BODY COMPOSITION, METABOLIC PARAMETERS, ABDOMINAL ADIPOSE TISSUE, ADIPOCYTOKINES AND MARKERS OF INFLAMMATION IN PATIENTS IN EVOLUTIVE AGE TREATED WITH KETOGENIC DIET

The ketogenic diet (KD) is a high-fat, low-carbohydrate, and normal-protein diet which increases the production of the ketone bodies providing an alternative fuel source for the brain, used worldwide for children with intractable epilepsy. Only few studies were performed to study the effect of KD on nutritional status; literature data show that growth may be impaired in children treated with KD. It has been observed an increment in adipose tissue and a change in the glucose tolerance in animals fed with KD, possibly resulting from insulin resistance. No data are available on VAT assessment and relationship with glucose intolerance, insulin resistance and markers of metabolic syndrome in human treated with KD. Aim #1. To assess the nutritional status of children on KD and to study the effect on growth, resting energy expenditure, subcutaneous and visceral adipose tissue, lipid and glucose metabolism. Aim #2. To understand the neurohormonal effects of KD and the neuronal network involved in regulating energy homeostasis and to clarify the role of KD on the inflammation patterns, well related with metabolic syndrome (MS). Patients and methods Aim #1 18 patients (6 M/12 F, mean age 3,5 years, range 3,5-23,9) performed anthropometric measurements, skinfold thickness measurements, Body composition by DXA, REE, blood metabolic parameters at baseline and after 12 months of KD. Aim#2 14 patients (5 M/9 F, mean age 10,02 years, range 1,9-36,8) performed plasmatic levels of adipocytokines and markers of inflammation at baseline and after 12 weeks of KD. Results Aim#1 None statistical difference were found regarding body weight, height, BMI, skinfold thickness measurements, waist circumference, waist circumference/height and body composition measured by DXA after 12 months of KD. None statistical difference was found regarding visceral and subcutaneous abdominal fat after 12 months of KD; the ratio VAT/SAT was significantly higher after KD. Lipid profile and fasting glucose values were unchanged; insulin and HOMA were significantly reduced. Daily REE was unchanged, instead the RQ was significantly lower. Aim #2 The levels of inflammatory markers (high sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), adiponectin), FFA levels and ghrelin concentrations were unchanged before and after 12 weeks of KD. Discussion Aim#1 Our data demonstrate that KD doesn't alter body composition and growth in children and we confirm that KD doesn't affect the bone health. This finding is reassuring for the safety of KD prolonged for several months. We found that increasing fat in the diet without achieving an hypercaloric intake did not increase visceral and subcutaneous abdominal fat in children after 12 months of KD; in prepubertal patients we found a trend of increment of VAT, suggesting different changes in abdominal body fat distribution according to age. As expected we found an increment of fat oxidation as an adaptation to the high fat and low carbohydrate intakes, previously described as the main independent predictor of the reduction in seizure frequency. Our data demonstrate that KD is probably safe on the short/medium term, by maintaining lipid profiles as at baseline. Discussion Aim#2 The absence of change in inflammatory markers levels should confirm that with KD treatment we don't detect signals of risk of MS and cardiovascular disease despite high fat intake. We didn’t find any significant increase in ghrelin concentration: it seems that the anticonvulsant effect by the KD is not linked to ghrelin levels.