Swine models of type 2 diabetes mellitus: Insulin resistance, glucose tolerance, and cardiovascular complications

In humans, diabetes mellitus (DM) is considered a heterogeneous metabolic disorder. Swine have been used as a model for many human conditions including type 1 (insulin-deficient) and type 2 (insulin-resistant) DM research because of their phenotypic similarities to humans including: cardiovascular anatomy and function, metabolism, lipoprotein profile, size, tendency to obesity, and omnivorous habits. There is phenotypic overlap between the two types of DM and pig models show characteristics and complications of both. Streptozotocin and alloxan have been used to create insulin deficient diabetes in pigs. One of the most unique and useful phenotypes is that these insulin-deficient pigs develop more severe coronary atherosclerosis than nondiabetic controls. It is not fully understood why patients with either type 1 or type 2 DM have increased severity and diffuseness of atherosclerosis compared with nondiabetic patients. The current human epidemic of type 2 DM and its attendant cardiovascular complications underscore the unmet need for creating a useful, readily available animal model of type 2 insulin resistant DM that also develops coronary artery atherosclerosis. The phenotypic susceptibility to coronary atherosclerosis makes pigs an attractive species to identify causative mechanisms. Suggested criteria for validation of an animal model of humanoid type 2 DM are described. The goal would be to develop a useful animal model for mechanistic studies as well as to develop and test novel therapeutics both for type 2 DM as well as its cardiovascular complications.