In the JournalsPerspective

Survivors of childhood acute lymphoblastic leukemia at higher risk for type 2 diabetes

Kirsten K. Ness, PT, PhD
Kirsten K. Ness

Survivors of childhood acute lymphoblastic leukemia, particularly those with obesity and/or who received treatment during adolescence, appeared to be at higher risk for type 2 diabetes than the general population, according to study results published in Cancer.

“We had previously noted a higher incidence of metabolic syndrome, including a constellation of problems of hypertension, hypertriglyceridemia, low high-density lipoprotein, elevated fasting glucose and abdominal obesity, in survivors of childhood acute lymphoblastic leukemia,” Kirsten K. Ness, PhD, researcher in the department of epidemiology and cancer control at St. Jude Children’s Research Hospital, told Healio.

“In the general population, metabolic syndrome often preceded diabetes. We wanted to see if the incidence of diabetes was also higher than expected compared with those with no childhood cancer history, and if we could identify survivors at highest risk so they could be closely monitored and counseled to prevent development of diabetes.”

Ness and colleagues sought to assess type 2 diabetes prevalence and risk factors among 1,044 adult survivors of childhood ALL (median age, 33.19 years; interquartile range [IQR], 26.78-40.53; 50.8% male) compared with 368 community controls with no childhood cancer history (median age, 34.48 years; IQR, 28.1-41.72; 45.6% male).

All participants had enrolled in the St. Jude Lifetime Cohort Study between October 2007 and June 2016. Survivors, who had been diagnosed with ALL at least 10 years earlier, and controls, who were frequency matched for age, sex and race, completed clinical and laboratory evaluations.

Survivors appeared more likely than controls to have obesity (BMI 30 kg/m², 45.31% vs. 34.78%) and less likely to be college graduates (32.95% vs. 53.28%).

Results showed 7.47% of survivors had type 2 diabetes, compared with 3.8% of controls (OR = 2.07; 95% CI, 1.11-3.87). Survivors also demonstrated a higher cumulative incidence of type 2 diabetes by age 50 years (16% vs. 9%; P = .01).

Factors associated with type 2 diabetes among survivors included older age (OR = 1.05 for each additional year; 95% CI, 1.02-1.08), BMI greater than or equal to 30 kg/m² (OR = 7.4; 95% CI, 2.61-20.97) and development of drug-induced diabetes during ALL treatment (OR = 4.67; 95% CI, 2.53-8.61), which occurred among 7.85% of survivors.

Limitations of the study included the fact that the results may have been influenced by selection bias due to a participation rate of less than 100%. Researchers also acknowledged that despite a lack of substantial demographic differences between study participants and nonparticipants, survivors who completed on-campus evaluations may have differed with regard to health status compared with nonparticipants.

“It is important to provide opportunities for both monitoring and lifestyle counseling interventions for these children early. A study evaluating progression of metabolic syndrome, or prediabetes, to diabetes among survivors is underway in our cohort and will provide important additional information,” Ness told Healio. “A diet and exercise intervention to promote weight loss in childhood ALL survivors who are obese is needed.” – by Jennifer Southall

For more information:

Kirsten K. Ness, PhD, can be reached at St. Jude Children’s Research Hospital, 262 Danny Thomas Place, MS735, Memphis, TN 38105; email: kiri.ness@stjude.org.

Disclosures: Grants from the NCI and American Lebanese Syrian Associated Charities supported this study. Ness reports grants from the NCI and other support from American Lebanese Syrian Associated Charities. Please see the study for all other authors’ relevant financial disclosures.

Kirsten K. Ness, PT, PhD
Kirsten K. Ness

Survivors of childhood acute lymphoblastic leukemia, particularly those with obesity and/or who received treatment during adolescence, appeared to be at higher risk for type 2 diabetes than the general population, according to study results published in Cancer.

“We had previously noted a higher incidence of metabolic syndrome, including a constellation of problems of hypertension, hypertriglyceridemia, low high-density lipoprotein, elevated fasting glucose and abdominal obesity, in survivors of childhood acute lymphoblastic leukemia,” Kirsten K. Ness, PhD, researcher in the department of epidemiology and cancer control at St. Jude Children’s Research Hospital, told Healio.

“In the general population, metabolic syndrome often preceded diabetes. We wanted to see if the incidence of diabetes was also higher than expected compared with those with no childhood cancer history, and if we could identify survivors at highest risk so they could be closely monitored and counseled to prevent development of diabetes.”

Ness and colleagues sought to assess type 2 diabetes prevalence and risk factors among 1,044 adult survivors of childhood ALL (median age, 33.19 years; interquartile range [IQR], 26.78-40.53; 50.8% male) compared with 368 community controls with no childhood cancer history (median age, 34.48 years; IQR, 28.1-41.72; 45.6% male).

All participants had enrolled in the St. Jude Lifetime Cohort Study between October 2007 and June 2016. Survivors, who had been diagnosed with ALL at least 10 years earlier, and controls, who were frequency matched for age, sex and race, completed clinical and laboratory evaluations.

Survivors appeared more likely than controls to have obesity (BMI 30 kg/m², 45.31% vs. 34.78%) and less likely to be college graduates (32.95% vs. 53.28%).

Results showed 7.47% of survivors had type 2 diabetes, compared with 3.8% of controls (OR = 2.07; 95% CI, 1.11-3.87). Survivors also demonstrated a higher cumulative incidence of type 2 diabetes by age 50 years (16% vs. 9%; P = .01).

Factors associated with type 2 diabetes among survivors included older age (OR = 1.05 for each additional year; 95% CI, 1.02-1.08), BMI greater than or equal to 30 kg/m² (OR = 7.4; 95% CI, 2.61-20.97) and development of drug-induced diabetes during ALL treatment (OR = 4.67; 95% CI, 2.53-8.61), which occurred among 7.85% of survivors.

Limitations of the study included the fact that the results may have been influenced by selection bias due to a participation rate of less than 100%. Researchers also acknowledged that despite a lack of substantial demographic differences between study participants and nonparticipants, survivors who completed on-campus evaluations may have differed with regard to health status compared with nonparticipants.

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“It is important to provide opportunities for both monitoring and lifestyle counseling interventions for these children early. A study evaluating progression of metabolic syndrome, or prediabetes, to diabetes among survivors is underway in our cohort and will provide important additional information,” Ness told Healio. “A diet and exercise intervention to promote weight loss in childhood ALL survivors who are obese is needed.” – by Jennifer Southall

For more information:

Kirsten K. Ness, PhD, can be reached at St. Jude Children’s Research Hospital, 262 Danny Thomas Place, MS735, Memphis, TN 38105; email: kiri.ness@stjude.org.

Disclosures: Grants from the NCI and American Lebanese Syrian Associated Charities supported this study. Ness reports grants from the NCI and other support from American Lebanese Syrian Associated Charities. Please see the study for all other authors’ relevant financial disclosures.

    Perspective

    Sogol Mostoufi-Moab, MD, MSCE
    Sogul Mostoufi-Moab

    The increasing survival rates for childhood ALL constitute one of the early success stories of contemporary oncology. With that success has come increasing awareness of the long-term treatment impact on the developing child, with pediatric oncologists more focused on achieving success while mitigating the costs of cure on children and their development through childhood and beyond.

    The Childhood Cancer Survivor Study (CCSS), initiated in 1994, has been a seminal source of understanding many late effects. Previous analyses from the CCSS demonstrated that adult survivors of childhood ALL have an increased risk for diabetes compared with siblings, with subsequent elevated risk for cardiovascular disease and early mortality beyond the risk conferred by the cancer treatment. In addition, the St. Jude Lifetime Cohort Study — which conducts direct in-person history assessments, physical examinations and laboratory tests — provides comprehensive comparative data for self-reported and screening-determined outcomes of a large cohort of childhood cancer survivors. Both cohorts have provided critical awareness of the incidence and time course of endocrine late effects, particularly in the aging population of survivors of childhood cancer.

    The timely article by Williams and colleagues is the first comprehensive study to provide unique insights into the prevalence and risk factors for type 2 diabetes among 1,044 long-term (10 years) adult survivors of childhood ALL compared with 368 community controls enrolled in the St. Jude Lifetime Cohort Study. Importantly, the researchers investigated the contributions of host (age, demographic factors, obesity) and lifestyle (physical activity) factors, as well as prior diagnosis of drug-induced diabetes during ALL treatment, concomitant with high doses of glucocorticoid and asparaginase exposures.

    The study findings are important on several levels. First, obesity, a known risk factor for type 2 diabetes in the general population, significantly increased the risk for this outcome among ALL survivors. Second, drug-induced diabetes — more prevalent in children aged 15 years or older at the time of ALL diagnosis who were exposed to higher doses of asparaginase and among children aged younger than 15 years at the time of ALL diagnosis treated with dexamethasone — is another significant risk factor for type 2 diabetes among ALL survivors and for gestational diabetes among women. These data provide a target for early intervention among ALL survivors with obesity and demonstrate the need for regular screening among survivors with history of drug-induced diabetes.

    Ultimately, these findings pave the way for better elucidation of the mechanisms of diabetes due to cancer treatment, thus allowing for primary prevention of type 2 diabetes using targeted prophylactic pharmacotherapy during cancer treatment for survivors identified at highest risk for this outcome. The high prevalence and increased risk for type 2 diabetes among survivors of childhood ALL underscore the importance of repeated surveillance and the need for early intervention in this growing survivorship population. The findings also emphasize the critical need for lifelong monitoring for endocrine late effects in adult survivors of childhood cancer and highlight the importance of endocrinologists’ familiarity with issues in this survivor population, which are fundamentally different from issues faced by survivors of adult cancers.

    References:

    Diller L, et al. J Clin Oncol. 2009;doi:10.1200/JCO.2008.21.1953.

    Meacham LR, et al. Arch Intern Med. 2009;doi:10.1001/archinternmed.2009.209.

    Mostoufi-Moab S, et al. J Clin Oncol. 2016;doi:10.1200/JCO.2016.66.6545.

    Oeffinger KC, et al. N Engl J Med. 2006;doi:10.1056/NEJMsa060185.

    • Sogol Mostoufi-Moab, MD, MSCE
    • Children's Hospital of Philadelphia
      Perelman School of Medicine at University of Pennsylvania

    Disclosures: Mostoufi-Moab reports no relevant financial disclosures.