COEXISTENCE OF SEVERE INSULIN-RESISTANCE AND HYPERINSULINEMIA IN PREADOLESCENT OBESE CHILDREN

To determine the time course of changes in insulin action and secretio n that occur early during the development of obesity, we studied child ren before the onset of puberty. The reason for choosing the prepubert al stage of development is that it is metabolically characterized by b oth a high sensitivity to insulin and low glucose stimulated insulin r esponses. Fifteen obese preadolescents (8 male/7 female, age 10 +/- 0. 4 years, body mass index (BMI) 31 +/- 1.2 kg/m(2) Tamer Stage I) with a duration of obesity of less than 5 years and 10 non-obese preadolesc ents (6 male/4 female, age 10+/-0.4 years, BMI 18 +/- 0.9 kg/m(2)) mat ched for gender were studied. In a cross-sectional analysis, we compar ed responses in obese preadolescents, with those in obese adolescents and obese adults with a longer duration of obesity. The euglycaemic hy perinsulinaemic clamp with 1-C-13-glucose (Hot Ginf) and indirect calo rimetry were used to quantitate insulin action and the hyperglycaemic clamp used to assess beta-cell function. Insulin-stimulated glucose up take measured at two physiological levels of hyperinsulinaemia (simila r to 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 oxidati ve and non-oxidative glucose metabolism were observed in all three gro ups 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 gl ucose-stimulated insulin levels during the hyperglycaemic damp mirrore d the reductions in glucose uptake during the insulin clamp in all obe se groups. These results indicate that insulin resistance and hyperins ulinaemia co-exist in preadolescent children with moderate to severe o besity.