Novel High-Fat Diet Formulation and Streptozotocin Treatment for Induction of Prediabetes and Type 2 Diabetes in Rats

Background: The previously established methods for type 2 diabetes (T2D) have mainly concentrated on overt diabetes model development. Here, our intention was to create an animal model passing through distinct phases such as obesity with insulin resistance, prediabetes, and gradual progress to the overt diabetes stage. A high-fat high-carbohydrate diet formulation was prescribed combined with multiple low-dose streptozotocin (STZ) injections after obesity establishment. Materials and Methods: Sixteen male Wistar rats were separated randomly into two groups and fed a normal diet for 1 week after which the body weight and biochemical indices of each rat were measured and recorded. Subsequently, one group (n = 8) switched to the high-fat high-carbohydrate diet formulated by us for 10 weeks, whereas the other group (n = 8) continued with the normal diet. Body weight and biochemical indices of the rats in the high-fat diet (HFD) group were measured at the end of 10 weeks, and each rat received 30 mg/kg intraperitoneal STZ injections with 1-week intervals in two steps and was continued on a high-fat high-carbohydrate diet. The differences between the groups were analyzed using the Student's t-test or one-way analysis of variance and by post hoc multiple comparisons. Results: A significant change in weight, fasting blood glucose, and triglyceride was observed in rats fed with a HFD after 10 weeks. The HFD rats showed typical characteristics of T2D mellitus (T2DM) such as insulin resistance and hyperglycemia following 30 mg/kg STZ. Conclusions: The novel high-fat high-carbohydrate formulation we used, along with multiple low doses of STZ, can mimic peculiar characteristics of T2DM development.