Adverse prognostic influence of diabetes mellitus and hyperglycemia on the clinical course of brain infarct: a review of its causes with special reference to the pathogenesis of hyperglycemia in the acute phase of stroke

André, Charles; Novis, Sérgio Augusto Pereira

doi:10.1590/S0004-282X1992000200003

Abstracts

In non-diabetic patients, the appearance of hyperglycemia in the acute phase of stroke is related to the extension of cellular injury, and hence to the physiologic stress response. In animal models of ischemic insult, the deleterious effects of hyperglycemia depend heavily on the production of lactic acid «via» activation of the glycolitic anaerobic pathway. The abnormal production of lactic acid and consequent tissular acidosis appear mainly in the early post-reperfusion period, or in states of marked but partial reduction of blood flow. A direct reduction of cerebral blood flow and, perhaps, the production of a hyperosmolar state may contribute to worsening of the ischemic injury. In diabetic patients, previous hemoreologic and microcirculatory changes, and a greater susceptibility to infections may additionally reduce the chances of complete recovery after stroke.

brain infarction; brain edema; hyperglycemia; diabetes mellitus

A gênese da hiperglicemia surgida na fase aguda do AVE em pacientes não diabéticos correlaciona-se basicamente ao grau de injúria celular e, portanto, à gravidade da reação fisiológica de «stress». Experimentalmente, o efeito deletério da hiperglicemia após a lesão isquêmica parece depender, em primeiro lugar, do acúmulo intracelular de ácido lático, gerado pela via glicolítica anaeróbica. Este acúmulo anormal de ácido lático, e consequente acidose tissular, parece ocorrer especialmente na fase inicial de reperfusão, ou na presença de fluxo sanguíneo residual - isquemia parcial. Fatores adicionais invocados para explicar o agravamento do insulto isquêmico pela hiperglicemia são a redução do fluxo sanguíneo cerebral e, talvez, a produção de um estado hiperosmolar. Em pacientes diabéticos alterações hemorreológicas e microcirculatórias específicas, bem como maior susceptibilidade às complicações infecciosas, vêm somar-se, para tornar também comum uma evolução clínica desfavorável.

infarto cerebral; acidente vascular encefálico; hiperglicemia; diabetes mellitus

Influência prognóstica adversa do diabetes mellitus e da higergliœmia sobre a evolução do infarto cerebral uma revisão de suas causas com menção aos mecanismos de gênese da hiperglicemia na fase aguda do acidente vascular encefálico

Adverse prognostic influence of diabetes mellitus and hyperglycemia on the clinical course of brain infarct: a review of its causes with special reference to the pathogenesis of hyperglycemia in the acute phase of stroke

Charles André^I; Sérgio Augusto Pereira Novis^II

^IMédico Neurologista, Serviço de Neurologia, HUCFF-UFRJ. Trabalho realizado no Serviço de Neurologia do Hospital Universitário Clementino Fraga Filho da Universidade Federal do Rio de Janeiro (HUCFF-UFRJ)

^IIProfessor Titular de Neurologia, Chefe do Serviço de Neurologia, HUCFF-UFRJ. Trabalho realizado no Serviço de Neurologia do Hospital Universitário Clementino Fraga Filho da Universidade Federal do Rio de Janeiro (HUCFF-UFRJ)

RESUMO

A gênese da hiperglicemia surgida na fase aguda do AVE em pacientes não diabéticos correlaciona-se basicamente ao grau de injúria celular e, portanto, à gravidade da reação fisiológica de «stress». Experimentalmente, o efeito deletério da hiperglicemia após a lesão isquêmica parece depender, em primeiro lugar, do acúmulo intracelular de ácido lático, gerado pela via glicolítica anaeróbica. Este acúmulo anormal de ácido lático, e consequente acidose tissular, parece ocorrer especialmente na fase inicial de reperfusão, ou na presença de fluxo sanguíneo residual isquemia parcial. Fatores adicionais invocados para explicar o agravamento do insulto isquêmico pela hiperglicemia são a redução do fluxo sanguíneo cerebral e, talvez, a produção de um estado hiperosmolar. Em pacientes diabéticos alterações hemorreológicas e microcirculatórias específicas, bem como maior susceptibilidade às complicações infecciosas, vêm somar-se, para tornar também comum uma evolução clínica desfavorável.

Palavras-chave: infarto cerebral, acidente vascular encefálico, hiperglicemia, diabetes mellitus.

SUMMARY

In non-diabetic patients, the appearance of hyperglycemia in the acute phase of stroke is related to the extension of cellular injury, and hence to the physiologic stress response. In animal models of ischemic insult, the deleterious effects of hyperglycemia depend heavily on the production of lactic acid «via» activation of the glycolitic anaerobic pathway. The abnormal production of lactic acid and consequent tissular acidosis appear mainly in the early post-reperfusion period, or in states of marked but partial reduction of blood flow. A direct reduction of cerebral blood flow and, perhaps, the production of a hyperosmolar state may contribute to worsening of the ischemic injury. In diabetic patients, previous hemoreologic and microcirculatory changes, and a greater susceptibility to infections may additionally reduce the chances of complete recovery after stroke.

Key words: brain infarction, brain edema, hyperglycemia, diabetes mellitus.

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Full text available only in PDF format.

Dr, Sérgio A. Pereira Novis Rua Visconde de Pirajá 330, sala 513 - 22410 Rio de Janeiro RJ - Brasil.

1. Alex M, Baron EK, Goldenberg S et al. An autopsy study of cerebrovascular accident in diabetes mellitus. Circulation 1962, 25:663-673.
2. André C, Novis SAP. Influência prognóstica adversa do diabetes mellitus e da hiperglicemia sobre a evolução do infarto cerebral. Arq Neuro-Psiquiat (Sao Paulo) 1992, 50:147-150.
3. Barnes AJ, Locke P, Seudder PR et al. Is hyperviscosity a treatable component of diabetic microvascular disease? Lancet 1977, 2:789-791.
4. Bell BA, Symon L, Branston NM. CBF and time tresholds for the formation of ischemic cerebral edema and effect of reperfusion in baboons. J Neurosurg 1985, 62:31-41.
5. Berger L, Hakim AM. The association of hyperglycemia with cerebral edema in stroke. Stroke 1986, 17:865-871.
6. Campbell JA. Increase in resistance to oxigen privation in animals on certain diets. Q J Exp Physiol 1938, 28:231-241.
7. Candelise L, Landi G, Orazio EN, Boccardi E. Prognostic significance of hyperglycemia in acute stroke. Arch Neurol 1985, 42:661-663.
8. Caronna JJ, Levy DE. Clinical predictors of outcome in ischemic stroke. Neurol Clinics 1983, 1:103-117.
9. Chopp M, Frinak S, Walton DR, Smith MB, Welch KMA. Intracellular acidosis during and after cerebral ischemia: in vivo nuclear magnetic resonance study of hyperglycemia in cats. Stroke 1987, 18:919-923.
10. Daalsgaard-Nielsen T. Some clinical experience in the treatment of cerebral apoplexy (1000 cases). Acta Psychiat Scand 1956, Suppl, 108:101.
11. Duckrow RB, Beard DC, Brennan RW. Regional cerebral blood flow decreases during hyperglycemia. Ann Neurol 1985, 17:267-272.
12. Feibel JH, Hardy PM, Campbell RG et al. Prognostic value of the stress response following stroke. JAMA 1977, 238:1374-1376.
13. Ginsberg MD, Welsh FA, Budd WW. Deleterious effect of glucose, pretreatment on recovery from diffuse cerebral ischemia in the cat: I. Local cerebral blood flow and glucose utilization. Stroke 1980, 11:347-354.
14. Hansen AJ. The extracellular potassium concentration in brain cortex following ischemia in hipo- and hyperglycemic rats. Acta Physiol Scand 1978, 102:324-329.
15. Howse DC, Caronna JJ, Duffy TE et al. Cerebral energy metabolism, pH and blood flow during seizures in the cat. Am J Physiol 1974, 227:1444-1451.
16. Kassel NF, Bauman KW, Hitchon PW et ai. The effect of nigh dose mannitol on cerebral blood flow in dogs with normal intracranial pressure. Stroke 1982, 13:59-61.
17. Kraig RP, Pulsinelli WA, Plum F. Hydrogen ion buffering during complete brain ischemia. Brain Res 1985, 342:281-290.
18. La Manna JC, Harik SI. Regional brain glucose extraction and CBF at various arterial glucose concentrations. J Cereb Blood Flow Metab 1983, 3(Suppl 1) :S409-S410.
19. Lassen NA. The luxury-perfusion syndrome and its possible relation to acute metabolic acidosis localized within the brain. Lancet 1966, 2:1113-1115.
20. McMillan DE, Utterbock NE, La Puma J. Reduced erythrocyte deformability in diabetes. Diabetes 1978, 27:895-901.
21. Melamed E. Reactive hyperglycemia in patients with acute stroke. J Neurol Sci 1976, 29:267-275.
22. Michenfelder JD, Mild JH. Influence of anesthetics on metabolic, functional and pathological responses to regional cerebral ischemia. Stroke 1975, 6:405.
23. Moncada S, Wane JR. Arachidonic acid metabolites and the interaction between platelets and blood-vessel walls. N Engl Med 1979, 300:1142-1147.
24. Myers RE, Yamagushi S. Nervous system effects of cardiac arrest in monkeys. Arch Neurol 1977, 34:65-74.
25. Nordström CH, Rehncrona S, Siesjö BK. Effects of phenobarbital in cerebral ischemia: II. Restitution of cerebral energy state, as well as of glycolytic metabolites, citric acid cycle intermediates. Stroke 1978, 9:335-343.
26. Nordström CH, Siesjô BK. Effects of phenobarbital in cerebral ischemia: I. Cerebral energy metabolism during pronounced ischemia. Stroke 1978, 9:335-343.
27. Pulsinelli WAA, Levy DE, Sigsbee B et al. Increased damage after ischemic stroke in patients with hyperglycemia with or without established diabetes mellitus. Am J Med 1983, 74:540-544.
28. Pulsinelli WA, Waldman S, Rawlinson D, Plum F. Moderate hyperglycemia augments ischemic brain damage: a neuropathological study in the rat. Neurology 1982, 32:1239-1246.
29. Pulsinelli WA, Waldman S, Sigsbee B, Rawlinson D, Scherer P, Plum F. Experimental hyperglycemia and diabetes mellitus worsen stroke outcome. Trans Am Neurol Assoc 1980, 105:21-24.
30. Robertson HD, Polk HCJ. The mechanism of infection in patients with diabetes mellitus: a review of leucocyte malfunction. Surgery 1974, 75:123.
31. Schvier FJ, Hossman KA. Experimental brain infarcts in cats: II. Ischemic brain edema. Stroke 1980, 11:593-601.
32. Siemkowicz E, Gjedde A. Postischemic coma in rat: effect of different pre-ischemic blood gilucose levels on cerebral metabolic recovery after ischemia. Acta Physiol Scand 1980, 110:225-232.
33. Siemkowicz E, Hansen AJ. Clinical restitution following cerebral ischemia in hypo, normo hyperglycemic rats. Acta Neurol Scand 1978, 58:1-8.
34. Siesjô BK. Cell damage in the brain: a speculative synthesis. J Cereb Blood Flow Metab 1981, 1:156-185.
35. Welsh FA, Ginsberg MD, Rieder W, Budd WW. Deleterious effect of glucose pretreat-ment on recovery from diffuse cerebral ischemia in the cat: II. Regional metabolite levels. Stroke 1980, 11:355-363.
36. Welsh FA, O'Connor MJ, Marcy VR, Spatacco AJ, Johns RL. Factors limiting regeneration of ATP following temporary ischemia in cat brain. Stroke 1982, 13:234-242.
37. Welsh FA, Sims RE, McKee AE. Effect of glucose on recovery of energy metabolism following hipoxia-glicemia in mouse brain: dose-dependence and carbohydrate specificity. J Cereb Blood Flow Metab 1983, 3:486-492.
38. Woo E, Chan YW, Yu YL, Huang CY. Admission glucose levels in relation to mortality and morbidity outcome in 252 patients. Stroke 1983, 19:185-191.

Publication Dates

Publication in this collection
22 Feb 2011
Date of issue
June 1992

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. Alex M, Baron EK, Goldenberg S et al. An autopsy study of cerebrovascular accident in diabetes mellitus. Circulation 1962, 25:663-673.

[2] 2. André C, Novis SAP. Influência prognóstica adversa do diabetes mellitus e da hiperglicemia sobre a evolução do infarto cerebral. Arq Neuro-Psiquiat (Sao Paulo) 1992, 50:147-150.

[3] 3. Barnes AJ, Locke P, Seudder PR et al. Is hyperviscosity a treatable component of diabetic microvascular disease? Lancet 1977, 2:789-791.

[4] 4. Bell BA, Symon L, Branston NM. CBF and time tresholds for the formation of ischemic cerebral edema and effect of reperfusion in baboons. J Neurosurg 1985, 62:31-41.

[5] 5. Berger L, Hakim AM. The association of hyperglycemia with cerebral edema in stroke. Stroke 1986, 17:865-871.

[6] 6. Campbell JA. Increase in resistance to oxigen privation in animals on certain diets. Q J Exp Physiol 1938, 28:231-241.

[7] 7. Candelise L, Landi G, Orazio EN, Boccardi E. Prognostic significance of hyperglycemia in acute stroke. Arch Neurol 1985, 42:661-663.

[8] 8. Caronna JJ, Levy DE. Clinical predictors of outcome in ischemic stroke. Neurol Clinics 1983, 1:103-117.

[9] 9. Chopp M, Frinak S, Walton DR, Smith MB, Welch KMA. Intracellular acidosis during and after cerebral ischemia: in vivo nuclear magnetic resonance study of hyperglycemia in cats. Stroke 1987, 18:919-923.

[10] 10. Daalsgaard-Nielsen T. Some clinical experience in the treatment of cerebral apoplexy (1000 cases). Acta Psychiat Scand 1956, Suppl, 108:101.

[11] 11. Duckrow RB, Beard DC, Brennan RW. Regional cerebral blood flow decreases during hyperglycemia. Ann Neurol 1985, 17:267-272.

[12] 12. Feibel JH, Hardy PM, Campbell RG et al. Prognostic value of the stress response following stroke. JAMA 1977, 238:1374-1376.

[13] 13. Ginsberg MD, Welsh FA, Budd WW. Deleterious effect of glucose, pretreatment on recovery from diffuse cerebral ischemia in the cat: I. Local cerebral blood flow and glucose utilization. Stroke 1980, 11:347-354.

[14] 14. Hansen AJ. The extracellular potassium concentration in brain cortex following ischemia in hipo- and hyperglycemic rats. Acta Physiol Scand 1978, 102:324-329.

[15] 15. Howse DC, Caronna JJ, Duffy TE et al. Cerebral energy metabolism, pH and blood flow during seizures in the cat. Am J Physiol 1974, 227:1444-1451.

[16] 16. Kassel NF, Bauman KW, Hitchon PW et ai. The effect of nigh dose mannitol on cerebral blood flow in dogs with normal intracranial pressure. Stroke 1982, 13:59-61.

[17] 17. Kraig RP, Pulsinelli WA, Plum F. Hydrogen ion buffering during complete brain ischemia. Brain Res 1985, 342:281-290.

[18] 18. La Manna JC, Harik SI. Regional brain glucose extraction and CBF at various arterial glucose concentrations. J Cereb Blood Flow Metab 1983, 3(Suppl 1) :S409-S410.

[19] 19. Lassen NA. The luxury-perfusion syndrome and its possible relation to acute metabolic acidosis localized within the brain. Lancet 1966, 2:1113-1115.

[20] 20. McMillan DE, Utterbock NE, La Puma J. Reduced erythrocyte deformability in diabetes. Diabetes 1978, 27:895-901.

[21] 21. Melamed E. Reactive hyperglycemia in patients with acute stroke. J Neurol Sci 1976, 29:267-275.

[22] 22. Michenfelder JD, Mild JH. Influence of anesthetics on metabolic, functional and pathological responses to regional cerebral ischemia. Stroke 1975, 6:405.

[23] 23. Moncada S, Wane JR. Arachidonic acid metabolites and the interaction between platelets and blood-vessel walls. N Engl Med 1979, 300:1142-1147.

[24] 24. Myers RE, Yamagushi S. Nervous system effects of cardiac arrest in monkeys. Arch Neurol 1977, 34:65-74.

[25] 25. Nordström CH, Rehncrona S, Siesjö BK. Effects of phenobarbital in cerebral ischemia: II. Restitution of cerebral energy state, as well as of glycolytic metabolites, citric acid cycle intermediates. Stroke 1978, 9:335-343.

[26] 26. Nordström CH, Siesjô BK. Effects of phenobarbital in cerebral ischemia: I. Cerebral energy metabolism during pronounced ischemia. Stroke 1978, 9:335-343.

[27] 27. Pulsinelli WAA, Levy DE, Sigsbee B et al. Increased damage after ischemic stroke in patients with hyperglycemia with or without established diabetes mellitus. Am J Med 1983, 74:540-544.

[28] 28. Pulsinelli WA, Waldman S, Rawlinson D, Plum F. Moderate hyperglycemia augments ischemic brain damage: a neuropathological study in the rat. Neurology 1982, 32:1239-1246.

[29] 29. Pulsinelli WA, Waldman S, Sigsbee B, Rawlinson D, Scherer P, Plum F. Experimental hyperglycemia and diabetes mellitus worsen stroke outcome. Trans Am Neurol Assoc 1980, 105:21-24.

[30] 30. Robertson HD, Polk HCJ. The mechanism of infection in patients with diabetes mellitus: a review of leucocyte malfunction. Surgery 1974, 75:123.

[31] 31. Schvier FJ, Hossman KA. Experimental brain infarcts in cats: II. Ischemic brain edema. Stroke 1980, 11:593-601.

[32] 32. Siemkowicz E, Gjedde A. Postischemic coma in rat: effect of different pre-ischemic blood gilucose levels on cerebral metabolic recovery after ischemia. Acta Physiol Scand 1980, 110:225-232.

[33] 33. Siemkowicz E, Hansen AJ. Clinical restitution following cerebral ischemia in hypo, normo hyperglycemic rats. Acta Neurol Scand 1978, 58:1-8.

[34] 34. Siesjô BK. Cell damage in the brain: a speculative synthesis. J Cereb Blood Flow Metab 1981, 1:156-185.

[35] 35. Welsh FA, Ginsberg MD, Rieder W, Budd WW. Deleterious effect of glucose pretreat-ment on recovery from diffuse cerebral ischemia in the cat: II. Regional metabolite levels. Stroke 1980, 11:355-363.

[36] 36. Welsh FA, O'Connor MJ, Marcy VR, Spatacco AJ, Johns RL. Factors limiting regeneration of ATP following temporary ischemia in cat brain. Stroke 1982, 13:234-242.

[37] 37. Welsh FA, Sims RE, McKee AE. Effect of glucose on recovery of energy metabolism following hipoxia-glicemia in mouse brain: dose-dependence and carbohydrate specificity. J Cereb Blood Flow Metab 1983, 3:486-492.

[38] 38. Woo E, Chan YW, Yu YL, Huang CY. Admission glucose levels in relation to mortality and morbidity outcome in 252 patients. Stroke 1983, 19:185-191.