The aim of this study was to determine serum insulin, insulin-like growth factor-I (IGF-I) and its binding proteins (IGFBP-1 and IGFBP-3) levels and their relationship with androgen levels and ovarian structure in 23 girls with premature pubarche (PP). Fasting levels of testosterone, dehydroepiandrosterone (DHEA) and its sulfate (DHEAS), androstenedione (delta4A), sex hormone binding globulin (SHBG), glucose (G), insulin (I), IGF-I, IGFBP-1, IGFBP-3 were measured. Androgens or steroid hormone levels > 3 SD of normal postpubertal levels were considered as an exaggerated response to the ACTH test. The fasting I to G ratio (FIGR) was calculated and FIGR > 22 was suggestive of insulin resistance (IR). A pelvic ultrasound (US) was carried out and the ovarian structure was divided into five classes (c): c1--homogeneous, c2--microcystic, c3--multicystic, c4--polycystic and c5--follicular. The girls with PP were divided into two groups according to the main ovarian classes observed: PPc1 (n = 6) and PPc2 (n = 15). The FIGR showed IR in 44% of patients. The androgens, SHBG, G, I, FIGR, IGF-I and IGFBP-1 levels were similar among the groups (PPc1 vs PPc2). An exaggerated response to ACTH was more common and IGFBP-3 levels were higher in the PPc2 than in the PPc1 group (p = 0.04). Regression analysis revealed that I was correlated with DHEAS (r = -0.43, p = 0.04) and IGFBP-1 (r = -0.51, p = 0.01); IGF-I was correlated with DHEA (r = -0.42, p = 0.05), delta4A (r = -0.47, p = 0.02), SHBG (r = -0.43, p = 0.04), IGFBP-1 (r = -0.61, p = 0.002) and IGFBP-3 (r = 0.56, p = 0.005); IGFBP-1 was correlated with SHBG (r = 0.56, p = 0.005). These findings suggest that there might be interactions between the insulin-IGF-I-IGFBPs system and hyperandrogenism. However, the possible causal role of adrenal androgen hypersecretion on the insulin-IGF-I-IGFBPs axis and ovarian structure in girls with PP remains to be established. Since studies reveal that IGFBP-3 levels could be a negative predictor for insulin sensitivity throughout puberty, we hypothesize that girls with PP and microcystic ovaries are at risk of developing IR in the course of normal puberty.

In order to study the discriminative capacity of the C-peptide basal values (BV) in a functional test, we analysed the C-peptide response curve after a mixed meal in 26 insulin-dependent patients. The five criteria of response used were: (1) any increment after the stimulus; (2) percentual increment above 21%; (3) absolute increment above 0.35 ng/ml; (4) incremental area above 42.76 ng.min.ml-1, and (5) peak value above 2.16 ng/ml. Considering the first two criteria, many patients showed positive responses, in the diabetic group as a whole and when we analysed patients with BV > or = 0.74 ng/ml and < 0.74 ng/ml separately. When we applied only the last three criteria the number of positive responses was considerably smaller. Moreover, the majority of patients with BV < 0.74 ng/ml could not increase their levels over the ones established above. In patients with BV > or = 0.74 ng/ml, the number of positive and negative responses were similar. The comparison between the subgroups achieves statistical significance only for incremental area (chi 2 = 3.55, p = 0.03). We conclude that the functional test was important mainly for patients with BV > or = 0.74 ng/ml, and could have been omitted for patients with BV < 0.74 ng/ml. The best criteria of response were those based on the mean minus two standard deviations of each parameter in a non-diabetic group (the last three criteria), especially the incremental area.

Arq Bras Endocrinol Metab vol 45 nº 3 Junho 2001 278 RESUMOO objetivo deste estudo foi descrever o perfil da insulina e determinar sua relação com o hiperandrogenismo na pubarca precoce (PP). Avaliamos 23 meninas com PP devido à adrenarca precoce e 5 controles (C) pré-puberais normais (7,3±1,1 x 7,1±1,8 anos). Os níveis de sulfato de deidroepiandrosterona (SDHEA), testosterona (T) e globulina ligadora dos hormônios sexuais (SHBG) foram medidos. O índice de massa corporal (IMC) e o índice do androgênio livre (IAL) foram calculados. O teste oral de tolerância à glicose (G) foi realizado; sendo calculadas a relação de jejum da insulina (I) pela G (FIGR= I/G) e as áreas abaixo das curvas da G e I (AACG e AACI). A FIGR > 22 foi considerada como sugestiva de resistência a I (RI). O IMC foi maior na PP do que nos C: 18,8±3,0 x 15,5±1,6, p= 0,03. Os níveis de SDHEA (71,7±40,6 x 34,2±6,9µg/dl, p= 0,02), T (0,41±0,4 x 0,17±0,1nmol/L, p= 0,02) e IAL (0,73±0,7 x 0,17±0,04, p= 0,001) foram maiores na PP, enquanto a SHBG (63,7±23,1 x 110,2±23,9nmol/L, p= 0,0006) foi menor. A FIGR foi sugestiva de RI em 44% dos casos de PP, mas os níveis de G, I, a AACG, a AACI e a FIGR foram semelhantes aos C. Na PP foi observada correlação inversa entre SDHEA e I (r = -0,43, p= 0,04) e entre SHBG e IMC (r = -0,74, p = 0,0001) e AACI (r=-0,36, p= 0,09). A AACI mostrou uma correlação positiva com o IMC (r=0,56, p= 0,006) e a FIGR (r= 0,86, p= 0,0001). Embora o hiperandrogenismo adrenal possa não ter um efeito adverso sobre a sensibilidade à I na infância, como demonstrado pela correlação inversa entre o SDHEA e a I em meninas com PP, a presença da FIGR sugestiva de RI foi relativamente comum, permanecendo incerta a relação entre os níveis dos androgênios adrenais e a sensibilidade à insulina. ABSTRACTThe aim of this study was to describe the insulin profile and to determine the relationship with hyperandrogenism in the premature pubarche (PP). Twenty-three girls with PP due to premature adrenarche and 5 normal prepubertal control (C) girls were studied (7.3 ± 1.1 x 7.1 ± 1.8 years). The fasting levels of dehydroepiandrosterone sulfate (SDHEA), testosterone (T) and sex hormone binding globulin (SHBG) were measured. The body mass index (BMI) and the free androgen index (FAl) were calculated. The oral glucose tolerance test was performed; the fasting insulin (I) to glucose (G) ratio (FIGR = I/G) and the areas under the curve for G (AUCG) and I (AUCI) were calculated. A FIGR > 22 was suggestive of I resistance (IR). The BMI was higher in PP than in C (18.8 ± 3.0 x 15.5 ± 1.6, p = 0.03). Plasma levels of SDHEA (71.7 ± 40.6 x 34.2 ± 6.9µg/dl, p = 0.02), T (0.41 ± 0.4 x 0.17 ± 0.1nmol/L, p = 0,02) and FAl (0.73 ± 0.7 x 0.17 ± 0.04, p = 0.001) were higher in PP than in C, but SHBG levels (63.7 ± 23.1 x 110.2 ± 23.9nmol/L, p = 0.0006) were lower. The FIGR showed IR in 44% of patients, but the G, I, AUGC, AUIC and FIGR were similar in both groups. A negative correlation between SDHEA and I (r = -0.43, p = 0.04) and between

No abstract

RESUMOCom o objetivo de analisar as concentrações plasmáticas de SHBG, dos esteróides sexuais, perfil glicídico, lipídico e suas relações com variáveis clínicas, demográficas e medidas antropométricas, estudamos um grupo de 80 mulheres na pós-menopausa, 40 com diabetes mellitus (DM) tipo 2, com idade de 64,9±7,1 anos e duração conhecida do diabetes de 13,4±1,4 anos e 40 não diabéticas com idade de ól±8,9 anos. Foram analisados: idade, índice de massa corporal (IMC), relação cinturaquadril (RCQ), cintura, pressão arterial sistólica (PAs) e diastólica (PAd). As mulheres diabéticas apresentaram maior freqüência de distribuição andróide de gordura (75% vs. 50%, p= 0,03), maior PAs (p= 0,01), maior testosterona total (p= 0,003), índice de testosterona livre (p= 0,002) e índice de resistência insulínica (IRI) (p= 0,000) do que as mulheres não diabéticas. As não diabéticas com distribuição andróide de gordura apresentaram menores níveis de SHBG do que aquelas com distribuição ginecóide (p= 0,008). No grupo com IMC ³30kg/m2 e no grupo com cintura ³88cm, as mulheres diabéticas apresentaram maior testosterona total e índice de testosterona livre do que as mulheres não diabéticas. As não diabéticas com distribuição andróide de gordura apresentaram maior índice de testosterona livre do que aquelas com distribuição ginecóide (p= 0,01). As diabéticas com distribuição andróide apresentaram maiores níveis de estradiol do que aquelas com distribuição ginecóide (p= 0,02). Em conclusão, mulheres diabéticas apresentaram maior freqüência de distribuição abdominal de gordura, estando associada à maiores concentrações de testosterona total, índice de testosterona livre e estradiol e menores concentrações de SHBG. ABSTRACTIn order to investigate the relationship between plasma leveis of SHBG, sex steroids and glucose metabolism, lipid profile, anthropometric measurements, clinical and demographic variables, we studied a group of 80 post-menopausal women, 40 with type 2 diabetes (DM2) aged 64.9±7.1 and with known DM duration of 13.4± 1.4 years and 40 non-diabetic aged 61 ±8.9. We analyzed: age, body mass index (BMI), waist to hip ratio (WHR), waist, systolic (sBP) and diastolic blood pressure (dBP). Diabetic women had higher frequency of android adiposity (75% vs. 50%, p= 0.03), higher sBP (p= 0.01), higher total testosterone (p= 0.003), free testosterone index (p= 0.02) and insulin resistance index (IRI) (p= 0.000) than non-diabetic women. Non-diabetics with android adiposity had lower levels of SHBG than those with ginecoid adiposity (p= 0.008). In the group with BMI ³30kg/m2 and in the group with waist ³88cm diabetic women had higher total testosterone and free testosterone index than non-dia-