Novel therapies in type 2 diabetes: insulin resistance

Insulin resistance plays an important role in the pathogenesis of type 2 diabetes and cardiovascular disease. Obesity is a major risk factor for the development of insulin resistance. Hence, treating obesity with lifestyle interventions is the cornerstone of managing insulin resistance. However, when lifestyle interventions fail to produce sustainable impact, then pharmacotherapy and/or bariatric surgery can produce significant improvements in weight, insulin resistance and glycaemic measures. Ectopic fat in the liver and muscle is one of the main mechanisms via which obesity impacts on insulin sensitivity. Hence, there are currently multiple therapeutic interventions in development that aim to improve ectopic fat. With better understanding of the insulin signalling pathways, multiple agents are under development targeting different components of this pathway from the level of insulin receptor to the level of protein kinase B activation and the translocation of glucose transporters. The development of these agents has been slow due to the complexity of the insulin signalling pathway, the multiple negative feedback signals and the fact that the molecules involved in insulin signalling are also involved in other pathways such as cell survival and apoptosis. Sleep-related disorders are increasingly recognised as independent risk factors for the development of insulin resistance and type 2 diabetes; targeting sleep-related disorders as a treatment strategy for insulin resistance is under evaluation. In this article, I will briefly review the future treatments of insulin resistance that are in the pipeline, and I will also briefly review the role of bariatric surgery and sleep-related disorders in the treatment of insulin resistance.