Early changes in postprandial insulin secretion, not in insulin sensitivity, characterize juvenile obesity.

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)