Co-existence of severe insulin resistance and hyperinsulinaemia in pre-adolescent obese children

Abstract

To determine the time course of changes in insulin action and secretion that occur early during the development of obesity, we studied children before the onset of puberty. The reason for choosing the prepubertal stage of development is that it is metabolically characterized by both a high sensitivity to insulin and low glucose stimulated insulin responses. Fifteen obese preadolescents (8 male/7 female, age 10 ± 0.4 years, body mass index (BMI) 31 ± 1.2 kg/m2 Tanner Stage I) with a duration of obesity of less than 5 years and 10 non-obese preadolescents (6 male/4 female, age 10 ± 0.4 years, BMI 18 ± 0.9 kg/m2) matched for gender were studied. In a cross-sectional analysis, we compared responses in obese preadolescents, with those in obese adolescents and obese adults with a longer duration of obesity. The euglycaemic hyperinsulinaemic clamp with 1-13C-glucose (Hot Ginf) and indirect calorimetry were used to quantitate insulin action and the hyperglycaemic clamp used to assess beta-cell function. Insulin-stimulated glucose uptake measured at two physiological levels of hyperinsulinaemia (~ 180 and 480 pmol) was reduced by 20 and 45% in all three groups of obese compared to non-obese subjects (p < 0.01). Defects in oxidative and non-oxidative glucose metabolism were observed in all three groups of obese subjects at the higher insulin infusion rate. The ability of insulin to inhibit lipid oxidation was impaired in all three obese groups at both levels of hyperinsulinaemia. Increases in basal and glucose-stimulated insulin levels during the hyperglycaemic clamp mirrored the reductions in glucose uptake during the insulin clamp in all obese groups. These results indicate that insulin resistance and hyperinsulinaemia co-exist in preadolescent children with moderate to severe obesity.