Effect of vitamin D on atorvastatin induced blood sugar changes in Wistar albino rats

R. Arunkumar, Vinayak Meti, A. Ruckmani, Shobita Devi

Abstract


Background: Statins are hypocholestrolemic agents used in atherosclerotic vascular disorders. They act by inhibiting hepatic hypoxanthine methyl glutaryl CoA reductase enzyme. They are reported to cause hyperglycemia as an important adverse event. This study was conducted to investigate atorvastatin induced blood sugar changes in Wistar, albino, male rats and the influence of vitamin D on the blood sugar changes. Methods: Forty, 12 weeks old male, Wistar albino rats, were selected and randomly allocated to 5 groups of 8 animals, each. Animals in Group 1 were administered normal saline orally and served as controls. Group 2 and 3 received atorvastatin 2 mg and 4 mg, respectively, orally. Group 4 and 5 received 200 IU of vitamin D along with 2 mg and 4 mg of atorvastatin respectively, orally. The drugs were administered once, every day for 3 months. Body weight and fasting blood sugar were estimated at baseline and at the end of every month for 3 months.

Results: In control animals (Group 1) and animals treated with atorvastatin along with vitamin D (Group 4 and 5), fasting blood sugar levels did not change significantly and the body weight increased. In animals treated with only atorvastatin (Group 2 and 3), fasting blood sugar was significantly increased and body weight did not change.

Conclusions: This study has demonstrated that chronic use of atorvastatin 2 and 4 mg may lead to fasting hyperglycemia and it could be prevented by co-administration of 200 IU of vitamin D, in male Wistar albino rats. Randomized control studies in humans are further required to recommend routine use of vitamin D in patients receiving atorvastatin.


Keywords


Statins, Hyperglycemia, Blood sugar, Vitamin D, Atorvastatin

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References


Pella D, Rybar R, Mechirova V. Pleiotropic effects of statins. Acta Cardiol Sin. 2005;21:190-8.

Lipitor® Prescribing Information. Pfizer. Distributed by Park Davis. USA. Oct, 2012.

While A, Keen L. The effects of statins on mood: a review of the literature. Eur J Cardiovasc Nurs. 2012;11(1):85-96. PubMed PMID: 20875773.

Steenland K, Zhao L, Goldstein FC, Levey AI. Statins and cognitive decline in older adults with normal cognition or mild cognitive impairment. J Am Geriatr Soc. 2013;61(9):1449-55. [DOI via Crossref] Epub 2013 Sep 3. [DOI via Crossref]

Glasser SP, et al. The Association of statin use and statin type on cognitive performance: Analysis of the reasons for geographic and racial differences in stroke (REGARDS) study. Clin Cardiol. 2010;33(5):280-8. [DOI via Crossref] [DOI via Crossref]

Belalcazar LM, Raghavan VA, Ballantyne CM. Tatin-induced diabetes: Will it change clinical practice? Diabetes Care. 2009;32(10):1941-3. [DOI via Crossref]

Preiss D, Sattar N. Statins and the risk of new-onset diabetes: a review of recent evidence. Curr Opin Lipidol. 2011;22(6):460-6. [DOI via Crossref] [DOI via Crossref]

Culver AL, et al. Statin use and risk of diabetes mellitus in postmenopausal women in the Women's Health Initiative. Arch Intern Med. 2012;172(2):144-52. [DOI via Crossref] Epub 2012 Jan 9. [DOI via Crossref]

FDA drug safety communication: Important safety label changes to cholesterol-lowering statin drugs. Available from: http://www.fda.gov/Drugs/DrugSafety/ucm293101.htm#sa. [Last accessed on 2012 Oct 16].

Labeling changes to statins address adverse health effects, March 2, 2012. The endocrine society. 8401 Connecticut Avenue, Suite 900 Chevy Chase, Maryland 20815-5817 Telephone 301.941.0200 Fax 301.941.0259. Available from: http://www.endo-society.org.

Sukhija R, Prayaga S, Marashdeh M, Bursac Z, Kakar P, Bansal D, et al. Effect of statins on fasting plasma glucose in diabetic and nondiabetic patients. J Investig Med. 2009;57(3):495-9.

Goldstein MR, Mascitelli L. Do statins cause diabetes? Curr Diab Rep. 2013;30(13):381-90. DOI 10.1007/s11892-013-0368-x. [DOI via Crossref]

Alvarez JA, Ashraf A. Role of vitamin d in insulin secretion and insulin sensitivity for glucose homeostasis. Int J Endocrinol. 2010;2010:351385. [DOI via Crossref] [DOI via Crossref]

Pera Ł, Sygitowicz G, Białek S, Łukaszkiewicz J, Sitkiewicz D. Vitamin D and statins: action in preventing cardiovascular events. Kardiol Pol. 2012;70, 12: 1296-1298.

Eisen A, Lev E, Iakobishvilli Z, Porter A, Brosh D, Hasdai D, Mager A. Low plasma vitamin d levels and muscle-related adverse effects in statin users. Isr Med Assoc J. 2014;16:42-5.

Yavuz B, Ertugrul DT, Cil H, Ata N, Akin KO, Yalcin AA, et al. Increased levels of 25 hydroxyvitamin D and 1,25-dihydroxyvitamin D after rosuvastatin treatment: a novel pleiotropic effect of statins? Cardiovasc Drugs Ther. 2009;23(4):295-9. [DOI via Crossref] [DOI via Crossref]

Aloia JF, Li-Ng M, Pollack S. Statins and vitamin D. Am J Cardiol. 2007;100(8):1329. [DOI via Crossref]

Sattar N, Preiss D, Murray HM, Welsh P, Buckley BM, de Craen AJM, et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomized statin trials. Lancet. 2010;375:735-42. [DOI via Crossref]

Ridker PM, Danielson E, Fonseca FAH, Genest J, Gotto AM, Kastelein JJP, et al. For the JUPITER Study Group. N Engl J Med. 2008;359:2195-207. [DOI via Crossref]

Zaharan NL, Williams D, Bennet K. Statins and risk of treated incident diabetes in a primary care population. Br J Clin Pharmacol. 2012;75(4):1118-24. [DOI via Crossref]

Binkley N, Ramamurthy R, Krueger D. Low vitamin D status: definition, prevalence, consequences, and correction. Endocrinol Metab Clin N Am. 2010;39:287-301. [DOI via Crossref]

Goswami R, Mishra SK, Kochupillai N. Prevalence and potential significance of vitamin D deficiency in Asian Indians. Indian J Med Res. 2008;127:229-38.

Andrade Chagas CE, Borges MC, Martini LA, Rogero MM. Focus on vitamin D, inflammation and type 2 diabetes. Nutrients. 2012;4:52-67. [DOI via Crossref] [DOI via Crossref]

Ishii H, Suzuki H, Baba T, Nakamura K, Watanabe T. Seasonal variation of glycemic control in type 2 diabetic patients. Diabetes Care. 2001;24:1503. [DOI via Crossref]

Campbell IT, Jarrett RJ, Keen H. Diurnal and seasonal variation in oral glucose tolerance: studies in the Antarctic. Diabetologia. 1975;11:139-45. [DOI via Crossref]

Pittas AG, Harris SS, Stark PC, Dawson-Hughes B. The effects of calcium and vitamin D supplementation on blood glucose and markers of inflammation in non-diabetic adults. Diabetes Care. 2007;30:980-6. [DOI via Crossref]

Von Hurst PR, Stonehouse W, Coad J. Vitamin D supplementation reduces insulin resistance in South Asian women living in New Zealand who are insulin resistant and vitamin D deficient - A randomized, placebo-controlled trial. Br J Nutr. 2010;103:549-55. [DOI via Crossref]

Ahmed W, Khan N, Glueck CJ, Pandey S, Wang P, Goldenberg N, et al. Low serum 25(OH) vitamin D levels (<32 ng/mL) are associated with reversible myositis-myalgia in statin-treated pa- tients. Transl Res. 2009;153:11-6. [DOI via Crossref]

Gupta A, Thompson PD. The relationship of vitamin D deficiency to statin myopathy. Atherosclerosis. 2011;215(1):23-9. [DOI via Crossref]