Establishing a Female Animal Model of Prediabetes Using a High-Carbohydrate, High-Fat Diet

Prediabetes is a condition that often precedes the onset of type 2 diabetes and is characterized by moderate levels of insulin resistance. This condition is well established in male animal models for diabetes; however, few female models exist. There is accumulating evidence that sex variations affect the pathogenesis, treatment, and consequences of numerous diseases, such as type 2 diabetes. Therefore, we sought to develop a diet-induced prediabetic female animal model to better understand prediabetes development and its effects in females. Female Sprague Dawley rats were randomly allocated to one of two groups: the standard diet (SD) group fed a standard diet with normal drinking water, and the high-carbohydrate, high-fat (HCHF) group fed a high-carbohydrate and high-fat diet with drinking water supplemented with fructose. During induction, we measured food intake, body weight, body mass index (BMI), and oral glucose tolerance response (OGT). After the induction period, biochemical analyses were conducted to assess the levels of plasma leptin, ghrelin, insulin, and glycated hemoglobin (HbA1c). Glycogen concentrations were quantified in the liver and skeletal muscles. The HCHF diet-fed group presented higher body weight gain, food intake, and BMI levels, which were accompanied by elevated plasma insulin, ghrelin, and liver and skeletal muscle glycogen levels compared to the SD-fed group. In the HCHF diet-fed group, the HOMA-IR was above 1.9, suggesting the presence of moderate levels of insulin resistance. The OGT response was significantly higher in the HCHF-fed group versus the SD-fed group, suggesting impaired glucose tolerance, thus displaying the signs and symptoms of prediabetes. The HCHF diet with fructose led to the induction of prediabetes in female Sprague Dawley rats. This model could be used to investigate and outline the pathophysiological complications associated with prediabetes in females as a result of the prolonged ingestion of a high carbohydrate, high-fat diet with fructose. The development of this model could also serve as an effort to further bridge the gap regarding the inclusion of females in biomedical research, thus providing advancements in deriving better, specified treatment strategies for women.