Background: Cardiac death among survivors of childhood cancer occurs at > 10 times the rate expected in the general population. Modifiable cardiovascular risk factors, including diabetes, increase risk for major cardiac events in a near multiplicative fashion. Thus, prevention of progression from prediabetes to diabetes could improve long-term cardiac morbidity and mortality. However, little is known about prediabetes in survivors. Methods: Prevalence of prediabetes (fasting glucose 100-125 mg/dL or HbA1c 5.7-6.4%) and diabetes were assessed in 3529 5+ year survivors ≥18 years of age and compared to 450 community controls stratified by age and matched for race/ethnicity, sex, and BMI using Chi-squared statistics. Logistic regression estimated risk factors for prediabetes and cox proportional hazards regression for progression from prediabetes to diabetes among survivors with multiple visits, reported as odds (OR) and hazard ratio (HR), respectively, with 95% confidence intervals (CI). Results: Among 3529 survivors (median age 30 years, range 18-65), the prevalence of prediabetes overall was 29.2% (95% CI 27.7-30.7) and diabetes was 6.5% (5.7-7.3). In each age strata, survivors had significantly higher prevalence of prediabetes and diabetes than controls with over 50% of middle-aged survivors (35-44 years) having prediabetes or diabetes (Table). In a multivariable model, therapy-related risk factors for prediabetes included high pancreatic tail dose (≥20 Gy: 2.9 [1.8-4.8]) and moderate prescribed cranial radiation dose (OR [95% CI] > 0- < 20 Gy: 1.4 [1.1-1.8], 20- < 30 Gy: 1.4 [1.0-1.9]) independent of age, sex, race/ethnicity and BMI. Among 695 survivors with prediabetes and longitudinal follow-up, median 5.1 years, 68 (10%) progressed to diabetes. After adjustment for age, sex, race/ethnicity and BMI, risk of progression from prediabetes to diabetes was increased by the presence of insulin resistance (HR 4.9 [95% CI 2.3-10.6]) or prior treatment with hematopoietic cell transplant (HR 2.9 [1.1-7.7]) or total body irradiation (HR 4.6 [1.6-13.5]). Conclusions: Survivors of childhood cancer have a high prevalence of prediabetes and high rates of progression to diabetes. Strategies that prevent progression to diabetes should be considered to decrease diabetes risk and subsequent cardiac morbidity and mortality in this high-risk population.

U.S. National Institutes of Health Athe American Lebanese-Syrian Associated Charities (ALSAC)