RELATIONSHIP OF DOCOSAHEXAENOIC ACID SUPPLEMENTATION AND INSULINE RESISTANCE IN OBESE CHILDREN

BACKGROUND: obesity may be associated with a later onset of chronic disorders and clinical complications. Insulin resistance, glucose intolerance and hyperinsulinemia are major components of the metabolic syndrome, which is highly prevalent among children and adolescents with severe obesity. Low levels of LCPUFAs, especially docosahexaenoic acid (C22:6 n-3, [DHA]) and a high n-6/n-3 LCPUFA ratio in skeletal muscle membrane phospholipids have been associated with insulin resistance in adults. Recent data suggest that the synthesis of DHA differs between obese children and normal weight children. In particular, in obese children, the highest quartile of BMI z-score was associated with higher plasma levels of the n-6/n-3 LCPUFA ratio. Given the high prevalence of insulin resistance in childhood obesity, we asked whether supplementation with DHA would be more effective than diet and physical activity alone in reducing this metabolic alteration. AIM: to determine whether DHA supplementation, in addition to adequate diet and lifestyle, may reduce insulin resistance compared with diet and physical activity only, in obese children. Secondary aims were to evaluate whether may exist an association of the change of steatosis degree after the intervention with DHA supplementation... SUBJECTS AND METHODS: this is a multicenter, longitudinal, double-blind, randomized, placebo-controlled trial that started on January 01, 2010. Up to September 30, 2012, thirty (14 boys, 16 girls, mean [SD] age, 11.4 [1.29] years, range 8-13), were recruited. All obese children consecutively admitted to the Department of Paediatrics, San Paolo Hospital, Milan, and to the Department of Paediatrics, Federico II Hospital, Naples, for routine examinations were assessed for eligibility. The study protocol scheduled daily oral supplementation of either an intervention “product”, that is two capsule of purified DHA (500 mg) or two capsule of wheat germ oil (500 mg). A nutritional-behavioural intervention was additionally recommended in all recruited children promoting a normocaloric balanced diet and an active lifestyle based on the Italian guidelines for treatment of childhood obesity. Additional recommendations were given to engage in a moderate daily exercise program (30-45 minutes/day aerobic physical exercise), tailored to individual preferences. Children were visited at the care centers within 3±1 days (baseline) after enrolment, and at 6 months after starting intervention. Evaluations included anthropometrical measurements, nutritional, metabolic assessment and liver ultrasonography. Children were randomly assigned to the intervention or control group based on a computer generated, blocked randomization list by each center. A block size of four was used, stratified according to gender. The investigator who generated the randomization sequence was independent of the research staff and unaware of children. RESULTS: at baseline there was no significant difference between groups for any anthropometrical (minimum P= 0.806) or dietary (minimum P= 0.318) or biochemical (minimum P=0.539) variable. No significant difference among groups occurred for daily intake of energy or any macronutrient and the end of the study (minimum P=0.111). At the end of the intervention a significant reduction of plasma fasting glucose (DHA group P=0.046; placebo group P=0.048), insulin (DHA group P=0.001; placebo group P=0.048) and HOMA (DHA group P=0.001; placebo group P=0.050) in both groups was observed. A higher percentage variation of plasma fasting insulin (P=0.0046) and HOMA (P=0.0045) in DHA than placebo group was showed. There was a difference between groups for percentage reduction of liver steatosis: in DHA group from 14 to 7 % (P=0.655), in placebo group from 20 to 13 % (P=0.275).