Modeling insulin resistance in Wistar rats induced by a combined high-fat diet as a predictor of type 2 diabetes (experimental phase 1 study)

The aim was to recreate an experimental model of insulin resistance in male Wistar rats by using a diet with a high fat content of combined origin. Materials and methods. 42 male Wistar rats were taken into the experiment and divided into 2 groups: 1st – control (n = 7) and 2nd – experimental (n = 35). For modelling the insulin resistance (IRS) the rats were fed with a commercial compound feed with a fat content of 40 % for 8 weeks. To control the dynamics of metabolic changes, the rats of the experimental groups were weighed weekly, fasting glucose was measured once every 2 weeks, a glucose tolerance test (GTT), blood pressure measurement (BP) and body composition bioimpedance analysis (BIS) were performed once every 4 weeks, and an insulin tolerance test (ITT) was performed once at 8 week after receiving convincing changes in the glucose tolerance test. Results. In rats of the IRS group, compared to the control group, body weight exceeded the control group by 13 % on the 4th week and by 9 % on the 8th week; fasting glucose concentration was higher by 11 % on the 4th week and by 37 % on the 8th week; GTT revealed changes towards impaired glucose tolerance at both periods, however, the hyperglycemic type of curve was detected on the 8th week, which was combinated by the absence of significant glucose changes during ITT; on the 4th week – systolic BP increase by 27 % and diastolic – by 6 %, and on the 8th week – by 21 % and 20 %, respectively; BIS on the 4th week revealed an increase in body fat mass, against which latent general dehydration with redistributive extracellular hyperhydration is formed, on the 8th week – progression of obesity and dehydration, but with redistribution of fluid towards intracellular hyperhydration. Conclusions. Feeding animals a high-fat diet of combined origin for 4 weeks led to obesity, as evidenced by increased body weight and body fat mass with altered fat distribution. This was accompanied by latent general dehydration and extracellular hyperhydration. However, 4 weeks was insufficient to induce insulin resistance. Extending the diet to 8 weeks resulted in further obesity progression and the development of insulin resistance, characterized by fasting hyperglycemia, a hyperglycemic-type curve on the GTT, the absence of significant glucose fluctuations during ITT, and persistently elevated BP. These metabolic disturbances contributed to a relative total body water deficit, driven by extracellular dehydration with fluid redistribution towards intracellular hyperhydration.