- OBJECTIVE: Skeletal muscle fat infiltration (known as myosteatosis) is greater in African compared with European ancestry men and may play an important role in the development of type 2 diabetes (T2D). However, prospective studies examining the magnitude of changes in myosteatosis with aging and their metabolic consequences are sparse. METHODS: Longitudinal changes in peripheral quantitative computed tomography measured calf myosteatosis [intermuscular fat (mm(2) ) and skeletal muscle density as a measure of intramuscular fat (mg/cm(3) )] were examined in 1515 Afro-Caribbean men aged 40+ years recruited without regard to their health status. RESULTS: During an average of 6.2 years of follow-up, an age-related increase in intermuscular fat and a decrease in skeletal muscle density were observed (all P < 0.0001), which remained significant in those who lost weight, gained weight, or remained weight stable (all P < 0.0001). In addition, muscle density loss accelerated with increasing age (P < 0.0001). Increased intermuscular fat during follow-up was associated with an increased incident risk of T2D independent of factors known to be associated with T2D (odds ratios per 1-SD increase in intermuscular fat = 1.29; 95% CI = 1.08-1.53). CONCLUSIONS: Our findings suggest that both inter- and intramuscular fat increase with advancing age and that intermuscular fat contributes to development of T2D among African ancestry men.