INSULIN REGULATION OF GLUCOSE-TURNOVER AND LIPID-LEVELS IN OBESE CHILDREN WITH FASTING NORMOINSULINEMIA

To evaluate the early metabolic alterations induced by obesity, we stu died glucose turnover and lipid levels in obese children with fasting normoinsulinaemia. Two experimental protocols were carried out. Protoc ol I consisted of a euglycaemic glucose clamp at two rates of insulin infusion, Protocol II was similar to protocol I except for a variable lipid infusion used to maintain basal non-esterified fatty acid (NEFA) levels, During protocol I, the glucose disappearance rates were lower in obese children, while no differences were found in hepatic glucose release. NEFA response to insulin was not substantially altered in ob ese children either at low or high insulin infusion. During protocol I I, the NEFA clamp induced a 25% reduction in peripheral insulin sensit ivity in control children whereas no changes were observed in obese ch ildren. Interestingly, lipid infusion in control children was not suff icient to reproduce the same degree of insulin resistance observed in obese children, suggesting that NEFA are only one of the determinants of insulin resistance at this stage of obesity. In conclusion, the pre sent study provides a portrait of glucose metabolism and lipid levels in normoinsulinaemic obese children. Our results document that periphe ral insulin resistance is the first alteration at this stage of obesit y, whereas an increase in insulin secretion and a defect in the inhibi tion of hepatic glucose release by insulin may develop at a later stag e. In addition, primarily receptor and post-receptor defects and some alterations of NEFA metabolism are likely to coexist in the induction of insulin resistance at this stage of obesity.