Abstract
Background/Objectives: Muscle loss is a serious complication in chronic disease patients, yet studies on long-term changes in muscle mass based on insulin sensitivity in the absence of diabetes mellitus are scarce. This community-based cohort study analyzed the longitudinal association between insulin sensitivity and muscle loss in middle-aged South Korean adults. Methods: This study included 6016 subjects (aged 40-65 years) from the Korean Genome and Epidemiology Study, conducted between 2001 and 2016. Fat-free mass, fat mass, body weight, and kidney function were assessed biennially. Subjects were categorized into four groups based on the composite (Matsuda) insulin sensitivity index (ISI) quartiles. The primary outcome was muscle loss, defined as a decline in fat-free mass of 10% or more from baseline. The secondary outcome was the occurrence of all-cause mortality. Results: During 69,480 person-years of follow-up, muscle loss occurred in 311 (5.2%) subjects. Multivariable Cox regression revealed a reverse-graded association between insulin sensitivity and muscle loss risk. Hazard ratios (95% confidence intervals) for the second, third, and highest ISI quartiles were 0.70 (0.51-0.94), 0.69 (0.50-0.95), and 0.65 (0.46-0.92), respectively, compared with the lowest quartile. Insulin sensitivity, however, was not significantly associated with all-cause mortality, though the mortality risk was higher in individuals with muscle loss. Conclusions: A reverse-graded relationship between insulin sensitivity and muscle loss risk was identified in middle-aged South Korean adults, with the lowest risk in the highest ISI quartile. These findings suggest that higher insulin sensitivity may reduce the risk of muscle loss.