Risk of Metabolic Syndrome and Glucose Homeostasis Among Childhood and Young Adult Acute Lymphoblastic Leukemia Survivors: Part of the ALL-STAR Study.

Abstract

Background: Metabolic syndrome (MetS), a risk factor for early cardiovascular morbidity and mortality, is seen in up to 34% of survivors of childhood acute lymphoblastic leukemia (ALL).

Procedure: We performed a Danish, national cross-sectional study of ALL survivors (aged 1-45 years at diagnosis) treated according to the NOPHO ALL2008 protocol, examined at least 1 year after treatment cessation. The study included non-cancer community controls, matched on sex and age. We explored the prevalence and components of the MetS criteria (hyperglycemia, hypertension, increased waist circumference (WC), and dyslipidemia) and glucose homeostasis (insulin and C-peptide).

Results: We included 366 survivors of ALL (participation rate 84%) and 368 controls. Median age (IQR) at follow-up examination was 14.1 (10.8-21.8) years, and follow-up time after the ALL diagnosis was 6.9 (4.7-9.1). The prevalence of MetS in survivors was 7.6% and in controls 3.8 % (p = 0.039). The increased MetS prevalence was driven by ALL patients undergoing total body irradiation (TBI), and age and body mass index (BMI) percentile ≥95 at diagnosis (p ≤ 0.01). The MetS prevalence in non-TBI patients did not differ from controls (p = 0.43), but non-TBI patients more often fulfilled the MetS criteria WC and/or elevated high-density lipoprotein (p < 0.03). Survivors had higher serum insulin and C-peptide than controls (p < 0.01).

Conclusions: ALL survivors have an increased risk of MetS compared with controls, essentially driven by the patients treated with TBI. The MetS frequency in non-TBI patients is equal to controls, but non-TBI patients more often have one or two components of Mets. ALL survivors seem slightly more insulin-resistant than controls.