Disruption of Circadian Rhythms and Development of Type 2 Diabetes Mellitus: Contributions to Insulin Resistance and Beta-cell Failure

The incidence of type 2 diabetes mellitus (T2DM) worldwide has reached an epidemic proportion and demonstrates an accelerated rise that threatens the health of the global population as well as economic stability. Insulin resistance in T2DM is largely attributed to ectopic lipid accumulation due to obesity and leads to impaired skeletal muscle and hepatic glucose disposal as well as inappropriately elevated hepatic glucose release. This chapter addresses potential mechanisms underlying the association between circadian disruption and insulin resistance, with particular emphasis on predisposition to obesity. Pathophysiology of insulin resistance in T2DM is largely attributed to ectopic lipid accumulation in insulin-sensitive tissues as a consequence of increased weight gain, visceral adiposity and consequent induction of obese phenotype. The association between circadian disruption and T2DM has also been attributed in part to promotion of beta-cell failure associated with the loss of beta-cell insulin secretory function and/or loss of beta-cell mass.