The effects of valproate on serum leptin, insulin, and lipid levels in epileptic children

Abstract

Background Weight gain is an important adverse effect of valproate (VPA) therapy. A number of mechanisms have been proposed for its pathophysiology. The aim of the present study is the evaluation of insulin, leptin and lipid levels in epileptic children on treatment with VPA. Methods Thirty epileptic children treated with VPA, and 20 age–sex‐matched healthy children, were enrolled in this study. Blood samples were taken and the body mass index was calculated for all of the subjects. Serum insulin, leptin, and lipid levels were compared between the two groups. Results Leptin levels were significantly higher in the patient group (P = 0.009) whereas body mass index values were comparable. There was a positive correlation between leptin and body mass index among both patient (r = 0.464, P = 0.01) and control groups (r = 0.734, P = 0.0001). Total cholesterol and low‐density lipoprotein (LDL) cholesterol levels were lower in VPA‐treated epileptic children than the control group (P = 0.008; P = 0.003, respectively). No significant difference was determined in insulin levels between the two groups. A negative correlation was observed between plasma VPA level and total cholesterol and LDL cholesterol levels in the patient group (r = −0.380, P = 0.03, r = −0.474, P = 0.008, respectively). Conclusion This study demonstrated higher leptin levels in the patient group despite similar BMI values. Hence, it seems likely that VPA causes leptin resistance. Unlike other anti‐epileptics, VPA does not produce an increase in serum cholesterol levels. On the contrary, lower levels of total and LDL cholesterol levels in VPA‐receiving patients have been observed in our study.

Effect of long‐term valproic acid therapy on lipid profiles in paediatric patients with epilepsy: a meta‐analysis

“…A total of 13 publications, involving 1,489 subjects (case group: 477, control group: 1012) [10, 12‐16, 18, 20‐25], summarized the effects of VPA monotherapy on TG levels in children with epilepsy. No significant heterogeneity ( p = 0.05, I 2 = 42%) was observed; therefore, we used a fixed‐effects model to conduct the meta‐analysis.…”

“…A total of 15 articles [10,[12][13][14][15][16][17][18][19][20][21][22][23][24][25], involving 1,649 subjects (case group: 506, control group: 1143), summarized the effects of VPA monotherapy on HDL levels in children with epilepsy. There was heterogeneity (p<0.00001, I 2 =82%), but the cause of heterogeneity was not detected by subgroup analysis.…”

Effect of valproic acid monotherapy on serum leptin and ghrelin levels in epileptic children (literature review)

“…This study demonstrated higher leptin levels in the patient group despite similar BMI values. Hence, it seems likely that VPA causes leptin resistance [28].…”