FV 330. Have We Done Wrong? Long-Term Follow-up of Cardiovascular Risk Factors in Glut1-Deficiency Treated with Ketogenic Diet Therapies

Background: Glut1 deficiency (GLUT1D) is a rare and treatable disorder of cerebral energy metabolism with ∼400 patients identified worldwide. A defect of the facilitated glucose transporter GLUT1 at the blood–brain barrier and in brain cells causes a cerebral energy crisis resulting in impaired development, epilepsy, and complex movement disorders. The resulting epileptic encephalopathy and movement disorders can be treated effectively by high-fat carbohydrate-restricted ketogenic diets (KDTs) mimicking fasting and providing ketones as an alternative cerebral fuel. Recent 6 to 24 months short-term follow-ups of epileptic patients reported elevated blood lipids and intima thickening of the carotid artery raising concerns about potential cardiovascular risks by KDTs.

Aims: To further clarify potential cardiovascular risks on KDTs therapy.

Methods: Between August 2001 and January 2008, we enrolled GLUT1D patients on KDT at two hospitals in Germany in this prospective, multicenter case series. The minimal follow-up was 10 years. Standard deviation scores (SDS) of body mass index (BMI), total cholesterol (TC), HDL/LDL cholesterol, and triglycerides (TG) before initiation of KDT were compared with the respective values at 6 months, 2, 5, and 10 years after initiation. After 10 years on KDT cardiovascular risk, assessed by BMI, carotid intima–media thickness (CIMT) measurement and blood pressure were compared with a healthy reference population (n = 550).

Results: Here, we provide the first long-term 10-year follow-up on cardiovascular risk of KDT in GLUT1D. Baseline and 10-year follow-up investigations were available from 10 individuals with GLUT1D on KDT. After 2 years on KDT BMI increased significantly, while TC, HDL cholesterol, and LDL cholesterol decreased. Within 3 to 5 years on KDT, these differences disappeared, and after 10 years, blood lipid parameters reflected the situation at initiation of KDT. Before initiation of KDT, one child had dyslipidemia, but no child after 10 years. No significant differences were observed with respect to BMI SDS (p = 0.26), CIMT (p = 0.63) as a surrogate marker for atherosclerosis, or systolic and diastolic blood pressure SDS (p = 0.11 and p = 0.37, respectively) in GLUT1D children treated with KDT for ≥ 10 years compared with healthy controls.

Conclusion: In contrast to previous short-term reports on adverse effects of KDTs, 10-year follow-up did not identify cardiovascular risks of KDTs therapy and confirm dietary therapy as the treatment of choice for GLUT1D. Results will also have implications for the use of KDTs therapies in other diseases such as intractable childhood epilepsy and metabolic disorders.

No conflict of interest has been declared by the author(s).