Adipokines, body fatness, and insulin resistance among survivors of childhood leukemia

Background: Following our previous reports of an increased prevalence of insulin resistance and adiposity among acute lymphoblastic leukemia (ALL) survivors, particularly women treated with cranial radiotherapy (CRT), we aimed to (1) assess the relationships between adipokines (leptin and adiponectin), CRT, and measures of body fatness and (2) determine correlates of insulin resistance, by gender. Methods: We conducted cross-sectional evaluation of 116 ALL survivors (median age: 23.0 years; range: 18-37; average time from treatment: 17.5 years), including fasting laboratory testing (adiponectin, leptin, insulin, and glucose), anthropometric measurements (weight, height, and waist circumference), DXA (total body fat and truncal-to-lower-body-fat ratio), and abdominal CT (visceral fat). We estimated insulin resistance using the homeostasis model for assessment of insulin resistance (HOMA-IR). Analytic approaches included regression models and Wilcoxon rank sum testing. Results: Mean leptin per kilogram fat mass was higher for females (0.7ng/ml/kg) than males (0.4ng/ml/kg, P<0.01), and among subjects who had received CRT compared to those who had not received CRT (females CRT=0.9ng/ml/kg, no CRT=0.7ng/ml/kg; P=0.1; males CRT=0.5ng/ml/kg, no CRT=0.3ng/ml/kg; P<0.01). Elevated HOMA-IR was nearly uniformly present, even among subjects with BMI<25kg/m ², and was associated with higher leptin:adiponectin ratio (LA ratio; P<0.01). Conclusions: Among survivors of childhood leukemia, higher leptin levels were associated with measures of body fat and insulin resistance. Anthropomorphic and metabolic changes many years after ALL treatment remain a major health problem facing survivors and may be related to central leptin resistance.