Risk of Prediabetes/Complications Seen in Adult Pediatric Cancer Survivors

“We have identified that prediabetes and diabetes each increase risk of future cardiovascular events and [chronic kidney disease] in survivors, independent of cancer treatment and other traditional cardiovascular risk factors," according to the study authors.

Prediabetes appears to frequently occur in adult survivors of pediatric cancer, with investigators also reporting an independent association with an increased risk of subsequent cardiovascular and kidney complications, according to data from a St Jude Lifetime Cohort Study (SJLIFE) published in the Journal of Clinical Oncology.

In the population of survivors with a median age of 30 years (IQR, 18-65), the prevalence of prediabetes was 29.2% (95% CI, 27.7%-30.7%) compared with 18.1% (95% CI, 14.5%-21.6%) in the control group. Additionally, diabetes was found in 6.5% (95% CI, 5.7%-7.3%) vs 4.7% (95% CI, 2.7%-6.6%), respectively. In the population of patients aged 40 to 49 years old, 45.5% had prediabetes, and 14.0% had diabetes.

Additionally, among those with prediabetes (n = 695), 68 were reported to have progressed to diabetes at a median follow-up of 5.1 years (IQR, 4.1-5.7).

“Prediabetes, [which] is highly prevalent in adult survivors of childhood cancer, progressed to diabetes at a high rate over observed follow-up, and occurred at a younger age than in controls,” the authors wrote. “We have identified that prediabetes and diabetes each increase risk of future cardiovascular events and [chronic kidney disease] in survivors, independent of cancer treatment and other traditional cardiovascular risk factors.

“Furthermore, the development of diabetes in survivors is associated with an increased risk of death from health-related causes, including deaths related to complications of previous treatment. On the basis of these findings, it is now clear that future interventions are needed to target prediabetes as a modifiable risk factor and determine the optimal strategy for prevention of diabetes and subsequent early morbidity and mortality.”

A total of 3529 patients were included in the SJLIFE cohort, as well as 448 community controls that were matched for age, sex, and race. To be included, patients needed to 18 years or older at evaluation and be 5 or more years from their original cancer diagnosis. Moreover, survivors needed to have been treated for pediatric cancer at St Jude Children’s Research Hospital between 1962 and June 30, 2012. Those with no available measure of glucose metabolism (n = 2) or who had a history of type 1 diabetes or a diabetes diagnosis prior to cancer diagnosis were excluded from the analysis.

To be included in the time-to-event analysis assessing progression from prediabetes to diabetes (n = 695), survivors needed to have completed a minimum of 1 subsequent assessment and not have received glucose-lowering agents.

Notably, survivors tended to be younger than community controls at assessment, as well as being more likely to be non-Hispanic Black (14.9% vs 7.6%, respectively). Investigators also reported that the likelihood of being overweight (28.0% vs 26.6%) and obese (34% vs 35%) was comparable between survivors and the control group, respectively (P = .424).

In terms of other findings, investigators reported that although the likelihood of prediabetes went up with body mass index (BMI) and age in survivors, all groups were considered at risk, including those with underweight and healthy BMIs, as well as those under 35 years of age. Moreover, those who survived Hodgkin lymphoma (40.9%) and Wilms tumors (35.9%) were found to have the highest likelihood of prediabetes. Conversely, the lowest likelihood was reported in patients with central nervous system tumors (20.7%) and retinoblastomas (23.9%).

When likelihood of prediabetes was assessed by treatment exposure, investigators reported the highest prevalence in those who had radiation exposure to the pancreatic tail at more than 0.2 Gy to less than 10 Gy (35.4%) and 10 Gy or more (37.9%), as well as those who received moderate doses of cranial irradiation ranging from 20 Gy to less than 30 Gy (39.7%).

Moreover, receipt of radiation to the pancreatic tail was the only treatment exposure that significantly increased prediabetes risk regardless of age, sex, race, BMI, physical activity level, and other treatment exposure; in particular, investigators reported a 30% increased risk in those who received less than 10 Gy of radiotherapy (OR, 1.3; 95% CI, 1.0-1.6) and a 4-fold increased risk in those who received a minimum of 10 Gy (OR, 3.9; 95% CI, 2.4-6.4).

In models that adjusted for demographic factors, physical activity, and BMI, investigators reported that only total body irradiation was associated with an increased likelihood of progressing to diabetes (HR, 5.1; 95% CI, 1.7-15.6).

Additionally, presence of diabetes at baseline was significantly associated with notable cardiovascular disease, including nonfatal myocardial infarction, cardiomyopathy, or vascular disease (OR, 1.67; 95% CI, 1.03-2.72). Prediabetes also correlated with a 2-fold increase in risk of subsequent myocardial infarction regardless of demographic factors, anthracycline and chest irradiation dose, and hypertension and dyslipidemia at baseline (HR, 2.39; 95% CI, 1.20-4.79).

Reference

Dixon SB, Wang F, Lu L, et al. Prediabetes and associated risk of cardiovascular events and chronic kidney disease among adult survivors of childhood cancer in the St Jude Lifetime Xohort. J Clin Oncol. Published online December 13, 2023. doi:10.1200/JCO.23.01005