The development of hyperinsulinemia and insulin resistance, both common in adults with established obesity, was studied in 16 children, weighing 169 +/- 8% ideal body weight who were 12.7 +/- 0.4 years of age with obesity duration of 0.5-8.5 years and continuous weight gain in excess of normal, and compared with 11 age-matched normal children. Early in the evolution of obesity, insulin and C-peptide responses to a normal meal were increased by 76 and 80%. The first insulin peak was higher (613 +/- 53 pmol/ml) than normal (413 +/- 59 pmol/ml, P < 0.02) and occurred only 50 +/- 7 min after onset of lunch versus 33 +/- 11 min in normal children (P < 0.0005). Obese patients had a total of 3.0 +/- 0.2 large insulin peaks within the 6-h period after the lunch versus only 1.5 +/- 0.2 peaks in normal children (P < 0.0005). In contrast, fasting plasma insulin and C-peptide levels remained normal during the initial years of obesity, then increased progressively with duration (r = 0.73, P < 0.001) and degree (r = 0.59, P < 0.02) of obesity. Insulin sensitivity evaluated as the rate of glucose uptake during a three-step hyperinsulinemic euglycemic clamp was comparable in the obese (20 +/- 1.5 mmol.m-2.min-1) and the normal (21.7 +/- 1.5 mmol.m-2.min-1) children. Initially higher than normal in obese children, the maximal rate of glucose uptake decreased with both obesity duration (r = -0.67, P < 0.005) and children's age (r = -0.66, P < 0.005), indicating the progressive development of insulin resistance.(ABSTRACT TRUNCATED AT 250 WORDS)