Multi-Hormonal Dysregulation in Obesity: Associations with Insulin Resistance and Metabolic Risk Markers

Abstract

This study systematically evaluated the profiles of ten key endocrine, adipokine, and metabolic hormones across individuals with obesity and healthy controls to determine if obesity-induced metabolic stress overrides baseline variations governed by biological sex, age, as well as the 3-way interaction of age x gender x health status. Serum concentrations of ten hormones (insulin, IGF-1, resistin, adiponectin, leptin, cortisol, Ghrelin, TSH, T3, and T4) were quantified. Statistical analysis was performed using a three-way analysis of variance followed by multiple pairwise comparisons. The three-way ANOVA revealed that obesity was the dominant factor driving systemic endocrine dysregulation. Obesity explained the vast majority of total variance in insulin (91.91%), leptin (91.91%), TSH (91.73%), ghrelin (90.89%), adiponectin (88.65%), resistin (81.04%), cortisol (80.13%), and T3 (72.57%) (p < 0.0001). Multiple comparisons confirmed significant elevations in circulating insulin, leptin, resistin, cortisol, and TSH, alongside marked reductions in adiponectin and ghrelin across all obese subgroups (p < 0.0001). Conversely, IGF-1 variation was predominantly driven by age (33.30%, p < 0.0001), while T4 showed a lower variance explained by obesity (57.31%). Crucially, biological sex and demographic interaction terms failed to reach statistical significance across the majority of the master metabolic hormones (p > 0.05). Advanced obesity functions as a universal endocrine equalizer, leading to significant metabolic syndrome and peripheral thyroid hormone resistance. Metabolic and inflammatory stress caused by excessive adiposity can surpass normal physiological variations related to age and gender. Consequently, therapeutic approaches should address the underlying mechanisms of adipose tissue dysfunction rather than relying on management strategies.