Longitudinal study on pubertal insulin resistance

Previous cross-sectional studies show that puberty is associated with a red uction in insulin sensitivity (S,), but no longitudinal studies have examin ed this change in detail. This study is a longitudinal study in 60 children (33 male and 27 female subjects; 32 Caucasian and 28 African-American) exa mined at Tanner stage I (age 9.2 +/- 1.4 years) and after 2.0 +/- 0.6 years of follow-up, by which time 29 children remained at Tanner stage I and 31 had progressed to Tanner stage III or IV. Tanner stage was assessed by phys ical examination. S-I, the acute insulin response (AIR), and the dispositio n index (DI) were determined by the tolbutamide-modified intravenous glucos e tolerance test and minimal modeling, body fat mass was assessed by dual-e nergy X-ray absorptiometry, visceral fat was determined by computed tomogra phy, and fasting blood was analyzed for hormone levels. In children progres sing to Tanner stage III, S, fell significantly by 32% (4.4 +/- 3.0 to 3.0 +/- 1.7 x 10(-4)min(-1)/[mu IU/ml]), AIR increased by 30%, DI fell by 27%, and there was a significant increase in fasting glucose (93.5 +/- 5.0 to 97 .0 +/- 4.1 mg/dl) and insulin (14.3 +/- 8.1 to 18.6 +/- 11.0 mu IU/ml). In children remaining at Tanner stage I, there was a slight increase in S-I (6 .4 +/- 3.1 to 7.4 +/- 3.5 x 10(-4)min(-1)/[mu IU/ml]) with no significant c hange in AIR or fasting glucose and insulin. The pubertal fall in S-I was m ore consistent in African-Americans; remained significant after controlling for age, sex, and change in fat mass, visceral fat, and fat-free mass; and was similar in children at low, medium, and high body fat. Change in S, wa s not significantly related to change in fasting hormone levels, but change in AIR was significantly related to change in androstendione (r = 0.39; P = 0.04). Pubertal transition from Tanner stage I to Tanner stage III was as sociated with a 32% reduction in S-I, and increases in fasting glucose, ins ulin, and AIR. These changes were similar across sex, ethnicity, and obesit y. The significant fall in DI suggests conservation in beta -cell function or an inadequate beta -cell response to the fall in S-I. The fall in S-I wa s not associated with changes in body fat, visceral fat, IGF-I, androgens, or estradiol.