Gut Permeability-related Inflammation and Cardiovascular Disease Risk in Normal-weight and Metabolically Healthy Obesity

The investigators are examining the extent gut permeability explains observed inflammation in normal-weight and metabolically healthy obesity (and potentially cardiovascular disease risk).

Study Overview

• Status: Recruiting
• Conditions: Obesity
• Intervention / Treatment: Other: No experimental intervention will take place - the study is cross-sectional. Each participant will provide biological samples.

Detailed Description

Cardiovascular disease (CVD) is responsible for 25% of deaths in the United States, and chronic inflammation contributes to risk. A growing body of evidence suggests that gut-derived bacterial components (e.g., lipopolysaccharide or LPS) entering the bloodstream when the gut barrier fails (i.e., intestinal permeability) are a prominent source of inflammation in cardiometabolic conditions such as metabolic syndrome, coronary artery disease, and type 2 diabetes. Two groups that are at > 2x the risk for CVD, but largely still free of overt disease, are those with metabolically healthy obesity and normal-weight obesity. Those with metabolically healthy obesity - defined as having an obese body mass index (BMI) but other clinical risk factors in the normal range (e.g., blood lipids) - and normal-weight obesity - defined as having a normal BMI yet high percent body fat - generally display little evidence of clinical risk, but present with elevated inflammatory markers including C-reactive protein (CRP), tumor necrosis factor (TNF)-a, and interleukin (IL)-6). Therefore, it is likely that chronic inflammation is largely driving CVD risk in metabolically healthy and normal-weight obesity, but the source of this inflammation remains unclear. The primary aim of the proposed project is to determine the extent that markers of intestinal permeability are elevated in metabolically healthy obesity and normal-weight obesity compared to healthy controls and individuals with metabolic syndrome.

• Study Type: Observational
• Enrollment (Anticipated): 80

Contacts and Locations

Study Locations

• United States
  • Oklahoma
    • Stillwater, Oklahoma, United States, 74078
      • Recruiting
      • 208 Nancy Randolph Davis, Oklahoma State University
      • Contact: Bryant H Keirns, MS; Phone Number: 316-689-1711; Email: bryant.keirns@okstate.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The study populations of interest are those with normal weight obesity (normal BMI and high body fat percent) and metabolically healthy obesity (obese BMI, but largely normal cardiovascular risk factors).

Description

Inclusion Criteria:

• Control group: normal BMI, body fat percentage < 25% for men and < 35% for women, < 1 of the following: blood pressure >130/85 mmHg, fasting glucose >100 mg/dL, fasting triglycerides >150 mg/dL, HDL cholesterol < 40 mg/dL (men) or < 50 mg/dL (women).
• Normal-weight obesity group: normal BMI, body fat percentage > 25% for men and > 35% for women.
• Metabolically healthy obesity: BMI > 30, body fat percentage > 25% for men and > 35% for women, and < 1 of the following: blood pressure >130/85 mmHg, fasting glucose >100 mg/dL, fasting triglycerides >150 mg/dL, HDL cholesterol < 40 mg/dL (men) or < 50 mg/dL (women).
• Metabolic syndrome group: BMI > 30, body fat percentage > 25% for men and > 35% for women, and 2 or more of the following: blood pressure >130/85 mmHg, fasting glucose >100 mg/dL, fasting triglycerides >150 mg/dL, HDL cholesterol < 40 mg/dL (men) or < 50 mg/dL (women).

Exclusion Criteria:

• Presence of pacemaker
• Pregnant
• Cardiometabolic disease (e.g., diabetes, cardiovascular disease)
• Disease that is inflammatory in nature (e.g., inflammatory bowel disease, rheumatoid arthritis)
• Postmenopausal status
• Use of tobacco products
• Using illicit drugs
• Using lipid lowering drugs

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Control group; The control group for this study will consist of individuals with normal BMI (18.5 - 24.9 kg/m2), body fat percent < 25% (male) or < 35% (female), and up to 1 other risk factor among the following: blood pressure > 130/85 mmHg, fasting glucose >100 mg/dL, fasting triglycerides >150 mg/dL, and HDL < 40 (male) or < 50 (female).	Other: No experimental intervention will take place - the study is cross-sectional. Each participant will provide biological samples.; Each participant will provide a blood and fecal sample.
Normal-weight obesity; Individuals with normal-weight obesity will be defined as having normal BMI (18.5 - 24.9 kg/m2), body fat percent > 25% (male) or > 35% (female).	Other: No experimental intervention will take place - the study is cross-sectional. Each participant will provide biological samples.; Each participant will provide a blood and fecal sample.
Metabolically Healthy Obesity; Metabolically healthy obesity will be defined as having an obese BMI (> 30 kg/m2), body fat percent < 25% (male) or < 35% (female), and up to 1 other risk factor among the following: blood pressure > 130/85 mmHg, fasting glucose >100 mg/dL, fasting triglycerides >150 mg/dL, and HDL < 40 (male) or < 50 (female).	Other: No experimental intervention will take place - the study is cross-sectional. Each participant will provide biological samples.; Each participant will provide a blood and fecal sample.
Metabolic Syndrome; Metabolic syndrome will be defined using the international Diabetes Federation criteria of an obese BMI ( > 30 kg/m2) and 2 or more of the following risk factors: blood pressure > 130/85 mmHg, fasting glucose >100 mg/dL, fasting triglycerides >150 mg/dL, and HDL < 40 (male) or < 50 (female).	Other: No experimental intervention will take place - the study is cross-sectional. Each participant will provide biological samples.; Each participant will provide a blood and fecal sample.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Indicators of gut permeability	The investigators will measure serum markers of gut permeability as primary outcomes (i.e., lipopolysaccharide binding protein, soluble cluster of differentiation (CD)14, intestinal fatty acid binding protein).	1 year
C-reactive protein	The investigators will measure the marker of chronic inflammation C-reactive protein (CRP) using an ELISA.	1 year
Inflammatory cytokines	The investigators will measure a panel of serum inflammatory cytokines that includes granulocyte macrophage-colony stimulating factor (GM-CSF), interferon (IFN)-γ, interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-17A, IL-23, and tumor necrosis factor (TNF)-α using a bioplex assay.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fecal microbiota	The investigators will assess microbiota composition in a subset of individuals (~n=10 per group).	1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body composition assessment with dual-energy X-ray absorptiometry (DXA)	The investigators will perform DXA scans on all participants to assess body composition parameters (i.e., body fat percent, lean mass, percent, visceral adipose tissue).	Through study completion, an average of 1 year
Lipid panel with Abbott Piccolo Xpress Clinical Chemistry Analyzer	The investigators will perform a lipid panel on all participants.	Through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Oklahoma State University

Study record dates

Study Major Dates

• Study Start (Actual): March 10, 2022
• Primary Completion (Anticipated): December 30, 2022
• Study Completion (Anticipated): December 30, 2022

Study Registration Dates

• First Submitted: March 11, 2022
• First Submitted That Met QC Criteria: March 25, 2022
• First Posted (Actual): April 4, 2022

Study Record Updates

• Last Update Posted (Actual): April 15, 2022
• Last Update Submitted That Met QC Criteria: April 8, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Cardiovascular Diseases; Obesity; Inflammation; Obesity, Metabolically Benign
• Other Study ID Numbers: IRB-22-28

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No