Long-term effect of a classical ketogenic diet on glucose metabolism: A 12-months longitudinal study

The classical ketogenic diet (cKD) is a normocaloric, high-fat, very low-carbohydrate diet that induces ketosis, mimicking starvation state. The ketone bodies are alternative body fuel and they pass into the brain, replacing glucose as an energy source; for these reasons, it’s used as a recognised treatment for drug-resistant epilepsy (DRE), GLUT1 Deficiency Syndrome (GLUT1DS) and PDH deficiency, and it’s currently assessed for obesity, metabolic syndrome and type 2 diabetes. Glucose profile on patients treated with a long- term cKD has poorly investigated, so we evaluated the effect of a 12-months cKD on glucose metabolism of 29 children affected by DRE and GLUT1DS (mean age: 8.0 y, range: 0.5- 16.6 y; 17 females; 22 GLUT1DS), to determine fasting HOmeostatic Model Assessment- Insulin Resistance (HOMA-IR) and Quantitative Insulin Sensitivity Index (QUICKI). BMI- zscore (-0.22±1.87 vs -0.38±1.39, P=0.453) and percentage of body fat (22.7±7.8 vs 22.2±1.3, P=0.488) didn’t change during the treatment. Children showed a not significant reduction in fasting blood glucose (84.9±1.6 mg/dl vs 80.8±1.6 mg/dl; P=0.085). However, fasting insulin significantly decreased (9.2±1.0 μU/mL vs 5.5±1.0 μU/mL; P=0.013), and both HOMA-IR and QUICKI indexes were significantly changed (2.0±0.2 vs 1.2±0.2; P=0.018; 0.51±0.00 vs 0.52±0.00; P=0.041, respectively). After 12 months of cKD, fasting blood glucose doesn’t change, but a significant improvement is observed in HOMA-IR and QUICKI indexes, corroborating our previously published data of short-term effect of cKD on glucose metabolism. These results suggest potential interesting implications of the KD in insulin metabolism alterations; however, long-term studies on adult patients are needed to confirm these adaptive metabolic changes during cKD.