Protective role of skeletal muscle mass against progression from metabolically healthy to unhealthy phenotype

Summary Objective Metabolically healthy individuals are known to be resistant to cardiovascular disease development. However, a considerable fraction of those individuals shows deteriorated metabolic health over time. Although skeletal muscle is the primary insulin‐responsive target organ, a longitudinal investigation of the skeletal muscle mass in relation to the development of metabolically unhealthy phenotype has not been performed. We aimed to evaluate whether greater skeletal muscle mass is an independent protective factor for the development of metabolically unhealthy phenotype. Design, Participants and Measurements We conducted a retrospective cohort study with 9033 metabolically healthy volunteers who underwent routine health examinations in 2012 and a follow‐up examination in 2016. Obesity was defined as Asian‐Pacific body mass index criterion ≥25 kg/m2. Subjects with fewer than two risk factors (elevated blood pressure, triglyceride, glucose, high‐sensitivity C‐reactive protein, insulin resistance and decreased high‐density lipoprotein cholesterol levels) were characterized as metabolically healthy using Wildman criteria. Results At the 4‐year follow‐up, approximately one‐fourth of the nonobese participants and half of the participants with obesity showed metabolic deterioration. In nonobese men and women, higher appendicular skeletal muscle mass (ASM)/weight at baseline was significantly associated with decreased risk of metabolic deterioration. Compared to the lowest quartile of ASM/weight, the adjusted odds ratios (95% confidence intervals) of the highest quartile were 0.68 (0.52‐0.89) in nonobese men and 0.64 (0.46‐0.90) in nonobese women. However, this association was not observed in obese subjects. Conclusions Greater skeletal muscle mass at baseline is significantly associated with maintenance of metabolically healthy status, especially in nonobese individuals.