Effects of metformin on middle cerebral artery flow velocity in newly diagnosed type 2 Diabetic patients

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Hassoun K. Hayder¹, Ghazal R. Mohammed², Mudhafar MH. Ahmed³, Hadi R. Najah³*mail of corresponding author

 

 

Abstract

Type 2 diabetes mellitus is a major cause of cerebrovascular disease. Risk of ischemic stroke is higher in diabetic patients and it is about 2-6 times that in normal population. Atherosclerotic lesions happen early in the disease and patients with type 2 diabetes mellitus. Transcranial Doppler can be used for examination of cerebral arteries and it can detect early atherosclerotic changes. Metformin an old oral anti-diabetic drug but still cornerstone in the treatment guidelines of type 2 diabetes mellitus. It improves endothelial function with preferable cardiovascular effects. Twenty patients were recruited for the study. Transcranial Doppler examination done for all patients before initiation of treatment. Patients received metformin for twelve weeks and they were re-examined with transcranial Doppler. The data of present study showed that a highly significant increase in diastolic velocity and mean flow velocity after treatment with significant reduction in pulsatility index and resistive index. In conclusion, metformin treatment increases cerebral diastolic flow velocity with reduction in vascular resistance in patients with type 2 diabetes.

Keywords: Metformin; Transcranial Doppler; Middle cerebral artery (MCA); Type 2 diabetes mellitus

Copyright © 2016 by The American Society for BioMedicine and BM-Publisher, Inc.

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References

  1. Mozaffarian D, Benjamin J, Go S, et al. Heart disease and stroke statistics-2016 update: a report from the American heart association. Circulation 2015;132:4.
  2. Tran J, Mirzaei M, Anderson L, et al. The epidemiology of stroke in the Middle East and North Africa. Journal of the neurological sciences 2010;295:1-2.
  3. Al-Shimmery K, Amein H, Al-Tawil G. Prevalence of silent stroke in Kurdistan, Iraq. Neurosciences (Riyadh) 2010;15:167-71.
  4. Robert A, Zamzami M. Stroke in Saudi Arabia: a review of the recent literature. Pan African Medical Journal 2014;17:14.
  5. Martín I, Sevillano C, Segura A, et al. Type 2 diabetes and cardiovascular disease: Have all risk factors the same strength? World Journal of Diabetes 2014;5:444-470.
  6. McFarlane I, SicaA, Sowers R. stroke in patients with diabetes and hypertension. The journal of clinical hypertension 2005;7:286-294.
  7. Zhou H, Zhang X, Lu J. Progress on diabetic cerebrovascular diseases. Bosnian Journal of Basic Medical Sciences 2014; 14:185-190.
  8. Widder B. Cerebral vasoreactivity. In: Michael G. H. and Stephen P. M., editor. Cerebrovascular ultrasound. 1st ed. Cambridge: Cambridge University Press; 2001. Pp 324-333.
  9. Kassab Y, Majid A, Farooq U, et al. Transcranial Doppler: An Introduction for Primary Care Physicians. J Am Board Fam Med 2007;20:65-71.
  10. Sloan A, AlexandrovV, Tegeler H, et al. Assessment: Transcranial Doppler ultrasonography: Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 2004;62:1468-81.
  11. Guyton C, Hall E. Cerebral Blood Flow, Cerebrospinal fluid, and brain metabolism. In: Arthur C. Guyton and John E. Hall, editors. Textbook of medical physiology; 11th edition: Philadelphia: Elsevier Inc.;2006. pp761-764.
  12. McHedlishvili G. Physiological mechanisms controlling cerebral blood flow. Stroke1980;11:240-48.
  13. Mitchell F, Van Buchem A, Sigurdsson S, et al. Arterial stiffness, pressure and flow pulsatility and brain structure and function: the Age, Gene/Environment Susceptibility Reykjavik Study. Brain 2011;134:3398-3407.
  14. Kidwell S, El-Saden S, Livshits Z, et al. Transcranial Doppler pulsatility indices as a measure of diffuse small vessel disease. J Neuroimaging 2001;11:229-235.
  15. Wijnhoud D, Koudstaal J, Dippel W. The prognostic value of pulsatility index, flow velocity, and their ratio, measured with TCD ultrasound, in patients with a recent TIA or ischemic stroke. Acta NeurolScand 2011;124:238-44.
  16. Bai H, Chen R, Chiu C, et al. Lower blood flow velocity, higher resistance index, and larger diameter of extracranial carotid arteries are associated with ischemic stroke independently of carotid atherosclerosis and cardiovascular risk factors. J Clin Ultrasound 2007;35:322-30.
  17. Abrahamson J, Barzilay I, Blonde L, et al. AACE/ACE comprehensive type 2 diabetes management algorithm 2016. EndocrPract 2016;22:84-113.
  18. Strack T. Metformin: a review. Drugs Today (Barc) 2008;44:303-14.
  19. Fontbonne A, Charles A, Juhan-Vague I, et al. The effect of Metformin on the metabolic abnormalities associated with upper body fat distribution. Results of the BIGPRO 1 trial. Diabetes Care 1996;19: 920-6.
  20. Dong Y, Zhang M, Wang S, et al. Activation of AMP-Activated Protein Kinase Inhibits Oxidized LDL-Triggered Endoplasmic Reticulum Stress In Vivo. Diabetes 2010;59:1386-396.
  21. Davis J, Xie Z, Viollet B, et al. Activation of the amp-activated kinase by antidiabetes drug metformin stimulates nitric oxide synthesis in vivo by promoting the association of heat shock protein 90 and endothelial nitric oxide synthase. Diabetes 2006;55:496-505.
  22. Lee H, Kim G. AMPK-dependent metabolic regulation by PPAR agonists. PPAR Research 2010;2010:549101.
  23. Hwang L, Jeong T, Li X, et al. Inhibitory cross-talk between the AMPK and ERK pathways mediates endoplasmic reticulum stress-induced insulin resistance in skeletal muscle. British Journal of Pharmacology 2013;169:69-81.
  24. De la Rosa C, Vrenken E, Buist-Homan M, et al. Metformin protects primary rat hepatocytes against oxidative stress-induced apoptosis. Pharmacology Research & Perspectives 2015;3:e00125.
  25. Viollet B, Guigas B, Sanz Garcia N, et al. Cellular and molecular mechanisms of metformin: an overview. Clinical Science (London, England: 1979) 2012;122:253-270.
  26. Kocer D, Bayram F, Diri H. The effects of metformin on endothelial dysfunction, lipid metabolism and oxidative stress in women with polycystic ovary syndrome. Gynecol Endocrinol 2014;30:367-71.
  27. Agarwal N, Rice S, Bolusani H, et al. Metformin Reduces Arterial Stiffness and Improves Endothelial Function in Young Women with Polycystic Ovary Syndrome: A Randomized, Placebo-Controlled, Crossover Trial. J ClinEndocrinolMetab 2010;95:722-30.
  28. King P, Peacock I, Donnelly R. The UK Prospective Diabetes Study (UKPDS): clinical and therapeutic implications for type 2 diabetes. British Journal of Clinical Pharmacology 1999;48:643-48.
  29. Bailey J. Metformin: effects on micro and macrovascular complications in type 2 diabetes. Cardiovasc Drugs Ther 2008;22: 215-24.
  30. Jia J, Cheng J, Ni J, et al. Neuropharma-cological actions of metformin in stroke. Current Neuropharmacology 2015;13:389-94.
  31. American Diabetes Association. Classification and Diagnosis of Diabetes. Diabetes Care 2016;39:S13-S22.
  32. Amran G, Zwain A, Hadi N, Al-Mudhaffer A. Autonomic cerebral vascular response to sildenafil in diabetic patient. Diabetology& Metabolic Syndrome 2012;4:2.
  33. Zwain A. A Study of Cerebral Vasoreactivity: Middle Cerebral Artery (MCA) Versus Ophthalmic Artery (OPA). Karbala J. Med 2009;2:604-15.
  34. Marshall M, Flyvbjerg A. Prevention and early detection of vascular complications of diabetes. BMJ: British Medical Journal 2006;333:475-80.
  35. Pryor R, Cabreiro F. Repurposing metformin: an old drug with new tricks in its binding pockets. Biochemical Journal 2015;471:307-22.
  36. Gong L, Goswami S, Giacomini M, et al. Metformin pathways: pharmacokinetics and pharmacodynamics. Pharmacogenetics and genomics 2012;22:820-27.
  37. Marchetti P, Del Guerra S, Marselli L, et al. Pancreatic islets from type 2 diabetic patients have functional defects and increased apoptosis that are ameliorated by metformin.  Journal of Clinical Endocrinology and Metabolism 2004;89:5535-41.
  38. Forouzandeh F, Salazar G, Patrushev N, et al. Metformin Beyond Diabetes: Pleiotropic Benefits of Metformin in Attenuation of Atherosclerosis. Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease 2014;3:e001202.
  39. Vitale C, Mercuro G, Cornoldi A, et al. Metformin improves endothelial function in patients with metabolic syndrome. Journal of Internal Medicine 2005;258:250-56.
  40. Tankova T. Current indications for metformin therapy. Rom J Intern Med 2003;41(3):215-25.
  41. Sloan A, Alexandrov V, Tegeler H, et al. Assessment: transcranial doppler ultrasonography: report of the therapeutics and technology assessment subcommittee of the American Academy of Neurology. Neurology 2004;62:1468-81.
  42. Lamanna C, Monami M, Marchionni N, et al. Effect of metformin on cardiovascular events and mortality: a meta-analysis of randomized clinical trials. Diabetes ObesMetab 2011;13:221-28.
  43. Cheng Y, Leu B, Chen J, et al. Metformin-inclusive therapy reduces the risk of stroke in patients with diabetes: a 4-year follow-up study. J Stroke Cerebrovasc Dis 2014; 23:e99-105.
  44. Li J, Benashski E, Venna V, et al. Effects of Metformin in Experimental Stroke. Stroke; a journal of cerebral circulation 2010;41:2645-52.
  45. Ashabi G, Khalaj L, Khodagholi F, et al. Pre-treatment with metformin activates Nrf2 antioxidant pathways and inhibits inflammatory responses through induction of AMPK after transient global cerebral ischemia. Metab. Brain Dis 2015;30:747-54.

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DOI: 10.18081/2333-5106/016-9/364-373
Cited by in Scopus
Research Article
American Journal of BioMedicine Volume 4, Issue 9, pages 364-373
Received June13, 2016; accepted August14, 2016; published September14, 2016
How to cite this article
Hayder HK, Mohammed GR, Ahmed M, Najah NR. Effects of metformin on middle cerebral artery flow velocity in newly diagnosed type 2 Diabetic patients. American Journal of BioMedicine 2016;4(9):364-373.
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