This study aims to develop a non-invasive diagnostic method for metabolic syndrome (MetS) and metabolically healthy obesity (MHO) through analysis of exhaled air. Using proton-transfer-reaction mass spectrometry combined with machine learning algorithms, we will characterize volatile organic compound profiles in 300 participants across three groups: MetS patients, MHO patients, and healthy controls. The primary goal is to create and validate a classification model capable of accurately differentiating these metabolic states based on breath analysis.

This study focuses on characterizing the volatilome - the complete set of volatile organic compounds in exhaled air - as a novel biomarker source for metabolic health assessment.

The study represents the first comprehensive attempt to compare volatilome signatures between metabolically healthy and unhealthy obesity phenotypes. Successful validation of this approach could establish breath analysis as a new diagnostic paradigm in metabolic medicine, enabling rapid, non-invasive screening and personalized treatment strategies for patients with obesity-related conditions.

Methodological innovations include real-time breath analysis capabilities and development of specialized machine learning algorithms for pattern recognition in complex mass spectrometry data. The findings are expected to contribute significantly to understanding metabolic pathway alterations in different obesity phenotypes.

Inclusion Criteria:

• For Group 1 (Metabolic syndrome): Age >18 years, signed informed consent, diagnosis of Metabolic Syndrome (IDF 2006 criteria: waist circumference >94 cm (men)/ >80 cm (women) + ≥2 of: BP ≥130/85 mmHg or antihypertensive therapy; TG ≥1.7 mmol/L; HDL-C <1.03 mmol/L (men) / <1.29 mmol/L (women); Fasting glucose ≥5.6 mmol/L).
• For Group 2 (Metabolically healthy obesity): Age >18 years, signed informed consent, waist circumference ≥94 cm (men) / ≥80 cm (women), absence of other Metabolic Syndrome criteria (hypertension, dyslipidemia, impaired fasting glucose).
• For Group 3 (Control): Age >18 years, signed informed consent, normal BMI, absence of signs of Metabolic Syndrome.

Non-inclusion criteria for all groups:

• Inability to provide informed consent;
• History of myocardial infarction or stroke;
• Chronic kidney disease stage 3B, 4, 5 (eGFR <30 ml/min/1.73m2);
• Acute or subacute cardiovascular disease;
• Familial hypercholesterolemia;
• Bronchopulmonary diseases;
• Acute or chronic infectious diseases;
• Type 1 or Type 2 diabetes mellitus;
• Systemic connective tissue diseases;
• Current or past history of oncological diseases;
• Severe liver dysfunction, decompensated liver cirrhosis (Child-Pugh class C);
• Pregnancy or lactation;
• Severe mental illness (severe dementia, schizophrenia);
• Comorbid conditions with life expectancy less than 1 year.

Exclusion Criteria:

• Patient refusal to continue participation in the study;
• Identification of any non-inclusion criteria after enrollment.

The study population consists of adults (≥18 years) from three groups: 1) Patients with Metabolic Syndrome (IDF, 2005 criteria), 2) Patients with metabolically healthy obesity (BMI≥30, no metabolic abnormalities), and 3) Healthy controls (BMI<25, no metabolic disorders).

IPD will not be available for public sharing. The local Ethics Committee and national data protection laws do not permit public deposition of individual patient data. The informed consent does not include such provisions.