Association between diabetes and sarcopenia in US adults and the role of adiposity

Sarcopenia and diabetes are major public health burdens. Body mass index (BMI) represents a complex factor in diabetes-sarcopenia relationship, implicated in both low muscle mass and the high-risk phenotype of sarcopenic obesity, but its role as a statistical mediator in this association remains unclear in population-based studies. This cross-sectional study included 7,037 U.S. adults aged 20–59 years from National Health and Nutrition Examination Survey (NHANES) 2011–2018. Sarcopenia was primarily defined by low appendicular skeletal muscle mass index (ASM/height2; sex-specific cut-offs), with BMI-adjusted low muscle mass (ASM/BMI) as a secondary definition. Survey-weighted multivariable logistic regression and non-parametric bootstrap formal mediation analyses were performed, adjusting for demographic, socioeconomic, lifestyle and comorbidity covariates. Using the ASM/height2 definition, diabetes was inversely associated with sarcopenia in models without BMI (Model 2 OR = 0.60, 95% CI 0.47–0.77), whereas the association reversed after additional adjustment for BMI (Model 3 OR = 1.84, 95% CI 1.42–2.39). Higher BMI was strongly associated with lower odds of sarcopenia (OR = 0.49 per kg/m2, 95% CI 0.46–0.53). Mediation analysis suggested inconsistent (competitive) mediation: diabetes was associated with higher BMI (OR = 1.13, 95% CI 1.09–1.17), producing a negative indirect effect via BMI that offset the positive direct effect and yielded an inverse total effect. In contrast, using the ASM/BMI definition, higher BMI was positively associated with sarcopenia (OR = 1.13, 95% CI 1.11–1.15) and explained approximately two-thirds of the diabetes-sarcopenia association (proportion mediated = 66.47%). The association between diabetes and sarcopenia differed by the operational definition of low muscle mass. BMI showed definition-dependent mediation: under ASM/height2, BMI acted as a suppressor (competitive) pathway that offset the positive direct association between diabetes and sarcopenia, whereas under ASM/BMI, BMI was a positive mediator accounting for about two-thirds of the association. These findings underscore the importance of specifying diagnostic criteria and body composition when interpreting relationships between diabetes and sarcopenia. Longitudinal studies with functional measures are needed to support causal inference

Body mass index · Comorbidity · Diabetes mellitus · Logistic regression · Mediation · National Health and Nutrition Examination Survey · Odds ratio · Sarcopenia · Sarcopenic obesity · Body Composition Measurement Techniques · Frailty in Older Adults · Nutrition and Health in Aging