Ketogenic Diet: a model to evaluate the effect of high fat diet on regional adiposity and glucose metabolism in humans

Ketogenic Diet (KD) is an isocaloric high-fat (80-90%), low carbohydrate (2-5%) diet, inducing ketone bodies production, applied effectively for treatment of refractory childhood epilepsy and other neurometabolic diseases. We considered KD an unique model to study in humans the effect of high fat diet on regional adiposity and glucose metabolism and to evaluate the “overflow hypothesis” proposed by Bergman et al (Obesity. 2006;14:16S-19S) about the development of visceral adiposity, hyperinsulinemia, and insulin resistance after isocaloric high fat diet in the dog model. Body composition by anthropometry, subcutaneous (SAT) and visceral abdominal fat (VAT) by ultrasonography, glucose and lipid metabolism were evaluated before and after 12 weeks of KD in 7 children (mean age: 8,4±2,0). After KD, BMI z-scores, VAT, SAT and total body fat were unchanged whereas fasting glucose (84,3±8,8 vs 75,7±6,1 p<0,01), insulin (5,5±2,8 vs 2,6±1,6 p<0,01), and HOMA, insulin resistance index, (1,1±0,6 vs 0,5±0,3 p<0,01) were significantly reduced. Lipid metabolism was unchanged. Thus, increasing fat in the diet without achieving an hypercaloric intake did not increase visceral and subcutaneous abdominal fat and did not cause peripheral insulin resistance in the short term in children. Longitudinal studies are need to provide a conclusive answer on the adaptive metabolic changes on regional adiposity and insulin resistance occurring in humans during isocaloric high fat diet.