Leptin Increase During Dexamethasone and Its Association With Hunger and Fat in Pediatric Acute Lymphoblastic Leukemia

Abstract

Context: During treatment, children with acute lymphoblastic leukemia (ALL) receive high doses dexamethasone, which induce acute side effects.

Objective: To determine the influence of a 5-day dexamethasone course on changes in leptin, fat mass, BMI, hunger, sleep, and fatigue and to explore associations between these changes.

Methods: Pediatric ALL patients were included during maintenance treatment. Data were collected before (T1) and after (T2) a 5-day dexamethasone course (6 mg/m2/day). At both time points, BMI, fat mass (bioelectrical impedance analysis), and leptin were assessed, as well as parent-reported questionnaires regarding hunger, fatigue, and sleep problems. Changes between T1 and T2 were assessed using paired tests. Correlation coefficients were calculated to assess associations between these changes (Delta scores: T2-T1). Univariable regression models were estimated to study associations between covariates and elevated leptin.

Results: We included 105 children, with median age 5.4 years (range, 3.0-18.8). Leptin and fat mass, as well as hunger scores, fatigue, and sleep deteriorated after 5 days of dexamethasone (P < .001), in contrast to BMI (P = .12). No correlations between delta leptin and delta fat mass, BMI, hunger, fatigue, or sleep were found. Elevated leptin on T1 was associated with older age (odds ratio [OR] 1.51; 95% CI, 1.28-1.77), higher fat mass (OR 1.19; 95% CI, 1.07-1.33), and earlier maintenance week (OR 0.96; 95% CI, 0.92-0.99).

Conclusion: Five days of high-dose dexamethasone treatment led to direct and significant changes in leptin, hunger scores, and fat mass. Since children with ALL are at increased risk for metabolic adverse events, understanding underlying mechanisms is important, and a dexamethasone-induced state of acute leptin resistance might play a role.

Keywords: acute lymphoblastic leukemia; dexamethasone; fat mass; hunger score; leptin.

Figure 1.

Regulation of energy balance through leptin pathway. Leptin is produced by adipose tissue and exerts its effect on both intake and energy expenditure through the hypothalamus. Low levels of leptin induce a physiological response, including a feeling of hunger, and decreases energy expenditure. High leptin levels reduce food intake and increases energy expenditure. The exact effect of dexamethasone and sleep and fatigue is unknown. Created with BioRender.com.

Figure 2.

Study design. Acute lymphoblastic leukemia patients were included during maintenance therapy. Assessments took place before (T1) and after (T2) a 5-day dexamethasone course. Leptin and fat mass were measured, and parents completed 3 questionnaires on both time points. Abbreviations: ALL, acute lymphoblastic leukemia; ET, Eating Thermometer (hunger scores); MR, medium risk; PedsQL-MFS, Pediatric Quality of Life Inventory—Multidimensional Fatigue Scale; SDSC; Sleep Disturbance Scale for Children.

Figure 3.

Flow diagram. After screening on inclusion and exclusion criteria, 163 eligible patients were asked to participate, of whom 105 were enrolled in the study. Complete data for both time points (ie, measurement before the start of a 5-day dexamethasone course (T1) and after this course (T2) is depicted. Abbreviations: ALL, acute lymphoblastic leukemia; HR, high risk; MR, medium risk; SR, standard risk.

Figure 4.

Boxplots before (T1) and after (T2) a 5-day dexamethasone course. Boxplots visualize measurements before (T1) and after (T2) a 5-day dexamethasone course. Abbreviations: BMI, body mass index, SDS, standardized deviation score, SDSC, Sleep Disturbance Scale for Children.