OBJECTIVE:To investigate the independent influence of alterations in fat mass, body fat distribution and hormone release on pubertal increases in fasting serum insulin concentrations and on insulin resistance assessed by the homeostasis model (HOMA). DESIGN AND SUBJECTS: Cross-sectional investigation of pre-(n ¼ 11, n ¼ 8), mid-(n ¼ 10, n ¼ 11), and late-pubertal (n ¼ 10, n ¼ 11) boys and girls with normal body weight and growth velocity. MEASUREMENTS: Body composition (by a four-compartment model), abdominal fat distribution and mid-thigh interfascicular plus intermuscle (extramyocellular) fat (by magnetic resonance imaging), total body subcutaneous fat (by skinfolds), mean nocturnal growth hormone (GH) release and 06:00 h samples of serum insulin, sex steroids, leptin and insulin-like growth factor-I (IGF-I). RESULTS: Pubertal insulin resistance was suggested by greater (P < 0.001) fasting serum insulin concentrations in the latepubertal than pre-and mid-pubertal groups while serum glucose concentrations were unchanged and greater (P < 0.001) HOMA values in late-pubertal than pre-and mid-pubertal youth. From univariate correlation fat mass was most related to HOMA (r ¼ 0.59, P < 0.001). Two hierarchical regression models were developed to predict HOMA. In one approach, subject differences in sex, pubertal maturation, height and weight were held constant by adding these variables as a block in the first step of the model (r 2 ¼ 0.36). Sequential addition of fat mass (FM) increased r 2 (r 2 (inc)remental ¼ 0.08, r 2 ¼ 0.44, P < 0.05) as did the subsequent addition of a block of fat distribution variables (extramyocellular fat, abdominal visceral fat, and sum of skinfolds; r 2 inc ¼ 0.11, r 2 ¼ 0.55, P < 0.05). Sequential addition of a block of hormone variables (serum IGF-I and log (10) leptin concentrations; r 2 inc ¼ 0.04, P > 0.05) did not reliably improve r 2 beyond the physical characteristic and adiposity variables. In a second model, differences in sex and pubertal maturation were again held constant (r 2 ¼ 0.25), but body size differences were accounted for using percentage fat data. Sequential addition of percentage body fat (r 2 (inc)remental ¼ 0.11, r 2 ¼ 0.36, P < 0.05), then a block of fat distribution variables (percentage extramyocellular fat, percentage abdominal visceral fat, and percentage abdominal subcutaneous fat; r 2 inc ¼ 0.08, r 2 ¼ 0.44, P ¼ 0.058), and then a block of serum IGF-I and log (10) leptin concentrations (r 2 inc ¼ 0.07, r 2 ¼ 0.51, P < 0.05) increased r 2 . Mean nocturnal GH release was not related to HOMA (r ¼ 7 0.04, P ¼ 0.75) and therefore was not included in the hierarchical regression models. CONCLUSION: Increases in insulin resistance at puberty were most related to FM. Accumulation of fat in the abdominal visceral, subcutaneous and muscular compartments may increase insulin resistance at puberty beyond that due to total body fat. Serum concentrations of leptin and IGF-I may further modulate HOMA beyond the effects of adiposity and fat distribution. However, the results...

Dysregulation of the growth hormone (GH)-insulin-like growth factor-I (IGF-I) axis in children and adolescents with insulin-dependent diabetes mellitus (IDDM) is well documented. Elevated levels of circulating GH, increased GH secretory amplitude, and decreased concentrations of IGF-I, IGFBP-3, and GHBP have been related to poor glycemic control. We proposed that pubertal maturation may be a more significant factor, potentially overriding the effects of metabolic control, especially during mid-puberty when the GH-IGF-I axis is maximally stimulated. We studied 24 male children and adolescents with IDDM over a 5 year period. Subjects were grouped both by pubertal stage (prepubertal vs mid-pubertal) and by level of glycemic control (hemoglobin A1 (<9%, 9-11.5%, and >11.5%). Twenty-four hour every 20 minute blood sampling for GH determination was analyzed using the Cluster algorithm, and static measures of IGF-I, IGFBP-3, and GHBP were obtained. When analyzed by pubertal status, we found no difference in the number of GH secretory peaks or the interval between concentration peaks. The sum of the peak heights and area under the curve were significantly greater in the mid-pubertal boys, as was the average GH nadir. Serum levels of IGF-I and IGFBP-3 were greater in the mid-pubertal boys, but levels of GHBP were higher in the prepubertal boys. When analyzed by level of glycemic control, we found no differences in the number of GH secretory peaks or interval between peaks among the 3 groups. However, the sum of the peak heights, area under the curve, and average GH nadir were all lower in the group with the intermediate level of glycemic control (HgbA1 9-11.5%); no differences were observed between the other 2 groups. This relationship persisted when the mid-pubertal subjects were analyzed separately. No differences were found among the 3 groups for levels of IGF-I, IGFBP-3, or GHBP. We conclude that normal increases in GH secretion and levels of IGF-I and IGFBP-3 occur during mid-puberty in boys with IDDM. A concomitant increase in average GH nadir may reflect an underlying effect of metabolic control. Greater GH secretion was observed in the groups with the lowest and highest levels of glycemic control. We speculate that this may be related to an increased incidence of severe hypoglycemic episodes in the group with the lowest levels of glycosylated hemoglobin, resulting in metabolic derangements similar to those with elevated glycosylated hemoglobin levels.

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