RESUMO
Small size at birth may result from fetal undernutrition which may occur at different times during gestation. Early postnatal catch-up growth and excess childhood weight gain are associated with an increased risk of adult cardiovascular disease and type 2 diabetes mellitus. The aim of this study was to assess the relative contributions of body composition and energy expenditure on fasting insulin sensitivity during late childhood. We took advantage of two previously described prospective cohorts of children born either at term or prematurely, with a wide range of birth weights adjusted for gestational age. Seventy-one prepubertal children (mean age 7.5 +/- 0.3 years) were examined: 23 term SGA (8 M, 15 F), 12 preterm SGA (7 M, 5 F), 16 term AGA (8 M, 8 F), and 20 preterm AGA (9 M, 11 F). Mean height SDS was -0.18 +/- 0.11 and mean BMI SDS was 0.27 +/- 0.03. Change in weight SDS was significantly higher in children born SGA compared to their AGA counterparts (p < 0.001). Change in weight SDS was highly correlated with fasting insulin (p < 0.03) and leptin (p < 0.001). Fasting insulin correlated only with serum leptin levels. Body composition appeared to be the main determinant of fasting leptin levels. No differences in lipid profile were observed between the different groups. There was a clear tendency to higher insulin and leptin levels in children born SGA compared with their AGA counterparts. IGF-I levels were significantly higher only in SGA term compared to AGA term. Resting energy expenditure (REE) was lower in SGA born at term and higher in SGA born preterm compared to their AGA counterparts. In conclusion, fasting insulin sensitivity is mainly determined by leptin levels which in turn are determined by body composition. IGF-I and REE showed a divergent pattern in SGA term compared to SGA preterm groups. IGF-I levels were determined only by weight change from birth to age 2 years, which may not be as pronounced in VLBW children compared to SGA term and thus may preclude a difference in IGF-I levels in the group of preterm children. The divergent effect in REE in SGA born at term compared to SGA born preterm compared to their AGA counterparts may explain the divergent effects on IGF-I. This difference might be a consequence of different timing in the exposure to intrauterine nutritional deficiency.
Assuntos
Composição Corporal/fisiologia , Metabolismo Energético/fisiologia , Recém-Nascido de Baixo Peso/fisiologia , Nascimento Prematuro/fisiopatologia , Nascimento a Termo/fisiologia , Densidade Óssea , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Insulina/sangue , Resistência à Insulina , Leptina/sangue , MasculinoRESUMO
Prader-Willi syndrome (PWS) is a genetic disorder characterized by dysmorphic features, obesity, hypogonadism, hypotonia and mental retardation. Obesity has been linked to insulin resistance and the latter has also been associated with premature adrenarche. Since up to date a controlled study to investigate adrenarche and its hormonal regulation was lacking in PWS, our aim was to assess whether prepubertal PWS patients develop premature adrenarche and its relationship with markers of insulin sensitivity. Fourteen prepubertal children with PWS (6 M, 8 F) and 10 non-syndromal simple obese matched controls (5 M, 5 F) participated (mean age: 7.62 +/- 1.84 years). A fasting blood sample was obtained for adrenal and ovarian androgens, sex hormone binding globulin, insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein-1, leptin, adiponectin and a lipid profile. Thereafter an oral glucose tolerance test was performed. PWS patients were smaller at birth and a higher proportion displayed premature pubarche. No differences were found in testosterone, androstenedione, sex hormone binding globulin, free androgen index, homeostatic model assessment-IR, 2-hour insulin, leptin or adiponectin levels. 17-hydroxyprogesterone and DHEAS levels however, were significantly higher in PWS. IGF-I levels were significantly lower in PWS and correlated significantly with height SDS (p < 0.05). In conclusion, a higher proportion of premature adrenarche in our PW patients was observed, which was not explained by differences in insulin sensitivity or plasma levels of adipokines and IGF-I.
Assuntos
Adrenarca/sangue , Resistência à Insulina , Síndrome de Prader-Willi/sangue , Síndrome de Prader-Willi/fisiopatologia , Adiponectina/sangue , Adrenarca/metabolismo , Estudos de Casos e Controles , Criança , Feminino , Glucose/metabolismo , Humanos , Metabolismo dos Lipídeos , Masculino , Síndrome de Prader-Willi/metabolismo , Puberdade/sangueRESUMO
INTRODUCTION: Insulin resistance (IR) develops as early as age 1 to 3 yr in small for gestational age (SGA) infants who show rapid catch-up postnatal weight gain. In contrast, greater insulin secretion is related to infancy height gains. We hypothesized that IGF-I levels could be differentially related to gains in length and weight and also differentially related to IR and insulin secretion. METHODS: In a prospective study of 50 SGA (birth weight < 5th percentile) and 14 normal birth weight [appropriate for gestational age (AGA)] newborns, we measured serum IGF-I levels at birth, 1 yr, and 3 yr. IR (by homeostasis model assessment) and insulin secretion (by short iv glucose tolerance test) were also measured at 1 yr and 3 yr. RESULTS: SGA infants had similar mean length and weight at 3 yr compared with AGA infants. SGA infants had lower IGF-I levels at birth (P < 0.0001), but conversely they had higher IGF-I levels at 3 yr (P = 0.003) than AGA infants. Within the SGA group, at 1 yr IGF-I was associated with length gain from birth and insulin secretion (P < 0.0001); in contrast at 3 yr IGF-I was positively related to weight, body mass index, and IR. CONCLUSIONS: IGF-I levels increased rapidly from birth in SGA, but not AGA children. During the key first-year growth period, IGF-I levels were related to beta-cell function and longitudinal growth. In contrast, by 3 yr, when catch-up growth was completed, IGF-I levels were related to body mass index and IR, and these higher IGF-I levels in SGA infants might indicate the presence of relative IGF-I resistance.
Assuntos
Recém-Nascido Pequeno para a Idade Gestacional/sangue , Resistência à Insulina , Fator de Crescimento Insulin-Like I/análise , Insulina/sangue , Insulina/metabolismo , Peso ao Nascer , Estudos de Casos e Controles , Desenvolvimento Infantil , Pré-Escolar , Teste de Tolerância a Glucose , Humanos , Lactente , Recém-Nascido de Baixo Peso/sangue , Recém-Nascido , Secreção de Insulina , Estudos ProspectivosRESUMO
CONTEXT: An increased prevalence of polycystic ovary syndrome (PCOS) has been reported in adult women with type 1 diabetes mellitus (DM1). We investigated whether these hormonal abnormalities begin during puberty by evaluating the ovarian steroidogenic response to leuprolide acetate. METHODS: We studied 56 adolescent girls with DM1 (aged 12.3 +/- 0.2 yr) and 64 healthy girls (C) (aged 11.9 +/- 0.2 yr) up to 2 yr post menarche, matched by age, body mass index, and pubertal development. We evaluated anthropometrical data and Ferriman-Gallway score and performed a leuprolide test (500 microg sc) to study ovarian function. Ovarian volume was determined by transabdominal ultrasonography. RESULTS: We found five DM1 but no C girls with abnormally located terminal hair (Fisher's exact, P < 0.05). Free androgen index increased throughout puberty in girls with DM1 (ANOVA, P < 0.0001), which was associated with a decrease in SHBG levels in girls with DM1 (ANOVA, P < 0.0001). Stimulated 17OH progesterone (17OHProg) increased throughout puberty only in girls with DM1 (ANOVA, P < 0.01). Girls with DM1 at Tanner stage 5 had higher stimulated LH to FSH ratio, testosterone, and 17OHProg levels than girls at Tanner stage 4. In contrast, in C girls the stimulated testosterone, 17OHProg, and LH to FSH ratio were similar at Tanner stages 4 and 5. Ovarian volumes and uterine length were larger in girls with DM1 (analysis of covariance, P < 0.05). CONCLUSIONS: These data suggest that patients with DM1 have differences in ovarian steroidogenic response to leuprolide, compared with C girls during puberty. Future studies in young women should clarify whether these findings are related to the pathogenesis of hyperandrogenism later in life.
Assuntos
Diabetes Mellitus Tipo 1/fisiopatologia , Leuprolida/farmacologia , Ovário/efeitos dos fármacos , Puberdade/fisiologia , 17-alfa-Hidroxiprogesterona/sangue , Criança , Estudos Transversais , Feminino , Hormônio Foliculoestimulante/sangue , Humanos , Hormônio Luteinizante/sangue , Ovário/fisiopatologia , Globulina de Ligação a Hormônio Sexual/análiseRESUMO
OBJECTIVES: We assessed pubertal development, height, weight, and waist-to-hip ratio (WHR), an index of central adiposity during puberty, in girls with type-1 diabetes mellitus (T1DM), compared to a contemporary control group. METHODS: Pubertal development, weight, height and WHR were studied in 100 pubertal girls with T1DM, and were compared to a control group of 576 normal girls (C), recruited from schools with a similar socioeconomic level and ethnicity. The age of onset of various pubertal stages was estimated by using probit analysis. RESULTS: Breast Tanner stage 2 (BT2) began at 8.89 +/- 0.11 and 9.10 +/- 0.28 yr in C and T1DM, respectively. A delay of 6 months was observed in T1DM for BT3 and BT4 (p < 0.05). Menarche occurred 6 months later in girls with T1DM (p = 0.03). WHR decreased during puberty in C (p < 0.001), but not in T1DM. In girls with T1DM, the body mass index standard deviation score (BMI-SDS) increased throughout puberty (p < 0.001), but it was stable in C. In T1DM girls, BMI-SDS, but not hemoglobin A1c levels (HbA1c), was a significant determinant of pubertal development. Final height was similar in T1DM and C. CONCLUSIONS: Pubertal development in girls with T1DM occurred earlier than described in historical cohorts, but a later onset of menarche and final stages of breast development were observed. The increase in BMI-SDS and the stability of WHR in girls with T1DM during puberty suggest that this period may be critical for determining later weight gain and body composition in adult women with this condition.
Assuntos
Diabetes Mellitus Tipo 1/fisiopatologia , Puberdade , Aumento de Peso , Adolescente , Antropometria , Tamanho Corporal , Criança , Chile , Feminino , Hemoglobinas Glicadas/análise , Humanos , Menarca/fisiologia , Valores de ReferênciaRESUMO
BACKGROUND: Recent studies in the United States have demonstrated that a significant proportion of girls show thelarche before the age of eight years. Nutritional status, geographic influences and racial factors are known to affect the timing of puberty. AIM: To evaluate the age of onset of puberty, development of secondary sexual characteristics and menarche in Chilean girls, and its relation to obesity and socioeconomic status. MATERIAL AND METHODS: Healthy girls attending elementary school, from first to ninth grade in Santiago, Chile, were studied. A pediatric endocrinologist evaluated pubertal development using Tanner classification. Breast development was assessed by inspection and breast palpation. Average age of onset of pubertal events was determined by probit analysis. RESULTS: A total of 758 girls, aged 5.8 to 16.1 years, were recruited. Obesity, defined as a BMI greater than 90th percentile, was found in 24.4%. The age of menarche was 12.7 years, the onset of Tanner stage 2 breast development and pubic hair was at 8.9 and 10.4 years, respectively. Sixteen percent of girls aged 7 to 7.9 years, had thelarche. Upper class girls showed a later onset of breast Tanner stage 4 stage than low-middle class girls. Obesity was not found in logistic regression analysis to be a significant predictive factor in the onset of puberty. CONCLUSIONS: The age of menarche has not changed in the last thirty years, but an earlier onset of thelarche has occurred. The high frequency of thelarche between 7 and 8 years suggests that the normal age of breast development should be revised.
Assuntos
Índice de Massa Corporal , Puberdade/fisiologia , Maturidade Sexual/fisiologia , Classe Social , Adolescente , Análise de Variância , Mama/crescimento & desenvolvimento , Criança , Chile , Estudos Transversais , Feminino , Cabelo/crescimento & desenvolvimento , Humanos , Menarca , Fatores SocioeconômicosRESUMO
In prepubertal children, low birth weight is related to reduced insulin sensitivity, particularly if a history of rapid postnatal weight gain is present. We sought to determine whether these associations were also evident in premature, very-low-birth-weight (VLBW) children. We studied 60 VLBW prepubertal children aged 5-7 yr (mean age 5.7 +/- 0.7 yr). Birth weights ranged from 690 to 1500 g (mean 1195 +/- 31 g), with gestational ages between 25 and 34 wk (median 29 wk). A short iv glucose tolerance test was carried out to assess fasting insulin sensitivity and glucose-stimulated insulin secretion. The effects of current body mass index, birth weight (SD scores), postnatal growth rates, and indicators of postnatal morbidity were evaluated by analysis of covariance. Twenty children were born small for gestational age, and 40 were appropriate for gestational age. Ninety-eight percent of them had attained a height within target range. Children who were small for gestational age had lower insulin sensitivity than children who were appropriate for gestational age (homeostasis model assessment insulin resistance index 1.24 +/- 0.17 vs. 0.94 +/- 0.08, P < 0.05). Moreover, birth weight SD scores correlated significantly with homeostasis model assessment insulin resistance index (r = -0.326, P = 0.01). This effect persisted after adjustment for current body mass index, gestational age, and perinatal morbidity. In addition, fasting and postload insulin secretion during the short iv glucose tolerance test correlated significantly with early postnatal growth rates, independently of birth weight SD scores. Our findings in a cohort of VLBW prepubertal children indicate that growth in utero as well as postnatal growth rates are independent determinants of subsequent insulin sensitivity and secretion.
Assuntos
Recém-Nascido de muito Baixo Peso/metabolismo , Resistência à Insulina , Insulina/metabolismo , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Teste de Tolerância a Glucose , Homeostase , Humanos , Recém-Nascido , Recém-Nascido de muito Baixo Peso/crescimento & desenvolvimento , Secreção de Insulina , MasculinoRESUMO
Strong associations between low birth weight and insulin resistance have been described. However, most of these studies have been retrospective. We aimed to determine whether infants born small for gestational age (SGA: birth weight <5th percentile for gestational age) have decreased insulin sensitivity, compared with appropriate for gestational age (AGA: birth weight >10th percentile) at 1 yr of age. We studied blood lipids, fasting insulin levels, other markers of insulin sensitivity, and insulin secretion during an iv glucose tolerance test in a cohort of 85 SGA and 23 AGA 1-yr-old infants. In addition, SGA infants were stratified according to catch-up growth (CUG) in weight (WCUG) or length (LCUG) during the first year of life. At 1 yr, SGA infants had a clear tendency to higher triglycerides. Fasting insulin was significantly higher in SGA infants with WCUG, compared with those who did not catch up and AGA infants (mean +/- SEM, 32.6 +/- 4.6 vs. 14.9 +/- 2.3 vs. 21.4 +/- 3.3 pM, respectively; P < 0.05). Length increment (in SD score) was the principal determinant of postload insulin secretion (R(2) = 0.1, P < 0.01). We conclude that insulin secretion and sensitivity are closely linked to patterns of rapid WCUG and LCUG during early postnatal life. Fasting insulin sensitivity is more related to WCUG and current body mass index, whereas insulin secretion seems to be directly related to LCUG.
Assuntos
Crescimento/fisiologia , Recém-Nascido Pequeno para a Idade Gestacional/crescimento & desenvolvimento , Resistência à Insulina/fisiologia , Insulina/metabolismo , Glicemia/metabolismo , Estatura/fisiologia , Peso Corporal/fisiologia , Estudos de Coortes , Feminino , Teste de Tolerância a Glucose , Humanos , Lactente , Recém-Nascido , Insulina/sangue , Secreção de Insulina , Masculino , Estudos ProspectivosRESUMO
OBJECTIVE: To study the consequences of low birth weight on glucose and lipid metabolism 48 hours after delivery. METHODS: We studied 136 small for gestational age (SGA) and 34 appropriate for gestational age (AGA) term neonates who were born in Santiago, Chile. Prefeeding venous blood was obtained 48 hours after birth for determination of glucose, free fatty acids, beta-hydroxy butyrate, insulin, C-peptide, leptin, sex hormone-binding globulin, insulin-like growth factor-binding protein-1 (IGFBP-1), and cortisol. RESULTS: SGA newborns had lower glucose (SGA versus AGA, median [interquartile range]: 3.6 mmol/L [2.9-4.1 mmol/L] vs 3.9 mmol/L [3.6-4.6 mmol/L]) and insulin levels (31.3 pmol/L [20.8-47.9 pmol/L] vs 62.5 pmol/L [53.5-154.9]) than AGA infants, and they had higher glucose/insulin ratios (13.9 mg/dL/uIU/mL [8.6-19.1 mg/dL/uIU/mL] vs 8.2 mg/dL/uIU/mL [4.6-14.1 mg/dL/uIU/mL]). SGA infants also had higher levels of IGFBP-1 (5.1 nmol/L [4.4-6.7 nmol/L] vs 2.9 nmol/l [1.4-4.2 nmol/L]), free fatty acids (0.72 mEq/L [0.43-1.00 mEq/L] vs 0.33 mEq/L [0.26-0.54 mEq/L]) and beta-hydroxy butyrate (0.41 mEq/L [0.15-0.91 mEq/L] vs 0.09 mEq/L [0.05-0.13 mEq/L]). Sex-hormone binding globulin levels were not significantly different between the 2 groups. CONCLUSIONS: In early postnatal life, SGA infants display an increased insulin sensitivity with respect to glucose disposal but not with respect to suppression of lipolysis, ketogenesis, and hepatic production of IGFBP-1. It will be important to determine how these differential sensitivities to insulin vary with increasing age.