Diet, Adiposity, and Metabolic Alterations

Obesity Clinical Trial

Official title:

Diet, Adiposity, and Metabolic Alterations: a Prospective Observational Study of Three US Cohorts

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03419455
• Other study ID #: 1999P011117/BWH
• Status: Active, not recruiting
• Start date: January 2017
• Est. completion date: June 2021

Study information

• Verified date: February 2019
• Source: Harvard Medical School
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Obesity is associated with increased risk of several cancers. Suggested mechanisms mediating the obesity-cancer associations include hyperinsulinemia and altered IGF signaling, changes in sex hormone levels as well as altered secretion of adipokines and inflammatory proteins. However, little is known about the influence of lifetime adiposity on the relevant biomarkers. Moreover, although diet has been suggested to ameliorate the adverse metabolic effects of obesity, convincing evidence regarding how dietary factors may influence obesity-related carcinogenic pathways remains lacking. Thus, in the current project, the investigators aim to 1) examine the associations between trajectories of body fatness and plasma biomarker levels of the insulin/IGF system, sex hormones and biomarkers of inflammatory response including adipokines; 2) investigate how nutritional factors may modulate these obesity-related biomarkers. The investigators propose to utilize two large ongoing cohorts of US men and women, the Nurses' Health Study and Health Professionals Follow-up Study.

Description:

According to the International Agency for Research on Cancer (IARC), there is sufficient evidence that avoidance of weight gain reduces the risk of several cancers, including colorectal, breast (postmenopause), pancreatic, endometrial, kidney (renal-cell), liver, gallbladder, oesophageal (adenocarcinoma), multiple myeloma, meningioma, ovarian, thyroid and stomach (cardia) cancer. Several mechanisms have been suggested to mediate the obesity-cancer association, including increased insulin levels and bioavailability of insulin-like growth factor (IGF)-1, low-grade chronic inflammation, and changes in sex hormone levels.

In previous studies, the investigators have identified five heterogeneous trajectory groups of body fatness from age five and up to 60 years (lean-stable, lean-moderate increase, lean-marked increase, medium-stable, and heavy-stable/increase). These trajectories have been associated with distinct patterns of cancer incidence and mortality. Having excess body weight at any life period have been associated with increased risk of total and obesity related cancers. How the various trajectories of body shape relate to cancer relevant risk biomarkers is however yet to be determined.

To gain a better understanding of the complex interplay between obesity, obesity-related risk biomarkers and cancer development, the investigators aim to examine the associations between trajectories of body fatness and cancer relevant risk biomarkers in the Nurses' Health Study and Health Professionals Follow-up Study. Moreover, the investigators will examine how nutritional factors, such coffee intake, may modulate the levels of these biomarkers.

The investigators hypothesize that in general individuals who have excess body weight at any life period will have a more unfavorable biomarker profile than those who are lean across the lifespan, although a different pattern may be expected for some markers. Also, the investigators hypothesize that some nutritional factors, such high intake of coffee, may ameliorate the adverse metabolic effects of obesity by modulating the levels of these biomarkers.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 173230
• Est. completion date: June 2021
• Est. primary completion date: June 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 75 Years

Eligibility

Inclusion Criteria:

• Adult health professionals

Exclusion Criteria:

• History of diabetes, CVD and cancer (except melanoma skin cancer) at blood draw

• Incomplete body fatness data

• Biomarker levels considered as statistical outliers

Related Conditions & MeSH terms

• Cancer
• Lifelong Obesity
• Obesity

Intervention

Other:
• Trajectories of body fatness and diet
There is no intervention. This is an observational study with trajectories of body fatness and diet as main exposure.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Harvard Medical School

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Biomarkers of the insulin/IGF pathway	Plasma biomarkers of insulin/IGF signalling, including C-peptide, IGF-1, IGFBP-1, IGFBP-3 and IGF-1/IGFBP-3 molar ratio	Biomarkers assessed in the time period 1993-2015 for women and 2001-2014 for men
Primary	Sex hormones	Plasma estrone, estradiol, testosterone and sex hormone-binding globulin (SHBG)	Biomarkers assessed in the time period 1993-2015 for women and 2001-2014 for men
Primary	Biomarkers of inflammatory response	Plasma CRP, IL-6, sTNFR2, adiponectin (total and HMW adiponectin), leptin and leptin receptor	Biomarkers assessed in the time period 1993-2015 for women and 2001-2014 for men