Type 2 diabetes is normally preceded by pre-diabetes, a condition that is not well established in animal models for diabetes. In this study, we evaluated the effects of a high-fat high-carbohydrate diet in the development of prediabetes. Animals were randomly assigned to the following diets ad libitum during experimentation; standard rat chow (ND+H2O), modern high-fat high-carbohydrate (HFHC+Fructose), high-fructose (ND+Fructose) and a high-fat high-carbohydrate (HFHC+H2O). We measured blood glucose, total cholesterol and triglyceride concentration, OGT response and the HOMA-IR index. Body weight gain, food intake, fluid intake and caloric intake were also monitored. Plasma insulin, ghrelin, leptin and glycosylated haemoglobin (HbA1c) were also measured. When compared to the other groups, the OGT response in correspondence with AUCglucose values in HFHC+Frucose group resulted in increased blood glucose concentration. This was accompanied by an increase in caloric intake, glucose, triglyceride and HbA1c concentration despite no difference in body weight gain. There was an increase in plasma insulin and ghrelin concentration while plasma leptin concentration was decreased. The HOMA-IR value was above 2.9 in the HFHC+Fructose group suggesting the presence of insulin resistance. Voluntary ingestion of a high-fat high-carbohydrate diet with fructose leads to sustained high blood glucose concentration despite increased plasma insulin concentration that is associated with increased HbA1c and ghrelin concentration suggesting reduced insulin sensitivity. This suggests that this model can be used to investigate pre-diabetes effects that emanate from voluntary ingestion of a high-fat high-carbohydrate diet with fructose thus opening new avenues for better understanding of this condition.

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