Mechanisms of muscle atrophy in type 2 diabetes mellitus: factors dysregulating muscle protein synthesis and breakdown

Type 2 diabetes mellitus (T2DM) is rising in prevalence and incidence, which is leading to increased burden on healthcare systems. A less recognized consequence of T2DM is the accelerated loss of skeletal muscle, which can reduce quality of life and further exacerbate T2DM progression. Insulin resistance disrupts skeletal muscle maintenance by impairing insulin- and leucine-mediated signalling-processes challenging to study due to the number and complexity of dysregulated components. Several key areas in this field remain underexplored, such as the causal relationship between T2DM and muscle atrophy, the impact of insulin resistance on muscle protein balance, and the mechanisms driving muscle atrophy in humans with T2DM. Advancing understanding in these areas requires the integration of evidence from experimental, prospective, and computational studies to more precisely characterize the mechanisms and progression of T2DM-related muscle atrophy and to inform targeted interventions to mitigate muscle loss.