Helena M. Gazolla

The relationship between ovarian structure and serum insulin, insulin-like growth factor-I (IGF-I) and its binding protein (IGFBP-1 and IGFBP-3) levels in premature pubarche.

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.

Resistência à insulina na pubarca precoce - Relação com os androgênios

The 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 SHBG and BMI (r = -0.74, p = 0.0001) and AUIC (r = -0.36, p = 0.09) were observed in PP. The AUIC showed a positive correlation with BMI (r = 0.56, p = 0.006) and FIGR (r = 0.86, p = 0.0001). Adrenal hyperandrogenism may not have adverse effects on I sensitivity at childhood, expressed here by the negative correlation between SDHEA and I, in girls with PP. But presence of the FIGR suggestive of IR was so common, that the exact relationship between the levels of adrenal androgens and I sensitivity remains unclear.

Discriminative capacity of fasting C-peptide levels in a functional test according to different criteria of response to a stimulus

Abstract 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 in-crement 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 ≥ 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 ≥ 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 (χ2 = 3.55, P = 0.03). We conclude that the functional test was important mainly for patients with BV ≥ 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.

Interrelações entre SHBG e esteróides sexuais com medidas antropométricas, pressão arterial e lipídeos em mulheres com e sem diabetes mellitus tipo 2

In 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-diabetic women. Non-diabetics with android adiposity had higher free testosterone index than those with ginecoid adiposity (p= 0.01). Diabetic women with android adiposity had higher estradiol than those with ginecoid adiposity (p= 0.02). In conclusion, diabetic women had higher frequency of android adiposity, associated with high total testosterone, free testosterone index and estradiol and low levels of SHBG. These results suggest that hyperandrogenism with low SHBG could be indicators of the insulin resistance syndrome, and could somehow increase the insulin resistance in these subjects.