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

Author:

van Hulst Annelienke M1ORCID,Verwaaijen Emma J1,van den Berg Sjoerd A A2,van Litsenburg Raphaële R L1,Grootenhuis Martha A1,Fiocco Marta134,Neggers Sebastian J C M M12ORCID,van den Heuvel-Eibrink Marry M15ORCID,van den Akker Erica L T6ORCID

Affiliation:

1. Pediatric Oncology, Princess Máxima Center , 3584 CS Utrecht , The Netherlands

2. Department of Internal Medicine, Division of Endocrinology, Erasmus Medical Center , 3015 GD Rotterdam , The Netherlands

3. Leiden University Mathematical Institute , 2333 CA Leiden , The Netherlands

4. Department of Biomedical Data Science, Medical Statistics, Leiden University Medical Centre , 2333 ZA Leiden , The Netherlands

5. Child Health, UMCU-Wilhelmina Children's Hospital , 3584 EA Utrecht , The Netherlands

6. Department of Pediatric Endocrinology, Erasmus MC- Sophia Children's Hospital , 3015 CN Rotterdam , The Netherlands

Abstract

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.

Funder

Stichting Kinderen Kankervrij

Publisher

The Endocrine Society

Subject

Biochemistry (medical),Clinical Biochemistry,Endocrinology,Biochemistry,Endocrinology, Diabetes and Metabolism

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