Targeting Obesity for the Treatment of Type 2 Diabetes Mellitus

The discovery of diabetes mellitus (simplified as “diabetes”) could be traced back to 1500 B.C. The first detailed description appeared in 1800, but in the last few decades, the prevalence of diabetes increases dramatically. Till present, according to WHO’s report, 247 million people worldwide have been diagonized Diabetes, among which 3.47 million died from diabetes. Thus, WHO projects that diabetes will become the 7th leading cause of death in 2030. The typical feature of diabetes is hyperglycemia as a result of metabolic disorder. As the disease progress, complications develop including macrovascular and microvascular abnormality, leading to multiple organ failure and mortality. Apart from diabetes-associated vascular diseases, numerous studies have documented the association between hyperglycemia and cancer. There are three main types of diabetes: (1) type 1 diabetes mellitus (T1DM) in which pancreatic β cell death by immune attack; (2) type 2 diabetes mellitus (T2DM) in which pancreatic β cells fail to produce sufficient amount of insulin; and (3) gestational diabetes which occurs in pregnant women due to high demand for insulin production. Type 2 DM accounts for 80-90% of diabetes and obesity has been identified as a strong and modifiable risk factor in type 2 DM. In this review, we first provide a general introduction of T2DM in the aspects of diagnosis, pathogenesis and clinical characteristics of T2DM. We will focus on how obesity has the adverse impact on insulin resistance, pancreatic β cell death and dysfunction and the development of T2DM. Next, we will summarize the animal models of T2DM including their advantages and drawbacks when compared to their clinical relevance. Finally, we will summarize the interventions that have been applied to treat obesity and T2DM and the remaining problems.