DOI: http://dx.doi.org/10.18203/2319-2003.ijbcp20195782

Evaluation of hyperglycaemic risk of atorvastatin: a dose dependent study on hyperlipidaemic rats

T. E. Prashanth Kumar, Mahammad Juber S., Swetha Vijetha M.

Abstract


Background: Statins (β-hydroxy β-methylglutaryl-CoA (HMG-CoA) reductase inhibitors) are the most prescribed medications worldwide to treat hyperlipidaemia with a proven ability to reduce major cardiovascular events. Recent data have revealed that statin therapy is associated with an increased risk for developing diabetes. The risk was most significant in patients taking atorvastatin, rosuvastatin and simvastatin.

Methods: Rats were divided into 3 groups, each comprising of 6 rats. Hyperlipidaemia was induced in all the animals after feeding with high fat diet for 15 days. Rats of groups 1, 2 and 3 were given atorvastatin 1.8 mg/kg (low-dose), 3.6 mg/kg (moderate-dose) and 7.2 mg/kg (intensive-dose) respectively orally for 60 days. 12 hours fasted blood samples were collected and analyzed for serum lipid profile, fasting blood glucose and HbA1c levels.

Results: The percentage increase in plasma blood glucose after 60 days of treatment in groups 1, 2, and 3 is 29.93%, 60.03% and 72.42% respectively and the variation in all the groups is statistically significant, p<0.0001. Regarding HbA1c values, the variation in low-dose group is statistically insignificant whereas the percentage increase in moderate-dose and intensive-dose groups is 19.45% (p<0.001) and 43.37% (p<0.0001) respectively.

Conclusions: In conclusion, there is significant increase in blood glucose and HbA1c levels leading to new-onset diabetes in both moderate-dose and intensive-dose groups. The risk is more in intensive-dose group when compared to moderate-dose group.


Keywords


Atorvastatin, HMG Co-A reductase inhibitors, Fasting blood glucose, HbA1c, New-onset diabetes

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References


Mukherjee AK. Prediction of coronary heart disease using risk factor categories.J Indian Med Assoc. 1995;93;312-5.

Gupta R, Joshi P, V Mohan V, Reddy KS, Yousuf S. Epidemiology and causation of coronary heart disease and stroke in India. Heart 2008;94:16-26.

Lloyd Johns DM, O`Donnell CJ, D`Agostino RB, Massaro J, Silbershatz H, Wilson PW, Applicability of cholesterol lowering primary prevention trials to a General population. The Framingham Heart study. Arch Intern Med. 2001;161;949-54.

Baigent C, Blackwell L, Emberson J, Holland LE, Reith C, Bhala N, et al. Efficacy: Safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376(9753):1670-81.

Mihaylova B, Emberson J, Blackwell L, Keech A, Simes J, Barnes EH. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. Lancet. 2012;380(9841):581-90.

ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2013.

Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, et al. American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014;63(25 Pt B):2889-934.

Ganda OP. Deciphering cholesterol treatment guidelines: a clinician's perspective. JAMA. 2015;313(10):1009-10.

Choudhry NK, Dugani S, Shrank WH, Polinski JM, Stark CE, Gupta R, et al. Despite increased use and sales of statins in India, per capita prescription rates remain far below high-income countries. Health Aff (Millwood). 2014;33:273-82.

Preiss D, Seshasai SR, Welsh P, Murphy SA, Ho JE, Waters DD, et al. Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a meta-analysis. JAMA. 2011;305:2556-64.

Dhande SR, Gursahani MS, Kadam VJ. Standardization of Cholesterol suspension induced Hyperlipidemia in rats. World J Pharma Pharma Sci. 2014;3(12):1107-23.

Waters DD, Ho JE, Demicco DA, Breazna A, Arsenault BJ, Wun CC, et al. Predictors of new-onset diabetes in patients treated with atorvastatin: results from 3 large randomized clinical trials. J Am Coll Cardiol. 2011;57:1535-45.

Kearney PM, Blackwell L, Collins R, Keech A, Simes J, Peto R, et al. Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: a meta-analysis. Lancet. 2008;371:117-25.

Shah RV, Goldfine AB. Statins and risk of new-onset diabetes mellitus. Circulation. 2012;126(18):282-4.