Acute Insulin Secretory Effects of a Classic Ketogenic Meal in Healthy Subjects

Classic Ketogenic Diet (KD) is a high-fat, low-carbohydrate diet that induces ketone body production through fat metabolism with the goal of mimicking a starvation state without depriving the body of necessary calories. KD is an established treatment of glucose transporter type 1 deficiency syndrome and drug-resistant epilepsy, and it is currently evaluated in the management of insulin resistant states as metabolic syndrome, obesity and type 2 diabetes. Insulin is required for effective storage of meal substrates, but insulin secretory rate (ISR) response after a classic ketogenic meal (cKDm) has never been investigated We measured ISR after a cross-over administrations of a cKDm and of a Mediterranean meal (Mm) providing 2%vs60% carbohydrates, 88%vs25%fat and 10%vs15% protein, respectively of 40% of individual’s total energy requirement in 12 healthy subjects (6F/6M, 19-31 year. Venous blood was sampled at 0, 10, 20, 30, 45, 60, 90, 120 and 180min to measure glucose, insulin and C-peptide concentrations. ISR was calculated from c-peptide deconvolution and normalized to estimated body surface area Glucose and insulin concentrations and ISR responses were markedly reduced (p<0,001 al parameters) after cKDm with respect to Mm (Figure). For the first time we have shown that cKDm is disposed with only a minimal ISR compared to a Mm. This finding may be of interest for patients with insulin resistance and or insulin secretory defects.