Skip to main content

Advertisement

SpringerLink
Log in

Diabetes mellitus, insulin resistance, hyperglycemia, and stroke

  • Published:
Current Neurology and Neuroscience Reports Aims and scope Submit manuscript

Abstract

It is well established that diabetes is associated with an increased risk of stroke. Once a stroke has occurred, patients with diabetes experience poorer outcomes (functional status, mortality). Convincing data now support aggressive glucose control and comprehensive cardiovascular risk factor management to prevent stroke in patients with diabetes. However, there remains a distinct paucity of information concerning secondary stroke prevention. Hyperglycemia in the acute stroke setting is a marker for poor outcomes, but it remains unclear whether intensive in-hospital lowering of blood glucose levels improves clinical outcomes. Targeting insulin resistance as a modifiable risk factor for stroke is a novel strategy currently under investigation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. American Diabetes Association: Standards of medical care in diabetes—2007. Diabetes Care 2007, 30(Suppl 1):S4–S41.

    Article  CAS  Google Scholar 

  2. US Preventive Services Task Force: Guide to Clinical Preventive Services, edn 2. Baltimore: Williams & Wilkins; 1996.

    Google Scholar 

  3. Burchfiel CM, Curb JD, Rodriguez BL, et al.: Glucose intolerance and 22-year stroke incidence. The Honolulu Heart Program. Stroke 1994, 25:951–957.

    PubMed  CAS  Google Scholar 

  4. Kannel WB, McGee DL: Diabetes and cardiovascular risk factors: the Framingham study. Circulation 1979, 59:8–13.

    PubMed  CAS  Google Scholar 

  5. Manson JE, Colditz GA, Stampfer MJ, et al.: A prospective study of maturity-onset diabetes mellitus and risk of coronary heart disease and stroke in women. Arch Intern Med 1991, 151:1141–1147.

    Article  PubMed  CAS  Google Scholar 

  6. Mast H, Thompson JL, Lee SH, et al.: Hypertension and diabetes mellitus as determinants of multiple lacunar infarcts. Stroke 1995, 26:30–33.

    PubMed  CAS  Google Scholar 

  7. Arauz A, Murillo L, Cantu C, et al.: Prospective study of single and multiple lacunar infarcts using magnetic resonance imaging: risk factors, recurrence, and outcome in 175 consecutive cases. Stroke 2003, 34:2453–2458.

    Article  PubMed  Google Scholar 

  8. Tuomilehto J, Rastenyte D, Jousilahti P, et al.: Diabetes mellitus as a risk factor for death from stroke. Prospective study of the middle-aged Finnish population. Stroke 1996, 27:210–215.

    PubMed  CAS  Google Scholar 

  9. Laing SP, Swerdlow AJ, Carpenter LM, et al.: Mortality from cerebrovascular disease in a cohort of 23 000 patients with insulin-treated diabetes. Stroke 2003, 34:418–421.

    Article  PubMed  Google Scholar 

  10. Belfiore F, Iannello S: Insulin resistance in obesity: metabolic mechanisms and measurement methods. Mol Genet Metab 1998, 65:121–128.

    Article  PubMed  CAS  Google Scholar 

  11. Balletshofer BM, Rittig K, Enderle MD, et al.: Endothelial dysfunction is detectable in young normotensive first-degree relatives of subjects with type 2 diabetes in association with insulin resistance. Circulation 2000, 101:1780–1784.

    PubMed  CAS  Google Scholar 

  12. Steinberg HO, Chaker H, Leaming R, et al.: Obesity/insulin resistance is associated with endothelial dysfunction. Implications for the syndrome of insulin resistance. J Clin Invest 1996, 97:2601–2610.

    Article  PubMed  CAS  Google Scholar 

  13. Sakkinen PA, Wahl P, Cushman M, et al.: Clustering of procoagulation, inflammation, and fibrinolysis variables with metabolic factors in insulin resistance syndrome. Am J Epidemiol 2000, 152:897–907.

    Article  PubMed  CAS  Google Scholar 

  14. Eckel RH, Grundy SM, Zimmet PZ: The metabolic syndrome. Lancet 2005, 365:1415–1428.

    Article  PubMed  CAS  Google Scholar 

  15. Lakka HM, Lakka TA, Tuomilehto J, et al.: Hyperinsulinemia and the risk of cardiovascular death and acute coronary and cerebrovascular events in men: the Kuopio Ischaemic Heart Disease Risk Factor Study. Arch Intern Med 2000, 160:1160–1168.

    Article  PubMed  CAS  Google Scholar 

  16. Pyorala M, Miettinen H, Halonen P, et al.: Insulin resistance syndrome predicts the risk of coronary heart disease and stroke in healthy middle-aged men: the 22-year follow-up results of the Helsinki Policemen Study. Arterioscler Thromb Vasc Biol 2000, 20:538–544.

    PubMed  CAS  Google Scholar 

  17. Folsom AR, Rasmussen ML, Chambless LE, et al.: Prospective associations of fasting insulin, body fat distribution, and diabetes with risk of ischemic stroke. The Atherosclerosis Risk in Communities (ARIC) Study Investigators. Diabetes Care 1999, 22:1077–1083.

    Article  PubMed  CAS  Google Scholar 

  18. Bravata DM, Wells CK, Kernan WN, et al.: Association between impaired insulin sensitivity and stroke. Neuroepidemiology 2005, 25:69–74.

    Article  PubMed  Google Scholar 

  19. Jeppesen J, Hansen TW, Rasmussen S, et al.: Insulin resistance, the metabolic syndrome, and risk of incident cardiovascular disease: a population-based study. J Am Coll Cardiol 2007, 49:2112–2119.

    Article  PubMed  CAS  Google Scholar 

  20. Winkler K, Konrad T, Fullert S, et al.: Pioglitazone reduces atherogenic dense LDL particles in nondiabetic patients with arterial hypertension: a double-blind, placebo-controlled study. Diabetes Care 2003, 26:2588–2594.

    Article  PubMed  CAS  Google Scholar 

  21. Kotchen TA, Reddy S, Zhang HY: Increasing insulin sensitivity lowers blood pressure in the fructose-fed rat. Am J Hypertens 1997, 10:1020–1026.

    Article  PubMed  CAS  Google Scholar 

  22. Takagi T, Akasaka T, Yamamuro A, et al.: Troglitazone reduces neointimal tissue proliferation after coronary stent implantation in patients with non-insulin dependent diabetes mellitus: a serial intravascular ultrasound study. J Am Coll Cardiol 2000, 36:1529–1535.

    Article  PubMed  CAS  Google Scholar 

  23. Takagi T, Yamamuro A, Tamita K, et al.: Pioglitazone reduces neointimal tissue proliferation after coronary stent implantation in patients with type 2 diabetes mellitus: an intravascular ultrasound scanning study. Am Heart J 2003, 146:E5.

    Article  PubMed  CAS  Google Scholar 

  24. Satoh N, Ogawa Y, Usui T, et al.: Antiatherogenic effect of pioglitazone in type 2 diabetic patients irrespective of the responsiveness to its antidiabetic effect. Diabetes Care 2003, 26:2493–2499.

    Article  PubMed  CAS  Google Scholar 

  25. Arenillas JF, Moro MA, Davalos A: The metabolic syndrome and stroke: potential treatment approaches. Stroke 2007, 38:2196–2203.

    Article  PubMed  Google Scholar 

  26. Dormandy JA, Charbonnel B, Eckland DJ, et al.: Secondary prevention of macro vascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet 2005, 366:1279–1289.

    Article  PubMed  CAS  Google Scholar 

  27. Nissen SE, Wolski K: Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med 2007, 356:2457–2471.

    Article  PubMed  CAS  Google Scholar 

  28. Lincoff AM, Nicholls SJ, Nissen SE: Pioglitazone and risk of cardiovascular events in patients with type 2 diabetes mellitus: a meta-analysis of randomized trials. JAMA 2007, 298:1180–1188.

    Article  PubMed  CAS  Google Scholar 

  29. Kothari V, Stevens RJ, Adler AI, et al.: UKPDS 60: risk of stroke in type 2 diabetes estimated by the UK Prospective Diabetes Study risk engine. Stroke 2002, 33:1776–1781.

    Article  PubMed  Google Scholar 

  30. Nathan DM, Cleary PA, Backlund JY, et al.: Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med 2005, 353:2643–2653.

    Article  PubMed  Google Scholar 

  31. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998, 352:854–865.

  32. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. UK Prospective Diabetes Study Group. BMJ 1998, 317:703–713.

  33. Lonn E, Yusuf S, Dzavik V, et al.: Effects of ramipril and vitamin E on atherosclerosis: the study to evaluate carotid ultrasound changes in patients treated with ramipril and vitamin E (SECURE). Circulation 2001, 103:919–925.

    PubMed  CAS  Google Scholar 

  34. Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Heart Outcomes Prevention Evaluation Study Investigators. Lancet 2000, 355:253–259.

  35. Yusuf S, Sleight P, Pogue J, et al.: Effects of an angiotensinconverting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 2000, 342:145–153.

    Article  PubMed  CAS  Google Scholar 

  36. Dahlof B, Devereux RB, Kjeldsen SE, et al.: Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet 2002, 359:995–1003.

    Article  PubMed  CAS  Google Scholar 

  37. Patel A, MacMahon S, Chalmers J, et al.: Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial. Lancet 2007, 370:829–840.

    Article  PubMed  CAS  Google Scholar 

  38. Colhoun HM, Betteridge DJ, Durrington PN, et al.: Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebocontrolled trial. Lancet 2004, 364:685–696.

    Article  PubMed  CAS  Google Scholar 

  39. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002, 360:7–22.

  40. Gaede P, Vedel P, Larsen N, et al.: Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med 2003, 348:383–393.

    Article  PubMed  Google Scholar 

  41. Hillen T, Coshall C, Tilling K, et al.: Cause of stroke recurrence is multifactorial: patterns, risk factors, and outcomes of stroke recurrence in the South London Stroke Register. Stroke 2003, 34:1457–1463.

    Article  PubMed  Google Scholar 

  42. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults Adult. JAMA 2001, 285:2486–2497.

    Article  Google Scholar 

  43. Lindsberg PJ, Roine RO: Hyperglycemia in acute stroke. Stroke 2004, 35:363–364.

    Article  PubMed  Google Scholar 

  44. Baird TA, Parsons MW, Phanh T, et al.: Persistent poststroke hyperglycemia is independently associated with infarct expansion and worse clinical outcome. Stroke 2003, 34:2208–2214.

    Article  PubMed  CAS  Google Scholar 

  45. Capes SE, Hunt D, Malmberg K, et al.: Stress hyperglycemia and prognosis of stroke in nondiabetic and diabetic patients: a systematic overview. Stroke 2001, 32:2426–2432.

    Article  PubMed  CAS  Google Scholar 

  46. Alvarez-Sabin J, Molina CA, Montaner J, et al.: Effects of admission hyperglycemia on stroke outcome in reperfused tissue plasminogen activator-treated patients. Stroke 2003, 34:1235–1241.

    Article  PubMed  Google Scholar 

  47. Kagansky N, Levy S, Knobler H: The role of hyperglycemia in acute stroke. Arch Neurol 2001, 58:1209–1212.

    Article  PubMed  CAS  Google Scholar 

  48. Anderson RE, Tan WK, Martin HS, Meyer FB: Effects of glucose and PaO2 modulation on cortical intracellular acidosis, NADH redox state, and infarction in the ischemic penumbra. Stroke 1999, 30:160–170.

    PubMed  CAS  Google Scholar 

  49. Alvarez-Sabin J, Molina CA, Ribo M, et al.: Impact of admission hyperglycemia on stroke outcome after thrombolysis: risk stratification in relation to time to reperfusion. Stroke 2004, 35:2493–2498.

    Article  PubMed  Google Scholar 

  50. Tracey F, Stout RW: Hyperglycemia in the acute phase of stroke and stress response. Stroke 1994, 25:524–525.

    PubMed  CAS  Google Scholar 

  51. Counsell C, McDowall M, Dennis M: Hyperglycaemia after acute stroke. Other models find that hyperglycaemia is not independent predictor. BMJ 1997, 315:810; author reply 811.

    PubMed  CAS  Google Scholar 

  52. Bruno A, Biller J, Adams HP Jr, et al.: Acute blood glucose level and outcome from ischemic stroke. Trial of ORG 10172 in Acute Stroke Treatment (TOAST) Investigators. Neurology 1999, 52:280–284.

    PubMed  CAS  Google Scholar 

  53. Malmberg K, Ryden L, Efendic S, et al.: Randomized trial of insulin-glucose infusion followed by subcutaneous insulin treatment in diabetic patients with acute myocardial infarction (DIGAMI study): effects on mortality at 1 year. J Am Coll Cardiol 1995, 26:57–65.

    Article  PubMed  CAS  Google Scholar 

  54. Gray CS, Hildreth AJ, Sandercock PA, et al.: Glucosepotassium-insulin infusions in the management of post-stroke hyperglycaemia: the UK Glucose Insulin in Stroke Trial (GIST-UK). Lancet Neurol 2007, 6:397–406.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. J. Philip Kistler MGH Stroke Research Center, 175 Cambridge Street, Suite 300, Boston, MA, 02114, USA

    Karen Furie

Authors
  1. Karen Furie
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Silvio E. Inzucchi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Karen Furie.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Furie, K., Inzucchi, S.E. Diabetes mellitus, insulin resistance, hyperglycemia, and stroke. Curr Neurol Neurosci Rep 8, 12–19 (2008). https://doi.org/10.1007/s11910-008-0004-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11910-008-0004-3

Keywords

Search

Navigation