Body composition in prepubertal girls: comparison of six methods

OBJECTIVE: To compare estimates of fat mass (FM), fat-free mass (FFM) and percentage body fat (%fat) by six different methods in prepubertal girls. DESIGN: Cross-sectional study. SUBJECTS: Normal-weight, multi-ethnic, prepubertal girls (age=8.5+/-0.4 y, n=101). MEASUREMENTS: Body composition was measured in each child by anthropometry (skinfold thickness using Slaughter equation), dual-energy X-ray absorptiometry (DXA), total body potassium (TBK), isotope dilution for total body water measurement (TBW), multifrequency bioelectrical impedance spectroscopy (BIS), and total body electrical conductivity (TOBEC). RESULTS: TOBEC and skinfold thickness yielded the lowest values of FM followed by DXA, TBK, TBW and BIS, with BIS giving the highest value of FM. All methods were significantly different for FFM, FM and %fat (P<0.001), except FFM by DXA and TBK. The Bland-Altman limits of agreement among the methods reveal that they are not directly interchangeable for FM, FFM, or %fat. The largest mean difference for FM was between TOBEC and BIS (-2.90 kg), whereas the smallest mean difference was between TOBEC and skinfold thickness (-0.14 kg). For FFM, the largest mean difference was also between TOBEC and BIS (2.83 kg), but the smallest mean difference for FFM was between DXA and TBK (-0.03 kg). For %fat, the mean differences were larger, -10.5% for TOBEC and BIS and+9.7% for skinfold thickness and BIS. The closest two techniques for %fat were TOBEC and skinfold thickness (mean difference of -0.62%) and DXA and TBK (-1.81%). CONCLUSIONS: We found that estimates of body composition in prepubertal 8-y-old girls are highly method-dependent and that the six methods studied (DXA, TBK, TBW, TOBEC, BIS and anthropometry) are not directly interchangeable.     

Body fat distribution in pubertal girls quantified by magnetic resonance imaging.

We examined body fat distribution in relation to anthropometrically derived variables in 24 girls in early and late stages of puberty. The amounts of subcutaneous and intra-abdominal body fat were derived from transverse slices at the levels of the waist, hip and trochanter using magnetic resonance imaging (MRI), and were compared to the related circumferences, the circumference ratios and the trunk-to-extremity skinfold ratios. Waist, hip and trochanter circumferences were highly correlated to the respective related MRI total fat surface area both in early and late pubertal girls (r = 0.79-0.97), while waist circumference, and waist-hip, waist-thigh or skinfold ratios were not significantly correlated to intra-abdominal fat areas. Late pubertal girls (n = 11) were significantly taller, heavier and fatter compared to early pubertal girls (n = 13), yet their anthropometric waist-to-hip or waist-to-trochanter circumference ratios were significantly lower. The intra-abdominal fat area measured in a transverse MRI section at the level of the waist was 24.1 +/- 4.1 cm2 in early pubertal girls and 25.7 +/- 4.1 cm2 in late pubertal girls (mean +/- s.e.m.). As compared to early pubertal girls, the MRI derived amount of subcutaneous fat in late pubertal girls was significantly higher at the trochanter level (142.1 +/- 12.7 vs. 201.3 +/- 26.3 cm2; P less than 0.05). We conclude that circumferences at the trunk are good measures for the related amounts of fat in pubertal girls. In contrast conventional anthropometric measurements, such as trunk-to-extremity skinfold ratio or waist-to-hip circumference ratio, cannot be used to predict the amount of intra-abdominal fat in pubertal girls.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma lipids and apoproteins, body fat distribution and body fatness in early pubertal children

Besides body fatness, the body fat distribution is associated with coronary risk in adults, but little has been reported on this aspect in children. This study describes body fatness, body fat distribution (waist-to-hip ratio, WHR) and the plasma lipid and apoprotein profile (TC, HDL-C, LDL-C, TG, apo A-I and apo B) in 60 boys (age 10.8 +/- 0.1 year; mean +/- s.e.m.) and 64 girls (age 10.2 +/- 0.1 year), all caucasian. To avoid interference by the large changes in plasma sex hormone levels during puberty, only pre- and early pubertal children (Tanner stages of genital c.q. breast development 1 or 2) participated. Physical and sports activity was scored in hours per week using a questionnaire. The boys were taller than the girls (146.2 +/- 0.7 vs 143.2 +/- 0.9 cm; ANOVA, P less than or equal to 0.05) and their WHR was larger (0.88 +/- 0.01 vs 0.83 +/- 0.01; ANOVA, P less than or equal to 0.05). The boys spent 8.0 +/- 0.4 hours weekly on physical and sports activities, the girls 5.5 +/- 0.3 (ANOVA, P less than or equal to 0.05). The plasma lipid and apoprotein profiles were similar in both groups. Body fatness was significantly associated with the lipid and apoprotein profile, although in different ways in boys and girls. In boys there was a relationship with TG (r = 0.49), with apo B (r = 0.33) and with the apo A-I to apo B ratio (r = -0.24); in girls with TG (r = 0.25), HDL-C (r = -0.39), apo A-I (r = -0.28) and with the HDL-C to TC ratio (r = -0.31); P less than 0.05 for all correlations. A regional component of the subcutaneous fatmass, assessed by the partial correlations of the individual skinfold thicknesses with the plasma lipid and apoprotein profile after controlling for body fatness, was lacking in these early and prepubertal children. The WHR was associated with TC (r = 0.35), LDL-C (r = 0.32), apo B (r = 0.36) and with apo A-I/apo B (r = -0.34) in the girls after controlling for body fatness. Although closer investigation into the validity of the WHR as a measure of fat distribution in children is needed, the tentative conclusion is that in pre- and early pubertal girls the WHR has an impact on the plasma lipid and apoprotein profile similar to that seen in adults. It is suggested that in boys these relationships develop later in puberty.     

Adiponectin before and after weight loss in obese children

Adiponectin is decreased in obesity and seems to be involved in insulin resistance. The influences of age, gender, puberty, and weight loss on adiponectin have not been studied in obese children. We measured body fat mass based on skinfold thickness, age, pubertal stage, gender, adiponectin, and insulin resistance (homeostasis model assessment) in 42 obese children. We analyzed adiponectin and homeostasis model assessment 1 yr later in these obese children and separated them into two groups according to degree of weight loss (decrease in sd score for body mass index, >or=0.5 vs. <0.5). Adiponectin was negatively correlated to percentage body fat (r = -0.44; P = 0.002), insulin resistance (r = -0.33; P = 0.016), and age (r = -0.41; P = 0.003). Adiponectin levels were significantly (P = 0.017) higher in pubertal girls compared with boys, but there was no significant difference in prepubertal children in respect to gender (P = 0.833). Adiponectin was significantly (P < 0.001) lower in pubertal compared with prepubertal children. The significant weight loss in 16 children was associated with a significant increase in adiponectin (P = 0.010) and a decrease in insulin resistance (P = 0.013), whereas there were no changes in the 26 children without significant weight loss. Adiponectin levels in obese children were negatively correlated to age, body fat, and insulin resistance and were decreased in puberty. Significant weight loss led to an increase in adiponectin levels and an improvement of insulin resistance.     

Sex and race differences in fat distribution among Asian, African-American, and Caucasian prepubertal children

Sexual dimorphism in fat distribution is thought to emerge during puberty. Truncal or android body fat distribution is characteristic of adult males but is also recognized as a human cardiovascular risk factor. Race differences in truncal fat are clearly evident in adults and have been described in prepubertal children but not between Asians and other race groups. The aim of this study in African-American, Asian, and Caucasian prepubertal children was to evaluate sex differences and race differences in body fat distribution. Analysis of covariance was used to explore fat distribution in 358 prepubertal children (176 girls and 182 boys; 143 Asians, 95 African-Americans, and 120 Caucasians), measured by skinfold thickness and dual-energy x-ray absorptiometry (DXA) in a cross-sectional study. Extremity and gynoid fat masses were evaluated after adjustment for trunk or android fat, respectively, and for covariates including age, weight, height, and interactions. In Asian children, sex differences were present in models for gynoid fat by DXA only (P < 0.001), with girls having greater gynoid fat than boys. In African-American and Caucasian children, sex differences were present in models for extremity and gynoid fat masses, measured by both methods. Among girls, Asians had generally lower adjusted extremity and gynoid fat than Caucasians and African-Americans. Among boys, Asians had lower adjusted extremity fat by DXA than Caucasians (P < 0.01) but greater gynoid fat by skinfolds than African-Americans (P < 0.01). This study of prepubertal children demonstrates that: 1) sex differences in body fat distribution are present in prepubertal children but that the specific characteristics for Asians differ from African-Americans and Caucasians, and 2) differences in body fat distribution in Asian children, compared with African-Americans and Caucasians, are present but vary by sex. This comparison of African-American, Asian, and Caucasian prepubertal children suggests phenotypic differences. Additional studies are needed to explore the metabolic and health risk implications of these findings.     

Body fat mass, body fat distribution, and pubertal development: a longitudinal study of physical and hormonal sexual maturation of girls.

The rate at which girls progress through the stages of puberty in relation to body fat mass and body fat distribution and its relation to their hormonal profiles was studied. Sixty-eight schoolgirls participated in a longitudinal study during 3 yr. The girls were divided into subgroups with increasing skinfold thicknesses and waist-hip ratio. They were also grouped depending on Tanner's breast development classification (M2 and M3). The age at M2 was only marginally correlated with the menarcheal age, but the age at M2 and the time interval from that age to menarche was negatively correlated. Age at the onset of puberty was not related to body fat mass or distribution. The rate of pubertal development after pubertal stage M3 was negatively related to the body fat mass. Age at M2 was only correlated with estrone (E1), while the rate of pubertal development was associated with higher FSH, E1, estradiol (E2), the fraction of E2 that was not bound to sex-hormone-binding globulin (non-sex-hormone-binding globulin bound E2) and androstenedione plasma levels at the onset of puberty. Body fat distribution, rather than body fat mass was related to the total and the non-sex-hormone-binding globulin bound plasma levels of E2 and testosterone at the onset of puberty. Changes in body fat distribution in early female puberty were chiefly related to the waist circumferences. We found no evidence that body fat mass or body fat distribution triggers the onset of puberty. Body fat distribution was related to early pubertal endocrine activity. Body fat mass was negatively related to the rate of pubertal development toward menarche, but no clear indications for an endocrine-related process is found. We conclude that onset of puberty and menarche are not parallel pubertal events, and that early pubertal plasma E1, E2 and androstenedione levels are predictors for the rate of pubertal development toward menarche. We propose that the control of the onset of puberty and maturation of the hypothalamic-pituitary gonadal axis, with regard to negative feedback control, are at least partially independent. This induces on the average a "catch up" pubertal maturation in girls with a late onset of puberty.     

Serum androgens in normal prepubertal and pubertal children and in children with precocious adrenarche.

Serum androgens testosterone (T), testosterone-like-substances (TLS), delta4-androstenedione (delta4), dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA) were measured in 85 normal girls and 101 normal boys grouped according to pubic hair development in Tanner stages I to IV/V. The pattern of change with puberty differed for each androgen. In boys T and TLS rose with the onset of puberty but showed a more abrupt rise later in puberty. DHT also was higher in boys in late puberty but did not demonstrate a steep rise. The other androgens did not show a sex difference at any stage of puberty. While delta4 steroids did not show an increase in the years before onset of puberty, DHEA was significantly higher in prepubertal children over 7 years than in those under 7 years (mean +/- SD 166 +/- 110 vs. 31 +/- 25, P less than 0.005). The most rapid increase of DHEA concentrations was observed with the appearance of pubic hair (Stage II) in boys and girls. This contrasted with the more gradual rise of delta4 in both sexes. The oldest boys and girls (Tanner stages IV/V) had mean concentrations of all androgens in the adult range except for DHT. Twenty-two girls with precocious adrenarche (PA) aged 3-8 years had mean concentrations of T, DHT, delta4 and DHEA that were significantly higher (P less than 0.05) than in prepubertal children, but similar to those of girls in stage II and significantly lower (P less than 0.02) than in late pubertal girls (stage IV/V). Longitudinal studies in 12 of the girls indicated fluctuation of androgen concentrations, especially DHEA, but in general no increase during the years of followup. Precocious adrenarche appears to be a non-progressive disorder associated with an advanced maturation of adrenal androgen to an early pubertal stage. A rise in all androgens measured was correlated with the development of sexual hair.     

Insulin resistance during puberty and future fat accumulation

Insulin resistance is a known sequela of obesity; however, the relationship of insulin resistance to future weight gain remains unclear. In several studies, insulin resistance has been associated with weight stabilization. For the most part, this relationship has been found in adults who are overweight. To evaluate the relationship of insulin resistance to future fat accumulation in pubertal children, a 3-yr prospective study was carried out. Insulin sensitivity (Si) was determined by Bergman's minimal model in 111 healthy children, aged 9.7-14.5 yr. All children were Tanner stage II or III pubertal development at baseline. Body composition was assessed by body mass index, skinfold thickness, hydrodensitometry, and bioelectric impedance analysis at baseline and annually thereafter for an additional 3 yr. A repeated-measures analysis showed that the change in percentage body fat estimated from skinfold thickness [%BF(SF)] over time changed with increasing Si (P < 0.0001). Si was divided into tertiles for each gender, with the lowest tertile representing the most insulin-resistant children. For girls, those in the lowest tertile maintained their %BF(SF) over 3 yr, whereas those girls in the middle and upper tertile had an increase in their %BF(SF). For boys, those in the lowest tertile showed a decrease in their %BF(SF), whereas those boys in the middle and upper tertile maintained their %BF(SF). These results suggest that during puberty, children who are more insulin resistant have decreased sc fat gain.     

Decreased growth hormone response to growth hormone-releasing hormone in Turner's syndrome: relation to body weight and adiposity

A decreased growth hormone response to various secretagogues has been described in Turner's syndrome, but the mechanisms responsible for this decrease are unknown. Seventeen prepubertal girls with Turner's syndrome (age 6.4 to 15.7 years; height -0.2 to -5.4 SD, bone age -3.7 to -0.3 SD; weight 93 to 169% of ideal body weight) underwent a stimulation test with GHRH (0.5 micrograms/kg). Plasma GH and prolactin were measured by radioimmunoassay from -30 to +120 min and insulin-like growth factor-I at time 0. These values were compared with those observed in lean children with constitutional short stature. Peak plasma GH after GHRH was 17.0 +/- 3.6 micrograms/l (mean +/- SEM), significantly lower (p less than 0.001) than in the short lean children (39.2 +/- 5.1 micrograms/l). In Turner's syndrome patients, the peak GH value was negatively correlated with the percentage of ideal body weight (r = -0.58, p less than 0.02) and of body fat (r = -0.59, p less than 0.02). Plasma prolactin levels in Turner's syndrome did not rise after GHRH and showed a normal circadian variation, from 8.0 +/- 1.0 micrograms/l at 08.30 h to 5.0 +/- 0.7 micrograms/l at 11.00 h (mean +/- SEM). Mean (+/- SEM) baseline plasma insulin-like growth factor-I concentrations was 0.88 +/- 0.14 kU/l, higher than in the short lean children (0.49 +/- 0.08 kU/l, p less than 0.05). We conclude that the decreased GH response to GHRH of girls with Turner's syndrome is related, at least in part, to their excess body weight and fat and is associated with higher IGF-I levels than in short lean children.     

Body composition in young female adults with Type 1 diabetes mellitus. A prospective case-control study.

AIMS: Overweight is common during late puberty in female patients with Type 1 diabetes. The aim of this study was to examine the change in body composition from late puberty to early adulthood in such female patients in comparison with age-matched control subjects. METHODS: Eighteen females with Type 1 diabetes and 19 healthy female control subjects were recruited for a case-control study at the age of 16-19 years (baseline). Six years later, 16 of the diabetic females and 17 of the control subjects were re-examined (follow-up). Body composition was assessed by dual energy X-ray absorptiometry. RESULTS: Body mass index (BMI) and fat mass index (total fat mass/height2) were significantly higher at baseline in the diabetic patients than in the control subjects (26.4 +/- 2.6 vs. 23.9 +/- 3.7 kg/m2, P < 0.05, and 10.0 +/- 2.4 vs. 8.0 +/- 2.8 kg/m2, P = 0.04, respectively). At follow-up, these parameters still tended to be higher in the diabetic group (27.8 +/- 4.9 vs. 24.6 +/- 5.7 kg/m2, P = 0.09, and 11.8 +/- 5.6 vs. 8.7 +/- 4.9 kg/m2, P = 0.05, respectively). BMI at baseline was strongly correlated to BMI at follow-up in both diabetic patients (r = 0.60; P < 0.05) and control subjects (r = 0.83; P < 0.01). CONCLUSIONS: Increased fat mass in pubertal girls with Type 1 diabetes seems to persist in young adulthood. This study emphasizes the need for new strategies to prevent the development of overweight during puberty in diabetic girls.     

Estrogen receptor alpha regulates area-adjusted bone mineral content in late pubertal girls

CONTEXT: Whether the action of estrogen in skeletal development depends on estrogen receptor alpha as encoded by the ESR1 gene is unknown. OBJECTIVES: The aim of this study was to establish whether the gain in area-adjusted bone mineral content (ABMC) in girls occurs in late puberty and to examine whether the magnitude of this gain is related to ESR1 polymorphisms. DESIGN: We conducted a cross-sectional analysis. SETTING: The study involved the Avon Longitudinal Study of Parents and Children (ALSPAC), a population-based prospective study. PARTICIPANTS: Participants included 3097 11-yr-olds with DNA samples, dual x-ray absorptiometry measurements, and pubertal stage information. OUTCOMES: Outcome measures included separate prespecified analyses in boys and girls of the relationship between ABMC derived from total body dual x-ray absorptiometry scans and Tanner stage and of the interaction between ABMC, Tanner stage, and ESR1 polymorphisms. RESULTS: Total body less head and spinal ABMC were higher in girls in Tanner stages 4 and 5, compared with those in Tanner stages 1, 2, and 3. In contrast, height increased throughout puberty. No differences were observed in ABMC according to Tanner stage in boys. For rs2234693 (PvuII) and rs9340799 (XbaI) polymorphisms, differences in spinal ABMC in late puberty were 2-fold greater in girls who were homozygous for the C and G alleles, respectively (P = 0.001). For rs7757956, the difference in total body less head ABMC in late puberty was 50% less in individuals homozygous or heterozygous for the A allele (P = 0.006). CONCLUSIONS: Gains in ABMC in late pubertal girls are strongly associated with ESR1 polymorphisms, suggesting that estrogen contributes to this process via an estrogen receptor alpha-dependent pathway.     

Regular participation in sports is associated with enhanced physical fitness and lower fat mass in prepubertal boys

OBJECTIVE: To study the effect of physical activity on whole body fat (BF), its regional deposition and the influence of body fatness on physical performance in prepubertal children. DESIGN: Cross-sectional study. SUBJECTS: A total of 114 boys (9.4+/-1.5 y, Tanner I-II), randomly sampled from the population of Gran Canaria (Spain), 63 of them physically active (PA, at least 3 h per week during the previous year) and 51 nonphysically active (non-PA). MEASUREMENTS: Body composition (DXA), anthropometric variables (body circumferences and skinfolds) and physical fitness were determined in all subjects. RESULTS: The PA obtained better results in maximal oxygen uptake, isometric leg extension force, vertical jump (muscular power), and 300 m (anaerobic capacity) and 30 m running tests (speed) than the non-PA. A lower percentage of body fat (% BF) (4 U less, P<0.05), whole BF mass (36% less, P<0.05) and regional fat mass (28, 25, and 30% less in the trunk, legs and arms, respectively, all P<0.05) was observed in the PA compared to the non-PA. The waist and hip circumferences correlated more closely with both the fat mass accumulated in the trunk region and the % BF (r=0.81-0.95, P<0.001) than the waist-to-hip ratio (WHR). The WHR correlated with the percentage of the whole fat mass accumulated in the trunk (PFT) (r=0.52-0.53, P<0.001). In both groups, the PFT increased curvilinearly with the % BF, regardless of the level of physical activity. ANCOVA analysis revealed that total and regional fat masses explained less than 40% of the difference in performance between the PA and non-PA group. The mean speed in the 30 m running test (V30), combined with the height and whole body mass, has predictive value for the BF mass (R=0.98, P<0.001). The % BF may be estimated from the body mass index (BMI) and V30 (% BF=8.09+2.44.BMI (kg m(-2))-5.8.V30 (m s(-1)), R=0.94, P<0.001) in prepubertal boys. CONCLUSIONS: Regular participation in at least 3 h per week of sports activities and competitions on top of the compulsory physical education program is associated with increased physical fitness, lower whole body and trunkal fat mass in prepubertal boys.     

Stimulated growth hormone (GH) secretion in children with delays in pubertal development before and after the onset of puberty: relationship with peripheral plasma GH-releasing hormone and somatostatin levels.

A reduced GH secretion has often been shown in prepubertal children with delays in pubertal development. In order to study the mechanism underlying this finding, we evaluated peripheral circulating levels of GH, GHRH, and somatostatin (SRIH) before and after the onset of sexual development in a group of eight late maturing children (six boys, two girls), comparing the results with those obtained in two groups of five prepubertal and four pubertal short children with familial short stature. GH was measured by a two-site immunoradiometric assay. Both GHRH and SRIH were assayed by specific RIAs after an acetone-petrolether extraction from plasma. Our data showed a significant increase (P less than 0.001) in GH, GHRH, and SRIH levels (peak vs. basal values) in response to L-dopa administration in all groups. In pubertal children with delays in pubertal development GH and GHRH peak values (15.8 +/- 2.2 micrograms/L and 120 +/- 18 pg/mL, respectively) were significantly greater (P less than 0.001) than in the same subjects before puberty (8.2 +/- 0.9 micrograms/L and 79 +/- 9 pg/mL, respectively), whereas SRIH peak values did not significantly change (41 +/- 6 vs. 41 +/- 5 pg/mL; P = NS). Furthermore, prepubertal subjects with delays in pubertal development showed GH and GHRH peak values lower (P less than 0.001) than those of prepubertal subjects with FSS (13.3 +/- 1.8 micrograms/L and 120 +/- 13 pg/mL, respectively), whereas no statistical difference was present between the two groups of subjects after pubertal development (18.2 +/- 2.9 micrograms/L and 128 +/- 11 pg/mL, respectively). In conclusion, these findings support the assumption that in late maturing subjects during prepubertal period the decreased GH secretion may be ascribed to a reduced GHRH secretion, reversible with the onset of puberty, without change in circulating SRIH levels.     

Associations of low-grade inflammation with physical activity, fitness and fatness in prepubertal children; the European Youth Heart Study

OBJECTIVE: To examine the associations of low-grade inflammation with objectively measured physical activity, cardiovascular fitness (CVF) and fatness in prepubertal children. DESIGN: Cross-sectional study. SUBJECTS: One hundred and forty-two children (74 boys and 68 girls) aged 9-10 years (pubertal stage I and II) from the Swedish part of the European Youth Heart Study. MEASUREMENTS: Total physical activity and its intensity levels (moderate, vigorous, moderate + vigorous) were measured by accelerometry. CVF was measured with a maximal ergometer bike test. Body fat was derived from the sum of five skinfold thicknesses. The measured low-grade inflammatory markers include C-reactive protein, fibrinogen, complement factors C3 and C4. RESULTS: C-reactive protein and C3 were negatively associated with CVF (beta=-0.254 and -0.267, respectively, P<0.05) and positively associated with body fat (beta=0.439 and 0.446, respectively, P<0.001), after controlling for sex, age and pubertal development. C-reactive protein and C3 were not significantly associated with CVF once body fat was in the model. Low-grade inflammation was not associated with physical activity, but physical activity was associated with CVF. CONCLUSIONS: The results showed that low-grade inflammatory markers were negatively associated with CVF and positively associated with body fat in prepubertal children. For most of the variables, the influence of fatness was slightly higher than the influence of CVF. The findings suggest that the potential beneficial effects of physical activity on low-grade inflammation may be explained by its association with CVF. Understanding the interplay between physical activity, CVF and fatness may be of importance to reducing cardiovascular disease risk in young people.     

Serum levels of growth hormone binding protein in children with normal and precocious puberty: relation to age, gender, body composition and gonadal steroids

AIM: To study the regulation of GHBP serum levels by gonadal steroids in normal and precocious puberty. STUDY PROTOCOL: We studied GHBP levels in relation to age, sex, pubertal maturation, body composition as well as to circulating IGF-I and gonadal steroid levels in 320 healthy children. Furthermore, we studied the regulation of circulating GHBP in 33 girls with central precocious puberty before and during gonadal suppression with GnRH agonist. METHODS: GHBP was determined by a time-resolved fluoroimmunoassay (GHBP TR-FIA) based on a commercially available immunoassay for GH, the DELFIA GH assay. RESULTS: In healthy children GHBP levels were significantly higher in normal girls compared with boys, and there was no significant increase in GHBP in puberty in both sexes. GHBP levels did not correlate with height (SDS), age, pubertal stage, IGF-I or testosterone/oestradiol levels in boys and girls, respectively. There were significant correlations between BMI and GHBP in boys and girls (R 2 = 0.14 and R 2 = 0.12, both P < 0.0001). Furthermore, GHBP correlated highly significantly with the percentage body fat, determined by BIA in 43 healthy girls (R 2 = 0. 40, P < 0.0001). GHBP levels were significantly higher in girls with central precocious puberty (CPP) (1.31 SDS (1.26), mean (SD)) compared to prepubertal controls (P < 0.0001), and above + 2 SD in 10 out of 33 patients. In girls with CPP, GHBP correlated inversely with oestradiol before treatment (R 2 = 0.26, P < 0.01) and there was a tendency towards a positive correlation with BMI (R 2 = 0.13, P = 0.078). By contrast, there were no signficant correlations between GHBP and IGF-I or height SDS. Gonadal suppression with GnRH agonist treatment caused a transient significant increase of 0.57 SD after 2 months of treatment (P < 0.001), but decreased to baseline levels hereafter. CONCLUSION: We conclude that in children, as in adults, body fat is the primary determinant for the circulating level of GHBP, and that the difference in body fat is probably the main factor for the higher levels of serum GHBP in girls compared with boys, as well as for the negative influence of testosterone levels in boys and of oestrogen levels in girls. The elevation in GHBP levels observed in girls with central precocious puberty is probably due their higher body fat content.     

Effect of an estrogen receptor-alpha intron 4 polymorphism on fat mass in 11-year-old children

CONTEXT: Polymorphisms in the ESR1 gene encoding estrogen receptor (ER)-alpha may be associated with fat mass in adults. OBJECTIVES: The objective of the study was to establish whether ESR1 polymorphisms influence fat mass in childhood. DESIGN: This was a cross-sectional analysis after genotyping of rs9340799, rs2234693, and rs7757956 ESR1 polymorphisms. SETTING: The Avon Longitudinal Study of Parents and Children (ALSPAC) was a population-based prospective study. PARTICIPANTS: Participants included 3097 11-yr-old children with results for ESR1 genotyping, puberty measures, and dual-energy x-ray absorptiometry results. OUTCOMES: Relationships between ESR1 polymorphisms and indices of body composition were measured. RESULTS: The rs7757956 polymorphism was associated with fat mass (P = 0.002). Total body fat mass (adjusted for height) was reduced by 6% in children with TA/AA genotypes, and risk of being overweight (> or =85th centile of fat mass) was decreased by 20%. This genetic effect appeared to interact with puberty in girls (P = 0.05 for interaction): in those with the TT genotype, total body fat mass (adjusted for height) was 18% higher in Tanner stages 3-5 vs. stages 1-2; the equivalent difference was 7% in those with TA/AA genotypes. Furthermore, the risk of being overweight was 36% lower in girls with TA/AA genotypes in Tanner stages 3-5, but no reduction was seen in those in stages 1-2. Neither rs9340799 nor rs2234693 polymorphisms were associated with body composition measures. CONCLUSIONS: Fat mass in 11-yr-old children was related to the rs7757956 ESR1 polymorphism. This association was strongest in girls in more advanced puberty, in whom the risk of being overweight was reduced by 36% in those with the TA/AA genotype.     

Relationship between insulin, insulin-like growth factor I, and dehydroepiandrosterone sulfate concentrations during childhood, puberty, and adult life

The relationships between plasma insulin, insulin-like growth factor I (IGF-I) and dehydroepiandrosterone sulfate (DHEAS) concentrations in normal subjects have not been defined. We performed iv glucose tolerance tests on 102 normal subjects, aged 5-20 yr. The subjects were divided into 4 groups according to pubertal stage (Tanner): A, stage 1 (n = 22); B, stages 2 and 3 (n = 17); C, stages 4 and 5 (n = 20); and D, adult, greater than 17 yr (n = 43). The basal plasma IGF-I and insulin concentrations and incremental 0-60 min insulin areas in response to glucose rose significantly throughout puberty (P less than 0.001 for all parameters) and declined to prepubertal levels by the third decade of life. There was a strong positive correlation between log fasting plasma insulin vs. log plasma IGF-I (r = 0.625; P less than 0.001) and log incremental 0-60 min insulin areas vs. log plasma IGF-I (r = 0.572; P less than 0.001). Plasma DHEAS concentrations were measured in groups A-C (n = 59); these also rose throughout puberty. There was strong correlations between log plasma DHEAS and log basal or stimulated (incremental 0-60 min areas) insulin responses (P less than 0.001). To assess the relationship between plasma DHEAS and insulin before puberty, we analyzed the data from group A separately. Plasma DHEAS concentrations tended to be higher in children 9 yr of age or older than in those less than 9 yr old, whereas basal and stimulated plasma insulin levels were similar. We found no correlation between log plasma insulin (fasting or stimulated responses) and log plasma DHEAS concentrations in group A (P greater than 0.05). In conclusion, we found a strong relationship between plasma insulin and IGF-I throughout childhood and puberty and during adult life. This finding suggests that insulin may be important for normal growth during childhood. There was no correlation between plasma insulin and DHEAS concentrations in prepubertal children, which suggests that adrenarche does not influence insulin levels.     

Body composition in adolescent girls with type 1 diabetes.

AIMS: To compare body composition in adolescent girls with Type 1 diabetes with healthy controls. RESEARCH DESIGN AND METHODS: In this population-based study, body composition was examined, using dual-energy X-ray absorptiometry (DXA) and skinfold measurements, in 18 adolescent post-menarcheal females, 16-19 years of age, with Type 1 diabetes since childhood in comparison to age-matched healthy control subjects. RESULTS: Body mass index was 2.7 kg/m2 higher in diabetic patients (26.3 +/- 2.6 vs. 23.6 +/- 3.8; P < 0.05). The overweight consisted almost entirely of increased fat mass, as evaluated by both skinfold measurements and DXA. Bone mineral density did not differ between the two groups. In diabetic females, the distribution of the fat mass was increased in the upper part of the body. The fat distribution, expressed as the abdominal-to-leg ratio, was significantly correlated to glycated haemoglobin (HbA1c) (r = 0.69; P < 0.005), daily dosage of insulin expressed per kilogram body weight (r = 0.78; P < 0.0005) and total cholesterol (r = 0.60; P < 0.001). CONCLUSIONS: The observed overweight in adolescent females with Type 1 diabetes is explained by an increased fat mass. Abdominal fat accumulation was associated with poor glycaemic control, increased need for insulin and elevated blood lipids.     

Alterations in the pulsatile properties of circulating growth hormone concentrations during puberty in boys

To investigate the mechanisms subserving physiological alterations in circulating GH concentrations during puberty, we assessed the GH pulse characteristics of 60 24-h serum GH profiles obtained from healthy male volunteers of normal stature (aged 7-27 yr) whose physical development spanned the entire pubertal range. Subjects were divided into five study groups based on degree of sexual maturation. The mean 24-h concentration of GH was greater in late pubertal boys than in all other groups (P less than 0.001). This elevation primarily reflected a greater size, rather than number, of GH pulses, whether assessed as mean GH pulse area (P = 0.004 vs. all other groups), mean GH pulse amplitude (P = 0.001), or sum of the GH pulse areas (P less than 0.001). GH pulse frequency was indistinguishable among all groups (P greater than 0.05). However, circadian GH rhythms varied significantly in amplitude and mean values (but not in phase) throughout puberty. Plasma insulin-like growth factor-I levels were greatest in the late pubertal boys (1.98 +/- 0.15 U/mL) and remained elevated in the postpubertal group (1.44 +/- 0.18). The mean value for the adult men (0.74 +/- 0.06) was indistinguishable from that of prepubertal boys (0.90 +/- 0.13). In addition, all assessed characteristics of GH pulses and circadian rhythms in adults were equal to or less than corresponding values in prepubertal boys. We conclude that circulating GH concentrations transiently increase during mid- to late puberty in normal boys, primarily through augmentation of the size of GH pulses, but return to or below prepubertal levels during early adulthood.     

Early pituitary-gonadal activation before clinical signs of puberty in 5- to 8-year-old adopted girls: a study of 99 foreign adopted girls and 93 controls

CONTEXT: Recent studies have indicated that internationally adopted girls are at high risk of developing precocious puberty. Clinical studies including a contemporary control group are lacking. OBJECTIVE: The objective was to study clinical, biochemical, and ultrasonographic markers of pituitary-gonadal activation in prepubertal adopted girls and a control group in the same age categories. SETTING: The study took place at University Hospital, Copenhagen, Denmark. DESIGN AND PARTICIPANTS: The study included randomly selected internationally adopted girls [(n = 99; mean age, 6.9 (5.1-8.5) yr] and controls of Danish origin [n = 93; mean age, 6.8 (5.2-8.5) yr] who were studied cross-sectionally. METHODS: Height, weight, and pubertal stage were assessed with serum levels of reproductive hormones. Size and morphology of internal genitals were evaluated by ultrasonography. Bone age was evaluated by x-ray of the left hand. RESULTS: Serum values of FSH were significantly higher in prepubertal adopted girls compared with controls [median, 1.4 (95% confidence interval, 0.4-3.6) vs. 1.0 (0.4-2.4) IU/liter; P <0.001]. Serum estradiol was above detection limit (>18 pmol/liter) in 46.5% of prepubertal adopted girls and 20.7% of controls (P = 0.001). In prepubertal adopted girls, the proportion of measurable samples increased significantly with age [odds ratio, 2.5 (95% confidence interval, 1.3-5.0; P = 0.009]. In controls, the odds ratio was 1.0 (0.6-1.7) (P = 0.9). Serum SHBG levels were significantly lower in prepubertal adopted girls compared with controls [99.0 (50.4-153.0) vs. 115.0 (53.1-202.1); P < 0.001]. CONCLUSION: Five- to 8-yr-old adopted girls showed signs of increased pituitary as well as gonadal activity despite prepubertal phenotype in the majority of girls. Our findings suggest that early onset of puberty in adopted girls is centrally driven.