The Effect of Thiazolidinediones and SGLT-2 Inhibitors on Minerals,VIT.D3, Blood Glucose and Weight Gain in Wistar Rats Induced with Type 2 Diabetes

Abstract

Type 2 diabetes mellitus and osteoporosis are among the most common health problems around the world. Diabetes is usually associated with increase a risk of bone fracture, Recent studies has indicated the harmful effects of some of anti-diabetic drugs on bone metabolism. Therefore, the goal of this study was to investigate the effect of two types of anti-diabetic drugs: Thiazolidinediones (TZDs) (30 mg/kg) and sodium-glucose cotransporter-2 (SGLT-2) inhibitors (10 mg/kg) on Vit.D and bone minerals on serum  of  laboratory female rats induced with type 2 diabetes mellitus. The study was conducted on animals Faculty of science/ Department of biology/University of kufa. And Central Laboratories/  In Medical City.  during the period from 27 october 2021 till the end of 22 February 2022. Thirty-two adults female Albino rats (Rattus norvigicus) were randomly divided to two main groups of sixteen animals, The first group was treated for a period of 2 weeks and the second group was treated for a period of 2 months. Each group of them was divided into secondary four groups of four rats including: a control (Co1 and Co2) were fed regular rats pellet, the second group (HFD 1 and HFD 2) were fed with high fat diet (42% lipid, 32%g sucrose, 14% protein), the third group were fed with high fat diet and treated with TZDs (30 mg/kg) and fourth group were fed with high fat diet and treated with SGLT-2i (10 mg/kg). After the end of the treatment period, which is two weeks and three months, the blood was drawn using a method of cardiac puncture technique for estimation of blood glucose, bone minerals in serum which include (calcium, magnesium, inorganic phosphate) and serum Vit.D₃ concentration. Body weight gain was significantly increased (p≤0.05) in animals treated with HFD high-fat diet (uncontrolled diabetic group) and in animals treated with TZDs compared to the control and animals treated with SGLT-2i. Also, the results of this study showing a significant increase (p£0.05) on blood glucose in animals fed with HFD compared with other groups and there was a significant decrease (p£0.05) in blood glucose in animals  group treated with TZDs and SGLT-2i compared with HFD. The diabetic induced group (HFD group) treated for two months showed a significant decrease (p≤0.05) in vitamin D₃ concentrations. The results of calcium concentrations in the blood showed a significant decrease (p≤0.05) in calcium concentration in the group induced with diabetes and the group treated with TZDs for two months compared to other groups. With regard to magnesium concentrations, the results showed a significant decrease (p≤0.05) in the group induced with diabetes and the group treated with TZDs for two months compared to other groups. While there was a significant increase (p≤0.05) in the concentrations of magnesium in the group treated with SGLT₂i for two months compared to other groups. Also, the results showed a significant increase in the concentrations of serum inorganic phosphate in the groups treated with high-fat diet (diabetic induced group) for two months and the group treated with SGLT2i for two months, compared to the control group and the groups treated with TZDs. In conclusion: Uncontrolled diabetes mellitus has adverse effects on the concentrations of Vit.D3 and bone minerals. Also, Long-term treatment with Thiazolidinedionse (TZDs) and SGLT-2 inhibitors, despite its control of blood sugar has harmful effects on bone minerals and Vit.D3.