Associations of systemic inflammatory indices and metabolically healthy vs. unhealthy obesity in children.

Abstract

OBJECTIVE: Childhood obesity, which continues to rise globally, is associated with inflammation-driven metabolic disturbances and increased cardiometabolic risk. Individual variability in metabolic health—independent of obesity severity—has led to the concept of metabolically healthy obesity (MHO). This study aimed to evaluate the relationship between metabolic health status and systemic inflammatory indices in childhood obesity, including analyses adjusted for sex and pubertal stage to account for physiologic developmental changes. METHODS: This retrospective study included children with BMI SDS ≥ 2, categorised as Metabolically Unhealthy Obese (MUO) if they had ≥ 1 of the following: fasting glucose ≥ 100 mg/dL, HOMA-IR ≥ 2.5 (prepubertal) or ≥ 4 (pubertal), triglycerides ≥ 150 mg/dL, HDL ≤ 40 mg/dL, or systolic/diastolic blood pressure ≥ 95th percentile. Children with none of these findings were classified as MHO. Inflammatory indices—neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), systemic inflammation index (SII), and systemic immune-response index (SIRI)—were analysed using ROC curves and multivariable regression. Additional analyses adjusted for age, sex, pubertal stage, and BMI SDS were performed to account for developmental influences on inflammatory markers. RESULTS: A total of 388 obese children (58.1% female, mean age 11.5 ± 2.9 years) were included; 35.4% were morbidly obese, and 45.6% were classified as MUO. MUO children had significantly higher white blood cell, neutrophil, and monocyte counts, as well as higher fasting glucose, HOMA-IR, triglycerides, and total cholesterol, with lower HDL levels. Dyslipidemia was the most common metabolic abnormality. SII demonstrated strong discriminatory ability for metabolic health (AUC = 0.854; 82% sensitivity; 72% specificity). SII was positively associated with HOMA-IR, TG/HDL-C, and non-HDL cholesterol (p = 0.006; p = 0.004; p = 0.01, respectively). After adjustment for age, sex, pubertal stage, and BMI SDS, the associations of SII and SIRI with metabolic health status were attenuated but remained directionally consistent, indicating that developmental factors partially influence systemic inflammatory responses. CONCLUSION: The high prevalence of MUO among obese children highlights their substantial cardiometabolic risk burden. SII and SIRI appear to be promising, readily accessible biomarkers for identifying metabolic deterioration, showing meaningful correlations with key cardiometabolic risk indicators. These indices may support clinicians in early detection and monitoring of metabolic dysfunction in pediatric obesity, even when accounting for developmental stage.