Prognostic Value of SII and SIRI in Obesity-Related Metabolic Complications

Obesity is a complex chronic disease associated with systemic low-grade inflammation, metabolic dysfunction, and increased risk of comorbidities such as type 2 diabetes, dyslipidemia, nonalcoholic fatty liver disease, and cardiovascular disease. Adipose tissue acts as an active endocrine organ, influencing immune regulation and inflammatory signalling. Although numerous inflammatory biomarkers have been evaluated in obesity, the diagnostic performance of novel composite systemic immune-inflammatory indices, particularly the systemic immune-inflammation index (SII) and the systemic inflammation response index (SIRI), remains inadequately characterised. SII and SIRI, derived from peripheral blood counts, have shown prognostic potential in various clinical settings but have not been systematically evaluated in predicting metabolic complications or treatment response in obesity. This study seeks to expand their application in patients with overweight and obesity by 1) evaluating the cross-sectional associations between SII/SIRI and obesity severity, inflammatory biomarkers, metabolic disorders, and dietary patterns; and 2) determining the prognostic value of SII/SIRI for predicting metabolic complications and clinical response to behavopural and lifestyle modification, pharmacotherapy, and bariatric surgery over a 1-year follow-up.

Participants will complete anthropometric measurements, comprehensive biochemical profiling, inflammatory cytokine assessment, dietary evaluation, and structured follow-up at 12 and 24 weeks, with continued monitoring of treatment response and metabolic outcomes over 1 year.

STUDY PROCEDURES (Structured per visit) Visit 1 - Baseline (Week 1)

• Informed consent
• Anthropometrics (height, weight, waist circumference, hip circumference, BIA)
• Venous blood sampling: complete blood count (CBC) and differential blood count (DBC), fasting glucose, HbA1c, lipid profile (cholesterol, LDL, HDL, triglycerides), thyroid panel (TSH, FT4, FT3), liver panel, renal panel, CRP, cortisol, bilirubin, iron status parameters, vitamins/minerals (Ca, P, Mg, vitamin D)
• Biobanking: 3 frozen aliquots for hs-CRP, adiponectin, IL-6, TNF-α
• Lifestyle and dietary questionnaires (socio-demographics, physical activity, smoking, sleep, stress, medication use; 24 h dietary recall + FFQ)
• Motivational and educational counselling (diet, activity, pharmacotherapy options)

Visit 2 - Week 12

• Anthropometrics + BIA
• Laboratory testing (repeated, as above)
• Assessment of dietary and lifestyle adherence
• Motivational counselling (in person or telephone)

Visit 3 - Week 24

• Anthropometrics + BIA
• Full biochemical panel
• Dietary questionnaires (24 h recall+MEDAS+Short Diet Screener)
• Evaluation of treatment response to lifestyle intervention, pharmacotherapy, or bariatric surgery
• Motivational counselling

LONG-TERM FOLLOW-UP (Year 1)

• Monitoring metabolic outcomes
• Evaluation of obesity treatment response
• Prognostic assessment of SII/SIRI

Inclusion criteria

• Age ≥ 18 years
• BMI 25.0-29.9 kg/m² (overweight) or BMI ≥ 30 kg/m² (obesity)
• Ability to attend scheduled clinical visits
• Willingness to provide informed consent

Exclusion criteria

• Pregnancy or breastfeeding
• Use of immunosuppressive therapy
• Active infection
• Inflammatory disease
• Malignancy
• Acute illness affecting immune parameters
• Conditions interfering with study participation (as assessed by the investigator)
• Known hematologic disorders affecting leukocyte or platelet counts
• Chronic inflammatory diseases requiring systemic therapy
• Recent major surgery (within the last 3 months)
• Any condition that could confound the relationship between SII/SIRI and obesity-driven inflammation, such as immune disorders