Insulin resistance in patients on valproic acid: relation to adiponectin

To investigate the presence of insulin resistance in obese children with idiopathic epilepsy on valproic acid (VPA) monotherapy in comparison to obese otherwise healthy subjects. Secondary outcome was to explore the relation between adiponectin and insulin resistance among those patients.

Fifty obese children with generalized idiopathic epilepsy on VPA monotherapy and a control group of 49 obese clinically healthy age and sex-matched children with simple obesity were recruited in the study. Anthropometric assessment, fasting plasma insulin (FI), fasting glucose (FG) and fasting adiponectin levels were measured. Fasting glucose insulin ratio (FGIR) and homoeostasis model assessment for insulin resistance (HOMA-IR) were calculated for both patients and control subjects. Measurement of serum VPA trough level was also performed in patients.

Patients had significantly higher fasting blood glucose, fasting insulin, lower FGIR and higher HOMA-IR values, compared to controls. Mean adiponectin level was significantly lower in patients compared to controls. The duration of treatment with valproic acid negatively correlated with adiponectin (r = -0.285, P = 0.045), but did not correlate with fasting glucose, insulin, FGIR or HOMA-IR. Total daily VPA dose significantly correlated with fasting insulin (r = 0.495, P < 0.001), FGIR (r = -0.525, P < 0.001) and HOMA-IR (r = 0.404, P = 0.004).

This study ascertains the relationship between dose and duration of VPA therapy, insulin resistance and the adipocytokine axis. We are reporting the novel proposal that obese VPA-treated children are more insulin resistant and have lower adiponectin levels than obese and otherwise healthy children.