Advertisement

Diabetes and Stroke: The Role of Glucose Regulation

  • Forrest Lowe
  • Wuwei (Wayne) FengEmail author
Chapter

Abstract

The relationship between stroke and diabetes mellitus (DM) though complex is undeniable. Numerous studies have delineated a clear correlate between prediabetes, diabetes mellitus type 1, and diabetes mellitus type 2 as they relate to cerebrovascular disease with decades of research detailing the causality between hyperglycemia and stroke risk. The global prevalence of stroke continues to rise despite the advances in treatment options for cardiovascular risk factor modification such as diabetes. Diabetics represent a subset of the patients who are at two to three times higher risk for mortality from stroke than the general population [1]. The purpose of this chapter is to detail the microvascular and macrovascular mechanisms that promote cerebrovascular disease in diabetics which leads to stroke. Additionally, the importance of glucose control for both primary and secondary stroke prevention will be discussed in terms of the role of therapeutical options for attaining normoglycemia. Finally, there will be in-depth discussion of the optimization of diabetic control as it relates to other stroke risk factors such as atherosclerosis, hypertension, and atrial fibrillation.

Keywords

Macrovascular Microvascular – primary stroke prevention Secondary stroke prevention Recurrent stroke prevention 

Notes

Acknowledgment

We would like to thank Dr. Tarun Girotra for his generous inputs and comments to this book chapter. Dr. Feng would like to acknowledge grant supports from the National Institutes of Health (P20GM109040 and HD086844), from the American Heart Association (14SDG1829003), and from the South Carolina Clinical and Translational Research Institute (UL1 TR001450).

References

  1. 1.
    Lieber B, Taylor B, Appelboom G, et al. Meta-analysis of telemonitoring to improve HbA1c levels: promise for stroke survivors. J Clin Neurosci. 2015;22:807–11.CrossRefPubMedGoogle Scholar
  2. 2.
    American Diabetes Association. Classification and diagnosis of diabetes. Diabetes Care. 2015;38(Suppl. 1):S8–S16.  https://doi.org/10.2337/dc15-S005.CrossRefGoogle Scholar
  3. 3.
    Funk S, Yurdagul A Jr, Orr A. Hyperglycemia and endothelial dysfunction in atherosclerosis: lessons from type 1 diabetes. J Vasc Med. 2012;2012:Article ID 569654, 19 pages.Google Scholar
  4. 4.
    Mishiro K, Imai T, Sugitani S, et al. Diabetes mellitus aggravates hemorrhagic transformation after ischemic stroke via mitochondrial defects leading to endothelial apoptosis. PLoS One. 2014;9(8):e103818.  https://doi.org/10.1371/journal.pone.0103818, pages 13.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Kikuchi K, Tancharoen S, Ito T, et al. Potential of the Angiotensin Receptor Blockers (ARBs) telmisartan, irbesartan, and candesartan for inhibiting the HMGB1/RAGE Axis in prevention and acute treatment of stroke. Int J Mol Sci. 2013;14:18899–924.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Kim E, Tolhurst A, Cho S. Deregulation of inflammatory response in the diabetic condition is associated with increased ischemic brain injury. J Neuroinflammation. 2014;11:83, 9 pages.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Bornfeldt K, Tabas I. Insulin resistance, hyperglycemia, and atherosclerosis. Cell Metab. 2011;14(5):575–85.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Node K, Inoue T, et al. Postprandial hyperglycemia as an etiological factor in vascular failure. Cardiovasc Diabetol. 2009;8:23.  https://doi.org/10.1186/1475-2840-8-23, pages 10.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Kitada M, Zhang Z, Mima A, et al. Molecular mechanisms of diabetic vascular complications. J Diabetes Investig. 2010;1(3):77–89.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998;352:837–53.CrossRefGoogle Scholar
  11. 11.
    Romero J, Morris J, Pikula A. Stroke prevention: modifying risk factors. Ther Adv Cardiovasc Dis. 2008;2(4):287–303.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    The Heart Outcomes Prevention Evaluation Study Investigators. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med. 2000;342(3):145–53.CrossRefGoogle Scholar
  13. 13.
    Chen G-P, Zhang X-Q, Wu T, et al. Alteration of mevalonate pathway in proliferated vascular smooth muscle from diabetic mice: possible role in high-glucose-induced atherogenic process. J Diabetes Res. 2015;2015:Article ID 379287, 11 pages.Google Scholar
  14. 14.
    Prasad S, Sajja R, Naik P, et al. Diabetes mellitus and blood-brain barrier dysfunction: an overview. J Pharm. 2014;2(2):125–38.Google Scholar
  15. 15.
    Sakaguchi T, Yan SF, Yan SD, et al. Central role of RAGE-dependent neointimal expansion in arterial restenosis. J Clin Invest. 2003;111(7):959–72.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Tchistiakova E, Anderson ND, Greenwood C, et al. Combined effects of type 2 diabetes and hypertension associated with cortical thinning and impaired cerebrovascular reactivity to hypertension alone in older adults. Neuroimage Clin. 2014;5:36–41.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Ergul A, Kelly-Cobbs A, Abdalla M, et al. Cerebrovascular complications of diabetes: focus on stroke. Endocr Metab Immune Disord Drug Targets. 2012;12(2):148–58.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Zhou Z, Wang K, Penn MS, et al. Receptor for AGE (RAGE) mediates neointimal formation in response to arterial injury. Circulation. 2003;107:2238–43.CrossRefPubMedGoogle Scholar
  19. 19.
    Califf RM, Boolell M, Haffner S, et al. Prevention of diabetes and cardiovascular disease in patients with impaired glucose tolerance: rationale and design of the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial. Am Heart J. 2008;156(4):623–32.CrossRefPubMedGoogle Scholar
  20. 20.
    Low Wang CC, Reusch JEB. Diabetes and cardiovascular disease: changing the focus from glycemic control to improving the long-term survival. Am J Cardiol. 2012;110:58B–68B.CrossRefGoogle Scholar
  21. 21.
    Mi D, Jia Q, Zheng H, et al. Metabolic syndrome and stroke recurrence in Chinese ischemic stroke patients – the ACROSS-China study. PLoS One. 2012;7(12):e51406.  https://doi.org/10.1371/journal.pone.0051406, pages 5.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Capes S, Hunt D, Malmberg K, et al. Stress hyperglycemia and prognosis of stroke in nondiabetic and diabetic patients. Stroke. 2001;32:2426–32.CrossRefPubMedGoogle Scholar
  23. 23.
    Scheen AJ. Pharmacokinetics of dipeptidylpeptidase-4 inhibitors. Diabetes Obes Metab. 2010;12(8):648–58.CrossRefPubMedGoogle Scholar
  24. 24.
    White AT, Murphy AN. Administration of thiazolidinediones for neuroprotection in ischemic stroke; a preclinical systematic review. J Neurochem. 2010;115(4):845–53.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Hoogwerf B, Lincoff A, Rodriquez A, et al. Major adverse cardiovascular events with basal insulin peglispro versus comparator insulins in patients with type 1 or type 2 diabetes: a meta-analysis. Cardiovasc Diabetol. 2016;15:78.  https://doi.org/10.1186/s12933-016-0393-6.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Al-Rubeaan K, Fawaz A-H, Amira MY, et al. Ischemic stroke and its risk factors in a registry-based large cross-sectional diabetic cohort in a country facing a diabetes epidemic. J Diabetes Res. 2016;2016:Article ID 4132589, 9 pages.CrossRefGoogle Scholar
  27. 27.
    Azimova K, San Juan Z, Debabrata M. Cardiovascular safety profile of currently available diabetic drugs. Ochsner J. 2014;14:616–32.PubMedPubMedCentralGoogle Scholar
  28. 28.
    Jeerakathil T, Johnson J, Simpson S, et al. Short-term risk for stroke is doubled in persons with newly treated type 2 diabetes compared with persons without diabetes. Stroke. 2007;38:1739–43.CrossRefPubMedGoogle Scholar
  29. 29.
    Gejl M, Starup-Linde J, Scheel-Thomsen J, et al. Risk of cardiovascular disease: the effects of diabetes and anti-diabetic drugs – a nested case – control study. Int J Cardiol. 2015;178:292–6.CrossRefPubMedGoogle Scholar
  30. 30.
    Cheng Y-Y, Leu H-B, Chen T-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(2):99–105.CrossRefGoogle Scholar
  31. 31.
    Navigator Study Group. Effect of nateglinide on the incidence of diabetes and cardiovascular events. N Engl J Med. 2010;362:1463–90.CrossRefGoogle Scholar
  32. 32.
    Fisman EZ, Tenenbaum A. Antidiabetic treatment with gliptins: focus on cardiovascular effects and outcomes. Cardiovasc Diabetol. 2015;14:129.  https://doi.org/10.1186/s12933-015-0294-0.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Enders D, Kollhorst B, Engel S, et al. Comparative risk for cardiovascular diseases of dipeptidyl peptidase-4 inhibitors vs. sulfonylureas in combination with metformin: results of a two-phase study. J Diabetes Complicat. 2016;  https://doi.org/10.1016/j.jdiacomp.2016.05.015.
  34. 34.
    Mearns ES, Sobieraj DM, White CM, et al. Comparative efficacy and safety of antidiabetic drug regimens added to metformin monotherapy in patients with type 2 diabetes: a network meta-analysis. PLoS One. 2015;10(4):28.  https://doi.org/10.1371/journal.pone.0125879.CrossRefGoogle Scholar
  35. 35.
    Ganda O. The role of bile acid sequestrants in the management of type 2 diabetes mellitus. Metab Syndr Relat Disord. 2010;8(1):S15–21.CrossRefPubMedGoogle Scholar
  36. 36.
    Porez G, Prawitt J, Gross B, et al. Bile acid receptors as targets for the treatment of dyslipidemia and cardiovascular disease. J Lipid Res. 2012;53:1723–37.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Pan Y, Wang Y, Li H, et al. Association of diabetes and prognosis of minor stroke and its subtypes: a prospective observational study. PLoS One. 2016;11(4):e0153178.  https://doi.org/10.1371/journal.pone.0153178, pages 12.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Kernan W, Ovbiagele B, Black H, et al. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack. Stroke. 2014;45:2160–236.  https://doi.org/10.1161/STR.0000000000000024.CrossRefPubMedGoogle Scholar
  39. 39.
    Meschia JF, Bushnell C, Boden-Albala B, et al. Guidelines for the primary prevention of stroke. Stroke. 2014;45:3754–832.  https://doi.org/10.1161/STR.0000000000000046.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Vazquez-Benitez G, Desai J, Xu S, et al. Preventable major cardiovascular events associated with uncontrolled glucose, blood pressure, and lipids and active smoking in adults with diabetes with and without cardiovascular disease: a contemporary analysis. Diabetes Care. 2015;38:905–12.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Ridker PM. The Jupiter trial. Circ Cardiovasc Qual Outcomes. 2009;2:279–85.CrossRefPubMedGoogle Scholar
  42. 42.
    O’Keefe JH, Carter MD, Lavie CJ. Primary and secondary prevention of cardiovascular diseases: a practical evidence-based approach. Mayo Clin Proc. 2009;84(8):741–57.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Chang S, Wu L-S, Chiou M-J, et al. Association of metformin with lower atrial fibrillation risk among patients with type 2 diabetes mellitus: a population-based dynamic cohort and in vitro studies. Cardiovasc Diabetol. 2014;13:123.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Dublin S, Glazer N, Smith N, et al. Diabetes mellitus, glycemic control, and risk of atrial fibrillation. J Gen Intern Med. 2010;25(8):853–8.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    De Sensi F, De Potter T, Cresti A, et al. Atrial fibrillation in patients with diabetes: molecular mechanisms and therapeutic perspectives. Cardiovasc Diagn Ther. 2015;5(5):364–73.PubMedPubMedCentralGoogle Scholar
  46. 46.
    Lin Y, Li H, Lan X, et al. Mechanism of and therapeutic strategy for atrial fibrillation associated with diabetes mellitus. Sci World J. 2013;2013:Article ID 209428, 6 pages.Google Scholar
  47. 47.
    Asghar O, Alam U, Hayat SA, et al. Obesity, diabetes and atrial fibrillation; epidemiology, mechanisms and interventions. Curr Cardiol Rev. 2012;8:253–64.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Pan A, Wang Y, Talaei M, et al. Relation of smoking with total mortality and cardiovascular events among patients with diabetes mellitus. Circulation. 2015;132:1795–804.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Olofindayo J, Peng H, Liu Y, et al. The interactive effect of diabetes and central obesity on stroke: a prospective cohort study of inner Mongolians. BMC Neurol. 2015;15:65.  https://doi.org/10.1186/s12883-015-0328-y, pages 7.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Shim U, Lee H, Oh J, et al. Sleep disorder and cardiovascular risk factors among patients with type 2 diabetes mellitus. Korean J Intern Med. 2011;26:277–84.CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Kent B, McNicholas W, Ryan S. Insulin resistance, glucose intolerance and diabetes mellitus in obstructive sleep apnoea. J Thorac Dis. 2015;7(8):1343–57.PubMedPubMedCentralGoogle Scholar
  52. 52.
    McEvoy R, Antic N, Heeley E, et al. CPAP for prevention of cardiovascular events in obstructive sleep apnea. N Engl J Med. 2016;375:919–31.CrossRefPubMedGoogle Scholar
  53. 53.
    McDonnell MN, Hillier SL, Hooker SP, et al. Physical activity frequency and risk of incident stroke in a national US study of blacks and whites. Stroke. 2013;44(9):2519–24.  https://doi.org/10.1161/STROKEAHA.113.001538, pages 12.CrossRefPubMedGoogle Scholar
  54. 54.
    Wu S, Shi Y, Wang C, et al. Glycated hemoglobin independently predicts stroke recurrence within one year after acute first-ever non-cardioembolic strokes onset in a Chinese cohort study. PLoS One. 2013;8(11):e80690.  https://doi.org/10.1371/journal.pone.0080690, pages 12.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Ray K, Seshasai S, Wijesuriya S, et al. Effect of intensive control of glucose on cardiovascular outcomes and death in patients with diabetes mellitus: a meta-analysis of randomised controlled trials. Lancet. 2009;373(9677):1765–72.CrossRefPubMedGoogle Scholar
  56. 56.
    Palacio S, McClure L, Benavente O, et al. Lacunar strokes in patients with diabetes: risk factors, infarct locations, and prognosis: the SPS3 study. Stroke. 2014;45(9):2689–94.CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Putaala J, Haapaniemi E, Metso A, et al. Recurrent ischemic events in young adults after first-ever ischemic stroke. Ann Neurol. 2010;68:661–71.CrossRefPubMedGoogle Scholar
  58. 58.
    Bohn B, Schofl C, Zimmer V, et al. Achievement of treatment goals for secondary prevention of myocardial infarction or stroke in 29,325 patients with type 2 diabetes: a German/Austrian DPV-multicenter analysis. Cardiovasc Diabetol. 2016;15(1):72.  https://doi.org/10.1186/s12933-016-0391-8.CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Jauch E, Saver J, Adams H, et al. Guidance for the early management of patients with acute ischemic stroke. Stroke. 2013;44:870–947.CrossRefPubMedGoogle Scholar
  60. 60.
    Tanaka R, Yamashiro K, Okuma Y, et al. Effects of pioglitazone for secondary stroke prevention in patients with impaired glucose tolerance and newly diagnosed diabetes: the J-SPIRIT study. J Atheroscler Thromb. 2015;22:1305–16.CrossRefPubMedGoogle Scholar
  61. 61.
    Gamboa J, Blankenship D, Niemi J, et al. Extension of the neuroprotective time window for thiazolidinediones in ischemic stroke is dependent on time of reperfusion. Neuroscience. 2010;170(3):846–57.CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Kernan W, Viscoli CM, Furie KL, et al. Pioglitazone after ischemic stroke of transient ischemic attack. N Engl J Med. 2016;372(14):1321–31.CrossRefGoogle Scholar
  63. 63.
    Viscoli C, Brass L, Carolei A, et al. Pioglitazone for secondary prevention after ischemic stroke and transient ischemic attack: rationale and design of the Insulin Resistance Intervention after Stroke (IRIS) trial. Am Heart J. 2014;168(6):823–9.CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Osei E, Fonville S, Zandbergen AAM, et al. Metformin and sitagliptin in patients with impaired glucose tolerance and a recent TIA or minor ischemic stroke (MAAS): study protocol for a randomized controlled trial. BioMed Central. 2015;16:332.  https://doi.org/10.1186/s13063-015-0882-z, pages 6.CrossRefGoogle Scholar
  65. 65.
    Kunte H, Schmidt S, Eliasziw M, et al. Sulfonylureas improve outcome in patients with type 2 diabetes and acute ischemic stroke. Stroke. 2007;38(9):2526–30.CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Abdelsaid M, Prakash R, Weiguo L, et al. Metformin treatment in the period after stroke prevents nitrative stress and restores angiogenic signaling in the brain in diabetes. Diabetes. 2015;64:1804–17.CrossRefPubMedGoogle Scholar
  67. 67.
    Hirst A, Farmer J, Feakins B, et al. Quantifying the effects of diabetics and β-adrenoceptor blockers on glycaemic control in diabetes mellitus- a systemic review and meta-analysis. Br J Clin Pharmacol. 2014;79(5):733–43.CrossRefGoogle Scholar
  68. 68.
    Fleg J, Forman D, Berra K, et al. Secondary prevention of atherosclerotic cardiovascular disease in older adults: a scientific statement from the American Heart Association. Circulation. 2013;128(22):2422–46.CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Macedo AF, Taylor FC, Casas JP, et al. Unintended effects of statins from observational studies in the general population: systemic review and meta-analysis. BMC Med. 2014;12:51, pages 13.CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Zhang Y, Hu C, Hong J, et al. Lipid profiling reveals different therapeutic effects of metformin and glipizide in patients with type 2 diabetes and coronary artery disease. Diabetes Care. 2014;37:2804–12.CrossRefPubMedGoogle Scholar
  71. 71.
    Cefulu W, et al. American Diabetes Association: standards of medical care in diabetes – 2015 l. J Clin Appl Res Educ Diabetes Care. 2015;38(1):S1–S93.Google Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of NeurologyUniversity of South CarolinaColumbiaUSA
  2. 2.Department of NeurologyDuke University School of MedicineDurhamUSA

Personalised recommendations