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. 2025 Jun 5.
doi: 10.1007/s00592-025-02527-x. Online ahead of print.

Obesity paradox: association between lipid metabolism indices and skeletal muscle mass in older adults: the mediating role of uric acid

Chaofan Sun  1   2   3 , Xiaohui Yang  4 , Xingzhong Feng  5
Affiliations

Obesity paradox: association between lipid metabolism indices and skeletal muscle mass in older adults: the mediating role of uric acid

Chaofan Sun et al. Acta Diabetol. .

Abstract

Aims: This study aimed to explore the relationships between lipid metabolism indices-the Lipid Accumulation Product (LAP), Visceral Adiposity Index (VAI), Cardiac Metabolic Index (CMI), and Atherogenic Index of Plasma (AIP)-and sarcopenia in individuals aged ≥ 60 years, and to investigate the mediating role of uric acid (UA) in these relationships. The goal was to provide scientific evidence and practical guidance for preventing and treating sarcopenia in older adults.

Methods: Data from 2001 participants aged ≥ 60 years in the 2003-2006 National Health and Nutrition Examination Survey (NHANES) were analyzed. Statistical analyses, including logistic regression, restricted cubic splines (RCS), subgroup analysis, and mediation analysis, were conducted to examine the associations among various lipid metabolism indices, UA levels, and sarcopenia.

Results: Multivariable-adjusted models revealed significant inverse associations between lipid metabolism indices and sarcopenia (all P < 0.05). In the fully adjusted model (model III), the adjusted odds ratios (OR) for LAP, VAI, CMI, and AIP were 0.97 (95% CI: 0.97-0.98), 0.78 (0.68-0.89), 0.32 (0.21-0.49), and 0.27 (0.15-0.52), respectively (all P < 0.05). RCS analyses revealed inverse dose-response relationships between lipid metabolism indices and sarcopenia. The ROC analysis revealed that LAP showed the highest diagnostic value among the four indices. Subgroup analyses showed no significant differences in this relationship across different subgroups. Notably, UA partially mediated these associations (mediation proportions: 8.91-20.66%). These findings suggest that maintaining lipid homeostasis and UA levels may offer protective benefits against age-related sarcopenia.

Conclusions: Our findings advance the understanding of the obesity paradox by revealing that higher lipid metabolism indices (LAP, VAI, CMI, AIP) and UA levels are inversely associated with sarcopenia in the elderly, with UA partially mediating these protective effects. These results highlight the importance of maintaining lipid and UA levels within normal ranges as a potential novel strategy for preventing and managing sarcopenia. These findings suggest that reconsidering these biomarkers in the management of geriatric muscle health is necessary, highlighting their importance in understanding and addressing the pathogenesis of sarcopenia in aging populations.

Keywords: Dyslipidemia; Lipid metabolism; Population-based study; Sarcopenia; Skeletal muscle mass; Uric acid.

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Conflict of interest statement

Declarations. Conflict of interest: The authors have no conflicts of interest to declare. Statement of ethics: The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). Consent to participate was obtained and the National Center for Health Statistics (NCHS) ethics committee approved NHANES study protocol. Study protocols for NHANES were approved by the NCHS ethnics review board (Protocol #2011–17). All information from the NHANES program is available and free for the public, so the agreement of the medical ethics committee board was not necessary. In this study, all human studies have been reviewed by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in an appropriate version of the 1964 Declaration of Helsinki.

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