Endocrine Abstracts

Background: Childhood acute lymphoblastic leukemia (ALL) is no longer a death sentence. With survival rates approaching 90%, focus needs to shift towards improving long-term quality of life. Compared to the general population, adult survivors have four-fold excess risk of mortality secondary to cardiovascular diseases. Thus, modifiable risk factors, such as altered glucose metabolism, are of great importance and should be actively sought after. Studies show high prevalences of insulin resistance(IR) from an early age in this population, but its pathophysiology is poorly understood. Proposed mechanisms include body compostion alterations, with increased fat mass, fat redistribution and decreased lean mass.

Study aim: We aimed to investigate the early development of glucose homeostasis disturbances in ALL survivors while still children and to determine the relationship of IR with body composition.

Methods: We registered 20 ALL survivors, aged under 18, in remission for at least one year, evaluated in the Pediatric Endocrinology Department between 2016 and 2022 (mean age 9.85 +/-3.68 years, range 4-17; average time from diagnosis 4.7 years). Anthropometric measurements (BMI, waist circumference, waist-to-hip ratio) and glycemic indices (fasting glucose and insulin, HbA1c, OGTT) were collected and compared with results from 12 healthy children matched for age and sex. IR was evaluated using HOMA-IR and QUICKI. DXA was performed to assess body composition in 12 survivors.

Results: Glycemic profile (fasting glucose, HbA1c, OGTT) was normal in both groups. However, ALL survivors were 50% more likely to have IR compared to healthy subjects (RR=1.5, 95%CI 1-2.23, P=0.047), despite no significant difference in BMI (mean z-score 0.26±1.38 vs 0.05±1.24, P=0.7). Higher mean HOMA-IR (2.76±1.88 vs 0.97±0.73, P=0.0095) and lower mean QUIKI (0.34±0.04 vs 0.425±0.08, P=0.02) were observed in ALL survivors. In the study population, HOMA-IR correlated with BMI (r=0.57, 95%CI 0.06-0.84, P=0.03), android-gynoid fat ratio (r=0.65, 95%CI 0.09-0.90, P=0.02) and appendicular lean mass index(ALMI) (r=0.75, 95%CI 0.24-0.93, P=0.01).

Conclusions: As children in remission after ALL are 50% more likely to have IR compared to healthy subjects, an early and regular screening for metabolic disturbances should be implemented in order to diminish cardiovascular risk among the growing population of survivors. Surprinsingly, in our study group, IR had a positive relationship not only with fat distribution, but aslo with ALMI, a surrogate for skeletal muscle mass. This is contrary to the general belief that high lean mass is beneficial for glucose regulation. Further studies are needed to clarify the effect of muscle mass on glucose homeostasis in ALL survivors.