Characterization of insulin resistance in young adult survivors of childhood acute lymphoblastic leukaemia and non-Hodgkin lymphoma.

Introduction: An increased prevalence of metabolic disorders and cardiovascular (CV) disease has been reported in childhood acute lymphoblastic leukaemia (ALL)/non-Hodgkin lymphoma (NHL) cancer survivors.

Objective: To characterize the determinants of insulin resistance (IR) observed in this population, according to the treatment received.

Methods: Ninety one patients (45 men, mean age: 24 ± 5 years; mean follow-up: 15 ± 5 years) previously treated for a childhood ALL (n = 76) or NHL (n = 15) were grouped according to their previous treatment: chemotherapy only (Group I; n = 43), chemotherapy + cranial irradiation (CI) (Group II; n = 32) and chemotherapy + bone marrow transplant (BMT)/total body irradiation (TBI) (Group III, n = 16).

Results: A high prevalence of IR (HOMA-S < 60%) was observed in the BMT/TBI group (88%) compared to groups I (9%) and II (16%). The IR patients from groups [I+II] (12% of these groups) showed higher BMI, fat mass (FM) and visceral fat when compared with the non-IR patients. In contrast, the IR patients from group III had mean BMI and total FM similar to those of non-IR patients but showed a reduction of lean body mass and an increase in the relative proportion of trunk FM similar to the IR patients from groups [I + II]. This was associated with an altered lipid profile, high TNF-α and IL-6 levels, and reduced adiponectin levels compared to IR patients from group [I + II] and non-IR patients.

Conclusion: Childhood ALL/NHL survivors treated by BMT/TBI frequently develop severe insulin resistance associated with peripheral-to-central fat redistribution, rather than increased total FM, and low adiponectin levels which may contribute to their increased CV risk.