PEDIATRIC OBESITY AND INSULIN RESISTANCE: ENDOCRINE MECHANISMS AND RISK OF CHILDHOOD DIABETES

Abstract

Background: Pediatric obesity is a growing public health crisis in Pakistan, yet region-specific data linking adipose endocrine dysfunction to insulin resistance and type 2 diabetes mellitus (T2DM) risk remain limited. This study investigated the endocrine mechanisms driving insulin resistance in obese children within the urban population of Islamabad, Pakistan. Methods: A cross-sectional analytical study was conducted from January 2024 to December 2025 at two tertiary care centers in Islamabad. Participants aged 8–16 years were stratified into overweight/obese (???? = 195) and normal-weight control (???? = 187) groups based on WHO growth standards. Anthropometric indices, fasting glucose, insulin, HbA1c, adiponectin, leptin, hs-CRP, and TNF-α were measured. Insulin resistance was defined as HOMA-IR ≥3.0. Statistical analyses included independent t-tests, Mann-Whitney U tests, Spearman correlations, and multiple logistic regression. Results: The overweight/obese group had significantly higher median HOMA-IR (4.32 vs. 1.85; p<0.001), with 72.8% of the overweight/obese group meeting criteria for insulin resistance, versus 15.0% of controls. The obese had significant endocrine abnormalities, lower adiponectin (4.8 vs. 11.2 µg/mL, p<0.001) and higher leptin (28.4 vs. 6.8 ng/mL, p<0.001) levels, as well as higher levels of inflammatory markers (hs-CRP: 3.8 vs. 1.1 mg/L, p<0.001 and TNF-α: 8.9 vs. 4.2 pg/mL, p<0.001). Waist-to-Height Ratio (WHtR) was the most strongly correlated with HOMA-IR (r=0.74, p<0.001). In multiple logistic regression, WHtR ≥0.5 (AOR: 4.85), family history of T2DM (AOR: 2.34), leptin/adiponectin ratio (AOR: 1.42 per unit) and hs-CRP >3.0 mg/L (AOR: 2.15) were found to be independent predictors of insulin resistance. Conclusions: Pediatric obesity in Islamabad is associated with a significant imbalance of adipokines and systemic inflammation levels which are associated with high insulin resistance. WHtR is a better and low-cost screening tool for metabolic risk in this population. Anthropometric and biomarker evaluation is essential for early detection of endocrine dysfunction and to avoid progression to youth onset T2DM in urban children of Pakistan.