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

• Conditions: Obesity
• Interventions: Other: No experimental intervention will take place - the study is cross-sectional. Each participant will provide biological samples.

• Registration Number: NCT05308394
• Lead Sponsor: Oklahoma State University

Brief Summary

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

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 Timeline

• Study Start: 2022-03-10
• Study First Submitted: 2022-03-11
• Study First Submitted QC: 2022-03-25
• Status Verified: 2022-04
• Study First Posted: 2022-04-04
• Last Update Submitted: 2022-04-08
• Last Update Posted: 2022-04-15
• Primary Completion: 2022-12-30
• Study Completion: 2022-12-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 80

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).

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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

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Control group	No experimental intervention will take place - the study is cross-sectional. Each participant will provide biological samples.	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).
Metabolic Syndrome	No experimental intervention will take place - the study is cross-sectional. Each participant will provide biological samples.	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).
Normal-weight obesity	No experimental intervention will take place - the study is cross-sectional. Each participant will provide biological samples.	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).
Metabolically Healthy Obesity	No experimental intervention will take place - the study is cross-sectional. Each participant will provide biological samples.	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).

Primary Outcome Measures

Name	Time	Method
Indicators of gut permeability	1 year	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).
C-reactive protein	1 year	The investigators will measure the marker of chronic inflammation C-reactive protein (CRP) using an ELISA.
Inflammatory cytokines	1 year	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.

Secondary Outcome Measures

Name	Time	Method
Fecal microbiota	1 year	The investigators will assess microbiota composition in a subset of individuals (\~n=10 per group).

Trial Locations

Locations (1)

208 Nancy Randolph Davis, Oklahoma State University; 🇺🇸 Stillwater, Oklahoma, United States