1. Introduction
obesity, epilepsy, ketosis, hyperinsulinemia, weight loss
OBESITY, EPILEPSY, KETOSIS, INSULIN RESISTANCE, HYPERINSULINEMIA, METABOLIC SYNDROME, TYPE 2 DIABETES, DISEASES
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/mThe ketogenic diet is a dietary regimen providing very low carbohydrate, high fat, and modest protein, that has an established role in the treatment of drug-resistant epilepsy [Low carbohydrate and ketogenic diets have become increasingly popular in the treatment of metabolic syndrome, obesity, and type 2 diabetes and various meta-analyses have shown their usefulness [International consensus establishes carbohydrates as the base of the food pyramid for healthy nutrition. Nevertheless, several studies have shown that an abundant intake of starchy foods and sugars, the main source of energy in Western diets including the Mediterranean Diet, may promote excessive insulin responses [In contrast, ketosis-inducing diets seem to reduce insulin resistance improving glucose and insulin levels, by requiring less insulin to be disposed of, suggesting being particularly useful in patients with insulin resistance triggered or maintained by hyperinsulinemia as well as in those with insulin secretory defects that prevent a normal glucose tolerance. Moreover, ketogenic diets seem to promote a non-atherogenic lipid profile and reduce blood pressure, particularly when associated with weight loss.Interestingly, ketogenic dietary interventions with ad libitum caloric intake or only moderate caloric restriction (trials reviewed in [A reasonable hypothesis is that each of the ketogenic meals in this dietary plan essentially produces an almost flat insulin-secretory response thanks to the very limited amount of carbohydrates provided, despite the presence of proteins and lipids that are known to stimulate insulin secretion, even prior to that ketosis is established and independently from weight loss. Support for this hypothesis would require the exact knowledge of the amount of insulin that is secreted after a ketogenic meal in comparison to an isocaloric Mediterranean meal, but this is not available.The quantification of insulin required to metabolize a certain meal type cannot be directly obtained by the observation of circulating peripheral insulin concentration profiles, because insulin extraction dynamically changes during the meal as insulin receptors are saturated [The aim of this study was therefore to measure the insulin secretory response to a typical ketogenic meal providing ~40% of individual energy needs and to compare it to the response to an isocaloric Mediterranean meal in healthy subjects, by modeling the circulating glucose, insulin, and 