The aims of the present study were to examine and compare the relationships between IGF-I and its binding proteins with total fat mass, SAAT, VAT, and HFF in overweight Latino and African American adolescents after adjusting for related covariates. We hypothesized that overweight Latino adolescents would show an inverse relationship between IGF-I, IGFBP-I, and IGFBP-3 with our dependent variables, similar to what we saw in overweight Latino children (15
). Although we saw similar results for the relationship between IGF-I and our dependent variables, we saw different results for IGFBP-I and IGFBP-3. These results indicate that by adolescence, Latinos no longer have a significant inverse relationship between IGFBP-3 and BMI, total fat mass, SAAT, VAT, and HFF. By adolescence Latinos and African Americans showed a large and significant inverse relationship between plasma IGFBP-I levels and these variables. We also hypothesized that overweight African American adolescents would show results that were similar to those seen in adult studies (14
). Despite this, we found that those with higher total fat mass had lower plasma IGF-I levels, as did those with a higher BMI.
Our findings illustrate similar relationships between IGF-I and IGFBP-I with adiposity in Latino and African American adolescents. Both ethnic groups showed significant inverse relationships between IGF-I and IGFBP-I with BMI, total fat mass, VAT, and HFF. Our results demonstrate that VAT has an inverse relationship with IGF-I in Latinos and African Americans while SAAT has an effect on IGF-I that is modified by ethnicity. Unique to this study, we show that IGF-I and IGFBP-I levels have a large inverse relationship with HFF in Latinos and African Americans and that the relationship between IGFBP-I and HFF is modified by ethnicity.
The observed negative correlation between HFF and IGF-I, as well as IGFBP-I, suggests an association between the amount of liver fat and serum IGF-I and IGFBP-I levels. Since serum IGF-I and IGFBP-I are mainly produced in the liver (30
), a higher fat content may be affecting the process in which the liver synthesizes IGF-I and IGFBP-I. This is consistent with a previous study that was able to show an association between hepatic steatosis and IGF-I, as well as IGFBP-3, serum levels. Their results suggest a relationship between elevated liver fat and low serum IGF-I levels and high IGFBP-3 levels (31
). In addition to these correlations, we determined that ethnicity significantly decreased mean predicted levels of IGF-I in our model containing HFF, and significantly modified the effect of HFF on predicted mean levels of IGFBP-I. These finding illustrate that, possibly as a result of higher liver fat, Latinos have lower predicted mean IGF-I levels and higher predicted mean levels of IGFBP-I.
Alternatively, our findings appear to support ethnic differences in fat depot accumulation. Other studies have shown that Latinos have a higher HFF compared to African Americans (32
). It is hypothesized that differences in fat depot accumulation stems from genetic differences in lipid storage pathways. African Americans may be able to expand SAAT stores, through proliferation and differentiation of new adipocytes, to sequester dietary lipids away from ectopic organs. The increased spillover of lipids into ectopic depots in Latinos may be explained by an impaired ability to expand their SAAT stores. Since IGF-I appears to control the expansion of adipocytes (33
), these results, in conjunction with higher total IGF-I levels in African American adolescents, suggest a possible mechanism in which adipocyte differentiation is impaired in Latinos.
One limitation of our study is that we did not directly analyze growth hormone levels, which, given its pulsatile secretion pattern, requires assessment over 24 hours. We enrolled only overweight Latino and African American adolescents and did not include normal weight participants. There were significant differences in fasting insulin and SI between African American and Latino adolescents () and SI was significantly correlated with IGFBP-I (r = 0.27, p<0.05). When controlling for HFF, SI was not significantly correlated with IGF-I (r = −0.04, p = 0.69) but was significantly correlated with IGFBP-I levels (r = 0.24, p<0.05). When adjusting for our a priori covariates and HFF, IGF-I and IGFBP-I were not significantly correlated with SI (r = −0.03, p = 0.77; r = 0.11, p = 0.30). Despite the inclusion of SI as a covariate in each model, we cannot rule out the possibility that insulin insensitivity, in addition to liver fat, may be affecting the process in which the liver synthesizes IGF-I and IGFBP-I. Since this analysis was cross-sectional, a longitudinal analysis is needed to determine if the progression of obesity and its distribution pattern affect plasma IGF-I levels over time. Despite these limitations, our study is unique in that we utilized accurate measurements of total and regional body fat composition, direct measures of SI, and were able to compare two homogeneous samples of understudied minority adolescents.
In summary, we identified strong inverse relationships between IGF-I and IGFBP-I with BMI, total fat mass, VAT, and HFF in Latinos and African Americans. Additionally, we identified a modifying effect of ethnicity on the relationship between IGF-I and SAAT as well as IGFBP-I and HFF. These potentially important ethnic differences were independent of age, gender, Tanner stage, total lean tissue mass, total fat mass, and SI. Our results demonstrate a larger predicted increase in African American plasma IGF-I levels in response to increasing SAAT compared to Latinos. In addition to this, we demonstrated that African Americans with a HFF at the 75th percentile have lower levels of IGFBP-I while Latinos at the 75th percentile show higher IGFBP-I levels. These findings illustrate that SAAT and HFF contribute to the higher plasma IGF-I levels, relative to obesity, seen in African American compared to Latino adolescents.