Elsevier

Annals of Epidemiology

Volume 19, Issue 12, December 2009, Pages 841-849
Annals of Epidemiology

Anthropometric Correlates of Insulin-Like Growth Factor 1 (IGF-1) and IGF Binding Protein-3 (IGFBP-3) Levels by Race/Ethnicity and Gender

https://doi.org/10.1016/j.annepidem.2009.08.005Get rights and content

Purpose

Insulin-like growth factor 1 (IGF-1) levels are positively related to some cancers and negatively related to cardiovascular disease. These conditions are also related to insulin resistance and high body weight, leading to the hypothesis that IGF-1 levels may, in part, mediate the association of high body weight with these health outcomes. Using the National Health and Nutrition Examination Survey (NHANES) III population, we examined the associations between IGF-1, IGF binding protein-3 (IGFBP-3), and the IGF-1/IGFBP-3 molar ratio with anthropometric measures in a large, U.S. population-based study where these associations could also be stratified by race/ethnicity and gender.

Methods

The study population consisted of 3,168 women and 2,635 men (44% non-Hispanic white, 28.2% non-Hispanic black, and 27.7% Mexican-American). Anthropometric measures were obtained by trained personnel in the NHANES mobile examination centers. IGF-1 and IGFBP-3 were measured using immunoassays by staff at Diagnostic System Laboratories (DSL) Inc. (Webster, TX). Associations of IGF-1, IGFBP-3, and IGF-1/IGFBP-3 molar ratio with anthropometric variables across race/ethnicity and gender were evaluated by using linear regression modeling.

Results

Body mass index (BMI) was inversely associated with IGF-1 levels across all of the race/ethnicity and gender subgroups. In contrast, BMI, waist to hip ratio (WHR), and waist circumference were positively associated with IGFBP-3 levels only in non-Hispanic black men and non-Hispanic white women. The IGF-1/IGFBP-3 molar ratio was inversely associated with all anthropometric measures, except height, in all subgroups of the population.

Conclusion

The significant inverse associations of BMI with IGF-1 levels and of all anthropometric variables, except height, with the IGF-1:IGFBP-3 molar ratio in all subgroups do not support existing hypotheses that associations of excess weight with negative health outcomes, such as specific cancer diagnoses, are mediated through high IGF-1 levels.

Introduction

Recent analysis of data collected from the National Health and Nutrition Examination Survey (NHANES) conducted in 2003–2004 demonstrated that there are significant differences in the prevalence of obesity by race/ethnicity in the U.S. population. In this study, 30% of non-Hispanic whites, 36.8% of Mexican Americans, and 40% of non-Hispanic black adults were obese as determined by measurement of body mass index (BMI, a measure of weight relative to height) (1). Obesity is associated with many health risks and, among them, increased risk of developing certain types of cancers and increased mortality related to these cancers. Specifically, high BMI has been associated with increased risk and mortality of breast (postmenopausal), endometrial, esophageal, colon, and kidney cancers 2, 3, 4, 5, 6. High BMI also has been associated with prostate cancer aggressiveness and mortality (7).

The biological mechanisms linking obesity with increased cancer risk and/or mortality are not fully understood and many hypotheses have been generated to explain this association. One of these hypotheses is that a persistent state of high insulin-like growth factor 1 (IGF-1) levels may be associated with excess weight and promote multiple aspects of tumorigenesis (8). In both in vitro and animal models, IGF-1 signaling has been shown to increase cell proliferation, angiogenesis, metastasis, and cell survival (9). Furthermore, numerous epidemiology studies have shown that high serum levels of IGF-1 correlate with increased cancer risk, including prostate 10, 11, 12, colon 13, 14, 15, ovarian 16, 17, and premenopausal breast cancer 18, 19. Therefore, high IGF-1 levels have been associated both with cancers where there is strong evidence that obesity may play a role in the development and/or aggressiveness of the cancer (e.g., prostate and colon cancer) and with cancers in which the association with obesity is less clear (e.g., ovarian cancer) or even protective (e.g., premenopausal breast cancer). It is possible that IGF-1 levels may mediate part of the association of anthropometric risk factors with cancer risk and other health outcomes.

Several prior studies have examined the association of IGF-1 levels with various anthropometric measures; however, the results have been mixed 20, 21, 22, 23, 24, 25, 26, 27. For most of these studies the populations have been relatively homogeneous or the sample sizes too small to examine these associations stratified by race/ethnicity and gender. Therefore, the goals of the analyses presented herein were to assess the relationship between IGF-1, IGFBP-3 and the IGF-1/IGFBP-3 molar ratio and anthropometric factors in a large, U.S. population-based study where it could be determined if the associations vary across race/ethnicity and gender. These analyses were conducted using data from a subset of the population of the Third NHANES (NHANES III) that was carried out from 1988–1994. We previously published analyses from these population-based data and showed differences in IGF-1, IGFBP-3, and the IGF-1/IGFBP-3 molar ratio by race/ethnicity (28). We now expand these analyses to determine if the associations between a variety of anthropometric factors and IGF-1, IGFBP-3, and the IGF-1/IGFBP-3 molar ratio differ by race/ethnicity and gender.

Section snippets

Methods and Procedures

This study population is from NHANES III, a nationally representative sample of the U.S. population with a stratified multistage probability design and oversampling of African- and Mexican-Americans (29). The survey, carried out from 1988–1994, included questionnaires, serum collection, and physical examination. A subset (n = 6,226) of the total sample of adults (n = 20,024) were selected at random and asked to fast overnight before attending a morning examination at which they supplied a serum

Results

For these analyses, data from a subset of the NHANES III population including 1,156 non-Hispanic white men, 702 non-Hispanic black men, 777 Mexican-American men and 1400 non-Hispanic white women, 939 non-Hispanic black women, and 831 Mexican-American women were examined. Mean age, anthropometric measures, and biomarker concentrations for each subgroup of the study population are presented in Table 1. Mean age was significantly different across all race/ethnicity subgroup comparisons for each

Discussion

These data demonstrate an inverse association of IGF-1 levels with BMI. The inverse association of BMI with IGF-1 has been reported or suggested previously from smaller studies, many of which focused predominantly on participants of Caucasian background and/or on one gender 19, 20, 21, 22, 23, 24, 25, 26, 36, 37. We were able to replicate this finding in a much larger study population and to examine this association by race/ethnicity and gender. The inverse association is consistent in all

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