Preservation of muscle mass during aging reduces the risk of frailty and age-related chronic diseases. Preservation of muscle mass during aging reduces the risk of frailty and age-related chronic diseases.We aimed to evaluate lifestyle factors and common cardiometabolic diseases as possible predictors of accelerated muscle loss in middle-aged and older men.Men aged 40 years and older who underwent health examinations at a tertiary care hospital in Korea in 2010-2011 and after a 6-year follow-up were included in the study. Lifestyle and health status were evaluated through a standardized questionnaire. Body composition including muscle mass was estimated using bioelectrical impedance analysis. Relative change in appendicular muscle mass (ASM) was calculated as the difference in ASM between the baseline and follow-up. Accelerated muscle mass loss was defined when ASM decreased greater than 3% for 6 years. Logistic regression analysis was executed to examine the association of muscle mass loss with lifestyle factors and common cardiometabolic diseases.A total of 2,270 men aged 40 years and older were included in this study. The number of participants with ASM loss more than 3% for 6 years was 467 (20.6%). Diabetes mellitus was associated with accelerated muscle mass loss after adjustment for age, body mass index, activity and calories intake (odds ratio [OR] 2.09, 95% confidence interval [CI] 1.39-3.14, P < 0.001)Sarcopenia is associated with resistance, impaired fasting glucose, and diabetes. The loss of muscle mass in older adults with diabetes is thought to be due to multiple factors, including the following possible mechanisms: First, loss of anabolic activity due to increased insulin resistance. Second, loss of anti-inflammatory responses (tumor necrosis factor-α, highly expressed in adipose tissue of insulin-resistant obese patients, induces interleukin-6, thereby inhibiting muscle tissue differentiation) leads to sarcopenia. This loss is also attributed to changes in muscle fiber composition (a decrease in aerobic type 1 fibers and an increase in glycolytic type 2 fibers) and mitochondrial dysfunction associated with muscle aging. Conversely, sarcopenia acts as a risk factor for diabetes.Diabetes mellitus is a predictor for accelerated muscle mass loss in middle-aged and older men.