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 β‐hydroxybutyrate 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.