Insulin regulation of glucose turnover and lipid levels in obese children with fasting normoinsulinaemia

Abstract

To evaluate the early metabolic alterations induced by obesity, we studied glucose turnover and lipid levels in obese children with fasting normoinsulinaemia. Two experimental protocols were carried out. Protocol 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 obese children either at low or high insulin infusion. During protocol II, the NEFA clamp induced a 25% reduction in peripheral insulin sensitivity in control children whereas no changes were observed in obese children. Interestingly, lipid infusion in control children was not sufficient 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 present study provides a portrait of glucose metabolism and lipid levels in normoinsulinaemic obese children. Our results document that peripheral insulin resistance is the first alteration at this stage of obesity, whereas an increase in insulin secretion and a defect in the inhibition of hepatic glucose release by insulin may develop at a later stage. 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.

Persisting obesity starting before puberty is associated with stable intraabdominal fat during adolescence

“…The majority of our subjects were prepubertal or in the early stages of pubertal development at the ®rst evaluation and they completed their sexual development at the last measurement. Changes due to pubertal development then lead to a metabolic situation similar to adults in spite of lower fat depots; in fact insulin metabolism has been described to be clearly affected by obesity in children 26,27 and related to IAT. 9 It is well-known that puberty causes a transient reduction in insulin sensitivity in normal subjects.…”

Relationship between high plasma leptin concentrations and metabolic syndrome in obese pre-pubertal children

“…Insulin resistance is one of the main disorders present in obese individuals. 6 The presence of hyperinsulinism and insulin resistance has been described in obese children of both sexes (mean age 10 y), using a hyperinsulinemic euglucemic clamp. 7 Some of the disorders related to this syndrome have been described in children, suggesting that it may have a pre-pubertal origin.…”

Comorbidities of Childhood Obesity

“…Yet it is unclear when these abnormalities occur in the setting of acute versus chronic obesity. Polonsky and coworkers [26] found that insulin secretory rates were significantly higher in the obese group when compared with the normal weight group. Furthermore, there was no difference in insulin clearance or hepatic insulin extraction between the groups.…”