Purpose

To evaluate the independent association between insulin resistance and sarcopenia in adults and to assess whether this relationship differs across sex, age, diabetes status, obesity, and dietary protein intake strata.

Methods

This cross-sectional analysis included 6,670 adults aged 20–70 years from the Monitoring of Metabolic Diseases Risk Factors in Tehran (MMRT) cohort. Sarcopenia was defined as the lowest two population quintiles of skeletal muscle index (SMI) measured via dual-energy X-ray absorptiometry (DXA). Insulin resistance was quantified using the Homeostasis Model Assessment (HOMA-IR). Multivariable logistic regression models adjusted for demographic, lifestyle, socioeconomic, biochemical, and clinical covariates. Subgroup and combined-phenotype analyses were performed by sex, age, diabetes, obesity, and protein intake levels.

Results

Sarcopenia prevalence was 39.6%. Participants with sarcopenia were older, had higher BMI and HOMA-IR, and lower physical activity, socioeconomic status, and macronutrient intake. Higher HOMA-IR was associated with 2.64-fold greater odds of sarcopenia (95%CI:2.25–3.10,p < 0.001). Associations persisted across subgroups and were stronger in females (OR = 3.43) than males (OR = 1.47). Insulin-resistant participants with obesity had the highest sarcopenia odds (OR = 4.47), followed by non-obese insulin-resistant individuals (OR = 2.96) and insulin-sensitive individuals with obesity (OR = 1.49). Low protein intake amplified the effect of insulin resistance (OR = 2.92), while higher protein intake partially mitigated risk (OR = 1.81). Mean SMI decreased progressively across HOMA-IR quartiles.

Conclusion

Insulin resistance is independently and strongly associated with sarcopenia, particularly among females and individuals with obesity. Coexistence of low protein intake and insulin resistance markedly worsens muscle loss, suggesting that targeted metabolic and nutritional interventions may help preserve muscle mass in insulin-resistant populations.