Childhood Adiposity and Adolescent Sex Steroids in the Exploring Perinatal Outcomes Among Children Study

Catherine Kim; Kylie K. Harrall; Deborah H. Glueck; Daniel Shumer; Dana Dabelea

Disclosures

Clin Endocrinol. 2019;91(4):525-533. 

In This Article

Results

Table 1 shows participant characteristics by sex. At the first visit, both boys and girls were between 6 and 14 years old (on average 10.5 ± 1.5 years), and at the second visit, both boys and girls were between 12 and 20 years old (on average 16.7 ± 1.2 years). At the first visit, approximately half of the boys were prepubertal compared to about 1/3 of the girls; by visit 2, all of the children had reached the onset of puberty. One boy was Tanner stage 2 at <11.5 years of age and one girl was Tanner stage 2 at <10.5 years of age, and conversely, no girls were Tanner stage 1 at 12 years of age and no boys were Tanner stage 1 at 14 years of age. About half were non-Hispanic white. Although most mothers had more than a high school education, almost half of the population had an annual income less than $50 000 per year. Table 1 also shows average adipose tissue areas and sex steroid levels. While DHEA concentrations were consistently above the level of detection, a substantial proportion of children had oestradiol and testosterone concentrations below the limit of detection. At visit 2, approximately 12% of girls and 1% of boys had undetectable testosterone levels, and 7% of girls and 6% of boys had undetectable oestradiol levels.

Among boys, Table 2 shows the association between change in adipose tissue depots between visit 1 and visit 2, as well as baseline adipose tissue, with the risk of undetectable hormones at visit 2. Even after adjustment for baseline VAT and SAT, more rapid growth in VAT and more rapid growth in SAT were both associated with higher risk of undetectable testosterone at follow-up (due to reverse-scale Cox proportional hazards modelling, an HR <1 indicates greater risk). For every 1 mm2 increase in VAT, there was a 14% increase in the risk of testosterone values below the limit of detection (HR: 0.86, P < .0001). For every 1 mm2 increase in SAT, there was a 4% increase in the risk of testosterone values below the limit of detection (HR: 0.96, P < .0001).

Figure 1 shows the estimated proportions of the adolescent male population below a specific testosterone level. Different lines show the different curves by percentile of VAT growth rate. The curve for the 10th percentile in VAT growth rate lies at the bottom, and the curve for the 90th percentile lies at the top. The estimates are drawn from reverse Cox proportional hazard models. The VAT growth rate is treated as a continuous predictor, so as the rate of growth in VAT increases, the proportion of the population below a specific testosterone value increases. Estimates can be obtained for any percentile desired: only the 10th, 50th and 90th are shown here for clarity.

Higher levels of VAT at baseline were also associated with a 2% increase in the risk of undetectable testosterone at visit 2 (HR: 0.98, P < .003). However, higher concentrations of VAT/SAT at baseline were associated with a lower risk of undetectable testosterone at future visits (HR: 4.04, P = .028), suggesting that boys with relative large amounts of visceral fat relative to subcutaneous fat prior to the pubertal transition were more likely to have detectable testosterone levels at follow-up. These patterns did not change with adjustment for race/ethnicity (results not shown). Among girls, no fat depots or change in fat depots were associated with future sex steroid levels (Table 2).

Among boys, the associations between growth rate of VAT and growth rate of SAT with testosterone persisted after adjustment for other variables, including insulin, LH, leptin and hepatic fat (Table 3), suggesting that these factors did not account for the association between growth of fat with future low testosterone. The association between baseline VAT with future testosterone was attenuated in models including fasting insulin and models including leptin, suggesting that these variables either confounded or mediated the relationship between baseline VAT and future testosterone. Similarly, the association between baseline VAT/SAT with future testosterone was also attenuated by fasting insulin and leptin, suggesting that these variables either confounded or mediated the relationship between baseline VAT/SAT and future testosterone. These associations also persisted after adjustment for race/ethnicity (results not shown).

Comments

3090D553-9492-4563-8681-AD288FA52ACE

processing....