Role of Atorvastatin in the Development and Progression of Glucose Intolerance in Albino Rabbits: An In-vivo Experimental Study

Abstract

Introduction: Type 2 diabetes is associated with obesity and dyslipidemia, which are risk factors for cardiovascular disease. The Food and Drug Administration (FDA)-approved indications for statins are being broadened due to their lipid-lowering and pleiotropic effects; statins are currently among the most widely used drugs in patients with and without diabetes. Aim: To evaluate the role of atorvastatin at different doses in the development and progression of glucose intolerance or diabetes in albino rabbits. Materials and Methods: An in-vivo experimental study on rabbits was conducted over a total duration of eight months in the Department of Pharmacology at SCB Medical College, Cuttack, Odisha, India. The animals were divided into five groups of six rabbits each. Atorvastatin at 4 mg/kg and 2 mg/kg was calculated based on human doses corresponding to 80 mg and 40 mg, respectively. Both doses were administered to non diabetic rabbits, and 4 mg/kg atorvastatin was administered to alloxan-induced diabetic rabbits orally for six months daily. Diabetes was induced in two groups of rabbits by administering 100 mg/kg alloxan monohydrate in a 5% (w/v) solution in sterile saline intravenously. Rabbits with stabilised moderate diabetes, characterised by a fasting blood glucose level above 200 mg/dL (at least one month after alloxan injection), were used for the experiments. The effect of atorvastatin on glucose tolerance was assessed by determining Fasting Blood Sugar (FBS) and Glycated Haemoglobin (HbA1c) levels. The results were compared with those of normal and diabetic control rabbits and statistically analysed using Analysis of Variance (ANOVA) and Repeated Measures ANOVA (RMANOVA), followed by appropriate post-hoc analysis. Results: Atorvastatin at a high dose resulted in a 26.74% increase in FBS and a 20.50% increase in HbA1c; at the standard dose, it produced a 21.3% increase in FBS and a 17.99% increase in HbA1c, respectively. The diabetic group receiving high doses also showed a significant increase in FBS (11.7%) and HbA1c (10.25%). The increase in blood glucose parameters was significant in the high-dose group from the fourth month of statin therapy and in the standard-dose group at six months of therapy. Conclusion: The study revealed that atorvastatin at both doses significantly contributed to the initiation and progression of glucose intolerance in diabetic and non diabetic rabbits.

Keywords

• alloxan-induced diabetic rabbits
• dyslipidemia
• glycated haemoglobin
• statins