Glucose blood levels as a therapeutic target in acute ischaemic stroke setting

Current Topics in Medicinal Chemistry

Volumn 9, Issue 14, 2009, Pages 1261-1277

  Guyomard, Veronique ^a   Jamieson, Elena I ^b   Myint, Phyo K ^a,c,d  

^a NORFOLK AND NORWICH UNIVERSITY HOSPITAL   (United Kingdom)

^b ADDENBROOKE S HOSPITAL   (United Kingdom)

^c UNIVERSITY OF EAST ANGLIA   (United Kingdom)

^d UNIVERSITY OF CAMBRIDGE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

2,4 THIAZOLIDINEDIONE DERIVATIVE; BIGUANIDE DERIVATIVE; DIPEPTIDYL PEPTIDASE IV INHIBITOR; EXENDIN 4; GLICLAZIDE; GLIMEPIRIDE; GLIPIZIDE; GLUCAGON RECEPTOR; GLUCOSE; HUMAN INSULIN; INDAPAMIDE PLUS PERINDOPRIL; INSULIN; INSULIN ASPART; INSULIN DETEMIR; INSULIN GLARGINE; INSULIN GLULISINE; INSULIN LISPRO; MEGLITINIDE; METFORMIN; METFORMIN PLUS ROSIGLITAZONE; NATEGLINIDE; PIOGLITAZONE; REPAGLINIDE; RESVERATROL; ROSIGLITAZONE; SIRTUIN 1; SITAGLIPTIN; SODIUM GLUCOSE COTRANSPORTER 2; SULFONYLUREA; UNINDEXED DRUG;

ABDOMINAL PAIN; AGRANULOCYTOSIS; ALOPECIA; ANAPHYLAXIS; ANEMIA; ANGIONEUROTIC EDEMA; ANOREXIA; APLASTIC ANEMIA; APPETITE; ASTHENIA; BLOOD DISEASE; CEREBROVASCULAR ACCIDENT; CLINICAL PRACTICE; CLINICAL STUDY; CLINICAL TRIAL; CONSTIPATION; DEHYDRATION; DIABETES MELLITUS; DIARRHEA; DIZZINESS; DROWSINESS; DRUG DOSE INCREASE; DRUG MEGADOSE; DRUG TARGETING; DYSPNEA; EDEMA; ERYTHEMA; EVENING DOSAGE; FATIGUE; FLATULENCE; FRACTURE; GASTROESOPHAGEAL REFLUX; GASTROINTESTINAL SYMPTOM; GLUCOSE BLOOD LEVEL; HEADACHE; HEART FAILURE; HEART MUSCLE ISCHEMIA; HEMOLYTIC ANEMIA; HEPATITIS; HUMAN; HYPERGLYCEMIA; HYPERSENSITIVITY REACTION; HYPOGLYCEMIA; INJECTION SITE REACTION; INSULIN DEPENDENT DIABETES MELLITUS; LACTIC ACIDOSIS; LEUKOPENIA; LIPID BLOOD LEVEL; LIVER FAILURE; LIVER FUNCTION; LIVER TOXICITY; LOW DRUG DOSE; LUNG EDEMA; METALLIC TASTE; MORNING DOSAGE; NAUSEA; NON INSULIN DEPENDENT DIABETES MELLITUS; OBSERVATIONAL STUDY; OBSTRUCTIVE JAUNDICE; OSTEOARTHRITIS; OUTCOME ASSESSMENT; PAIN; PANCREATITIS; PANCYTOPENIA; PARESTHESIA; PATHOPHYSIOLOGY; PERIPHERAL EDEMA; PRURITUS; RASH; RETINA MACULA EDEMA; REVIEW; RHINOPHARYNGITIS; RISK FACTOR; SCHILLING TEST; SIDE EFFECT; SINGLE DRUG DOSE; STROKE; SWEATING; TASTE DISORDER; THROMBOCYTOPENIA; UPPER RESPIRATORY TRACT INFECTION; URTICARIA; VASCULAR DISEASE; VASCULITIS; VISUAL DISORDER; VOMITING; WEIGHT GAIN;

BLOOD GLUCOSE; BRAIN ISCHEMIA; DIABETES MELLITUS; HUMANS; HYPERGLYCEMIA; STROKE;

EID: 74249085911     PISSN: 15680266     EISSN: None     Source Type: Journal    
DOI: 10.2174/156802609789869600     Document Type: Review

References (112)

1. Diagnosis and initial management of acute stroke and transient ischaemic attack (TIA) National Institute for Health and Clinical Excellence. May 2008, Royal College of Physicians, London, 2008. http://www.nice.org.uk/ nicemedia/pdf/CG68FullGuideline.pdf [Accessed July 2009]
2. National Audit Office. Reducing brain damage: faster access to better stroke care (HC 452 Session 2005-2006). London: NAO, 2005.
3. US National Diabetes Statistics. 2007 available at: http://diabetes. niddk.nih.gov/DM/PUBS/statistics/) [Accessed July 2009].
4. Howard, G.; Bergman, R.; Wagenknecht, L.E.; Haffner, S.M.; Savage, P.J.; Saad, M.F.; Laws, A.; D'Agostino, R.B. Jr. Ability of alternative indices of insulin sensitivity to predict cardiovascular risk: comparison with the "minimal model". Insulin Resistance Atherosclerosis Study (IRAS) Investigators. Ann. Epidemiol. 1998, 8(6), 358-369.
5. Saydah, S.H.; Miret, M.; Sung, J.; Varas, C.; Gause, D.; Brancati, F.L. Postchallenge hyperglycemia and mortality in a national sample of US adults. Diabetes Care 2001, 24(8), 1397-1402.
6. Folsom, A.R.; Rasmussen, M.L.; Chambless, L.E.; Howard, G.; Cooper, L.S.; Schmidt, M.I.; Heiss, G. 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(7), 1077-1083
7. Kuusisto, J.; Mykkanen, L.; Pyorala, K.; Laakso, M. Non-insulin-dependent diabetes and its metabolic control are important predictors of stroke in elderly subjects. Stroke 1994, 25, 1157-1164.
8. Boden-Albala, B.; Cammack, S.; Chong, J.; Wang, C.; Wright, C.; Rundek, .T.; Elkind, M.S.; Paik, M.C.; Sacco, R.L. Diabetes, fasting glucose levels, and risk of ischemic stroke and vascular events: findings from the Northern Manhattan Study (NOMAS). Diabetes Care 2008, 31(6), 1132-1137.
9. King H.; Aubert R. E.; Herman W.H. Global burden of diabetes, 1995-2025: prevalence, numerical estimates, and projections. Diabetes Care 1998, 21, 1414-1431.
10. Sinha, R.; Fisch, G.; Teague, B.; Tamborlane, W.V.; Banyas, B.; Allen, K.; Savoye, M.; Rieger, V.; Taksali, S.; Barbetta, G.; Sherwin, R.S.; Caprio, S. Prevalence of impaired glucose tolerance among children and adolescents with marked obesity. N. Engl. J. Med. 2002, 346(11), 802-810.
11. Poppe, A.; Majumdar, S.; Jeerakathi, T.; Ghali, W.; Buchan, A.; M. Admission hyperglycaemia predict worse outcome in stroke patient treated with intravenous thrombolysis. Diabetes Care 2009, 32, 617-622.
12. Yong, M.; Kaste, M. Dynamic hyperglycaemia as a predictor of stroke outcome in the ECASS-II trial. Stroke 2008, 39, 2749-2755.
13. Bruno, A.; Levine, SR.; Frankel, M.R.; Brott, T.G.; Lin, Y.; Tilley, B.C.; Lyden, P.D.; Broderick, J.P.; Kwiatkowski, T.G.; Fineberg, S.E. NINDS rt-PA Stroke Study Group. Admission glucose level and clinical outcomes in the NINDS rt-PA Stroke Trial. Neurology 2002, 59(5), 669-674.
14. Williams, L.S.; Rotich, J.; Qi, R.; Fineberg, N.; Espay, A.; Bruno, A.; Fineberg, S.E.; Tierney, W.R. Effects of admission hyperglycemia on mortality and costs in acute ischemic stroke. Neurology 2002, 59(1), 67-71
15. Baird, T.A.; Parsons, M.W.; Phanh, T.; Butcher, K.S.; Desmond, P.M.; Tress, B.M.; Colman, P.G.; Chambers, B.R.; Davis, S.M. Persistent poststroke hyperglycemia is independently associated with infarct expansion and worse clinical outcome. Stroke 2003, 34(9), 2208-2214.
16. World health organisation. Department of Non-communicable disease surveillance. Definition, diagnosis and classification of Diabetes Mellitus, 1999. Available at: http://www.staff.ncl.ac.uk/ philip.home/who-dmc.htm [Accessed July 2009]
17. The DECODE study group on behalf of the European Diabetes Epidemiology Study Group Glucose tolerance and cardiovascular mortality. Comparison of the 2-hour and the ADA fasting diagnostic criteria. Arch. Inter. Med. 2001, 161, 397-404.
18. Expert committee on the diagnosis and classification of diabetes mellitus. Report the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 2003, 26 (suppl. 1): 5-20.
19. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2009, 32, 561-567.
20. Voll, C.L.; Auer, A.N. Insulin attenuates ischaemic brain damage independent of its hypoglycaemic effect. J. Cereb. Blood Flow Metab. 1991, 11, 1006-1014.
21. Auer, R.N. Insulin, blood glucose levels, and ischemic brain damage. Neurology 1998, 51, 39-43
22. Martin, A.; Rojas, S.; Chamorro, A.; Falcon, C.; Bargallo, N.; Planas, A.M. Why does hyperglycaemia worsen the outcome of transient focal cerebral ischaemia? Role of corticosteroids, inflammation, and protein O-glycosylation. Stroke 2006, 37, 1288-1295.
23. Capes, S.E.; Hunt, D.; Malmberg, K.; Pathak, P.; Gerstein, H.C. Stress hyperglycaemia and prognosis in nondiabetic and diabetic patients: a systematic overview. Stroke 2001, 32, 2426-2432.
24. Dungan, K.; Braithwaite, S.; Preiser, J. Stress hyperglycaemia. Lancet 2009, 373, 1799-1807.
25. Urabe, T.; Watada, H.; Okuma, Y.; Tanaka, .R.; Ueno, Y.; Miyamoto, N.; Tanaka, Y.; Hattori, N.; Kawamori, R. Prevalence of abnormal glucose metabolism and insulin resistance among subtypes of ischemic stroke in Japanese patients. Stroke 2009, 40(4), 289-295.
26. Vancheri, F.; Curcio, M.; Burgio, A.; Salvaggio, S.; Gruttadauria, G.; Lunetta, M.C.; Dovico, R.; Alletto, M. Impaired glucose metabolism in patients with acute stroke and no previous diagnosis of diabetes mellitus. QJM 2005, 98(12), 871-878.
27. Kernan, W.N.; Viscoli, C.M.; Inzucchi, S.E.; Brass, L.M.; Bravata, D.M.; Shulman, G.I.; McVeety, J.C. Prevalence of abnormal glucose tolerance following a transient ischemic attack or ischemic stroke. Arch. Intern. Med. 2005, 165(2), 227-233.
28. Centers for diabetes control and prevention. National diabetes fact sheet: general information and national estimates on diabetes in the United States, 2005. Atlanta, GA: Department of Health and Human Services, Centers for Disease Control and Prevention, 2005.
29. McCowen, K.C.; Malhorta, A.; Britrian, B.R.B. Stress induced hyperglycaemia. Crit. Care Clin. 2001, 17, 107-124.
30. O'Neill, P.A.; Davies, I.; Fullerton, K.J.; Bennett, D. Stress hormone and blood glucose response following acute stroke in the elderly. Stroke 1991, 22, 842-847.
31. Gürün, M.S.; lçöl, Y.O.; Taga, http://www. sciencedirect.com/ - aff3 Y.; Ulus, I.H. Hyperglycemia induced by intracerebroventricular choline: involvement of the sympatho-adrenal system. Eur. J. Pharmacol. 2002, 438, 197-205.
32. Van Kooten, F.; Hoogerbrugge, N.; Naarding, P.; Koudstaal, P.J. Hyperglycemia in the acute phase of stroke is not caused by stress. Stroke 1993, 24(8), 1129-1132.
33. Harada, S.; Fujita, W.; Shichi, K.; Tokuyama, S. The development of glucose intolerance after focal cerebral ischemia participates in subsequent neuronal damage. Brain Res. 2009, 1279, 174-181.
34. Cechetto, D.F. Experimental cerebral ischaemic lesions and autonomic and cardiac effects in cats and rats. Stroke 1993, 24, 16-19
35. rd ed, New Hyde Park, NY: Medical Examination Publishing Company, 1983, pp267-294.
36. Oppenheimer, S.M.; Gleb, A.; Girvin, J.P.; Hachinski, V.C. Cardiovascular effects of human insular cortex stimulation. Neurology 1992, 42, 1727-1732.
37. Allport, L.E.; Butcher, K.S.; Baird, T.A.; MacGregor, L.; Desmond, P.M.; Tress, B.M.; Colman, P.; Davis, S.M. Insular cortical ischemia is independently associated with acute stress hyperglycemia. Stroke 2004, 35(8), 1886-1891.
38. Christensen, H. Insular lesions and hyperglycaemia in acute stroke revisited. Stroke 2005, 36, 229-230.
39. Moreton, F.C.; McCormick, M.; Muir, K.W. Insular cortex hypoperfusion and acute phase blood glucose after stroke. Stroke 2007, 38, 407-410.
40. Pulsinelli, W.A.; Waldman, S.; Rawlinson, D.; Plum, F. Moderate hyperglycemia augments ischemic brain damage: a neuropathologic study in the rat. Neurology 1982, 32, 1239-4126.
41. Nedergaard, M. Transient focal ischemia in hyperglycemic rats is associated with increased cerebral infarction. Brain Res. 1987, 408, 79-85.
42. Li, P.; Siejo, B. Role of hyperglycaemia-related acidosis in ischaemic brain damage. Acta Physiol. Scand. 1997, 161, 567-580.
43. Rehnocrona, S.; Rosen, I.; Siesjo, B. Brain lactic acidosis and ischemic brain damage: biochemistry and neurophysiology. J. Cereb. Blood Flow Metabol. 1981, 3: 297-311.
44. Hattori, H.; Wasterlain, C. Post-hypoxic glucose supplement reduces hypoxic-ischaemic brain damage in the neonatal rat. Ann. Neurol. 1990, 28, 122-128.
45. Nagai, H.; Yoshioka, H.; Ohmae, T.; Tanaka, T.; Sugimoto, T. The effects of hyperglycemia on ischemic cell change and reactive neuronal change in neonatal rat brain following transient forebrain ischemia. Brain Dev. 2008 30(2), 137-145.
46. Cronberg, T.; Rytter, F.; Weiloch, T. Glucose but not lactate in combination with acidosis aggravates ischaemic neuronal death in vitro. Stroke 2004, 35, 735-737.
47. Madrigal, J.L.; García-Bueno, B.; Caso, J.R.; Pérez-Nievas, B.G.; Leza, J.C. Stress-induced oxidative changes in brain. CNS Neurol. Disord. Drug Targets 2006, 5, 561-568.
48. Siesjö, B.K.; Zhao, Q.; Pahlmark, K.; Siesjö, P.; Katsura, K.; Folbergrová, J. Glutamate, calcium, and free radicals as mediators of ischemic brain damage. Ann. Thorac. Surg. 1995, 59(5), 1316-1320.
49. Coyle, J.T.; Puttfarcken, P. Oxidative stress, glutamate, and neurodegenerative disorder. Science 1993, 262, 689-695.
50. Li, P.A.; Shuaib, A.; Miyashita, H.; He, Q.P.; Siesjö, B.K.; Warner, D.S. Hyperglycemia enhances extracellular glutamate accumulation in rats subjected to forebrain ischemia. Stroke 2000, 31(1), 183-192.
51. Dietrich, W.D.; Alonso, O.; Busto, R. Moderate hyperglycemia worsens acute blood-brain barrier injury after forebrain ischemia in rats. Stroke 1993, 24, 111-116.
52. Zhang, R.L.; Lu, C.Z.; Ren, H.M.; Xiao, B.G. Metabolic changes of arachidonic acid after cerebral ischemia-reperfusion in diabetic rats. Exp. Neurol. 2003, 184, 746-752.
53. Mohanty, P.; Hamouda, W.; Garg, R.; Aljada, A.; Ghanim, H.; Dandona, P. Glucose challenge stimulates reactive oxygen species (ROS) generation by leucocytes. J. Clin. Endocrinol. Metab. 2000, 85, 2970-2973.
54. Chan, P.H. Reactive oxygen radicals in signaling and damage in the ischemic brain. J. Cereb. Blood Flow Metab. 2001, 21, 2-14.
55. Asahi, M.; Wang, X.; Mori, T.; Sumii, T.; Jung, J.C.; Moskowitz, M.A.; Fini, M.E.; Lo, E.H. Effects of matrix metalloproteinase-9 gene knock-out on the proteolysis of blood-brain barrier and white matter components after cerebral ischemia. J. Neurosci. 2001, 21(19), 7724-7732.
56. Kamada, H.; Yu, F.; Nito, C.; Chan, P.H. Influence of hyperglycaemia on oxidative stress and matrix metalloproteinase-9 activation after focal cerebral ischaemia/reperfusion in rats. Stroke 2007, 38, 1044-1049.
57. Bayraktutan, U. Free radicals, diabetes, and endothelial dysfunction. Diabetes Obes. Metab. 2002, 4, 224-238.
58. .Bayraktutan, U.; Yang, Z.K.; Shah, A.M. Selective dysregulation of nitric oxide synthase type 3 in cardiac myocytes but not coronary microvascular endothelial cells of spontaneously hypertensive rat. Cardiovasc. Res. 1998, 38, 719-26.
59. Crack, P.J.; Taylor, J.M. Reactive oxygen species and the modulation of stroke. Free Radic. Biol. Med. 2005, 38:1433-44.
60. Allen, C.L.; Bayraktutan, U. Antioxidants attenuate hyperglycaemia- mediated brain endothelial cell dysfunction and blood-brain barrier hyperpermeability. Daibetes Obes. Metab. 2009, 11, 480-90.
61. Traystman, R.J.; Moore, L.E.; Helfaer, M.A.; Davis, S.; Banasiak, K.; Williams, M.; Hurn, P.D. Nitro-L-arginine analogues: dose-and time-related nitric oxide synthase inhibition in brain. Stroke 1995, 26, 864-869.
62. Zang, j.; Jing, L.; Ma, A.L. Hyperglycaemia increased brain injury through extracellular signal-related protein kinase. Pathology, Res. Prac. 2005, 202 31-36.
63. Dukrow, R.B.; Beard, D.C.; Brennan, R.W. Regional cerebral blood flow decreases during chronic and acute hyperglycaemia. Stroke 1987, 18, 52-58.
64. Wang, Z.; Luo, W.; Li, P.; Qiu, J.; Luo, Q. Acute hyperglycaemia compromises cerebral blood flow following cortical spreading depression in rats monitored by laser speckle imaging. J. Biomed. Optics 2008, 13, 060423.
65. McMillan, D.E.; Utterback, N.G.; LaPuma, J. Reduced erythrocyte deformability in diabetes. Diabetes 1978, 27, 895-901.
66. Duckrow, R.B. Effect of haemodilution on regional blood flow during chronic hypergycaemai in rats. Stroke 1990, 21, 1072-1076.
67. Zhang, T.; Pan, B.S.; Zhao, B.; Zhang, L.M.; Huang, Y.L.; Sun, F.Y. Exacerbation of poststroke dementia by type 2 diabetes is associated with synergistic increases of beta-secretase activation and beta-amyloid generation in rat brains. Neuroscience 2009, 161(4), 1045-1056.
68. Duelli, R.; Maurer, M.; Staudt, R.; Heiland, S.; Duembgen, L.; Kuschinsky, W. Increased cerebral glucose utilization and decreased glucose transporter Glut1 during Chronic hyperglycemia in rat brain. Brain Res. 2000, 858, 338-47.
69. Ribo, M.; Molina, C.; Montaner, J.; Rubiera, M.; Delgado-Mederos, R.; Arenillas, J.F.; Quintana, M.; Alvarez-Sabín, J. Acute hyperglycemia state is associated with lower tPA-induced recanalization rates in stroke patients. Stroke 2005, 36(8), 1705-1709.
70. Kase, C.S.; Furlan, A.J.; Wechsler, L.R.; Higashida, R.T.; Rowley, H.A; Hart, R.G.; Molinari, G.F.; Frederick, L.S.; Roberts, H.C.; Gebel, J.M.; Sila, C.A.; Schulz, G.A.; Roberts, R.S.; Gent, M. Cerebral hemorrhage after intra-arterial thrombolysis for ischemic stroke: the PROACT II trial. Neurology 2001, 57(9), 1603-1610.
71. Bruno, A.; Levine, S.R.; Frankel, M.R.; Brott, T.G.; Lin, Y.; Tilley, B.C.; Lyden, P.D.; Broderick, J.P.; Kwiatkowski, T.G.; Fineberg, S.E. NINDS rt-PA Stroke Study Group. Admission glucose level and clinical outcomes in the NINDS rt-PA Stroke Trial. Neurology 2002, 59(5), 669-674.
72. Albers, G.W.; Clark, W.M.; Madden, K.P.; Hamilton. S.A. ATLANTIS trial: results for patients treated within 3 hours of stroke onset. Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke. Stroke 2002, 33(2), 493-495.
73. Paciaroni, M.; Agnelli, G.; Caso, V.; Corea, .F.; Ageno, W.; Alberti, A.; Lanari, A.; Micheli, S.; Bertolani, L.; Venti, M.; Palmerini, F.; Billeci, A.M.; Comi, G.; Previdi, P.; Silvestrelli, G. Acute hyperglycemia and early hemorrhagic transformation in ischemic stroke. Cerebrovasc. Dis. 2009, 28(2), 119-1123.
74. Ergul, A.; Li, W.; Elgebaly, M.M.; Bruno, A.; Fagan, S.C. Hyperglycemia, diabetes and stroke: focus on the cerebrovasculature. Vascul. Pharmacol. 2009, 51, 44-49.
75. Fuentes, B.; Castillo, J.; San José, B.; Leira, R.; Serena, J.; Vivancos, J.; Dávalos, A.; Nuñez, A.G.; Egido, J.; Díez-Tejedor, E.; Stroke, Project of the Cerebrovascular Diseases Study Group, Spanish Society of Neurology. The prognostic value of capillary glucose levels in acute stroke: the GLycemia in Acute Stroke (GLIAS) study. Stroke 2009, 40(2), 562-568.
76. Kruyt, N.D.; Nys, G.M.; van der Worp, H.B.; van Zandvoort, M.J.; Kappelle, L.J.; Biessels, G.J. Hyperglycemia and cognitive outcome after ischemic stroke. J. Neurol. Sci. 2008, 270(1-2), 141-147.
77. Gilmore, R.M.; Stead, L.G. The role of hyperglycemia in acute ischemic stroke. Neurocrit. Care 2006, 5, 153-158.
78. Furie, K.; Inzucchi, S.E. Diabetes mellitus, insulin resistance, hyperglycemia, and stroke. Curr. Neurol. Neurosci. Rep. 2008, 8, 12-19.
79. Matthews, D.R.; Holman, R. UKPDS 30 year data-are there legacy effects of improved glucose and blood pressure control? Presentation at the 44th Annual Meeting of the European Association for the Study of Diabetes. Rome, Italy, September 7-11, 2008.
80. Van den Berghe, G.; Wouters, P.; Weekers, F.; Verwaest, C.; Bruyninckx, F.; Schetz, M.; Vlasselaers, D.; Ferdinande, P.; Lauwers, P.; Bouillon, R. Intensive insulin therapy in the critically ill patients. N. Engl. J. Med. 2001, 345(19), 1359-1367.
81. Gray, C. S.; Hildreth, A. J.; Sandercock, P.A.; O'Connell, J.E.; Johnston, D.E.; Cartlidge, N.E.; Bamford, J.M.; James, O.F.; Alberti, K.G. GIST Trialists Collaboration. Glucose-potassium-insulin infusions in the management of post-stroke hyperglycaemia: the UK Glucose Insulin in Stroke Trial (GIST-UK). Lancet Neurol. 2007, 6(5), 397-406.
82. Levetan, C.S. Effect of hyperglycemia on stroke outcomes. Endocr. Pract. 2004, 10, 34-39.
83. International diabetes Federation. Available On-line: www. Eatlas.idf.org [Assessed July 2009].
84. Agyemang, C.; Addo, J.; Bhopal, R.; de Graft Aikins, A.; Stronks, K. Cardiovascular disease, diabetes and established risk factors among populations of sub-Saharan African descent in Europe: a literature review. Global Health 2009, 11, 5-7.
85. The ACCORD Study Group: Effects of intensive glucose lowering in type 2 diabetes. N. Engl. J. Med. 2008, 358, 2545-2559.
86. Idris, I. Safety of very tight glucose control in type 2 diabetes in question diabetes, obesity and metabolism. Diabetes Obes. Metab. 2008, 10, 438-440.
87. Gaede, P.; Lund-Andersen, H.; Parving, H.H.; Pedersen, O. Effect of a multifactorial intervention on mortality in type 2 diabetes. N. Engl. J. Med. 2008, 358, 580-591.
88. The ADVANCE Collaborative Group: Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N. Engl. J. Med. 2008, 358, 2560-2572.
89. Goldstein, L.B.; Adams, R.; Becker, K.; Furberg, C.D.; Gorelick, P.B.; Hademenos, G.; Hill, M.; Howard, G.; Howard, V.J.; Jacobs, B.; Levine, S.R.; Mosca, L.; Sacco, R.L.; Sherman, D.G.; Wolf, P.A.; del Zoppo, G.J. Primary prevention of ischemic stroke: A statement for healthcare professionals from the Stroke Council of the American Heart Association. Stroke 2001, 32(1), 280-299.
90. UK Prospective Diabetes Study Group: Intensive blood-glucose with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998, 352, 837-853.
91. National Heart, Lung, and Blood Institute: For safety, NHLBI changes intensive blood sugar treatment strategy in clinical trial of diabetes and cardiovascular disease [press release]. Available at http://public.nhlbi.nih. gov/newsroom/home/GetPressRelease.aspx?i d=2551 [Accessed March 2009].
92. UK Prospective Diabetes Study (UKPDS) Group: Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 1998, 352, 854-865.
93. Riddle, M.; Rosenstock, J.; Gerich, J. Insulin Glargine 4002 Study Investigators: The treat-to-target trial: randomized addition of glargine or human NPH insulin to oral therapy of type 2 diabetic patients. Diabetes Care 2003, 26, 3080-3086.
94. Holman, R.R.; Thorne, K.I.; Farmer, A.J.; Davies, M.J.; Keenan, J.F.; Paul, S.; Levy, J.C. 4-T Study Group. Addition of biphasic, prandial, or basal insulin to oral therapy in type 2 diabetes. N. Engl. J. Med. 2007, 357(17), 1716-1730.
95. Myint, P.K.; Sinha, S.; Wareham, N.J.; Bingham, S.A.; Luben, R.N.; Welch, A.A.; Khaw, K.T. Glycated hemoglobin and risk of stroke in people without known diabetes in the European Prospective Investigation into Cancer (EPIC)-Norfolk prospective population study: a threshold relationship? Stroke 2007, 38(2), 271-275.
96. Mellbin, L.G.; Malmberg, K.; Norhammar, A.; Wedel, H.; Rydén, L. DIGAMI 2 Investigators. The impact of glucose lowering treatment on long-term prognosis in patients with type 2 diabetes and myocardial infarction: a report from the DIGAMI 2 trial. Eur. Heart J. 2008, 29(2), 166-176.
97. Lapcević, M.; Vuković, M.; Dimitrijević, I.; Kalezić, N.; Ristić, J. [The effect of medicamentous and non-medicamentous therapy on lowering risk factors for cardiovascular and cerebrovascular episodes in an interventional study]. Srp. Arh. Celok. Lek. 2007, 135(9-10), 554-561.
98. Kunte, H.; Schmidt, S.; Eliasziw, M.; del Zoppo, G.J.; Simard, J.M.; Masuhr, F.; Weih, M.; Dirnagl, U. Sulfonylureas improve outcome in patients with type 2 diabetes and acute ischemic stroke. Stroke 2007, 38(9) 2526-2530.
99. Mazzone, T. Prevention of macrovascular disease in patients with diabetes mellitus: opportunities for intervention. Am. J. Med. 2007, 120(Suppl 2), S26-S32.
100. Sobel, B.E. Optimizing cardiovascular outcomes in diabetes mellitus. Am. J. Med. 2007, 120(Suppl 2), S3-S11.
101. Ivey, F.M.; Ryan, A.S.; Hafer-Macko, C.E.; Goldberg, A.P.; Macko, R.F. Treadmill aerobic training improves glucose tolerance and indices of insulin sensitivity in disabled stroke survivors: a preliminary report. Stroke 2007 38(10), 2752-2758.
102. The Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Study Group: Continuous glucose monitoring and intensive treatment of type 1 diabetes. N. Engl. J. Med. 2008, 359, 1464-1476.
103. Ligaray, K.P.; Isley, W.L. Diabetes mellitus, type 2-endocrinology. Emedicine website. http://emedicine.medscape.com/ [Accessed: August 2009].
104. Votey, S.R.; Peters, A.L. Diabetes mellitus, type 2-a review-emergency medicine. Emedicine website. http://emedicine. medscape.com/ [Accessed: July 2009].
105. Lamb, W.H. Diabetes mellitus, type 1-pediatrics: general medicine. Emedicine website. http://emedicine.medscape.com/ [Accessed: August 2009].
106. British National Formulary: BNF 57. Available at www. bnf.org/bnf/bnf/56/104945.htm
107. Type 2 Diabetes. Management of type 2 diabetes. National clinical guideline for management in primary and secondary care (update). National Institute for Health and Clinical Excellence. May 2008, Royal College of Physicians, London, 2008. http://www.nice.org. uk/nicemedia/pdf/ CG66FullGuideline0509.pdf [Accessed July 2009].
108. Meriden, T. Progress with thiazolidinediones in the management of type 2 diabetes mellitus. Clin. Ther. 2004, 26, 177-190.
109. Pittas, A.G.; Seigel, R.D.; Lau, J. Insulin therapy and in-hospital mortality in critically ill patients: systematic review and meta-analysis of randomised controlled trials. J. Parenteral. Enteral. Nut. 2006, 30, 164-172.
110. Munro, N.; Feher, M.D. Current, new, and emerging therapies for managing hyperglycaemia in type 2 diabetes. Br. J. Gen. Pract. 2008, 58, 531-533.
111. Jiang, W.J. Sirtuins: novel targets for metabolic disease in drug development. Biochem. Biophys. Res. Commun. 2008, 373, 341-344.
112. Nayagam, V.M.; Wang, X.; Tan, Y.C.; Poulsen, A.; Goh, K.C.; Ng, T.; Wang, H.; Song, H.Y.; Ni, B.; Entzeroth, M.; Stünkel, W. SIRT1 modulating compounds from high-throughput screening as anti-inflammatory and insulin-sensitizing agents. J. Biomol. Screen. 2006, 11(8), 959-967.