Longitudinal changes in insulin resistance in children with epilepsy on ketogenic diet: Prevalence and risk factors

Introduction: The aim of the study was to evaluate the incidence of insulin resistance (IR) and the associated risk factors in children with epilepsy on a ketogenic diet (KD).

Methods: This longitudinal cohort study analyzed data of children with epilepsy on KD. Insulin resistance was assessed using the homeostasis model assessment of insulin resistance (HOMA-IR). The HOMA-IR value, fasting serum insulin levels, fasting glucose (FG) levels, and lipid profiles were measured before the initiation of the KD and at 6- to 12-month intervals.

Results: A total of 28 children were enrolled. The median age at the initiation of KD was 2.7 ± 2.4 years, and the median follow-up duration was 2.1 ± 1.4 years. The median HOMA-IR (HOMA-IR-1) value before the initiation of KD was 1.2 ± 0.2, which significantly increased to 1.8 ± 0.3 at the last follow-up (HOMA-IR-2; ∆HOMA-IR = 0.6 ± 0.3, p < 0.001). The following factors were associated with patients with higher HOMA-IR-2 values (≥1.9): younger age at seizure onset (0.3 ± 0.2 years, p < 0.001), at the initiation of antiepileptic drugs (AEDs; 0.3 ± 0.3 years, p < 0.001), and at the initiation of KD (1.3 ± 0.5 years, p < 0.001) and higher serum alanine transaminase (ALT; 84.0 ± 17.8 U/L, p = 0.022), total cholesterol (TC; 245.0 ± 20.1 mg/dL, p = 0.001), low-density lipoprotein cholesterol (LDL-C, 103.0 ± 6.7 mg/dL, p = 0.003), and triglyceride (387.0 ± 28.8 mg/dL, p < 0.001) levels. Multivariate regression analysis revealed that the age at seizure onset (p = 0.002), at initiation of AEDs (p = 0.021), and at initiation of KD (p = 0.022) and serum levels of LDL-C (p = 0.012) and triglycerides (p = 0.026) were associated with a significantly high HOMA-IR-2 value.

Conclusion: Close monitoring of serum lipids levels, especially at younger age, may aid in detecting exacerbation of IR.

Keywords: Child; Epilepsy; Hyperlipidemia; Insulin resistance; Ketogenic diet.