Thiamine pyrophosphate improved vascular complications of diabetes in rats with type 2 diabetes by reducing glycation, oxidative stress, and inflammation markers

Background: Thiamine deficiency contributes to hyperglycemia and diabetes complications. Thus, in this study, the effect of thiamine pyrophosphate (TPP) on the in vivo and in vitro formation of glycation, oxidative stress, and inflammatory markers (the main contributors of vascular diabetes complications) was examined in type 2 diabetes rat model. Methods: Type 2 diabetes was induced in rats with a combination of streptozotocin and nicotinamide (55+200 mg/kg). Two groups of rats, healthy and diabetic, were treated with 0.1% TPP in drinking water daily for 3 months and the 2 others received water only. The glucose, insulin, early to end glycation products, the activity of glyoxalase system, lipid profile, LDL oxidation markers, inflammatory markers, creatinine in the serum, and proteinuria in the urine of all rats were determined. Moreover, albumin and LDL were incubated with glucose in the presence and absence of TPP, and the samples were investigated for glycation and oxidation products. Different variables in all 4 groups were compared with multiple analysis of variance (MANOVA-Tukey) test using SPSS version 16. Significance level was set at p<0.05. Results: TPP decreased the formation of diverse glycation and oxidation products in both in vivo (glycated LDL= 144.50±3.48 and oxidized LDL= 54.08±2.67 μmol/l) and in vitro (glycated LDL= 107.00±2.82 and oxidized LDL= 50.83±1.22 μmol/l). In addition, the vitamin reduced fasting blood sugar (9.23±0.29), insulin resistance (9.10±0.50), tumor necrosis factor-α (285.43±15.97), interleukin-6 (257.65±13.06), and improved the lipid profile, the activity of Glo system (Glo-I= 31.65±1.06 and Glo-II= 27.01±0.90 U/mL) and renal function in the diabetic rat (p<0.001). Conclusion: TPP decreased the major risk factors for diabetic complications and corrected the alternations of glucose and lipid metabolism in type 2 diabetic rats; thus, it is recommended for diabetes treatment.

Keywords: Diabetic vascular complications; Glycation; Glyoxalase system; Inflammation; Oxidative stress; Proteinuria; Streptozotocin; Type 2 diabetes.