BACKGROUND: Sarcopenic obesity (SO) is a clinical condition defined by the coexistence of high body fat mass and low muscle function and mass, which increases the risk of adverse health outcomes, including disability and mortality. Early detection and frequent monitoring of SO are essential for preventive interventions and management strategies. The current binary approach for SO diagnosis is limited in capturing the spectrum of SO or its progression over time. The main objective of this study was to develop a continuous SOPi that integrates diagnostic criteria such as muscle function and body composition. We aimed to evaluate the association between SOPi and all-cause mortality, to identify baseline-related factors with SOPi and to assess changes in the SOPi over time. METHODS: Participants from the Rotterdam Study with baseline and follow-up measures of handgrip strength (HGS), dual-energy X-ray absorptiometry-measured appendicular lean mass index (ALM/kg) and body fat percentage (BF%) were included. SOPi was calculated as a sex-specific equation integrating z-scores (Z) of (BF%)-(HGS)-(ALM/kg). Cox regression and multivariable linear regression models were fitted to evaluate mortality risk and associated factors with SOPi, respectively. Subgroup analysis of SOPi changes was performed by linear mixed-effects models. RESULTS: In the total population (n = 5888, age 69.5 ± 9.1 years, BMI 27.5 ± 4.3 kg/m2, 56.8% females) and over the 9.9-year median follow-up period, 1538 (26.1%) participants died. Each standard deviation (SD) increase in sex-specific SOPi was associated with a 10% higher risk of premature death (HR = 1.10 [95%CI: 1.07; 1.13]). Thirteen factors were associated with high SOPi, such as reduced physical activity, higher triglyceride-glucose index, HOMA-IR, systemic inflammation, osteopenia, hypertension, liver steatosis, asthma, coronary heart disease, oral corticosteroid use, lower protein intake, lower quality of life and lower educational status. In participants with obesity, lower physical activity and/or insulin resistance (n = 1682), a significantly higher and faster increase in SOPi was observed compared to participants without these factors (males: β = 2.63 [95%CI: 2.22; 3.03]; females: β = 2.90 [95%CI: 2.58; 3.23]). CONCLUSION: SOPi is a significant predictor of premature death and can identify associated factors, particularly useful among persons at risk of SO. SOPi is higher and increases faster in individuals with specific phenotypes. SOPi integrates prognosis information, which could be used as a risk indicator and for prevention of SO.

Clinical Nutrition Department Clermont Ferrand University Hospital Clermont Ferrand France

Department of Biostatistics Erasmus MC University Medical Center Rotterdam Rotterdam the Netherlands

Department of Epidemiology Erasmus MC University Medical Center Rotterdam Rotterdam the Netherlands

Department of Experimental Medicine Section of Medical Pathology Endocrinology and Human Nutrition Sapienza University of Rome Rome Italy

Department of Geriatrics 1st Faculty of Medicine Charles University and General University Hospital Prague Czech Republic and University of South Bohemia Faculty of Health and Social Sciences Ceske Budejovice Czech Republic

Department of Internal Medicine Erasmus University MC Rotterdam the Netherlands

Department of Medical Surgical and Health Sciences University of Trieste Trieste Italy

Department of Nutrition and Dietetics Amsterdam University Medical Centers Amsterdam Public Health Institute VU University Amsterdam the Netherlands

Department of Nutrition and Dietetics Faculty of Health Sport and Physical Activity Amsterdam University of Applied Sciences Amsterdam the Netherlands

Division of Human Nutrition and Health Wageningen University Wageningen the Netherlands

Human Nutrition Unit Clermont Auvergne University Institut National de Recherche Pour l'Agriculture l'Alimentation et l'Environnement Centre de Recherche en Nutrition Humaine Clermont Ferrand France

Institute of Nursing Science Medical University of Graz Graz Austria

Servicio de Geriatria Hospital Universitario Ramon y Cajal Madrid Spain

Unit of Biostatistics Clermont Ferrand University Hospital Clermont Ferrand France

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