The association of plasma IGF-I with dietary, lifestyle, anthropometric, and early life factors in postmenopausal women

doi:10.1016/j.ghir.2015.01.001

Growth Hormone & IGF Research

Volume 25, Issue 2, April 2015, Pages 90-95

https://doi.org/10.1016/j.ghir.2015.01.001 Get rights and content

Highlights

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We investigate correlates of circulating IGF-I in 1883 postmenopausal women.
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Protein and dairy protein intakes were positively associated with IGF-I.
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Current HRT users had 9.9% lower IGF-I than non-users.
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Obese women had 6.8% lower IGF-I than overweight women.
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Women reporting wearing larger vs smaller clothes sizes at age 20 had lower IGF-I.

Abstract

Objective

Higher circulating concentrations of insulin like growth factor (IGF-I) are associated with an increased risk of breast cancer. The objective of this study was to investigate associations between circulating IGF-I concentrations and dietary factors (intakes of protein, dairy protein, and alcohol), lifestyle factors (smoking and HT use), anthropometric indices (height and adiposity) and factors in early life (birth weight, having been breastfed, body size at age 10, and at age 20) in postmenopausal women in the UK.

Design

An analysis of plasma IGF-I concentrations (measured by immunoassay) in 1883 postmenopausal women. Multivariate analysis was used to examine correlates of plasma IGF-I concentrations.

Results

Women in the highest quintile of total protein and dairy protein intakes had, respectively, 7.6% and 5.5% higher plasma IGF-I concentrations than women in the lowest quintile (p trend < 0.05 for both). Other factors significantly (p < 0.05) associated with reduced IGF-I concentrations were: consuming 14 or more vs 3–7 alcoholic drinks per week (8.8% lower IGF-I); current vs non-current HT users (9.9% lower IGF-I); current use of oestrogen alone vs oestrogen + progestagen (16.9% lower IGF-I); obese vs overweight (6.8% lower IGF-I); and women who reported wearing larger vs smaller clothes sizes at age 20 (4.9% lower IGF-I).

Conclusions

This study in post-menopausal women identified several potentially modifiable determinants of circulating IGF-I concentrations. There is now strong evidence from this and other studies that IGF-I concentrations are associated with dietary protein intakes.

Introduction

Insulin-like growth factor I (IGF-I) is a polypeptide hormone that stimulates cell proliferation and inhibits apoptosis [1]. Higher circulating concentrations of IGF-I are associated with an increased risk of breast cancer [2]. In well-nourished populations higher total protein and dairy protein intakes have been associated with higher circulating IGF-I concentrations [3], [4].

Some [2], [5], but not all [6], investigators have reported a modest positive association between adult height and circulating IGF-I concentrations, and others have found an inverted-U-shaped association between body mass index (BMI) and circulating IGF-I concentrations, with a peak occurring around 23 to 27 kg/m², and those with low or high BMIs having relatively low circulating IGF-I concentrations [2], [7], [8]. Early life body size was inversely associated with circulating IGF-I concentrations in one study, with adult women who reported being comparatively heavy at birth, age 10, and age 18 having relatively low IGF-I concentrations [9]. Most previous studies in women are small, and have been conducted in exclusively premenopausal women [5], [6], or a combination of pre-and post-menopausal women [4], [7], [8]; less is known about the predictors of circulating IGF-I concentrations in well-nourished postmenopausal women.

The objective of this study is to investigate the associations between dietary factors (intakes of protein, dairy protein, and alcohol), lifestyle factors (smoking and HT use), anthropometric indices (height and BMI), and factors in early life (birth weight, having been breastfed, and body size at age 10, and at age 20) and plasma IGF-I concentration in a sample of postmenopausal women enrolled in the Million Women Study.

Section snippets

Study population

This study was based on a sample of participants in the Million Women Study, a prospective cohort of approximately 1.3 million women in the UK. The study has been described in detail elsewhere [10]. The study was approved by the Anglia and Oxford Multi-Centre Research Ethics Committee and all participants gave written informed consent. At recruitment in 1996–2001, participants completed a self-administered questionnaire that collected information on socio-demographic, lifestyle and reproductive

Results

Table 1 describes the characteristics of the 1833 Million Women Study participants included in these analyses. The mean age of the participants when blood was collected was 63.6 years. On average, protein and dairy protein contributed 15% and 4% of daily energy intakes, respectively. The prevalence of smoking (5.5%) and HT-use (10.8%) was low. The geometric mean (95% CI) plasma IGF-I concentration was 14.4 (14.2–14.6) nmol/L.

Table 2 presents the associations between dietary factors, current

Discussion

In this analysis of nearly 2000 post-menopausal women, we found significant associations between total protein and dairy protein intakes and circulating IGF-I concentrations. Others have also reported similar associations between total protein intake and circulating IGF-I in men, women, and children [3], [4], [13], [14], [15], [16], [17], [18]. Similarly, others have shown positive associations between dairy protein [3], [4], [14], milk [13], [18], and dairy products [3], [18] intakes and

Role of the funding source

The Million Women Study is supported by Cancer Research UK and the UK Medical Research Council. The funders did not influence the conduct of the study, the preparation of this report, or the decision to publish. The authors had full access to all the data in the study and had final responsibility for the decision to submit for publication.

Conflicts of interest statement

The authors have no conflicts of interest to declare.

Acknowledgements

We thank the women who participated in the Million Women Study. We would also like to acknowledge James Chivenga and Lee Fletcher for assisting in the laboratory analysis of plasma IGF-I.

Million Women Study Steering Committee: Emily Banks, Valerie Beral, Ruth English, Jane Green, Julietta Patnick, Richard Peto, Gillian Reeves, Martin Vessey and Matthew Wallis.

Million Women Study Coordinating Centre staff: Hayley Abbiss, Simon Abbott, Miranda Armstrong, Angela Balkwill, Emily Banks, Vicky

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IGF1 has been shown to promote cellular proliferation in colorectal tissue, and the blockade of the IGF1-receptor by a monoclonal antibody inhibits cell proliferation.41 Potentially modifiable determinants of circulating IGF1 levels include dietary protein intake,42–44 BMI,43 and physical activity.45 In addition, a number of pharmacologic agents targeting the IGF system have been developed, although, as of yet, they have not been successful in treating colorectal cancer patients in clinical trials.46
Human studies examining associations between circulating levels of insulin-like growth factor 1 (IGF1) and insulin-like growth factor binding protein 3 (IGFBP3) and colorectal cancer risk have reported inconsistent results. We conducted complementary serologic and Mendelian randomization (MR) analyses to determine whether alterations in circulating levels of IGF1 or IGFBP3 are associated with colorectal cancer development.
Serum levels of IGF1 were measured in blood samples collected from 397,380 participants from the UK Biobank, from 2006 through 2010. Incident cancer cases and cancer cases recorded first in death certificates were identified through linkage to national cancer and death registries. Complete follow-up was available through March 31, 2016. For the MR analyses, we identified genetic variants associated with circulating levels of IGF1 and IGFBP3. The association of these genetic variants with colorectal cancer was examined with 2-sample MR methods using genome-wide association study consortia data (52,865 cases with colorectal cancer and 46,287 individuals without [controls])
After a median follow-up period of 7.1 years, 2665 cases of colorectal cancer were recorded. In a multivariable-adjusted model, circulating level of IGF1 associated with colorectal cancer risk (hazard ratio per 1 standard deviation increment of IGF1, 1.11; 95% confidence interval [CI] 1.05–1.17). Similar associations were found by sex, follow-up time, and tumor subsite. In the MR analyses, a 1 standard deviation increment in IGF1 level, predicted based on genetic factors, was associated with a higher risk of colorectal cancer risk (odds ratio 1.08; 95% CI 1.03–1.12; P = 3.3 × 10^–4). Level of IGFBP3, predicted based on genetic factors, was associated with colorectal cancer risk (odds ratio per 1 standard deviation increment, 1.12; 95% CI 1.06–1.18; P = 4.2 × 10^–5). Colorectal cancer risk was associated with only 1 variant in the IGFBP3 gene region (rs11977526), which also associated with anthropometric traits and circulating level of IGF2.
In an analysis of blood samples from almost 400,000 participants in the UK Biobank, we found an association between circulating level of IGF1 and colorectal cancer. Using genetic data from 52,865 cases with colorectal cancer and 46,287 controls, a higher level of IGF1, determined by genetic factors, was associated with colorectal cancer. Further studies are needed to determine how this signaling pathway might contribute to colorectal carcinogenesis.
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In addition, we have shown that 20 g or more of alcohol consumption correlated with decreased IGF-I levels. Other cross-sectional studies have reported that habitual drinkers have lower circulating IGF-I levels than controls [38–40]. In addition, Lavigne et al. reported the result of interventional study, in which all food and beverages were provided and found that the intake of 30 g alcohol/day for 8 weeks decreased IGF-I levels by 4.9%, whereas that of 15 g alcohol did not [41].
Most of circulating IGF-I is derived from the liver and circulating IGF-I levels are decreased in several pathological conditions, such as liver cirrhosis, uncontrolled diabetes, renal failure, and malnutrition. However, it has not fully been elucidated which factors modify IGF-I level in a physiological condition.
To identify the factors which are associated with circulating IGF-I levels.
Cross-sectional study.
This study included 428 subjects who undertook health check-up. Subjects diagnosed with non-alcoholic fatty liver disease (NAFLD) by ultrasonography were analyzed separately. Univariate and multivariate regression analyses were conducted to identify the factors associated with circulating IGF-I levels.
Regression analyses revealed that serum albumin levels, total-bilirubin levels, calcium levels, and HOMA-IR were positively correlated with IGF-I levels. Serum transaminase levels and habitual drinking (ethanol intake >20 g/day) were negatively correlated with serum IGF-I levels. Although serum IGF-I standard deviation scores (SDS) in subjects with and without NAFLD were comparable, after adjusting confounding factors clarified by multivariate regression analysis, IGF-I SDS negatively correlated with the presence of NAFLD.
In this study, we demonstrated that serum bilirubin and calcium levels are correlated with serum IGF-I levels. Although further study is necessary, these data suggest a presence of interaction between GH-IGF-I axis and bilirubin and calcium metabolism.
Non-linear causal association of body mass index with serum insulin-like growth factor 1: A Mendelian randomization study
2023, Research Square
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2023, Cancer Medicine
Relationship of circulating insulin-like growth factor-I and binding proteins 1-7 with mammographic density among women undergoing image-guided diagnostic breast biopsy
2019, Breast Cancer Research
Cellular and molecular signatures of alcohol-induced myopathy in women
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^☆: Conflict of interest: The authors have no conflicts of interest to declare.

View full text

The association of plasma IGF-I with dietary, lifestyle, anthropometric, and early life factors in postmenopausal women☆

Highlights

Abstract

Objective

Design

Results

Conclusions

Introduction

Section snippets

Study population

Results

Discussion

Role of the funding source

Conflicts of interest statement

Acknowledgements

Am. J. Clin. Nutr.

Am. J. Clin. Nutr.

Fertil. Steril.

Maturitas

Growth Hormon. IGF Res.

Int. J. Biochem. Cell Biol.

Insulin-like growth factors and neoplasia

Nat. Rev. Cancer

Insulin-like growth factor 1 (IGF1), IGF binding protein 3 (IGFBP3), and breast cancer risk: pooled individual data analysis of 17 prospective studies

Lancet Oncol.

A cross-sectional analysis of the association between diet and insulin-like growth factor (IGF)-I, IGF-II, IGF-binding protein (IGFBP)-2, and IGFBP-3 in men in the United Kingdom

Cancer Causes Control

The association between diet and serum concentrations of IGF-I, IGFBP-1, IGFBP-2, and IGFBP-3 in the European Prospective Investigation into Cancer and Nutrition

Cancer Epidemiol. Biomarkers Prev.

An investigation of fetal, postnatal and childhood growth with insulin-like growth factor I and binding protein 3 in adulthood

Clin. Endocrinol.

Body shape throughout life and correlations with IGFs and GH

Endocr-Relat Cancer

A cross-sectional analysis of the associations between adult height, BMI and serum concentrations of IGF-I and IGFBP-1 -2 and -3 in the European Prospective Investigation into Cancer and Nutrition (EPIC)

Ann. Hum. Biol.

Nonlinear relationship of insulin-like growth factor (IGF)-I and IGF-I/IGF-binding protein-3 ratio with indices of adiposity and plasma insulin concentrations

Cancer Causes Control

Body size in early life and adult levels of insulin-like growth factor 1 and insulin-like growth factor binding protein 3

Am. J. Epidemiol.

The Million Women Study: design and characteristics of the study population

Breast Cancer Res.