Prevalence and Determinants of Diabetes Mellitus in 2338 Long-Term Dutch Childhood Cancer Survivors (DCCS-LATER2 Study)

Context: Diabetes mellitus (DM), a possible adverse effect of childhood cancer treatment, is strongly associated with cardiovascular disease and early mortality in adult childhood cancer survivors (CCS). Objective: Here, we assess the prevalence and determinants of DM in our nationwide CCS cohort. Methods: In this cross-sectional study, the prevalence of DM was assessed in 2338 CCS, using the Lifelines cohort (n = 132 226 adults with no history of cancer) as a reference. DM was defined through serum glucose measurement (fasting glucose ≥7.0 mmol/L or nonfasting ≥11.1 mmol/L) and/or self-report (previous diagnosis and/or medication use). Multivariable logistic regression models, adjusted for age, sex, and body mass index (BMI), were used to assess the cohort effect on the presence of DM. Multivariable logistic regression analysis was used to identify determinants of DM in CCS. Results: Survivors (median age 34.7 years, median follow-up time 27.1 years) showed increased odds for hyperglycemia (aOR = 2.72; 95% CI, 2.06-3.59), previous DM diagnosis (aOR = 3.03; 95% CI, 2.33-3.95), and antidiabetic medication use (aOR = 2.94; 95% CI, 2.17-3.99), compared to the reference cohort. Age (OR = 4.32; 95% CI, 1.84-10.15, >35 vs 18-35 years), BMI (OR = 1.12; 95% CI, 1.08-1.16, per point), family history of DM (OR = 2.38; 95% CI, 1.51-3.76), prior abdominal/pelvic radiotherapy (OR = 4.19; 95% CI, 2.32-7.55), total body irradiation (OR = 14.31; 95% CI, 6.98-29.34), hypogonadism (OR = 2.40; 95% CI, 1.15-4.99), hypertension (OR = 1.71; 95% CI, 1.06-2.76), and dyslipidemia (OR = 3.81; 95% CI, 2.15-6.75) were associated with DM in CCS. A statistically significant interaction between age and sex on the development of DM in survivors was identified. Conclusion: The identified 3-fold increased risk of DM in CCS, along with the clinically relevant and some modifiable determinants, underscores the importance of early risk-based screening and the exploration of lifestyle interventions in this population.