Bone mineral in prepubertal children: gender and ethnicity.

Previous reports of gender and ethnic differences in bone mineral in prepubertal children have been inconsistent due to different methodologies, the problematic nature of bone density by dual-energy X-ray absorptiometry (DXA) calculated as the ratio of bone mineral mass to projected bone area (BA), and the generally small study populations. The aim of this study was to test the hypothesis that gender and ethnic differences in bone mineral by DXA are present in prepubertal children. The subjects were 336 healthy Asian, black, and white prepubertal children (172 females and 164 males). Total body bone mineral content (TBBMC) was adjusted for total body BA (TBBA), age, height, and weight. Adjusted mean TBBMC was greater in males than in females (p = 0.01). The gender difference was independent of ethnicity. Adjusted mean TBBMC was different for black compared with nonblack children (p = 0.001). The ethnic difference was a function of TBBA and weight. This study in a multiethnic population of prepubertal children shows (1) a gender difference in TBBMC and (2) an ethnic difference in TBBMC.

Effect of puberty on the relationship between circulating leptin and body composition.

Circulating concentrations of leptin are better correlated with absolute amounts of adipose tissue [fat mass (FM)] than with relative body fatness (body mass index or percent body fat). There is a clear sexual dimorphism in circulating concentrations of leptin (females > males) at birth and in adulthood. However, whether such dimorphism is present in the interval between these periods of development remains controversial. We examined body composition and clinical (Tanner stage) and endocrine (pituitary-gonadal axis hormones) aspects of sexual maturation in relationship to circulating concentrations of leptin in 102 children (53 males and 49 females, 6-19 yr of age) to evaluate the relationship between circulating leptin concentrations and body composition before and during puberty. Pubertal stage was assigned by physical examination (Tanner staging) and also assessed by measurement of plasma estradiol, testosterone, and pituitary gonadotropins. Body composition was determined by dual-energy x-ray absorptiometry and by anthropometry. Circulating concentrations of leptin in the postabsorptive state were determined by a solid-phase sandwich enzyme immunoassay. The effect of gender on the relationship between circulating leptin concentrations and FM was determined by ANOVA at each Tanner stage. Stepwise multiple linear regression analyses, including circulating concentrations of pituitary-gonadal axis hormones, and FM were performed, by gender, to determine whether the relationship between circulating concentrations of leptin and FM changes during puberty. Plasma leptin concentrations were significantly correlated with FM at all Tanner stages in males and females. Plasma leptin concentrations, normalized to FM, were significantly higher in females than males at Tanner stages IV and V but not at earlier stages of pubertal development. Plasma leptin concentrations, normalized to FM, were significantly greater in females at Tanner stage V compared with females at Tanner stage I and significantly lower in males at Tanner stage IV and V compared with males at Tanner stage I. These significant gender and maturational differences were confirmed by demonstrating that the regression equation relating circulating leptin concentrations to FM in females and males at Tanner stages IV and V were significantly different (predicted lower leptin concentrations in males than females with identical body composition) and that the regression equations relating circulating concentrations of leptin to FM in each gender before puberty (Tanner stage I) were significantly different (predicted higher plasma concentrations of leptin in prepubertal males and lower leptin concentrations in prepubertal females) than the same regression equations in later puberty. Circulating concentrations of testosterone were significant negative correlates of circulating concentrations of leptin normalized to FM in males when considered as a group over all pubertal stages. The inclusion in multivariate regression analyses of circulating concentrations of testosterone and estradiol, FM, fat-free mass, and gender did not eliminate a significant gender-effect (P < 0.05) on circulating concentrations of leptin at Tanner stages IV and V. The circulating concentration of leptin, normalized to FM, declines significantly in males and rises significantly in females late in puberty to produce a late-pubertal/adult sexual dimorphism. These studies confirm a potent role for gonadal steroids as mediators of this sexual dimorphism in circulating concentrations of leptin. (ABSTRACT TRUNCATED)

Body composition changes during Tanner stage 5.

Clinicians use the combination of Tanner stage 5 (T5) of puberty, final height, and epiphyseal fusion to define maturity. We tested the hypothesis that changes in body composition related to age are identifiable during T5. Asian, Black, Hispanic, and White T5 adolescents (n = 148, 72 females) had measurements taken of their height, weight, total body potassium by 40K counting, total body water by D2O dilution; and total body bone mineral, fat-free mass, and fat mass by dual-energy X-ray absorptiometry. The relative increases with age in lean body components were greater than those in height and weight, and were greater in males. Age was a significant determinant of all body components in males, but of only bone mineral in females. The effect of age was independent of ethnicity. These findings suggest an independent effect of age on body composition during T5, especially in males. We propose that peak levels of lean body components should be included in the definition of maturity in certain clinical and metabolic situations.

Growth in congenital rubella syndrome and correlation with clinical manifestations.

Growth patterns, final stature, and clinical manifestations were studied in a review of the records of 105 patients with congenital rubella syndrome followed longitudinally. Of the patients (35 male, 51 female), 86 had achieved final heights. Three patterns of growth were observed: normal growth, growth consistently below the 5th percentile, and growth within the normal range or slightly below the 5th percentile followed by early cessation of growth and final height usually below the 5th percentile. Significant cognitive deficits were not observed in patients with normal growth patterns, except for one patient with profound mental retardation. The magnitude of the cognitive deficits was closely correlated with the degree of growth failure (p less than 0.001). We postulate that the rubella virus exerts its effect on somatic growth both in utero and postnatally, at a central and peripheral level, through multiple mechanisms.

Diabetes mellitus and autoimmunity in patients with the congenital rubella syndrome.

An increased incidence of insulin-dependent diabetes mellitus (IDDM) has been reported in patients with congenital rubella syndrome (CRS). Thus, studies of children with CRS would be of great importance in following the development of IDDM in a susceptible population. A total of 242 children with CRS, 30 of whom already have diabetes (mean age, 17.4 +/- 0.3 years) have been evaluated. In this latter group, the frequency of HLA DR3 is significantly increased and that of HLA DR2 significantly decreased. While pancreatic islet cell cytotoxic or surface antibodies (ICSA) are found in 20.2% of the total population of patients with CRS, they are present in 50%-80% of patients with glucose abnormalities. In all but five of the ICSA-positive patients, glucose abnormalities are currently present. In addition, glucose intolerance is found in greater than 50% of the DR3-positive nondiabetic patients with CRS evaluated to date. The data demonstrate that patients with CRS at risk for IDDM have the same genetic and immunologic features seen in classic IDDM, namely the presence of HLA DR3 and the absence of HLA DR2 and the high prevalence of ICSA before decompensation.

Congenital rubella syndrome as a model for type 1 (insulin-dependent) diabetes mellitus: increased prevalence of islet cell surface antibodies.

An increased prevalence of Type 1 (insulin-dependent) diabetes has been reported in patients with congenital rubella. Rubella virus multiplies in the pancreas, and we have hypothesized that studies of children with congenital rubella would be of great importance in following the development of Type 1 diabetes in a defined, susceptible population. Two hundred and forty-one children with congenital rubella (mean age 17.4 +/- 0.3 years; 65% black and hispanic) have been evaluated, 30 of whom already have diabetes and 17 of whom have borderline glucose tolerance. In these latter two groups, HLA-DR3 is significantly increased and HLA-DR2 significantly decreased. Pancreatic islet cell cytotoxic surface antibodies are found in 20% of the total congenital rubella population, including in more than 50% in the time period before they develop diabetes and are not related to any specific HLA type. In addition, anti-microsomal and anti-thyroglobulin antibodies are found in 34% of this population. The data demonstrate that Type 1 diabetes developing in congenital rubella patients has the genetic and immunological features of classical Type 1 diabetes, namely the presence of HLA-DR3, the absence of HLA-DR2, islet cell surface antibodies before decompensation and an increased prevalence of anti-thyroid antibodies. Patients with non-diabetic congenital rubella represent an easily identifiable group in whom other immunological factors associated with Type 1 diabetes can be elucidated and possibly modified.

The HLA system in congenital rubella patients with and without diabetes.

The HLA antigens of 173 patients with the congenital rubella syndrome (CR) are reported. Twenty-one of these patients are also clinically diabetic, and among them the frequencies of the HLA antigens DR2 and DR3 are significantly lower and higher, respectively, than in CR patients without diabetes or in controls. These data suggest that the genes that control susceptibility to type I or insulin-dependent diabetes mellitus are necessary for the development of glucose intolerance in CR patients.