ABSTRACT
PURPOSE: The clinical efficacy of the ketogenic diet as therapy for patients with difficult-to-treat epilepsy prompted us to investigate the glucose metabolism of these patients under an oral overload of glucose, that is, in the oral glucose tolerance test (OGTT). METHODS: Thirty patients (12 males, 18 females; age range: 17-59, mean: 35.1) with difficult-to-treat epilepsy, 23 patients with controlled epilepsy (11 males, 12 females; age range: 14-66, mean: 36.9), and 39 control subjects (18 males, 21 females; age range: 16-58, mean: 33.3) were evaluated with the OGTT. For patients with epilepsy, we also measured C-peptide and glycosylated hemoglobin in the fasting state. Glucose levels lower than 70 mg/dL at any point of the curve were considered to be abnormal. RESULTS: All subjects in the control group and the group with controlled epilepsy had a normal OGTT. In contrast, all 30 patients with difficult-to-treat epilepsy had at least one point on the OGTT curve below the normal range (P<0.001), most often 180 and 240 minutes after the oral glucose load (P<0.001). C-peptide levels were significantly lower in the group with difficult-to-treat epilepsy as compared with the group with controlled epilepsy. Fasting glycohemoglobin and insulin levels did not differ between the two patient groups. CONCLUSIONS: We suggest that undiagnosed metabolic disturbances in patients with difficult-to-treat epilepsy may somehow contribute to their refractoriness to conventional pharmacological therapy. We propose the hypothesis that calorie-restricted diets aimed at correcting OGTT curves may prove beneficial in treating patients with difficult-to-treat epilepsy. Our hypothesis generates a clear endpoint for the diet, and its demonstration would provide new standards for diet-based antiepileptic regimens. Accordingly, our results may help in understanding the positive consequences of ketogenic or calorie-restricted diets in persons with seizures.
