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Updated: May 19, 2026

Lipidomics and Transcriptomics in Neurological Diseases
Published on: March 18, 2022
Risks of using standard reference ranges for carbohydrate and lipid metabolism in low-carbohydrate diets: insights
Katsuyuki Matsui1,2, Mioko Mori3, Tomohiro Kumada3
1Division of Endocrinology, Metabolism and Diabetes, Shiga Medical Center for Children, 5-7-30, Moriyama, Moriyama, Shiga 524-0022 Japan.
Introduction:
Ketogenic diet (KD) therapy is effective for refractory epilepsy but significantly impacts carbohydrate and lipid metabolism. We previously encountered a patient who developed diabetes during KD; metabolic abnormalities were undetected by conventional criteria for diabetes, suggesting standard criteria are inapplicable. This study aimed to establish specialized metabolic reference ranges for patients on KD.
Methods:
We retrospectively analyzed laboratory data from 18 pediatric patients with refractory epilepsy treated with KD. Geometric means and reference ranges (mean ± 2SD) were calculated using mixed-effects models to account for repeated measures.
Results:
Before KD, geometric means (reference ranges) were: random plasma glucose (RPG), 96.7 (79.1-118.3) mg/dL; HbA1c (NGSP), 4.76% (4.22-5.36); HbA1c (IFCC), 29 (23-35) mmol/mol; total cholesterol (T-Cho), 159.1 (98.8-256.5) mg/dL; and triglycerides (TG), 107.3 (41.4-277.8) mg/dL. During KD, values were: RPG, 77.6 (59.8-100.6) mg/dL; HbA1c (NGSP), 4.09% (3.58-4.69); HbA1c (IFCC), 21 (16-28) mmol/mol; T-Cho, 184.5 (113.3-300.7) mg/dL; and TG, 155.5 (48.2-501.7) mg/dL. Multiple mixed-effects models showed that KD significantly lowered HbA1c and RPG but increased T-Cho, HDL-Cho, TG, and free fatty acids. Changes in LDL-Cho were not statistically significant.
Conclusion:
KD therapy significantly lowers HbA1c and RPG while increasing lipid profiles. Consequently, impaired glucose tolerance may be masked by "normal" values if conventional criteria are used. To avoid delayed diagnosis, patients on KD should be evaluated using specialized reference ranges specific to their dietary therapy.
Supplementary Information:
The online version contains supplementary material available at 10.1007/s13340-026-00906-5.
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