Metabolic Obesity in Normal Weight (MONW): Diagnostic Markers Stud

Disorders Hidden Under the Guise of BMI - Metabolic Obesity in People With Normal Body Weight (MONW) - the Search for Diagnostic Markers and Its Consequences for Health

Metabolically Obese Normal Weight (MONW) represents a phenotype affecting individuals with a normal Body Mass Index (BMI) but characterized by excessive adipose tissue accumulation. This condition is associated with increased cardiovascular risk, insulin resistance, and endothelial dysfunction, yet remains underdiagnosed.

This observational longitudinal study aims to comprehensively evaluate the relationship between excessive adipose tissue deposition, endothelial dysfunction, and asprosin concentrations in young women. The study will recruit 176 healthy women aged 18-35 years with normal BMI (<25 kg/m²). Participants will be divided into two groups based on body fat percentage (PBF) assessed by dual-energy X-ray absorptiometry (DXA): the MONW group (PBF ≥ 35.78%) and the Control group (PBF < 35.78%).

The specific objectives of the study include:

• Assessment of vascular endothelial function using flow-mediated dilation (FMD) of the brachial artery.
• Evaluation of asprosin as a novel biomarker in the MONW phenotype.
• Analysis of biochemical indices including asymmetric dimethylarginine (ADMA) and von Willebrand factor (vWF).
• Advanced metabolomic profiling to identify metabolic signatures.

Participants will undergo anthropometric measurements, body composition analysis (DXA), and blood sampling for biochemical and hormonal analyses. The study aims to develop predictive models for early cardiovascular risk detection in normal-weight individuals.

Study Design and Population:

This is a longitudinal observational study involving 176 healthy women aged 18-35 years. The primary aim is to identify diagnostic markers for Metabolically Obese Normal Weight (MONW) individuals. Recruitment is conducted via digital prescreening and university networks. Eligible participants must have a normal BMI (18.5-24.9 kg/m²) and stable body weight.

Group Allocation:

Participants will be divided into two groups based on Body Fat Percentage (PBF) assessed by Dual-Energy X-ray Absorptiometry (DXA):

1. MONW Group: BMI < 25 kg/m² and PBF ≥ 35.78% (threshold derived from pilot population studies).
2. Control Group: BMI < 25 kg/m² and PBF < 35.78%.

Study Procedures:

The study involves a baseline visit and a follow-up visit after 12 months.

1. Standardization: Visits are scheduled during the early follicular phase of the menstrual cycle (days 3-7) to minimize hormonal variability affecting endothelial function. Participants must fast for at least 12 hours and abstain from caffeine, smoking, and strenuous exercise for 24 hours prior.

2. Anthropometry and Body Composition: Height, weight, and circumferences (waist, hip) are measured. Whole-body composition is analyzed using DXA (Hologic QDR 4500W) to determine total and visceral fat mass.

3. Endothelial Function Assessment (FMD): Flow-mediated dilation of the brachial artery is measured using high-resolution ultrasound (Alpinion Xcube 90, linear probe L3-12). The protocol includes:

   • 1-minute baseline imaging.
   • 5-minute occlusion (cuff inflation to 250 mmHg).
   • 3-minute continuous post-occlusion imaging to assess peak diameter.

4. Biochemical Analysis: Fasting blood samples are collected for:

   • Lipid profile (TC, LDL, HDL, TG) and glucose metabolism markers (glucose, insulin, HbA1c).
   • ELISA quantification of specific biomarkers: Asprosin, Asymmetric Dimethylarginine (ADMA), von Willebrand Factor (vWF), and sex hormones (Estradiol, Testosterone, SHBG).

5. Metabolomics: Targeted and untargeted metabolomic profiling (LC-MS/MS) is performed on a subset of plasma samples to identify metabolic signatures associated with the MONW phenotype.

Data Collection:

Participants also complete standardized questionnaires regarding physical activity (IPAQ) and dietary habits (62-item FFQ-6, KomPAN). All data is pseudonymized and stored on a secured server.

Inclusion Criteria:

• Written, informed consent to participate in the research.
• Gender: Female.
• Age 18-35 years.
• BMI in the range of 18.5-25 kg/m².

Exclusion Criteria:

• Thyroid disease.
• Pregnancy or breastfeeding.
• Eating disorders.
• Polycystic ovary syndrome (PCOS).
• Hormone therapy and/or use of hormonal contraceptives.
• Smoking.
• Metal or silicone implants (contraindication for DXA/body composition accuracy).
• Vitamin and/or mineral supplementation.
• Acute and/or chronic illnesses.
• Type I or II diabetes, dyslipidemia, hypertension.
• Use of hypolipemic, antihypertensive, antiglycemic, or insulin medications.