Glycemic biomarkers in children with drug‐resistant epilepsy on various types of ketogenic diet therapies: A cross‐sectional study

Abstract

Objective: This study was undertaken to determine the hemoglobin A1c (HbA1c) and modified glucose-ketone index (mGKI) in children on different types of ketogenic diet (KD) for treatment of drug-resistant epilepsy, with attempts to evaluate their relationships with components of diet regime and other biomarkers. Methods:We conducted a cross-sectional study in children with drug resistant epilepsy aged between 6 months and 18 years, who were on various types of KD therapies without any change in regime for at least 3 months. Parental interview, review of medical records, and a single measurement for blood ketone, HbA1c, and plasma carnitine were performed. mGKI was the ratio of an average plasma glucose estimated from HbA1c to blood βhydroxybutyrate level.Results: Thirty-four patients were recruited with a median blood ketone of 2.90 mmol•L -1 and median HbA1c of 4.55%. Those on classical KD (cKD) had higher blood ketone (p = .031) and lower HbA1c (p = .010) and mGKI (p = .021) than those receiving modified Atkins diet, although both shared similar percentages of calories from carbohydrate (p = .211). The cKD and medium-chain triglyceride (MCT) KD groups had similar HbA1c (p = .252) and mGKI (p = .510).Blood ketone (p = .045) and the percentage of calories from MCT (p = .037) were the two main independent variables, inversely correlating with HbA1c. Other than plasma acylcarnitine (p = .047), neither blood ketone (p = .188) nor HbA1c (p = .170) could predict seizure reduction reliably. Both plasma acylcarnitine ≥ 6 μmol•L -1 (p = .013) and mGKI ≤ 2.2 (p = .013) were significantly associated with good seizure control.Significance: HbA1c could potentially be useful for monitoring KD adherence or, indirectly, systemic ketosis in nondiabetic children on KD for drug-resistant epilepsy. Plasma acylcarnitine and mGKI could be important biomarkers in the management of KD therapy.

Clinical characteristics of 27 children with febrile infection‐related epilepsy syndrome in a single center

“…The consensus on KD from the China Association Against Epilepsy regarding the optimal state of ketosis suggests that urine ketone level should be maintained above 3, blood ketone level should be 1.2-4.9 mmol/L, blood glucose level should be controlled at approximately 4.0 mmol/L, and blood glucose/ketone ratio (glucose/ketone index) should be 1:1-2:1. 10 Because the definition of ketosis varies, some studies maintained a goal of a serum BHB level of 4-6 mmol/L in refractory epilepticus (RE) patients, 24 some maintained a goal of >2-3 mmol/L in SRSE patients, 25,26 and some maintained a goal of ≥1.5 mmol/L in FIRES/SRSE patients. 27 From these studies, we can see that the BHB value in FIRES patients was lower than that in RE and SRSE patients.…”

“…Some studies have shown that the classical KD results in higher blood ketone level than a modified Atkins diet. 24 We found that two patients (S-3, S-8) had a lower level of ketosis (BHB 1-2 mmol/L, urine ketone 2þ) even with the classical 4:1 KD but their SE stopped, and they regained consciousness and could be taken off the ventilator, which was similar to the result of the study in which two SRSE patients got benefits at lower levels of ketosis (neither urine ketone ≥2þ nor serum B O H ≥ 2 mmol/L). 26 This finding may suggest that low level of ketosis may still reach the threshold for seizure control for a few FIRES patients.…”

A Pilot Study of a Ketogenic Diet in Bipolar Disorder: Clinical, Metabolic and Magnetic Resonance Spectroscopy Findings

“…Epilepsy research indicates that glucose ketone index may be more strongly correlated to seizure control than either ketone or glucose level alone. 24, 25 In an analysis of GKI we observed covariation and significant granger causality between GKI level and mood (Z = 2.32, p < 0.05), energy (Z = 2.28, p < 0.05) and anxiety (44.51, p < 0.001) and particularly in the responder group who remained on the diet (mood (Z = 3.11 p < 0.01), energy (Z = 3.60 p < 0.001) and anxiety (Z = 55.14 p < 0.001)). The GKI plots exhibit further evidence of an adaptation period where mood and energy increase as GKI falls (indicating an increasing ratio of ketones to glucose).…”

Response to “Pediatric refractory epilepsy: Exploring the ketogenic diet's influence on seizure recurrence”

“…It was reported that the blood ketone levels did not proportionately correlate with KD efficacy. 2 Therefore, we did not analyze the relationship between ketone levels and the effect on seizure control in this study. To ensure the homogeneity of research, for patients enrolled in 2011, we retrospectively reclassified them according to the ILAE 2017 classification.…”