ≥ 30 kg/m(2)) at FH was compared with age-matched controls. The association between underweight/overweight at FH and treatment was assessed by multivariate logistic regression. Annual BMI increase after treatment was assessed by multilevel analysis. Analyses were adjusted for age and underweight/overweight at diagnosis, and age at FH. At FH the prevalence of overweight had not increased, while CCS experienced more underweight as compared to controls (14% vs. 4%, P < 0.001). Overweight at FH was associated with cranial/craniospinal radiotherapy (CRT; OR, 2.23; 95% CI, 1.17-4.26) and underweight at FH with anthracyclines > 300 mg/m(2) (OR, 2.84; 95% CI, 1.33-6.06). Annual BMI increase was +0.47 (0.34-0.60) kg/m(2)/year. In CCS, the annual BMI increase was greater in those with CRT ≥ 30 Gy as compared with those with less or no CRT (+0.15 kg/m(2)/year [0.04-0.25 kg/m(2)/year], P = 0.008) and smaller in those with a higher cumulative anthracycline dose (-0.03 kg/m(2)/year [-0.05 to -0.0005 kg/m(2)/year] per 100 mg/m(2), P = 0.046). After treatment with anthracyclines, platinum, and/or radiotherapy, CRT-treated survivors have more overweight at FH, and a greater annual BMI increase, while anthracycline-treated survivors have more underweight at FH and a lower annual BMI increase.
    Full-text · Article · Feb 2011 · Supportive Care in Cancer
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