Obesity and low lean mass are associated with dysregulated IGFBP-3, inflammatory biomarkers, and physical impairment in older adult women with frailty

Introduction Prior studies indicate sex-specific obesity-frailty interactions, with postmenopausal estrogen decline increasing sarcopenic obesity risk and inflammation in women. This study evaluated circulating cytokines (IL-6, TNF-α), adipokines (adiponectin, resistin), myokines (GDF-15, BDNF, myostatin), health-related biomarkers (IGF-1, IGFBP-3), and physical performance (five-times chair stand, grip strength) in pre-frail and frail older adult women classified as having low appendicular lean mass (LALM), obesity, or obesity plus LALM. Methods In this cross-sectional study, community-dwelling women aged ≥65 years from São Paulo, Brazil were screened (July 2022–September 2023); among 280 eligible, 88 met Fried frailty criteria. Body composition was assessed by DXA and participants were categorized as LALM (<20th percentile of residuals, −1.45), obesity (body mass index, BMI ≥30 kg/m 2 ), or both. Generalized Estimating Equations (GEE) with Bonferroni post hoc adjustments, χ 2 , or Fisher’s exact tests were adopted. Unadjusted (P 1 ) and age-adjusted (P 2 ) P-values were reported. Results Among 88 frail women (72.7% pre-frail and 27.3% frail), obesity plus LALM showed lower IGFBP-3 and higher GDF-15 vs. LALM (P 2 = 0.041 and P 2 = 0.032); obesity had higher resistin vs. LALM (P 2 = 0.012), replicated in sensitivity analysis frail-only (P 2 = 0.002), elevated insulin (P 2 = 0.002) and a trend slower chair stand (P 2 = 0.055). GDF-15 was related with chair stand time (Pearson r = 0.285, P = 0.006; and multiple regression β = 0.309, P = 0.013). Conclusion Among pre-frail and frail older adult women, obesity—with or without low lean mass—was associated with adverse metabolic/inflammatory profiles (higher resistin, GDF-15, insulin; lower IGFBP-3) in full and frail-only analyses, alongside a trend toward slower chair-stand performance. These cross-sectional findings highlight obesity-frailty interactions, warranting prospective validation.