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Background: Reduced fetal growth is a potential risk factor for development of metabolic abnormalities in later life. The relationship between low birthweight and impaired glucose tolerance, type 2 diabetes and insulin resistance in adulthood has been well documented., Purpose: Assuming that fetal undernutrition is associated with insulin resistance in middle age, we elected to study whether this process may already be present in young adults and adolescents born small for gestational age (SGA)., Subjects and Methods: Children born in Vall d'Hebron Hospital Infantil, Barcelona, between 1986 and 1989 and between 1978 and 1983 with birthweights below the third centile for the local standard values, were invited to participate in the present study. Of those, 51 (22 girls and 29 boys) were pre-pubertal with 9.4 +/- 0.2 years of age and 49 (29 girls and 20 boys ) were post-pubertal, with 17.3 +/- 0.3 years of age. All patients underwent a standard, 2-hour oral glucose tolerance test. Insulin and glucose responses were compared with our previously published data in control children with normal birthweight., Results: The insulin response at 30 min after glucose load was significantly higher (p < 0.001) in pre- and post-pubertal girls and boys formerly SGA than in controls. In addition, the girls also had a higher insulin response at 60 and 120 min. Mean serum insulin (MSI), the area under the insulin curve during the glucose challenge, was statistically increased in pre- and post-pubertal boys and girls born SGA when compared to controls., Conclusion: The presence of high insulin levels after an oral glucose challenge in children and adolescents born SGA might be considered as an early marker of subsequent insulin resistance in adulthood. Furthermore, our population offers the opportunity to study the natural course of hyperinsulinemia and its outcome. Follow-up of this cohort may be helpful in distinguishing a subset of young children and adolescents in whom therapeutic intervention could be done., (Copyright 2002 S. Karger AG, Basel)

Type A insulin resistance syndrome is characterized by the association of ovarian hyperandrogenism, acanthosis nigricans, and severe insulin resistance. We have identified three novel mutant alleles of the insulin receptor gene in 3 patients with type A syndrome, a severe form of insulin resistance. Two of the patients were sisters (A1, A2), 1 of them was a compound heterozygote for a mutation at the 3'-splice acceptor site of intron 21 (AG-->AA), and a missense mutation Val140Leu in exon 2. Her sister was a simple heterozygote for the 3'-splice acceptor mutation. The third patient (A3) was heterozygous for the missense mutation Ala1028Val in exon 17, in the consensus sequence for ATP binding.

In girls, pronounced adrenarche with precocious pubarche (PP) has been related to reduced fetal growth and to a cluster of endocrine-metabolic abnormalities. We examined whether these associations are also evident in boys with PP. The study population consisted of matched groups of boys (n = 58; age range 5-15 years) without or with a history of PP. After stratification for pubertal development, non-PP and PP boys displayed comparable results for the studied variables, including serum insulin-like growth factor I, sex hormone binding globulin, insulin-like growth factor binding proteins 1 and 3, indices of circulating glucose and insulin responsiveness to an oral glucose load, and birth weight SD score. In conclusion, the present results indicate that adrenarche-driven PP in boys is, in contrast to PP in girls, not associated with a cluster of endocrine-metabolic abnormalities and is not related to reduced fetal growth. These observations support the view that adrenarche-driven PP in boys may be regarded as a variant of normal development. Copyrightz1999S.KargerAG,Basel

Objective: To evaluate leptin values in placental cord blood of newborns with normal intrauterine growth after 30-42 weeks of gestation., Design: Leptin, a protein encoded by the ob gene, plays an important role in the regulation of feeding behaviour and energy balance in rodents, primates and humans. The presence of leptin in human amniotic fluid and cord blood has recently been reported in human gestations at term and the possible role of leptin in human fetal growth suggested. However, little is known of leptin synthesis during human foetal development. Thus, the aim of our work was to measure leptin (RIA, Linco Research, Inc.) in placental cord blood of human newborns at different fetal ages., Patients: One hundred and twenty-six healthy newborns with normal intrauterine growth were studied. Twenty-nine were preterm (15 males and 14 females; gestational age: 30-36 weeks) and 99 were at term (49 males and 48 females; gestational age: 37-42 weeks)., Results: Leptin values increase progressively throughout gestation from 1.30 +/- 0.53 ng/ml at 30 weeks of gestation to 7.98 +/- 4.96 ng/ml (mean +/- SD) at term, and correlate positively with birth weight (r = 0.56, p < 0. 005, n = 126), length (r = 0.37, p < 0.005, n = 126), BMI (r = 0.57, p < 0.005, n = 126), head circumference (r = 0.37, p < 0.005, n = 126), gestational age (r = 0.48, p < 0.005, n = 126) and placental weight (r = 0.38, p < 0.003, n = 59). Leptin values are statistically significantly lower (p < 0.005) preterm (median: 2.05 ng/ml; range: 0.7-8.3 ng/ml) than at term (median: 7.0 ng/ml; range: 1.1-28.1 ng/ml). Leptin values are also significantly (p < 0.005) higher in females (median: 7.2 ng/ml; range: 0.9-23.6 ng/ml, n = 62) than in males (median: 4.8 ng/ml; range: 0.7-28.1 ng/ml, n = 64), although there are no differences in weight (2,864 +/- 536 g in females vs. 2,937 +/- 744 g in males). Multiple regression analysis shows weight to be a positive sex-independent predictor of serum leptin values (p < 0.0005). Sex also proves to be a predictor of leptin, independently of weight and is higher in females than in males (p < 0.003)., Conclusion: Leptin is present in placental human cord blood after 30-42 weeks of gestation. Newborn weight and sex are independent predictors of leptin values.

The fasting insulin resistance index, mean blood glucose, mean serum insulin (MSI), early insulin response to glucose, glucose uptake rate in peripheral tissues, and insulin sensitivity indexes in response to a standard oral glucose tolerance test; serum insulin-like growth factor I (IGF-I), IGF-binding protein-1 (IGFBP-1), IGFBP-3, and sex hormone binding-globulin (SHBG) levels; and the free androgen indexes were evaluated in 98 girls with premature pubarche [PP; prepubertal (B1; n = 32), early pubertal (B2; n = 27), midpubertal (B3; n = 23), and postmenarcheal (B5; n = 16)] and in 86 Tanner stage- and bone age-matched controls. We ascertained whether hyperinsulinemia is already present in PP girls before or during pubertal development and whether these patients show a similar pattern of growth factor secretion as normal girls. Body mass indexes did not differ significantly between patients and controls within the same pubertal stage. MSI levels showed a significant increase with pubertal onset in all subjects, as expected. Patients showed significantly higher MSI values than controls at all Tanner stages (P < 0.03, P = 0.03, P = 0.03, and P < 0.05 for B1, B2, B3, and B5, respectively); higher insulin response to glucose at B1, B2, and B3 (P < 0.03, P = 0.03, and P < 0.05, respectively); higher glucose uptake rate in peripheral tissues at B1 and B2 (P < 0.04 and P = 0.02, respectively); and a later rise in insulin sensitivity compared to controls. PP girls also showed lower IGFBP-1 levels at B1 and B5 (P < 0.01 and P = 0.02, respectively), lower SHBG concentrations at B5 (P < 0.0005), and higher free androgen indexes at B1, B3, and B5 (P < 0.01, P < 0.05, and P < 0.001, respectively) compared to controls. Among others, significant correlations between SHBG and MSI levels (r = -0.49; P < 0.0001) and between SHBG and IGFBP-1 levels (r = 0.41; P < 0.0001) were found in all subjects. Hyperinsulinemia, increased early insulin responses to glucose, increased glucose uptake rate in peripheral tissues, elevated free androgen indexes, and decreased SHBG and IGFBP-1 levels are present in most girls with PP from childhood. These findings lend strong support to the concept that PP is not a benign condition, and long term follow-up of these patients into adulthood is recommended. The possible causal role of hyperinsulinemia in adrenal and/or ovarian androgen hypersecretion remains to be established.

Despite contradictory observations, it has been postulated that early age of adrenarche predisposes to an increased risk of cardiometabolic complications in further ontogeny due to greater body fatness. The aim of this study was to test the above postulates. We present the results of research on 67 men aged 50–52 – participants of the Krakow Longitudinal Study conducted in the years 1976–2022 – from two birth cohorts 1970 and 1972. Boys were examined annually, aged 6–18, initially 940 people, at the age of eighteen – 358. They were examined again as adult men in 2004 (age 32–34) – 122 people and again in 2022 (age 50–52 years) 67 men. Based on the pubarcheal age, 50-year-olds were divided into 3 groups: early (11 people), average maturing (44 people) and (12 people), where the following were compared: resting systolic and diastolic blood pressure, basic parameters lipid profile – total cholesterol and its fractions, triglycerides, fasting glucose, body height and weight, waist and hip circumferences, indicators – Body Mass Index (BMI), Waist–hip Ratio (WHR), the thickness of 6 skinfolds and the prevalence of metabolic syndrome. The results of the analyses showed that: (1) there is a clear gradation, i.e., the earlier the age of pubarche, the worse the metabolic health of men; (2) compared to the other groups, the total adiposity in men with early pubarche is slightly higher, with clearly marked abdominal obesity; BMI and WHR showed a contrasting picture. At this stage of the analyses, it is difficult to clearly judge whether the cause of the increased cardiometabolic risk in the studied men with early pubarche is related to earlier age of adrenarche and the mechanisms and stimuli causing it, or to greater adiposity. [ABSTRACT FROM AUTHOR]

Endocrine care of pediatric and adult patients continues to be plagued by health and health care disparities that are perpetuated by the basic structures of our health systems and research modalities, as well as policies that impact access to care and social determinants of health. This scientific statement expands the Society's 2012 statement by focusing on endocrine disease disparities in the pediatric population and sexual and gender minority populations. These include pediatric and adult lesbian, gay, bisexual, transgender, queer, intersex, and asexual (LGBTQIA) persons. The writing group focused on highly prevalent conditions--growth disorders, puberty, metabolic bone disease, type 1 (T1D) and type 2 (T2D) diabetes mellitus, prediabetes, and obesity. Several important findings emerged. Compared with females and non-White children, non- Hispanic White males are more likely to come to medical attention for short stature. Racially and ethnically diverse populations and males are underrepresented in studies of pubertal development and attainment of peak bone mass, with current norms based on European populations. Like adults, racial and ethnic minority youth suffer a higher burden of disease from obesity, T1D and T2D, and have less access to diabetes treatment technologies and bariatric surgery. LGBTQIA youth and adults also face discrimination and multiple barriers to endocrine care due to pathologizing sexual orientation and gender identity, lack of culturally competent care providers, and policies. Multilevel interventions to address these disparities are required. Inclusion of racial, ethnic, and LGBTQIA populations in longitudinal life course studies is needed to assess growth, puberty, and attainment of peak bone mass. Growth and development charts may need to be adapted to non-European populations. In addition, extension of these studies will be required to understand the clinical and physiologic consequences of interventions to address abnormal development in these populations. Health policies should be recrafted to remove barriers in care for children with obesity and/or diabetes and for LGBTQIA children and adults to facilitate comprehensive access to care, therapeutics, and technological advances. Public health interventions encompassing collection of accurate demographic and social needs data, including the intersection of social determinants of health with health outcomes, and enactment of population health level interventions will be essential tools. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is increasingly being characterized as an evolutionary mismatch disorder that presents with a complex mixture of metabolic and endocrine symptoms. The Evolutionary Model proposes that PCOS arises from a collection of inherited polymorphisms that have been consistently demonstrated in a variety of ethnic groups and races. In utero developmental programming of susceptible genomic variants are thought to predispose the offspring to develop PCOS. Postnatal exposure to lifestyle and environmental risk factors results in epigenetic activation of developmentally programmed genes and disturbance of the hallmarks of health. The resulting pathophysiological changes represent the consequences of poor-quality diet, sedentary behaviour, endocrine disrupting chemicals, stress, circadian disruption, and other lifestyle factors. Emerging evidence suggests that lifestyle-induced gastrointestinal dysbiosis plays a central role in the pathogenesis of PCOS. Lifestyle and environmental exposures initiate changes that result in disturbance of the gastrointestinal microbiome (dysbiosis), immune dysregulation (chronic inflammation), altered metabolism (insulin resistance), endocrine and reproductive imbalance (hyperandrogenism), and central nervous system dysfunction (neuroendocrine and autonomic nervous system). PCOS can be a progressive metabolic condition that leads to obesity, gestational diabetes, type two diabetes, metabolic-associated fatty liver disease, metabolic syndrome, cardiovascular disease, and cancer. This review explores the mechanisms that underpin the evolutionary mismatch between ancient survival pathways and contemporary lifestyle factors involved in the pathogenesis and pathophysiology of PCOS. [ABSTRACT FROM AUTHOR]

Objective: Premature pubarche (PP) is a risk factor for metabolic syndrome (MS). The aim was to evaluate if glucose-insulin metabolism, cardiovascular risk factors, familial cardiovascular risk factors (FCVRF) created a risk for insulin resistance (IR) and if PP was a risk factor alone for MS in normal weight prepubertal girls with PP. Methods: Thirty-five prepubertal, non-obese girls with PP with normal birth weight and 35 age-matched control girls were evaluated for FCVRF, anthropometric measurements, blood pressure, lipid profile, fasting blood glucose-insulin, hemoglobin A1c (HbA1c), sex hormone binding globulin (SHBG), leptin, adiponectin, tumor necrosis factor-alpha (TNF-α), androgen levels, and bone age. Oral glucose tolerance test was performed in PP participants. Homeostasis model of assessment of IR (HOMA-IR), fasting glucose/insulin ratio, atherogenic index (AI), and free androgen index (FAI) were calculated. PP participants were further stratified by FCVRF. Results: HbA1c, lipid profile, testosterone, leptin, adiponectin, TNF-α, HOMA-IR, glucose/insulin ratio, AI, and fasting glucose-insulin levels were similar. In the PP group FAI was significantly higher (p=0.001), whereas SHBG was significantly lower (p=0.010) than the control group. Leptin levels of FCVRF+ and FCVRF-subgroups were 15.2±9.1 and 9.7±7.2 ng/mL, respectively and the difference was significant (p=0.016). Conclusion: As PP does not appear to be a risk factor alone for impaired glucose metabolism and IR in prepubertal non-obese girls with normal birth weight, it is our opinion that it is unnecessary to examine in detail such cases before puberty. Low SHBG levels in the PP group and high leptin levels in FCVRF+ subgroup might suggest that these may be predictive for MS in the future. [ABSTRACT FROM AUTHOR]

Objective: The objectives of this study were to compare the serum inflammatory markers, interleukin-6 (IL-6), highly sensitive C-reactive protein (hs-CRP), and fetuin-A, in patients with premature adrenarche (PA) and the control group. Materials and Methods: This single-center cross-sectional study included 85 non-obese and pre-pubertal children. After 8--12 h of fasting, blood glucose, HDL, LDL, triglyceride, cholesterol, insulin, dehydroepiandrosterone sulfate, total testosterone, 17-OH PG, IL-6, hs-CRP, and Fetuin-A levels were measured and compared in a convenience sample of PA (n=35) and a healthy volunteers of control (n=50) group. Results: The mean age (7.34±0.62 years vs. 7.09±0.77 years, respectively) and sex (82% girl vs. 80% girl, respectively) of the PA and control groups were similar (p>0.05). Fasting insulin levels (10.9±6.21 Uu/mL vs. 7.4±5.9 Uu/mL; p<0.001), HOMA-IR (2.06±0.63 vs. 1.36±1.00; p=0.017), FGIR (11.31±5.60 vs. 16.46±8.52; p=0.004), and QUICKI (0.35±0.02 vs. 0.37±0.03; p<0.001) levels were different in PA and control groups. IL-6 level higher in PA group than controls [2.7 (3.30) pg/mL vs. 3.02 (1.31) pg/mL, p=0.035], while plasma Fetuin-A [522.02 (715.86) mg/L; 519.4 (945.97) mg/L, p=0.434] and hs-CRP [0.73 (1.02) mg/dL; 1.0 (1.12) mg/dL, p=0.439] levels were similar. IL-6 cutoff value for PA was calculated as 2.06 with 72.7% sensitivity and 48.8% specificity for all study groups (AUC=0.641, p=0.036). Conclusion: The high IL-6 levels may be an indicator of chronic subclinical inflammation in PA cases. These children should be followed closely in terms of metabolic disorders. [ABSTRACT FROM AUTHOR]

Polycystic ovarian syndrome (PCOS) is a prevailing endocrine and metabolic disorder occurring in about 6–20% of females in reproductive age. Most symptoms of PCOS arise early during puberty. Since PCOS involves a combination of signs and symptoms, thus it is considered as a heterogeneous disorderliness. The most accepted diagnostic criteria is Rotterdam criteria which involves two of the latter three features: (a) hyperandrogenism, (b) oligo- or an-ovulation, and (c) polycystic ovaries. The persistent hormonal imbalance leads to multiple small antral follicles formation and irregular menstrual cycle, ultimately causing infertility among females. Insulin resistance, cardiovascular diseases, abdominal obesity, psychological disorders, infertility, and cancer are also related to PCOS. These pathophysiologies associated with PCOS are interrelated with each other. Hyperandrogenism causes insulin resistance and hyperglycemia, leading to ROS formation, oxidative stress, and abdominal adiposity. In consequence, inflammation, ROS production, insulin resistance, and hyperandrogenemia also increase. Elevation of AGEs in the body either produced endogenously or consumed from diet exaggerates PCOS symptoms and is also related to ovarian dysfunction. This review summarizes how AGE formation, inflammation, and oxidative stress are significantly essential in PCOS progression. Alterations during prenatal development like exposure to excess AMH, androgens, or toxins (bisphenol-A, endocrine disruptors, etc.) may also be the etiologic mechanism behind PCOS. Although the etiology of this disorder is unclear, environmental and genetic factors are primarily involved. Physical inactivity, as well as unhealthy eating habits, has a vital role in the progression of PCOS. This review outlines a collection of specific genes phenotypically linked with PCOS. Furthermore, beneficial effect of metformin in maintaining endocrine abnormalities and ovarian function is also mentioned. Kisspeptin is a protein which helps in onset of puberty and increases GnRH pulsatile release during ovulation as well as role of KNDy neurons in GnRH pulsatile signal required for reproduction are also elaborated. This review also focuses on the immunology related to PCOS involving chronic low-grade inflammation, and how the alterations within the follicular microenvironment are intricated in the development of infertility in PCOS patients. How PCOS develops following antiepileptic and psychiatric medication is also expanded in this review. Initiation of antiandrogen treatment in early age (≤ 25 years) might be helpful in spontaneous conception in PCOS women. The role of BMP (bone morphogenetic proteins) in folliculogenesis and their expression in oocytes and granulosa cells are also explained. GDF8 and SERPINE1 expression in PCOS is given in detail. [ABSTRACT FROM AUTHOR]

Introduction: Premature adrenarche (PA) for long time was considered a benign condition but later has been connected to various diseases in childhood and adulthood which remains controversial. Objective: To investigate the effect of premature adrenarche on the metabolic phenotype, and correlate the clinical and biochemical data with the metabolic profile of children with PA. Methods: Nuclear magnetic resonance (NMR)-based untargeted and targeted metabolomic approach in combination with multivariate and univariate statistical analysis applied to study the metabolic profiles of children with PA. Plasma, serum, and urine samples were collected from fifty-two children with Idiopathic PA and forty-eight age-matched controls from the division of Pediatric Endocrinology of the University Hospital of Patras were enrolled. Results: Metabolomic results showed that plasma and serum glucose, myo-inositol, amino acids, a population of unsaturated lipids, and esterified cholesterol were higher and significantly different in PA children. In the metabolic profiles of children with PA and age-matched control group a gradual increase of glucose and myo-inositol levels was observed in serum and plasma, which was positively correlated their body mass index standard deviation score (BMI SDS) values respectively. Urine 1H NMR metabolic fingerprint of PA children showed positive correlation and a clustering-dependent relationship with their BMI and bone age (BA) respectively. Conclusion: This study provides evidence that PA driven metabolic changes begin during the childhood and PA may has an inductive role in a BMI–driven increase of specific metabolites. Finally, urine may be considered as the best biofluid for identification of the PA metabolism as it reflects more clearly the PA metabolic fingerprint. [ABSTRACT FROM AUTHOR]

Here, we seek to identify metabolite predictors of dysglycemia in youth. In the discovery analysis among 391 youth in the Exploring Perinatal Outcomes among CHildren (EPOCH) cohort, we used reduced rank regression (RRR) to identify sex-specific metabolite predictors of impaired fasting glucose (IFG) and elevated fasting glucose (EFG: Q4 vs. Q1 fasting glucose) 6 years later and compared the predictive capacity of four models: Model 1: ethnicity, parental diabetes, in utero exposure to diabetes, and body mass index (BMI); Model 2: Model 1 covariates + baseline waist circumference, insulin, lipids, and Tanner stage; Model 3: Model 2 + baseline fasting glucose; Model 4: Model 3 + baseline metabolite concentrations. RRR identified 19 metabolite predictors of fasting glucose in boys and 14 metabolite predictors in girls. Most compounds were on lipid, amino acid, and carbohydrate metabolism pathways. In boys, no improvement in aurea under the receiver operating characteristics curve AUC occurred until the inclusion of metabolites in Model 4, which increased the AUC for prediction of IFG (7.1%) from 0.81 to 0.97 (p = 0.002). In girls, %IFG was too low for regression analysis (3.1%), but we found similar results for EFG. We replicated the results among 265 youth in the Project Viva cohort, focusing on EFG due to low %IFG, suggesting that the metabolite profiles identified herein have the potential to improve the prediction of glycemia in youth. [ABSTRACT FROM AUTHOR]

Context: Adrenarche reflects the developmental growth of the adrenal zona reticularis, which produces increasing adrenal androgen secretion (eg, dehydroepiandrosterone [DHEA]/dehydroepiandrosterone sulfate [DHEAS]) from approximately age 5 to 15 years. Objective: We hypothesized that the study of the genetic determinants associated with variations in serum DHEAS during adrenarche might detect genetic variants influencing the rate or timing of this process. Methods: Genome-wide genotyping was performed in participants of the Chilean pediatric Growth and Obesity Chilean Cohort Study (GOCS) cohort (n = 788). We evaluated the genetic determinants of DHEAS levels at the genome-wide level and in targeted genes associated with steroidogenesis. To corroborate our findings, we evaluated a polygenic risk score (PRS) for age at pubarche, based on the discovered variants, in children from the same cohort. Results: We identified one significant variant at the genome-wide level in the full cohort, close to the GALR1 gene (P = 3.81 × 10–8). In addition, variants suggestive of association (P < 1 × 10–5) were observed in PRLR, PITX1, PTPRD, NR1H4, and BCL11B. Stratifying by sex, we found variants suggestive of association in SERBP1 and CAMTA1/VAMP3 for boys and near ZNF98, TRPC6, and SULT2A1 for girls. We also found significant reductions in age at pubarche in those children with higher PRS for greater DHEAS based on these newly identified variants. Conclusion: Our results disclose one variant associated with DHEAS concentrations at the level of genome-wide association study significance, and several variants with a suggestive association that may be involved in the genetic regulation of adrenarche. [ABSTRACT FROM AUTHOR]

Hyperandrogenism—clinical features resulting from increased androgen production and/or action—is not uncommon in peripubertal girls. Hyperandrogenism affects 3 to 20% of adolescent girls and often is associated with hyperandrogenemia. In prepubertal girls, the most common etiologies of androgen excess are premature adrenarche (60%) and congenital adrenal hyperplasia (CAH; 4%). In pubertal girls, polycystic ovary syndrome (PCOS; 20–40%) and CAH (14%) are the most common diagnoses related to androgen excess. Androgen-secreting ovarian or adrenal tumors are rare (0.2%). Early pubic hair, acne, and/or hirsutism are the most common clinical manifestations, but signs of overt virilization in adolescent girls—rapid progression of pubic hair or hirsutism, clitoromegaly, voice deepening, severe cystic acne, growth acceleration, increased muscle mass, and bone age advancement past height age—should prompt detailed evaluation. This article addresses the clinical manifestations of and management considerations for non-PCOS-related hyperandrogenism in adolescent girls. We propose an algorithm to aid diagnostic evaluation of androgen excess in this specific patient population. [ABSTRACT FROM AUTHOR]

'Small for gestational age' (SGA) is an auxological and not an etiological definition that characterizes children born small based upon low-birth-weight and/or birth-length criteria [≥ 2 standard deviations (SD) below the mean for gestational age]. Most SGA children exhibit catch-up growth into the normal range within 6 mo of age. Overall SGA children are 4 cm shorter than expected based upon midparental height and being born SGA is a common cause of adult short stature. Recombinant human growth hormone (rhGH) has been shown to improve adult height by 0.9 SDs and is a safe treatment. Surprisingly, a higher rhGH dose (67 μgm/kg/d) did not lead to a greater adult height than a conventional dose (33 μgm/kg/d). At least 85% of SGA children treated through childhood with rhGH achieve a height within the normal adult range. Other long-term consequences for children born SGA include insulin resistance, abdominal adiposity, dyslipidemia, type 2 diabetes mellitus, and metabolic syndrome. Cross-sectional studies have found reduced insulin sensitivity in the neonatal, childhood, and young adult periods. Increased abdominal fat has been shown in preschool SGA children and is more evident in young adults. Increased adiposity markedly accentuates reduction in insulin sensitivity. Many SGA children have suffered from in utero nutritional restriction that leads to long-term growth restriction and adverse metabolic sequelae. [ABSTRACT FROM AUTHOR]

Purpose: Premature adrenarche (PA) often leads to polycystic ovary syndrome (PCOS). Higher anti-mullerian hormone (AMH) levels are reported in PCOS. We studied the androgen profile and AMH profiles in Hispanic girls with PA (aged 5-8 years) and age and body mass index (BMI) matched controls. Methods: Retrospective review of electronic medical records of girls who met the inclusion criteria for premature adrenarche were done. Results: PA girls (n=76) were matched to control girls (n=12) for age (mean±standard deviation) (6.7±1 years vs. 6.2±1.3 years) and BMI (20±10 kg/m² vs. 17.8±2.7 kg/ m²). Dehydroepiandrostenedione sulfate (63.3±51.3 µg/dL vs. 29.8±17.3 µg/dL, P<0.001) and testosterone levels (11.4±4.8 ng/dL vs. 8.2±2.9 ng/dL, P=0.001) were significantly higher in the PA group than controls. AMH values (<14 years: reference range, 0.49-3.15 ng/mL) were 3.2±2.2 ng/mL vs. 4.6± 3.2 ng/mL respectively in the PA and control groups and were not different (P=0.4). AMH did not show a correlation with bone age (P=0.1), and testosterone (P=0.9) in the PA group. 17-hydroxyprogesterone levels (17-OHP ng/dL) were 39.5±30.5 ng/dL vs. 36.8±19.8 ng/dL in PA versus control girls. The concentration of 17-OHP was not statistically different between the control and PA groups. Conclusion: Higher AMH was not observed in PA girls and no correlation with BA and androgen levels was observed. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to investigate the cardiovascular risk of children with premature adrenarche (PA). Methods: A total of 75 children (44 with PA and 31 control subjects) aged 6-10 years were included in the study. Their metabolic, anthropometric, and echocardiographic parameters were recorded and compared. Results: Triglyceride, DHEASO 4, and 17-hydroxyprogesterone levels were significantly higher in the PA group (p = 0.04, p = 0.002, and p = 0.01, respectively). The echocardiographic assessments revealed that the left ventricular end-diastolic diameter (LVEDD) (p < 0.001), left ventricle (LV) and right ventricle (RV) ejection times (p = 0.031 and p = 0.035, respectively), and LV and RV Tei index measurements (p = 0.033 and p = 0.006, respectively) were significantly higher in the PA group than in the control group, whereas the E/e' ratio of the mitral lateral annulus was significantly lower in the PA group (p = 0.006). Additionally, carotid intima-media thickness and epicardial adipose tissue measurements were significantly increased in the PA group compared to the control group (p < 0.001). Conclusion: Early atherosclerotic changes and subclinical impairment of cardiac function were observed in children with PA. It is possible that these children are on a course for early cardiovascular disease. [ABSTRACT FROM AUTHOR]

Background/Aims: The diagnostic criteria for polycystic ovary syndrome (PCOS) in adolescence are controversial, primarily because the diagnostic pathological features used in adult women may be normal pubertal physiological events. Hence, international pediatric and adolescent specialty societies have defined criteria that have sufficient evidence to be used for the diagnosis of PCOS in adolescents. Methods: The literature has been reviewed and evidence graded to address a series of questions regarding the diagnosis of PCOS during adolescence including the following: clinical and biochemical evidence of hyperandrogenism, criteria for oligo-anovulation and polycystic ovary morphology, diagnostic criteria to exclude other causes of hyperandrogenism and amenorrhea, role of insulin resistance, and intervention. Results and Conclusion: Features of PCOS overlap normal pubertal development. Hence, caution should be taken before diagnosing PCOS without longitudinal evaluation. However, treatment may be indicated even in the absence of a definitive diagnosis. While obesity, insulin resistance, and hyperinsulinemia are common findings in adolescents with hyperandrogenism, these features should not be used to diagnose PCOS among adolescent girls. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective To determine if insulin-like growth factor-1 (IGF-1) is a significant predictor of body fat percentage (%BF), lean body mass, and insulin resistance (IR) in black adolescents presenting with overnutrition and undernutrition. Methods A cross-sectional study was undertaken in 181 adolescents (111 girls, 70 boys, 13-20 years old) from a low socio-economic population in the North-West Province, South Africa. Anthropometric measurements were performed, and %BF and lean mass were assessed by air displacement plethysmography. Serum glucose, leptin, insulin, IGF-1 and IGF-binding protein-3 (IGFBP-3) were measured and homeostasis model assessment of IR (HOMA-IR) was calculated. Predictors of body composition and HOMA-IR were determined in multivariate linear regressions. Results Of the boys, 31% had a %BF >20%, whereas 42% of girls had a %BF >30%. Furthermore, 17.1% male and 18.9% female adolescents were stunted, indicating overnutrition and undernutrition in the same group. IGF-1 showed a negative association with %BF in both sexes, and a positive correlation with height-for-age z-score (HAZ) and lean mass, respectively, in the boys. IGF-1 correlated positively and physical activity correlated negatively with fasting insulin and HOMA-IR in the girls. In both sexes, leptin had the strongest association with %BF in multiple regressions. Leptin and Tanner stage were significant predictors of HOMA-IR in girls, but not in boys. Conclusions IGF-1 was positively associated with lean mass and HAZ in boys, indicating a beneficial relationship with linear growth, but with IR in the girls, indicating possible adverse metabolic effects in the presence of high %BF and physical inactivity. Am. J. Hum. Biol. 26:189-197, 2014. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

OBJECTIVE--Insulin resistance (IR) is associated with diabetes. IR is higher during puberty in both sexes, with some studies showing the increase to be independent of changes in adiposity. Few longitudinal studies have reported on children, and it remains unclear when the rise in IR that is often attributed to puberty really begins. We sought to establish from longitudinal data its relationship to pubertal onset, and interactions with age, sex, adiposity, and IGF-1. RESEARCH DESIGN AND METHODS--The Early Bird Diabetes study is a longitudinal prospective cohort study of healthy children aged 5-14 years. Homeostasis model assessment (HOMA-IR), skinfolds (SSF), adiposity (percent fat, measured by dual-energy X-ray absorptiometry), serum leptin, and IGF-1 were measured annually in 235 children (134 boys). Pubertal onset was adduced from Tanner stage (TS) and from the age at which luteinizing hormone (LH) first became serially detectable (≥0.2 international units /L). RESULTS--IR rose progressively from age 7 years, 3-4 years before TS2 was reached or LH became detectable. Rising adiposity and IGF-1 together explained 34% of the variance in IR in boys and 35% in girls (both P, 0.001) over the 3 years preceding pubertal onset. The contribution of IGF-1 to IR was greater in boys, despite their comparatively lower IGF-1 levels. CONCLUSIONS--IR starts to rise in mid-childhood, some years before puberty. Its emergence relates more to the age of the child than to pubertal onset. More than 60% of the variation in IR prior to puberty was unexplained. The demography of childhood diabetes is changing, and prepubertal IR may be important. [ABSTRACT FROM AUTHOR]

Aims: Isolated premature pubarche (PP) is commonly caused by premature adrenarche (PA), and links between PA, children born small for gestational age (SGA) and insulin resistance have already been made in some populations. Subjects and Methods: We assessed anthropometric data, pubertal landmarks and metabolic profile at diagnosis and during the study in 52 girls with the diagnosis of isolated PP from a Brazilian cohort. Results: The prevalence of obesity (25%), dyslipidemia (63.5%) and born SGA children (21.2%) was greater among PP girls than in the reference population (4, 46.8 and 10%, respectively). There was no increase in the prevalence of insulin resistance and no correlation with birth weight, onset of PP or other pubertal signs. The Z score of heights at PP diagnosis was greater than the Z score of mid-parental height, but achieved final height (n = 16 girls, p = 0.002) was similar to normal population standards and to the predicted final height based on bone age at PP diagnosis (p = 0.08). Thelarche and menarche occurred at normal age, just earlier than expected. Conclusion: The prevalence of children born SGA, obese and dyslipidemic, but not of hyperinsulinemic children, was high in our cohort of PP girls. Puberty started earlier than usual but within the normal range. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

OBJECTIVE -- Serine-threonine kinase STK11 catalyzes the AMP-activated protein kinase complex. We tested the hypothesis that a gene variant in STK11 contributes to variation in insulin sensitivity and metformin efficacy. RESEARCH DESIGN AND METHODS-- We studied the effects of a single nucleotide polymorphism (SNP) (rs8111699) in STK11 on endocrine-metabolic and body composition indexes before and after I year of metformin in 85 hyperinsulinemic girls with androgen excess, representing a continuum from prepuberal girls with a combined history of low birth weight and precocious pubarche over to postmenarchial girls with hyperinsulinemic ovarian hyperandrogenism. Metformin was dosed at 425 rag/day in younger girls and 850 mg/day in older girls. STK11 rs8111699 was genotyped. Endocrine-metabolic features were assessed in the fasting state; body composition was estimated by absorptiometry. RESULTS -- Genotype effects were similar in younger and older girls. At baseline, the mutated G allele in STK11 rs8111699 was associated with higher insulin and IGF-I levels (both P < 0.005). The response to metformin differed by STK11 genotype: GG homozygotes (n = 24) had robust metabolic improvements, GC heterozygotes (n = 38) had intermediate responses, and CC homozygotes (n = 23) had almost no response. Such differences were found for 1-year changes in body composition, circulating insulin, IGF-I, free androgen index, and lipids (all P < 0.005). CONCLUSIONS -- In hyperinsulinemic girls with androgen excess, the STK11 rs8111699 SNP influences insulin sensitivity and metformin efficacy, so that the girls with the least favorable endocrine-metabolic profile improve most with metformin therapy. [ABSTRACT FROM AUTHOR]

Puberty is a crucial developmental stage in the life span, necessary to achieve reproductive and somatic maturity. Timing of puberty is modulated by and responds to central neurotransmitters, hormones, and environmental factors leading to hypothalamic-pituitary-gonadal axis maturation. The connection between hormones and nutrition during critical periods of growth, like fetal life or infancy, is fundamental for metabolic adaptation response and pubertal development control and prediction. Since birth weight is an important indicator of growth estimation during fetal life, restricted prenatal growth, such as intrauterine growth restriction (IUGR) and small for gestational age (SGA), may impact endocrine system, affecting pubertal development. Successively, lactation along with early life optimal nutrition during infancy and childhood may be important in order to set up timing of sexual maturation and provide successful reproduction at a later time. Sexual maturation and healthy growth are also influenced by nutrition requirements and diet composition. Early nutritional surveillance and monitoring of pubertal development is recommended in all children, particularly in those at risk, such as the ones born SGA and/or IUGR, as well as in the case of sudden weight gain during infancy. Adequate macro and micronutrient intake is essential for healthy growth and sexual maturity. [ABSTRACT FROM AUTHOR]