Acute Insulin Secretory Effects of a Classic Ketogenic Meal in Healthy Subjects: A Randomized Cross-Over Study

The classic ketogenic diet (KD) is a high-fat, low-carbohydrate diet that mimics a starvation state with sufficient caloric intake to sustain growth and development. KD is an established treatment for several diseases, and it is currently evaluated in the management of insulin-resistant states, although insulin secretion after a classic ketogenic meal has never been investigated. We measured the insulin secretion to a ketogenic meal in 12 healthy subjects (50% females, age range 19–31 years, BMI range 19.7–24.7 kg/m2) after cross-over administrations of a Mediterranean meal and a ketogenic meal both satisfying ~40% of an individual’s total energy requirement, in random order and separated by a 7-day washout period. Venous blood was sampled at baseline and at 10, 20, 30, 45, 60, 90, 120, and 180 min to measure glucose, insulin, and C-peptide concentrations. Insulin secretion was calculated from C-peptide deconvolution and normalized to the estimated body surface area. Glucose, insulin concentrations, and insulin secretory rate were markedly reduced after the ketogenic meal with respect to the Mediterranean meal: glucose AUC in the first OGTT hour −643 mg × dL−1 × min−1, 95% CI −1134, −152, p = 0.015; total insulin concentration −44,943 pmol/L, 95% CI −59,181, −3706, p < 0.001; peak rate of insulin secretion −535 pmol × min−1 × m−2, 95% CI −763, −308, p < 0.001. We have shown that a ketogenic meal is disposed of with only a minimal insulin secretory response compared to a Mediterranean meal. This finding may be of interest to patients with insulin resistance and or insulin secretory defects.