Serum Insulin, Cortisol, Leptin, Neuropeptide Y, Galanin and Ghrelin Levels in Epileptic Children Receiving Valproate

Abstract

Aims: The objective of this study was to investigate the cause of valproate (VPA)-associated weight gain in children. Methods: Eighteen children (10.94 ± 3.78 years) with epilepsy were assigned to VPA therapy. Serum levels of glucose, insulin, cortisol, leptin, neuropeptide Y (NPY), galanin and ghrelin were assessed before (month 0) and after 18 months of therapy. Eighteen age- and gender-matched patients (10.78 ± 3.95 years) were enrolled as the control group. Results: Excess per capita weight of 2.3 kg was determined in the children receiving VPA over 18 months compared to the control group. In these patients, a statistically significant increase in standardized weight score, Homeostasis Model Assessment index, serum leptin, NPY and galanin values was determined at the 18th month compared to those before VPA treatment and in the control group, and there was also a significant decrease in ghrelin values. Conclusion: Increased serum levels of leptin, NPY and galanin play an important role in VPA-associated weight gain in children. While ghrelin is not directly associated with weight gain, its serum levels decline as a response to weight gain.

Physiology, Signaling, and Pharmacology of Galanin Peptides and Receptors: Three Decades of Emerging Diversity

“…Furthermore, there was a positive association between galanin levels and body mass index (Celi et al, 2005). In another study, elevated serum levels of galanin were associated with a gain in body mass index in epileptic children treated with valproate (Cansu et al, 2011). Similarly, plasma galanin levels were increased in female patients with obesity and obese women with type 2 diabetes (Baranowska et al, 1997), although a separate study reported comparable plasma galanin concentrations in obese and normal weight women (Invitti et al, 1995).…”

Impact of early life exposure to antiepileptic drugs on neurobehavioral outcomes based on laboratory animal and clinical research

“…Recent research has found that children with epilepsy who were treated with valproate tend to be shorter in stature and have higher body mass index (BMI) than children who had not taken valproate [112,113]. In a different series of studies with a similar approach, valproate use in children with epilepsy was associated with increased weight gain [114–122]. It has been suggested that weight gain is due to altered expression of growth hormones or ghrelin [113,123].…”

Ghrelin: An emerging new anticonvulsant neuropeptide

“…It has been suggested that valproic acid (VPA) treatment could affect ghrelin stimulation in a manner different from that of other AEDs, and prolonged treatment could lead to higher ghrelin levels (Berilgen et al., 2006; Prodam et al., 2010). Moreover, decreases in serum ghrelin levels were observed in VPA‐treated children but not in oxcarbazepine‐treated children (Cansu et al., 2011a,b). The effect of VPA on ghrelin levels may be due merely to its ability to induce weight gain in treated subjects.…”