Increasing the Incidence of Type 2 Diabetes in UCD-T2DM Female Rats

The prevalence of type 2 diabetes mellitus (T2DM) is higher for men compared with women, yet women present with a greater risk factor burden at the time of their diagnosis. Currently, research is lacking that addresses these sex-specific differences in disease onset and progression, research that is critical to understanding the pathophysiology of diabetes and developing optimal treatment strategies for both women and men. These same sex differences are present in animal models of T2DM. The paucity of suitable T2DM animal models is a barrier to investigations of these sex differences. The University of California Davis (UCD)-T2DM rat model, bred to become spontaneously diabetic over time with a similar pathophysiology to humans, exhibits a lower incidence of T2DM in females (43%) compared with males (92%). PURPOSE: To investigate if a higher fat diet, accompanied by 40% sucrose water, increases the incidence of T2DM in female UCD-T2DM rats. METHODS: Beginning at 2 months old, female UCD-T2DM rats (n=8) were fed a chow with 21% fat and 34% sucrose. At 8 months old, their drinking water was replaced with 40% sucrose water. Bi-weekly measurements of random glucose and HbA1c were performed, and a HbA1c of >5.6% was used to diagnose diabetes onset. Blood was drawn and body weight was assessed at 6 and 9 months, before and after the addition of 40% sucrose water. ELISA’s were performed to assess insulin. Data are presented as mean SD. RESULTS: One out of eight rats became diabetic at 4.5 months, before the sucrose water was added. The female rats experienced a significant increase in body weight (431.5 ± 28.6 g vs. 458.9 ± 39.6 g; P=0.013) and insulin (1.37 ± 0.71 ng/mL vs. 1.84 ± 0.51 ng/mL; P=0.057) after the addition of the sucrose water. CONCLUSION: These findings suggest that implementing a higher fat diet and 40% sucrose water intervention does not increase the incidence of T2DM in female UCD-T2DM rats. However, it does appear that the dietary changes lead to greater weight gain and worsen insulin resistance in UCD-T2DM female rats. This project was supported by NIH R01 HL144723.