Skeletal muscle is the largest lean tissue mass and plays a pivotal role in insulin-stimulated glucose disposal. Therefore, it may play a causal role in the development of insulin resistance and eventually type 2 diabetes. Muscle tissue is composed of a mixture of slow- and fast-twitch fibers and diabetic muscles typically show features of a fast muscle fiber type composition, including reduced insulin sensitivity. Yet, it remains to be elucidated if these muscle characteristics are a cause or consequence of the disease. Therefore, we will use a proteome-analysis to unreavel, in a comprehensive cross-sectional study with an unprecedented large (n=215) cohort of young and healthy individuals, the role of muscle phenotype in the early signs of insulin resistance. This is complemented with a meticulous participant characterization to adjust for lifestyle factors such as physical activity level. Gaining insight into these relationships holds significant clinical value for the development of targeted individualized preventive strategies against insulin resistance and associated cardiometabolic risk factors