MedPath

Individual Factors Related to Chronic Low-grade Inflammation and Cardiometabolic Disease Risk

Not yet recruiting
Conditions
Risk Factor, Cardiovascular
Low-grade Inflammation
Overweight
Obesity
Metabolic Syndrome
Healthy
Hypertension
Metabolically Healthy Controls
Normal Weight Adults
Hypercholesterolemia
Registration Number
NCT06355544
Lead Sponsor
Integrative Phenomics
Brief Summary

The goal of this observational study is to learn about low-grade inflammation in healthy individuals and individuals with overweight or obesity.

The main questions it aims to answer are:

* Whether it is possible to predict low-grade inflammation

* What are the medical, biological, and lifestyle variables related to low-grade inflammation?

Participants will be asked to:

1. Attend a general medical visit to collect vital signs, anthropometric measurements, and collect blood samples.

2. Complete questionnaires and collect a stool sample at home.

Detailed Description

Cardiometabolic diseases (CMDs) are a heterogeneous spectrum of nutrition-related chronic diseases, ranging from obesity to diabetes and, ultimately, to acute and chronic cardiovascular diseases. Once established, these diseases are usually irreversible and evolve over time. Since these diseases are born out of societal and lifestyle changes, the cornerstones of prevention and management are changes in nutrition and lifestyle. This inevitable increase in CMDs, including obesity, particularly affects socially vulnerable populations.

The etiology of cardiometabolic diseases is complex and involves environmental, biological and genetic elements. Weight gain is at the heart of these pathologies: it frequently precedes their development or contributes to the progression of these diseases. To this end, even modest weight loss is suggested as an important line of prevention or treatment of cardiometabolic diseases. For example, diabetes remission can be achieved with weight loss and is directly correlated with the amount of weight lost. Despite the beneficial effects of weight loss on preventing the progression of cardiometabolic diseases, maintaining weight loss is difficult, with only 30% of individuals achieving long-term weight loss (5 years). The same is true with the development of anti-obesity treatments (new analogues of glucagon-like peptide 1 (GLP1)); Discontinuation of treatment is accompanied by weight gain. In the case of diabetes, weight gain is associated with the recurrence of previously remitted diabetes.

Chronic low-grade inflammation is tightly linked with obesity and a central feature of cardiometabolic diseases and associated diseases. Furthermore, it paves the way for future comorbidities. This inflammation is characterized by a rise of systemic or circulating inflammatory molecules. However, no single cytokine can reflect the inflammatory state seen in cardiometabolic diseases and these systemic factors are highly variable from subject to subject. Recently, combinatorial indexes, using multiple inflammatory markers have been strongly associated with coronary risks and Metabolic alterations.

Over the past 10 years, the gut microbiome has become a recognized contributor to our metabolic health. Accumulating evidence has shown that the gut microbiome strongly reflects environmental and lifestyle changes (including nutrition) by altering its diversity and composition as well as its functions by producing molecules that interact with host organs, including the brain. The excess or deficit production of molecules produced by the microbiota, bacterial metabolites (such as trimethylamine oxide (TMAO), Imidazole propionate, branched-chain amino acids (BCAAs), or short-chain fatty acids (SCFAs), etc.) are molecules implicated in the link between the environment, microbiota and metabolic and inflammatory disturbances.

Current strong evidence indicates that the gut microbiota is altered early in people with inflammatory diseases that include CMDs. Relationships between the inflammatory component of the diet and the gut microbiome have also been identified.

In an effort to predict chronic-low grade inflammation in a real-world population and decipher the relationships between chronic low-grade inflammation and individual factors, comprising lifestyle, diet, behavior, environment, the gut microbiome, and health-related clinical data, the present study recruits a cohort of participants across age, sex, body mass index, and metabolic health spectra. Chronic low-grade inflammation markers of interest will be measured to establish a multi-component index of inflammation relative in the population.

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
3000
Inclusion Criteria
  • Male or female between the ages of 18 and 70 included,
  • One of the following two criteria:
  • Clinically at-risk group Body Mass Index between 25 (included) and up to 35 kg/m2 (excluded)
  • Non-clinically at-risk group Body Mass Index between 18.5 (included) and up to 25 kg/m2 (excluded) and absence of metabolic syndrome criteria
  • Subject covered by social security or a similar system.
  • Ability to use a mobile phone application on a daily basis (food intake).
  • Subject, after being informed of the contents of this study, fully understanding and accepting its purpose; and able to personally sign a written informed consent
Exclusion Criteria
  • Subject with diagnosed inflammatory disease or infection-related inflammation (viral or bacterial) or medical history (viral) within the last 2 months:
  • Rheumatoid arthritis, reactive or psoriatic arthritis (non-osteoarthritis)
  • Inflammatory bowel disease (IBD) (Crohn's disease or ulcerative colitis) or irritable bowel syndrome
  • Systemic lupus erythematosus
  • Uncontrolled psoriasis
  • Viral hepatitis or ongoing viral infection
  • Seasonal virus (influenza-like illness)
  • Subjects who have taken antibiotics in the last 2 months
  • Subject under treatment within the last 2 months of an:
  • Antiviral (for HIV, hepatitis, influenza, chickenpox/shingles)
  • Oral, topical, or injectable treatment of a drug that modulates the inflammatory response (e.g. Corticosteroid, non-steroidal anti-inflammatory drugs (e.g. ibuprofen, diclofenac, celecoxib, naproxen, aspirin, etc.)
  • Dietary supplement that can modulate the inflammatory response (e.g.
  • Omega 3 fatty acid, curcuma/turmeric, probiotic, prebiotics)
  • Subject with diabetes (type 1 or 2) known treated prior to the inclusion visit (specifically subjects recently diagnosed or diagnosed with diabetes at the time of the laboratory assessment may be retained in the study if they are not taking anti-diabetic treatment): i.e. exclusion of subject with diabetes diagnosed with fasting blood glucose ≥ 126 mg/dL (7.0 mmol measured twice/L OR glycated hemoglobin ≥ 6.5% (48 mmol/mol) AND anti-diabetic therapy (metformin, GLP-1 receptor agonist, insulin, sulphonylurea, alpha-glucosidase inhibitor)
  • Subject with severe or unstable hepatic, renal, cardiovascular, respiratory, endocrine, or metabolic disorders or cancer diagnosed with or without treatment
  • Subject suffering from gastrointestinal disorders resulting in the use of laxatives or drugs for intestinal transit (e.g., loperamide) in the last 2 months.
  • Subject with a complication or procedure in the last 2 months that could result in inflammation
  • Minor or acute tendonitis, sprain, or contusion
  • Severe contusion (e.g. Bone contusion)
  • Major or invasive surgery
  • Subject in a situation that, in the opinion of the investigator, could interfere with optimal participation in the present study or pose a particular risk to the subject.
  • Subject currently participating in an interventional clinical study
  • Subject not affiliated to the Social Security scheme
  • Subject who did not comply with the exclusion period of the study in which they would have previously participated
  • Subject not being able to use the internet

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Low-grade inflammationBaseline

Assessed as a z-score composed of six markers (C reactive protein (CRP), interleukin (IL)-6, serum amyloid-A (SAA), soluble intracellular adhesion molecule (sICAM), tumor necrosis factor alpha (TNF)-alpha) and categorized into 3 tertiles: Low/ Moderate/High

Secondary Outcome Measures
NameTimeMethod
Fasting glucoseBaseline

Serum glucose in mg/dl

Systolic blood pressureBaseline

mmHg

HeightBaseline

Centimeters

Waist circumferenceBaseline

Centimeters

Hip circumferenceBaseline

Centimeters

Body fat massBaseline

Percentage of bodymass measured by impedance

Neck circumferenceBaseline

Centimeters

Consumption of dietary micronutrientsBaseline

Daily micronutrient consumption (mg/d) assessed by dietary records and food frequency questionnaire

Food item consumptionBaseline

Consumption of food items in g/day assessed by dietary records and food frequency questionnaires

Serum Aspartate Aminotransferase (ALT)Baseline

Serum Units per Liter (U/L)

Fasting serum uric acidBaseline

mmol/L

Fasting serum creatinineBaseline

mmol/L

Fasting serum insulinBaseline

mmol/L

Blood hemoglobinBaseline

grams per 100 milliliters (g/100ml)

Red blood cellsBaseline

Cell counts in 10\^9 per liter (10\^9/L)

White blood cellsBaseline

Cell counts expressed in billions/L (10\^9/L) and differential

Gut microbiome metabolitesBaseline

Consumption and production in mmol/day assessed through in silico metabolic modeling

Serum glycated hemoglobin (HbA1c)Baseline

Percentage of HbA1c or mmol/L

Diastolic blood pressureBaseline

millimeters mercury (mmHg)

Lean body massBaseline

Percentage of body mass measured by impedance

Fasting serum high-density lipoproteinBaseline

mmol/L

Food group consumptionBaseline

Consumption of food groups in g/day assessed by dietary records and food frequency questionnaires

Blood hematocritBaseline

Percentage (%) of whole blood sample

Red blood cell volumeBaseline

Mean volume in cubic micrometers (um\^3)

Hemoglobin relative red blood cell sizeBaseline

Mean relative hemoglobin relative to red blood cell size in percentage

Perceived quality of lifeBaseline

Self-perceived measurements of mental, physical, emotional, social, and general quality of life, fatigue, energy assessed by questionnaire

Physical activityBaseline

Total, leisure, work, and sports physical activity assessed by questionnaire

Stool microbiome compositionBaseline

Relative abundance of microbiome taxonomies (Phyla, Order, Class, Family, Genus, Species), metagenomic species (MGS), and co-abundance genes (CAGs) in stool samples assessed through shot-gun sequencing

Stool microbiome functional pathwaysBaseline

Relative abundances of microbiome functional pathways assessed through metagenomics and in silico metabolic modeling

Resting heart rateBaseline

Beats per minute

Water body massBaseline

Percentage of body mass measured by impedance

Fasting total serum cholesterolBaseline

mmol/L

Consumption of dietary metabolitesBaseline

Dietary metabolite consumption expressed in mmol/day assessed by dietary records and food frequency questionnaire

Serum Alanine Transaminase (ALT)Baseline

Serum Units per Liter (U/L)

Serum gamma-glutamyl transferase (GGT)Baseline

Serum Units per Liter (U/L)

Eating behaviorBaseline

Self-perceived emotional, uncontrolled, and eating restriction assessed by questionnaire

SleepBaseline

Sleep latency, duration, efficiency, quality, disturbances, and daytime dysfunction assessed by questionnaire

Sleep apneaBaseline

Binary value (yes/no) assessed from questionnaire

Mean cell hemoglobin (MCH)Baseline

Mass of hemoglobin per red blood cell in picograms (pg)

Blood plateletsBaseline

Cell counts expressed in billions/L (10\^9/L)

StressBaseline

Self-perceived stress assessed by questionnaire

Consumption of dietary macronutrientsBaseline

Dietary macronutrient consumption assessed in g/day from dietary records and food frequency questionnaires

Body weightBaseline

Kilograms

Fasting serum triglyceridesBaseline

mmol/L

Stool consistencyBaseline

Stool consistency assessed and self-reported by Bristol Stool Scale

DeprivationBaseline

Economic, material, and social deprivation assessed by questionnaire

Serum fasting low-density lipoproteinBaseline

mmol/L

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