Abstract
Type 2 diabetes mellitus (T2DM) is a complex metabolic disease characterized by the loss of beta-cell secretory function and mass. The pathophysiology of beta-cell failure in T2DM involves a complex interaction between genetic susceptibilities and environmental risk factors. One environmental condition that is gaining greater appreciation as a risk factor for T2DM is the disruption of circadian rhythms (eg, shift-work and sleep loss). In recent years, circadian disruption has become increasingly prevalent in modern societies and consistently shown to augment T2DM susceptibility (partly mediated through its effects on pancreatic beta-cells). Since beta-cell failure is essential for development of T2DM, we will review current work from epidemiologic, clinical, and animal studies designed to gain insights into the molecular and physiological mechanisms underlying the predisposition to beta-cell failure associated with circadian disruption. Elucidating the role of circadian clocks in regulating beta-cell health will add to our understanding of T2DM pathophysiology and may contribute to the development of novel therapeutic and preventative approaches.