EARLY CHANGES IN INSULIN SECRETION AND SENSITIVITY IN OBESE CHILDREN

Abstract

Hyperinsulinism and insulin resistance characterize obesity in adults. The natural history of these abnormalities was studied in 16 children aged 12.8 ± 1.4 years with obesity of 0,5-8.5 yr duration, compared with 11 age-matched children. Fasting insulin was normal initially, then increased with obesity duration (r=O.68, p<0.005), not with children age (r=0.30, NS). in contrast insulin response to a normal meal was increased by 75% in the lirst years of obesity without later augmentation, (p<0.0005). Neither fasting nor post-prandial insulin correlated with weight. Insulin sensitivity was evaluated with a 3 step hyperinsulinemic euglycemic clamp. The maximal rate of glucose uptake was initially normal (19±1 vs 21±1 mmol/m2.min), then decreased with obesity duration (r=0.66, p<0.005) and children age (r=0.60, p<0.01), indicating the development of insulin resistance. Fasting insulin and maximal glucose uptake were inversely related (r=0.65, p<0.005). Insulin concentration corresponding to half-maximal uptake was normal (677 vs 654 pM) and did not vary with obesity duration. Abnormal insulin response to meals is an early metabolic alterations in obesity, followed by iho co-development of insulin resistance aind fasting hyperinsulinemia.