Effect of Glycemic Control Using Different Antidiabetic Drugs on Cognitive Functions in Experimentally-Induced Type 2DM: A Comparative Study

Abstract

Background: Neurocognitive impairment is recognized as the fourth microvascular complications of type 2 diabetes mellitus (T2DM). Objectives: To compare the effect of glycemic control on cognitive functions in diabetic rats by using different anti-diabetic drugs. Materials and Methods: Fifty male albino rats were equally categorized into: Control group, Janumet group, Diabetic non-treated group, Diabetic+Insulin group and Diabetic+Janumet group. At the end of 4 weeks, neurocognitive assessment was done by using Morris water maze (MWM) and Y-maze tests. Blood samples were collected to estimate glycemic state, lipid profile and total antioxidant capacity level (TAC). Rats' brains were extracted. The right half of the brain was utilized for lipid peroxidation marker (MDA), tumor necrosis factor alpha (TNF-α), superoxide dismutase (SOD), and interleukin 1B (IL-B) measurement. The left half was utilized for histopathological study of the hippocampal tissue. Results: Diabetic group showed significant increase in FBG, HBA1C, HOMA-IR, total cholesterol, triglyceride, MDA, TNF-alpha and IL-1B, and decrease in serum insulin, HDL, TAC and SOD. Neurocognitive impairment and hippocampal degenerative changes were also obvious in diabetic rats. Diabetic+ Janumet group demonstrated significant improvement in the measured biomarkers and neurobehavioral tests with restoration of the hippocampal tissue structure in comparison with Diabetic+ Insulin group. However, there was an insignificant difference in lipid profile markers between Diabetic+ Janumet group and Diabetic+ Insulin group. Insignificant difference between Control and Janumet groups regarding all measured parameters was detected. Conclusion: Both insulin and Janumet drugs alleviates the metabolic, neurocognitive impairment and hippocampal changes associated with T2DM. However, the improvement was more pronounced with Janumet treatment than insulin treatment. The synergistic hypoglycemic, anti-oxidant and anti-inflammatory effects of Janumet's components may account for this improvement.