BRIEF RESEARCH REPORT article
Front. Aging
Sec. Musculoskeletal Aging
This article is part of the Research TopicBiomarkers of Healthy and Pathological Aging: From Intrinsic Capacity to Frailty SyndromesView all articles
Obesity and Low Lean Mass Are Associated with Dysregulated IGFBP-3, Inflammatory Biomarkers, and Physical Impairment in Older Adult Women with Frailty
Provisionally accepted
Alan Lins Fernandes1,2*
Rosa Maria Rodrigues Pereira1Valeria de Falco Caparbo1Camila Santos Figueredo3
Caroline Freitas Gomes1
EDUARDO BORBA1
Diogo Souza Domiciano1- 1Division of Rheumatology, Faculty of Medicine, University of São Paulo, São Paulo, Brazil
- 2Universidade Federal da Bahia Escola de Enfermagem, Salvador, Brazil
- 3Acreditando Centro Integrado, São Paulo, Brazil
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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/m²), or both. Generalized Estimating Equations (GEE) with Bonferroni post-hoc adjustments, χ², or Fisher’s exact tests were adopted. Unadjusted (P1) and age-adjusted (P2) 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 (P2=0.041 and P2=0.032); obesity had higher resistin vs LALM (P2=0.012), replicated in sensitivity analysis frail-only (P2=0.002), elevated insulin (P2=0.002) and a trend slower chair stand (P2=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.
Keywords: fat mass, Frailty, Inflammation, muscle mass, Obesity, performance, physical function, Sarcopenia
Received: 10 Dec 2025; Accepted: 03 Feb 2026.
Copyright: © 2026 Fernandes, Pereira, Caparbo, Figueredo, Gomes, BORBA and Domiciano. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Alan Lins Fernandes
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