Characterization of glucose homeostasis and lipid profile in adult, seizure-free, epileptic patients in Asian population.

OBJECTIVE

The most common prescribed antiepileptic drugs (AEDs), phenytoin and valproate, are potent enzyme inducers and inhibitors of the cytochrome P450 system, which interfere with lipid profile and glucose homeostasis. Studies on this topic have suffered from inadequate assessment of confounders and have rarely included glucose homeostasis and lipid profile as well as both enzyme inducers and inhibitors in the same study. We sought to determine whether these drugs had an effect on lipid profile and glucose homeostasis in Thai epileptic patients.

METHODS

We recruited 98 patients with epilepsy (45 taking phenytoin, 27 taking valproate, and 26 not taking any AED). Fasting blood samples were obtained to measure serum lipid, and glucose homeostasis was evaluated via the oral glucose tolerance test. We calculated the homeostasis model assessment index for each patient.

RESULTS

Our study revealed that CYP450 was induced by AEDs, and that patients on phenytoin had an increased mean value of serum total cholesterol, serum total triglycerides, and serum LDL cholesterol when compared with patients with epilepsy taking valproate and those taking no AEDs. No statistical significant difference was observed between patients taking valproate and patients taking no AEDs. In addition, patients with epilepsy taking phenytoin had higher fasting plasma glucose levels at fasting state than both those taking valproate and those taking no AEDs. Thirty percent of the patients taking phenytoin exhibited insulin resistance. We have found a negative correlation between log insulin sensitivity and log TG, but not high-density lipoprotein (HDL).

CONCLUSIONS

CYP450-induced phenytoin produces significant amelioration in several serologic markers of atherosclerosis. These findings suggest that phenytoin may substantially increase the risk of vascular events.