SULFONYLUREA AND THE HEART: THEORETICALLY A COMPOUNDED QUESTION FROM A PATHOPHYSIOLOGICAL PERSPECTIVE

Main Article Content

Pendar Farahani

Keywords

diabetes, sulfonylurea, hypoglycemia, obesity, elderly, cardiovascular risks

Abstract

Evidence from literature illustrates that from a pathophysiological perspective, sulfonylureas (SU) may impact the heart three ways: directly by intrinsic properties from a pharmacological receptor perspective, indirectly by adverse effects related to hypoglycemia, and obesity. From a pharmacologlogical receptor perspective, SU can bind to ATP-sensitive potassium channels in cardiomyocytes. Channel binding by SU in cardiac tissue may prevent ischemia myocardial protective mechanisms. From a pathophysiological perspective, obesity is associated with cardiac issues such as pulmonary hypertension, left ventricular hypertrophy, arrhythmia, and atrial fibrillation. From a pathophysiological perspective, hypoglycemia is associated with cardiac sympathetic activation and QT prolongation. With the high prevalence and incidence of diabetes, obesity and aging, future basic and clinical studies should further explore the questions related to the pathophysiology of SU utilization and potential cardiac impact in randomized clinical trials and real-world outcome research settings

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References

1. Forst T, Hanefeld M, Jacob S, et al. Association of sulphonylurea treatment with all-cause and cardiovascular mortality: a systematic review and meta-analysis of observational studies. Diab Vasc Dis Res 2013;10:302-14.
2. Monami M, Genovese S, Mannucci E. Cardiovascular safety of sulfonylureas: a meta-analysis of randomized clinical trials. Diabetes Obes Metab 2013;15:938-53.
3. Roumie CL, Hung AM, Greevy RA et al. Comparative effectiveness of sulfonylurea and metformin monotherapy on cardiovascular events in type 2 diabetes mellitus: a cohort study. Ann Intern Med 2012;157:601-10.
4. Simpson SH, Majumdar SR, Tsuyuki RT, et al. Dose-response relation between sulfonylurea drugs and mortality in type 2 diabetes mellitus: a population-based cohort study. CMAJ 2006;174:169-74.
5. Anderson JW, Kendall CW, Jenkins DJ. Importance of weight management in type 2 diabetes: review with meta-analysis of clinical studies. J Am Coll Nutr 2003;22:331-39.
6. Twells LK, Gregory DM, Reddigan J, Midodzi WK. Current and predicted prevalence of obesity in Canada: a trend analysis. CMAJ Open 2014;2:E18-E26.
7. Kalra S, Mukherjee JJ, Venkataraman S et al. Hypoglycemia: The neglected complication. Indian J Endocrinol Metab 2013;17:819-34.
8. Shafiee G, Mohajeri-Tehrani M, Pajouhi M, Larijani B. The importance of hypoglycemia in diabetic patients. J Diabetes Metab Disord 2012;11:17.
9. Engler RL, Yellon DM. Sulfonylurea KATP blockade in type II diabetes and preconditioning in cardiovascular disease. Time for reconsideration. Circulation 1996;94:2297-301.
10. Greiver M, Williamson T, Barber D et al. Prevalence and epidemiology of diabetes in Canadian primary care practices: a report from the Canadian Primary Care Sentinel Surveillance Network. Can J Diabetes 2014;38:179-85.
11. Hux JE, Booth GL, Slaughter PM, Laupacis A, editors. Drug use in older people with diabetes. Diabetes in Ontario: an ICES practice atlas. Toronto:ICES; 2003.
12. Clemens KK, Shariff S, Liu K et al. Trends in antihyperglycemic medication prescriptions and hypoglycemia in older adults: 2002- 2013. PLoS One 2015;10:e0137596.
13. Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Canadian Diabetes Association 2013 clinical practice guidelines for the prevention and management of diabetes in Canada. Can J Diabetes 2013;37:S1-S212.
14. Farahani P, Khan S, Oatway M, Dziarmaga A. Exploring the distribution of prescription for sulfonylureas in patients with type 2 diabetes according to cardiovascular risk factors within a Canadian primary care setting. J Popul Ther Clin Pharmacol 2015;22:e228-e236.
15. Canadian Diabetes Association. An economic tsunami: the cost of diabetes in Canada. Hamilton, ON: Author; 2009. Available at: http://www diabetes ca/economic report/ [serial online].
16. Canadian Diabetes Association. The prevalence and costs of diabetes. Hamilton, ON: Author; 2013. Available at: http://www diabetes ca/diabetes-and-you/what/prevalence/ [serial online].
17. Public Health Agency of Canada. Diabetes in Canada: Facts and figures from a public health perspective. Ottawa: Author; 2011. Available at: http://www phac-aspc gc ca/cd-mc/publications/ diabetes-diabete/facts-figures-faits-chiffres-2011/ [serial online].
18. Whitlock G, Lewington S, Sherliker P et al. Body-mass index and cause-specific mortality in 900 000 adults: collaborative analyses of 57 prospective studies. Lancet 2009;373:1083-96.
19. Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 2004;27:1047-53.