Early Pubertal Development and Insulin Sensitivity among School-Aged Girls: Mediation Via Adiposity
ABSTRACT STUDY OBJECTIVE: To examine whether the known association between early pubertal breast maturation and insulin sensitivity (SI) is mediated by adiposity. DESIGN: Cross-sectional analyses. SETTING: Observational study examining the roles of environment, diet, and obesity on puberty. PARTICIPANTS: 379 girls with a mean age, 7.03 years; 62% were white and 29% black. MAIN OUTCOME MEASURES: Pubertal development was assessed via physical examination and adiposity by body mass index Z score (BMI Z) and waist-to-height ratio. Fasting blood samples were obtained for insulin and glucose concentrations. SI was calculated with the quantitative insulin sensitivity check index (QUICKI). Analysis of variance and Sobel's test was used to assess mediation. RESULTS: Fifty-five girls were pubertal (Tanner 2 breast). Breast maturation was inversely associated with SI (P = .005) and positively associated with BMI Z (P < .001) and waist-to-height ratio (P < .001). The effect of breast maturation on SI was no longer significant (P = .41) after adjusting for the effect of BMI Z, which remained significant (P < .001). Similar results were obtained when waist-to-height ratio replaced BMI Z in the models. Mediation analyses demonstrated that 75% of the association between breast maturation and SI is mediated by adiposity. CONCLUSIONS: In girls, decreased SI during early puberty is largely mediated by total and visceral adiposity.
SourceAvailable from: highwire.orgArchives of Disease in Childhood 07/1969; 44(235):291-303. DOI:10.1136/adc.44.235.291 · 2.91 Impact Factor
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ABSTRACT: 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)Journal of Clinical Endocrinology & Metabolism 07/2000; 85(7):2509-18. · 6.31 Impact Factor
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ABSTRACT: Abdominal obesity is closely associated with the presence of metabolic risk factors and elevated blood pressure in selected materials. This has, however, never been analyzed quantitatively in a non-selected cohort. Therefore, in a population-based study of 1462 Swedish women, four selected risk factors for non-insulin dependent diabetes mellitus (NIDDM) and cardiovascular disease (CVD), serum triglycerides, blood glucose and systolic blood pressure and also serum insulin in a subsample, were examined in relation to regional and overall obesity. This was performed by subdividing the age adjusted sample into quintiles of waist to hip circumference ratio (WHR) or body mass index (BMI) as indicators of abdominal distribution of body fat and overall obesity, respectively. The risk factors serum triglycerides, blood glucose, blood pressure and serum insulin were defined as being elevated when the value of the risk factor was higher than the mean plus one or two standard deviations of the total age-adjusted cohort. The percentage of women with elevated risk factors according to this definition was then calculated in each of these quintiles. Having a risk factor which was elevated according to the definition was significantly correlated to WHR and BMI (p<0.0001) independent of age. The presence of one or several of these elevated risk factors was clearly higher than expected in the fifth quintile of WHR, and to a lesser extent in the fifth quintile of BMI while this was not the case in the lower quintiles of WHR and BMI. When studying the combination of the WHR and BMI, the presence of risk factors higher than the mean plus two standard deviations increased gradually with WHR in all five quintiles of BMI. A significant association was observed between WHR and presence of risk factors independent of BMI (p<0.0001) but BMI did not remain significantly correlated to presence of risk factors when controlling for WHR (p=0.09). These results indicate that abdominal distribution of body fat in women independently of general obesity is closely associated with metabolic risk factors including elevated blood pressure, a metabolic syndrome with increased risk for cardiovascular disease and non-insulin dependent diabetes mellitus.Obesity research 07/1994; 2(4):372-7. DOI:10.1002/j.1550-8528.1994.tb00077.x · 4.95 Impact Factor