Diabetes and the risk of stroke

J Diab Comp 1993; 7:250-262 RENEW Diabetes and the Risk of Stroke Chrysanthus Chukwuma, Jaakko T u o m i l e h t o Sr. ABSTRACT Diabetes is an important risk factor for the development of ischemic cerebrovascular disease or stroke. Diabetic patients are more susceptible to atherothromboembolic brain infarction and its consequent mortality than nondiabetic patients. Cerebrovascular disease in the diabetic population somewhat follows the same pattern as in the nondiabetic population, however, with greater severity in outcome for the former. The etiopathogenetic mechanisms of strokes and transient ischemic attacks in diabetic patients are apparently due to cerebral hemodynamic and vascular derangements, hyperglycemia, and other related risk factors. There is a great disparity in the wider information on coronary heart disease and stroke than on diabetes and stroke. A better understanding is required for the determinants of stroke and diabetes, and the epidemiology and pathophysiology of specific risk factors in different racial groups. There is a similarity in the evaluation, assessment, and management of diabetic and nondiabetic patients. (Journal of Diabetes and Its Complications 7;4:250-262, 1993). Diabetes mellitus constitutes a risk factor for CHD, arterial hypertension, and ischemic cerebrovascular he nonspecific term stroke is applied to some disease or stroke. The impact of diabetes as a risk factor functional neurological perturbations of the for stroke, and the relative prognosis of the diabetic arteriovenous circulatory systems or the inpatient with stroke may have been somewhat neclusions in the central nervous system (CNS) 1 glected. Most studies of late complications in diabetes resulting in sudden onset of a focal neurologic synhave not focused on the significance of stroke as have drome, for instance, a hemiparesis. It is indicative of been extensively done for diabetic patients with CHD. the suddenness with which symptoms occur after the The presence of arterial hypertension commonly cessation of blood supply or abrupt arterial circulatory found among diabetic patients compounds the probinsufficiency to a part of the CNS leading to infarction. lem. Hyperglycemia, advanced age, and smoking The incidence of atherothromboembolic cerebral inworsen the outcome for the diabetic patient with cerefarction in diabetic individuals is definitely higher than brovascular lesions. Clinical features such as grossly may be realized. As is evident in coronary heart diselevated hematocrit values, other hematological and ease (CHD), morbidity and mortality from cerebrovasvascular derangements, as well as abnormal tomocular disease are apparently more common in diabetic graphic findings worsen the outcome in the diabetic subjects than in nondiabetic stroke patients. stroke patient more than in the nondiabetic stroke patients. A combination of stroke and diabetes has, therefore, been shown to lead to disability and death in the diaDepartment of Epidemiologyand Health Promotion, National Public Health Institute, Helsinki, Finland. betic patient .2-5They are involved with other complicaReprint requests to be sent to: Dr. ChrysanthusChukwuma,Sr., Departmentof Epidemiologyand HealthPromotion,NationalPub- tions in different racial g r o u p s . 6'7 There exists a relalic Health Institute, Elim/ienkatu25A, SF-00510Helsinki, Finland. tionship of parental history in the adult progeny8'9with INTRODUCTION T © 1993Journal of Diabetes and Its Complications 0891-6632/93/$6.O0 J Diab Comp 1993; 7:250-262 regard to myocardial infarction (MI), hypertension, diabetes, and stroke to CHD risk factors. Examination of the familial contributions to stroke risk could assist in developing interventions at an early age, w h e n preventive measures are likely to have the greatest impact. 1° Adequate information on the occurrence and determinants of stroke in diabetic patients may be of immense value in the prevention, evaluation/assessment, and management of stroke in diabetic patients. EPIDEMIOLOGY Natural History. Stroke is a global problem whose effects are adversely manifested in persons in their fifth decade of life and over. The incidence of stroke has somewhat declined in recent years, but heart disease and cancer surmount stroke as a cause of mortality and morbidity in industrialized countries. 1 A twofold excess mortality has been attributed to cerebrovascular disease in both sexes. ~ The incidence of atherothrombotic cerebral infarction for both sexes aged 45-74 years was greater by a factor of 2.5-3.5 in diabetic than in nondiabetic subjects. 12Ischemic cerebral infarction was ascribed 88% of stroke events among the diabetic cohort (13). Of these, 8% were secondary to subarachnoid or intracerebral hemorrhage, and the rest were of u n k n o w n causes. However, a negative correlation was found between diabetes, especially type I, and aneurysmal subarachnoid hemorrhage. 14 Stroke events are more commonly encountered in Asian and African Americans than in their white counterparts. Between racial groups, there is a difference in the pattern of arterial involvement. Asian and African Americans present with intracranial atherosclerotic derangements compared with extracranial cerebrovascular occlusions, especially at the carotid bifurcation, in whites. Although, blacks are more susceptible to diabetes, the contrast in racial distribution of cerebrovascular occlusive disease is likely to be due to other factors besides diabetes. ~s'~6Genetic factors, age, and dietary or other environmental factors may be important. Risk Factors. In the general population, several conditions such as arterial hypertension, diabetes, cardiovascular perturbations including congestive heart failure, MI, atrial fibrillation, hyperlipidemia, smoking, obesity, and excessive alcohol and salt intake are major risk factors for stroke. 1'17-22 Serum triglyceride concentration, classification of diabetes, and the response to diabetes treatment have been suggested as being risk factors for ischemic brain stroke. 2~ There is no significant relationship between ischemic brain stroke to diabetes duration, fasting blood glucose level, relative body mass, glycosylated hemoglobin level, and the serum high-density lipo- DIABETES AND THE RISK OF STROKE 251 protein cholesterol. 21 In another study, 22 no association was found between diabetes, glucose intolerance, and hemorrhagic stroke. In the absence of diagnosed hyperglycemic patients, diabetes conferred an amplified independent stroke risk inexplicable by clinically determined risk factors. Arterial hypertension is the most important single risk factor for stroke. Diabetic subjects are highly prone to both arterial hypertension and stroke. Hypertension causes perturbation of the heart and induces progressive constrictive narrowing of the cerebral arterioles. The successful treatment of hypertension has contributed to the decline of the incidence and mortality of stroke. Population studies have revealed a strong correlation between hypertension, dietary salt intake, and cerebral hemorrhage. 1 It is not, however, clear if diabetes confers an excess risk of stroke in the absence of raised arterial blood pressure. An investigation showed that diabetic subjects have higher systolic blood pressure than the general population, particularly females, a3 It is suggested that diabetes may enhance the risk of stroke even in the absence of increased arterial blood pressure. In nondiabetic populations, there is a 40% increase in stroke risk and a 25% increase in CHD risk with an elevation of 6 mm Hg in excess of 75 mm Hg in normal diastolic blood pressure. Diabetes increases the risk of both conditions by a factor of two or three, and in diabetic subjects, hypertension augments these risks. 24 In the presence of most major modifiable risk factors, diabetes constitutes an absolute excess risk in CHD, ischemic stroke, and total cardiovascular mortality among middle-aged women. 2s In addition, 6-28% of patients with transient ischemic attacks (TIAs) have diabetes. 26In a cohort of patients with type II diabetes, the occurrence of TIAs was three times more frequent than expected. 27 It is, however, suggested in other studies that diabetes and not TIAs constitutes a risk factor for stroke. 28'29From a study of TIA and stroke in a community-based diabetic cohort, 13hypertension was only partially implicated in the increased frequency of TIAs in diabetic subjects, but was entirely implicated for the increased frequency of stroke in them. It is important to note that the relative significance of vascular risk factors for stroke apparently varies with age and sex. 3° Apparently, hypertension, blood pressure, smoking, hematocrit, and left-ventricular hypertrophy are strongly associated with stroke in patients younger than 65 years of age. Diabetes seems to be a strong factor for stroke in females. Elevation of serum lipids has not been generally associated with increased stroke risk, except in males younger than 60 years of age.31 In geriatric patients, low-density lipoprotein and high-density lipoprotein rather than serum cholesterol have a high predictive value; 32 and 252 CHUKWUMAAND TUOMILEHTO carotid stenosis may be associated with hypercholesterolemia, but this is not very evident. 33Therefore, an age dependency of MI, hypertension, and diabetes exists mostly in the elderly. 34 Besides being a risk factor for stroke, diabetes invariably has been shown to have deteriorating effects in both the short- and long-term prognosis of stroke. 35 Diabetic individuals are more susceptible to nonreversible derangement of ischemic brain substance irrespective of the presentation of circulatory perturbation. 36 There is also an association between the duration and intensity of smoking with an increased incidence of MI as well as stroke. A combination of progesterone/ estrogen oral contraceptives, particularly in smokers, increases the risk of stroke by a factor of three in w o m e n of child-bearing age. 1 Many studies have shown an increase of stroke events soon after excessive alcohol intake. However, a very moderate wine intake could obviate the early occurrence of a stroke event. 1 Prospective population cohort study of mostly type II diabetic and alcoholic subjects showed that alcohol combined with diabetes are important risk factors of cerebral infarction. 37 Family History. Diabetes is a disorder with a strong genetic disposition. Therefore, it would not be unexpected to find familial clustering of complications associated with diabetes. Studies are, however, rare. It has been speculated that the linkage between diabetes and cardiovascular disease could at least partially be caused by a common genetic antecedent or both. Few studies have been involved in the examination of familial risk factors for stroke. 38 Excessive mortality from cerebrovascular derangements have been detected among parents and relatives of stroke patients. 39 Another study 4° suggests that familial factors may play a role in a few subtypes of cerebrovascular perturbations with varying influences in cerebrovascular and cardiovascular lesions. Relationship of the parental history of heart disease to hypertension, diabetes, and stroke has been attempted, s,9 but a more extensive possible role of diabetes in familial aggregation of stroke is necessary. Comparison of Type I versus Type II Diabetes. Based on some studies, there is an increase of cerebrovascular mortality in type I diabetic patients, although the excess may be less than that from CHD; and even though it is reported that cerebrovascular disease is more frequent in type II diabetic patients, there is less consistency in the excess compared to CHD.41 Studies which differentiated between types of stroke showed that type II diabetes or hyperglycemia was mainly associated with hemorrhagic strokes. 42,43The prevalence of stroke events has no relation to the duration of type II diabetes. 44 The increased incidence of stroke in pa- J Diab Comp 1993; 7:250-262 tients with impaired glucose tolerance, 41,4sand the association of stroke and type II diabetes observed in many study populations may not be one of cause and effect as concretely defined for CHD. 41 PATHOGENESIS Vascular Abnormalities in Diabetes Mellitus. The etiopathogenesis of stroke may be (1) anoxia and ischemia from vasogenic incapacitatition resulting in insufficient supply of oxygen and substrate to the pertinent tissue; (2) derangement in vascular structures, thereby having hemorrhagic manifestations inside the CNS and its periphery; and (3) arteriovenous malformations of the cerebrospinal cord may be hemorrhagic causing ischemia and/or act as space-filling lesions with concommitant neurological derangements. 1 The cerebral arterial circle is an important part of the collateral circulation in the event that one of the major arteries entering the circle becomes occluded. In geriatric patients, the anastomotic formation in the circle may be inadequate in the event of a sudden obstruction of a large artery such as the internal carotid. The identification of asymptomatic carotid stenosis may become more frequent in diabetic individuals. This is important because diabetes is an important risk factor for disease progression. 46,47 The effect of stroke in the diabetic aging population is presently one of major concern in industrialized countries as well as in nonindustrialized ones if adequate monitoring and screening procedures are made available. Stroke occurs at any age including childhood. 48-5sIn childhood, circulatory occlusion of arteries and veins may occur from local or distant thrombosis or embolization. The heart and the carotid artery in the neck are the most common sources of cerebral emboli in all age groups. The emboli may be (1) blood clots, (2) aggregations of platelets, (3) gas bubbles, or (4) masses of atheromatous material. 56 These may cause hyperviscosity, hemodynamic derangements, nonatherosclerotic vasculopathies followed by infarction and then stroke. Most thrombotic occlusions are atherosclerotic and take a rapid progressive course especially in younger diabetic subjects when compared with their nondiabetic counterparts. The frequency of atherosclerotic vascular disease is similar in both diabetic males and females. 46,47,s7-59 Sudden rupture of a cerebral aneurysm, for instance, the saccular berry aneurysm that arises from the cerebral arterial circle and the mediumsized arteries lying in the base of the brain is one of the causes of stroke. There is either an occurrence of either a spontaneous subarachnoid hemorrhage, intracerebral hemorrhage, or subdural hemorrhage. Diabetic patients may not present with aneurysmal subarachnoid hemorrhages or intracerebral hemorrhages. 6° J Diab Comp 1993; 7:250-262 Unruptured cerebral aneurysms are usually asymptomatic, but symptoms (e.g., severe throbbing headaches) and neurological signs (e.g., occulomotor nerve palsy in association with posterior communicating artery aneurysm) may occur due to intermittent enlargement. Throbbing headaches result from either stretched meninges or release of blood from the aneurysm into the subarachnoid space. Ptosis, pupil dilation, and squint divergence result from occulomotor nerve palsy. 56Occulomotor nerve palsy in diabetic patients is due to midbrain infarction rather than a peripheral nerve lesion as seen in the general population. 61 Irrespective of the etiology, a cerebral infarct presents with a similar pattern of evolution. Necrosis is well established within 48-72 h with disintegration of the area of ischemia and well-defined circumlesional swelling. Small infarcts called lacunes usually associated with systemic arterial hypertension are located anywhere in the brain especially in the brainstem or deeper regions of the brain. 62 They are due to obstructed small penetrating branches arising from the anterior, middle, and posterior cerebral arteries and the basilar artery. Frequently, lacune infarcts are found in the internal capsule, basis pontis, putamen, caudate neuclus, thalamus, and hemispheric white matter. Pure motor hemiparesis, pure sensory stroke, sensory-motor stroke, ataxic hemiparesis syndrome, and dysathria-clumsy-hand syndrome are typically found with lacune infarcts. 63'64 Postanoxic demyelination of the brain is an uncommon disease state in which prolonged severe hypoxemic exposure usually in association with severe systemic hypotension results in diffuse derangement of the hemispheric white matter without affecting most of the cerebral neurons. Orthostatic hypotension resulting from cardiovascular autonomic neuropathy is present in few specific patients at risk for ischemic lesions at the border zones between two major arterial locales (e.g., the anterior and middle or the middle and posterior cerebral arteries). 65-67 These are watershed infarctions, which may be unilateral or bilateral. Unilaterally, they occur in severe ipsilateral vascular lesion and low focal cerebral perfusion in the distal territories during arterial hypotensive episodes. Bilaterally, they are involved in profound hypotension. 66 Ultrastructural studies of diabetic cases have revealed uncomplicated, proliferative hemodynamic lesions of small intraparenchymal cerebral vascular vessels supporting the hypothesis that the diabetic disease is an important risk factor for stroke. 68'69 Hematologic Abnormalities in Diabetes. Rheological abnormalities may be involved in the pathogenesis of cerebrovascular lesions in diabetic subjects. Apparently, several hemorheological perturbations influ- DIABETESAND THE RISK OF STROKE 253 ence the development of diabetic microvascular lesions leading to cerebrovascular ischemia. Hyperreactivity is one derangement of the hemostatic system in diabetes. 7°,71Diabetes has numerous effects on hemostatic factors that alter their internal balance towards thrombogenesis. This may be important in risk enhancement of cerebrovascular disease in diabetic patients. 72Alterations in hemorheological dynamics are perhaps due to hyperviscosity of the blood following elevated fibrinogen factors V and VII, augmented adhesiveness and aggregation of platelets, deranged erythrocyte deformability, and reduction in fibrolysis. 73'74 Hematological perturbations that predispose to stroke are sickle cell disease, lupus anticoagulant, cardiolipin antibody, paraproteinemia, platelet hyperaggregability, white blood cells greater than 500,000, thrombocytosis greater than 600,000, and hematocrit greater than 55.1 In ischemic stroke patients, diabetic subjects have significantly higher hematocrit and plasma glucose levels including higher morbidity and mortality rates than nondiabetic subjects.75 The clinical characteristics in diabetic patients augment the risk for stroke through other concurrent factors especially as related to cardiac perturbations. 76 Abnormalities Due to Impaired Glucose Metabolism. Transient hyperglycemia is common but rarely persists during the phase of acute stroke. Glucose tolerance may be impaired due to prolonged bed rest or immobility of the stroke patient. Within certain circumstances, stroke patients have a greater likelihood of being tested for diabetes. Increased serum glucose levels cause augmented anaerobic metabolism resulting in high lactic acid production in ischemic brain tissue followed by an acidotic cellular stateP 7,77There may also be the intensification of the risk of cerebral edema and inpatient mortality following stroke. 78 Besides cerebral edema, hemorrhagic infarctions or multifocal hemorrhages presumably due to herniation, cerebral intravascular coagulation, or other related hematologic perturbations may be encountered in diabetic ketoacidotic patients. 79 There is increased derangement in neurological outcome following ischemic stroke in hyperglycemic patients in the presence or absence of diabetes .80Furthermore, experimental hyperglycemia in association with diabetes worsens stroke outcome. 5 It has been shown 77'81with some exceptions, 82 that initially increased blood glucose level after a stroke predicts a poor outcome even without clinical diabetes. Following stroke, hyperglycemia coupled with normal glycosylated hemoglobin is suggestive of a poor prognosis. 83 Diabetes or hyperglycemia may influence the extent of recovery by triggering an already severe acute ischemic stroke, with an increased risk of early recurrence. 84-88 254 CHUKWUMA AND TUOMILEHTO The prevalence of undetected hyperglycemia as a risk factor for stroke may have been underreported. It is suggested that admission blood glucose levels may be crucial as a predictor of early morbidity and mortality. 89 In the absence of diabetes, hyperglycemia due to a stress response can occur following a stroke event. The resultant effect is increased catecholeamine release, augmented lipolysis with concomittant increased levels of free fatty acids, and constitute a marker of poor prognosis. 9° A prospective study to confirm the relation of the concentration of blood glucose to outcome after stroke showed that it may be indicative of the intensity of the stress hormone response. 91The association of glucose concentration and outcome reflects stress relating to stroke severity, rather than the effect of glucose on deranged neuronal structures. 92 As a life-threatening condition in diabetic individuals, hyperosmolar nonketotic coma should be taken into cognizance particularly in patients with hyperglycemia. Augmented endogeneous production of glucose and a reduction in glucose renal clearance may be contributory to the triggering of hyperosmolar nonketotic coma. 8° Diabetic patients consuming excessive quantities of alcohol or treated with either oral hypoglycemic agents or insulin may present with hemiparetic attacks secondary to hypoglycemia. Hypoglycemic hemiplegic attacks may be suggestive of a defined neuronal susceptibility rather than an underlying arterial occlusion.93,94 EVALUATION~ASSESSMENT The pertinent questions are multiple with regard to a stroke event. Evaluation of risk factors makes provision for the elucidation of the etiopathogenesis of cerebrovascular disease and promotion of preventive measures. Most of all is the realization of the occurrence of stroke and its severity combined with confirmed laboratory studies. In the general population, approximately 25% of hospitalized patients diagnosed as having completed stroke do not survive while only 40% of the survivors reach good functional recovery. 1 Contributory factors are increasing age, severe dysfunctional brainstem, and coma. In combination with cardiac lesions the outcome is not favorable. Diabetes augments the risk of mortality subsequent to a stroke event, and the risk among stroke survivors of MI and the recurrence of stroke. 95 Advanced age is of paramount importance as a mortality predictor, but blood glucose seems to be prognostically valuable, particularly in young stroke patients. 96 There are variations in the size, anatomic cerebral location, and temporal pattern with regard to ischemic stroke. In patients with TIAs, the presence or absence J Diab Comp 1993; 7:250-262 of other associated risk factors such as cardiac disorders may determine the outcome. TIAs are ephemeral focal neurological symptoms and signs that are frequently indicative of atherosclerotic cerebrovascular lesions, and of future cerebral infarction before total occlusion. 62 They are ischemic events of focal acute neurological insufficiency lasting less than 24 hours, followed by complete functional recovery. TIAs frequently result from soft emboli that have slowly disintegrated and/or successively passed in a gradual motion through small arteries causing temporary neurological deficits such as amaurosis fugax. 1 About 33% of untreated patients with TIAs may present with stroke within a period of 5 years. Following TIAs, 21% of patients with cerebral infarction will present with stroke within the first month, and 51% in the first year. 26 Several TIAs originate from the carotid circulation, and the ratio of cerebroischemic infarct to hemorrhagic disturbances is higher in the diabetic than in the nondiabetic population.13 One-half of the TIAs is associated with stenosis-ulceration or severe stenosis (>75%) usually in the bifurcation of the ipsilateral common or internal carotid artery. 1 In about 4% of the general population over 45 years of age, asymptomatic bruits are evident, and stroke risk occurs about 2% annually. Later occurrence of strokes are not frequently ipsilateral to the involved vessel. 97 There is an increased prevalence of asyrnptomatic carotid bruits with age, hypertension, and diabetes. Asymptomatic carotid artery stenosis is encountered in about 10%-25% of subjects with symptomatic atherosclerosis in other vascular beds, and in about 25%-40% of individuals with contralateral carotid endarterectomy. The annual ipsilateral neurological rate is 5% with most of the initial events being TIAs. There is a high correlation of 80% progressive stenosis with ischemic cerebrovascular symptoms or occlusion of the internal carotid artery. 46'47 Lacune infarcts represent about 10%-23% of symptomatic cerebral infarcts; 2%-34% of patients with lacune infarcts are diabetics.63,64The prevalence of diabetes may not be different in patients with lacune infarcts from the various types of ischemic stroke. 63 Most of the studies have concerned stroke patients with hypertension, diabetes, carotid and vertebrobasilar TIA, CHD, age, race, sex, smoking history, and admission date. A comparison of the relative frequency of stroke symptoms was undertaken for the evaluation of the relative magnitude of diabetes as a risk factor for stroke in both diabetic and nondiabetic persons. 98 The symptoms ascribed to stroke were atherothrombotic cerebral infarctions, TIAs, reversible ischemic neurologic deficits, and multi-infarct dementia. Arterial hypertension, cardiac disease, and stroke J Diab Comp 1993; 7:250-262 were found more in diabetic than in nondiabetic individuals matched for age. In the diabetic group, inception of stroke was at an early age with predominance in the male sex. In descending order of magnitude, regression analyses assigned the risk factors for stroke as arterial hypertension, diabetes, cardiac disease, and smoking. Diabetes complicated with either arterial hypertension or hyperlipidemia increases the risk for stroke. The values of cerebrovascular hemodynamics and cognitive tests were identical among diabetic and nondiabetic subjects at the initial stage.98 However, there was significant impairment of cognition after 3 years in the diabetic subjects irrespective of augmented treatment regimen and cerebral blood flow compared with the nondiabetic subjects.98 Diabetes seems to augment the risk for stroke by both the promotion of cerebroatherogenesis and the triggering of other major risk factors. The management of cerebrovascular lesions in diabetic patients is essentially the same as for nondiabetic subjects. Following a cerebroischemic event, the outcome of the injury is not favorably affected by any treatment regimen. An adequate form of management is the provision of medical and nursing care, reduction of identified hypertension, and the usage of pertinent measures in the prevention of acute or future deterioration of the neurological deficit. In acute stroke, the progression may be arrested by the prevention of recurrent cerebral embolism, and the stabilization of deteriorating diabetic patients. Diabetes is associated with progressive incidence of complications into old age. Adequate facilities are needed for the assessment and treatment of the concomitant morbidity in an increasing geriatric population. 99 Arteriography (the risk factor is about 1%-2%) and vascular surgery have been indicated for stroke prevention (1) in doubtful diagnosis, (2) to identify the source of an arteriovenous malformation, (3) to explain a lobar cerebral hemorrhage, and (4) to determine potential surgically treatable stenoses or carotid arterial ulcerations. 1 By the means of computer tomographic findings, patients can be classified as presenting with intracerebral hemorrhage or cerebral infarction. 1°° It could be beneficial for screening if the cost effectivity is not an inhibitory factor. Clinical results and computer tomographic (CT) scan has been used to reveal stroke in patients. TM A strong association between cerebrothrombotic events and hypertension, diabetes, and smoking was observed. In addition, cerebral emboli formation was associated with hypertension, atrial fibrillation, and TIAs including cerebrohemorrhagic events specific to hypertension. There is no specific diagnostic standard of TIAs ex- DIABETES AND THE RISK OF STROKE 255 cept a consensual interpretation of the history of the patient. I°2,1°3An appropriate infarct (e.g., cerebral infarction with transient signs) can be detected from a CT scan for a TIA of a few minutes duration. TM Pathophysiologically, there is no distinction between stroke and TIA. Moreover, 11%-18% of the initial CT scans of patients with either stroke or TIA depict hypodense ischemic lesions unconnected to the presenting symptoms, unraveling the previous event of subclinical cerebral infarction. I°5-1°s These kinds of lesions may be actually asymptomatic, not reported, or never recognized. Silent strokes make it possible to study previous impact of cerebrovascular lesions on the brain. A previously recognized stroke possibly leads to a higher risk for stroke recurrence.l°9,1~° TIAs may not constitute an independent risk factor for mortality, but make it possible to recognize patients at increased risk for other significant concurrent conditions, m Asymptomatic neck bruits are a risk factor for subsequent stroke, MI, and mortality, u2-117Even though the risk for stroke and mortality is slightly more than that of an aged-matched population, 1~7 evaluation of the outcome of asymptomatic carotid stenosis is necessary because neck bruits do not reflect significant carotid stenosis or any arterial pathology. ~12-114,116The monitoring of the clinical outcome and extracranial carotid Doppler ultrasound evaluation at regular intervals of asymptomatic neck bruits is pertinent. 113,118Diabetic patients have a higher degree of thickening of the walls of carotid arteries, u9 This may have relevance for the increased risk of stroke in diabetic patients. The rapid decrease in overall mortality in industrial countries is probably due to CHD and stroke. The decrease in stroke mortality has been related to either decreasing incidence and/or improved prognosis; 120,121 but it may be due to improved survival rather than decreased incidence. 122Interracial and socioeconomic differentials may provide potential clues in high rates of diabetes and stroke in the black population. Racial disparities in the incidence of stroke and stroke-related mortality are evident. 17Blacks, especially those living in the rural areas, experience higher incidence and mortality rates for stroke than whites.123-12s Racial disparities in stroke disability such as cognitive and physical perturbations, and their later implications on rehabilitation and productive life have not been given due cognizance. Few studies have reported slight racial differences in clinical impairments following stroke and in the prognosis of stroke patients. 126-13°Blacks may possess stronger disposition to residual physical deficits from stroke than whites. TM When there is adjustment for severity of stroke and other predictors of stroke outcome, race differentials do not have any impact on mortality among hospitalized patients. 126-13° 256 CHUKWUMAAND TUOMILEHTO J Diab Comp 1993; 7:250-262 moglycemic diabetic patients could underestimate both the cerebral glucose level and the severity of postischemic neurologic derangement. 16° Speculations are rife as to whether blood hypervisCOMMENTS AND CONCLUSION cosity in acute stroke patients is causally related to the Diabetes has been associated with an increased risk ischemia or is just a reflection of secondary acute phase of atherosclerotic complications and cerebrovascular reactants. An etiologic role of elevated blood viscosity disease. The mortality from cerebrovascular disease has been recognized in stroke risk factors such as diain the diabetic population is greater by a factor of from betes, 161CHD,162 and smoking.163 Increase in either hetwo to five among nondiabetic persons. 132-134Identifi- matocrit or fibrinogen level, two components of wholecation of the etiopathogenesis of stroke in relation to blood viscosity, is associated with an increased stroke diabetes poses a problem in its prevention, evaluation, r i s k . 164-166 An increase of the magnitude of viscous deor management. rangements and their contributory factors demonIschemic cerebrovascular events may be a manifes- strates that blood hyperviscosity is observable not only tation of extra- and intracranial atherosclerotic lesions in patients presenting with acute cerebral infarction, as well as nonatherosclerotic perturbations due to in- but also in patients having risk factors for stroke, and tracranial aneurysm or an embolus from the heart. The also that chronicity characterizes these perturbations pathogenetic mechanism of symptomatic cerebral va- to an appreciable extent. 167 sospasm after aneurysmal subarachnoid hemorrhage The evaluation/assessment of cerebrovascular dismay be unclear, but arterial luminal constriction could ease or stroke in diabetic patients is similar to that of result in cerebral ischemia. Usually, there is no correla- the general population. However, effective intervention between angiographic vasospasm and cerebral tions to decrease CHD and stroke-important compliischemic symptoms or cerebral blood circulation, 135-137 cations of d i a b e t e s - a r e inadequate, especially in spebut there is a probable effect of intravascular compo- cific racial groupsJ 68 nents on cerebral ischemic events. 138,139HistopathologThere is a frequent recurrence after ischemic stroke, ically, vascular vasospasm shows endothelial derange- with a yearly incidence of 4%-14%. 169-171Nondiabetic, ment and luminal surface adhesion of aggregated normotensive patients without history of stroke, and platelets.14°-143 Pathologically, the platelet system plays an infarct of unknown etiology have the lowest risk a vital role in microthrombi formation in cerebral pe- for stroke. 172Interests presently exist in the impact of ripheral vessels 142'143and by thromboxane A2 synthe- aggressive management of hypertension, diabetes, sis.145'147Further studies are imperative to elucidate the and cardiac disorders on the risk of the recurrence of correlation between diabetes and intracranial aneu- stroke. 173 Focus on prospective studies to determine rysms. the impact of effective management of these risk facLocal or general degenerative cerebrovascular tors toward the decline in stroke recurrence is needed, v2 changes due to nonatherosclerotic and nonhemodyCT scan detects a cerebral infarct in 10%-40% of TIA namic factors may also precipitate these events; hyper- patients, even without a clinical history of stroke, v4 tension plays a major role in cerebrovascular disor- Patients with CT-verified infarcts will have increased ders, but the impact of lipoprotein derangement is risk of mortality even after adjusting for risk factors smaller. 148The modification of associated risk factors such as hypertension, diabetes, and CHD. CT scan is important in the management of diabetic patients has important prognostic value following a TIA.17sThe with cerebrovascular disease. 149 The risk factors that prognosis of the patient is dependent on age, smoking have been well documented for stroke include hyper- history, and pattern of concurrent illnessesJ 76 Intertension, diabetes, heart disease, smoking, lipid abnor- ventions are deemed appropriate in those diabetic pamalities, advanced age, fibrinogen levels, and coagu- tients with CT-verified infarcts. Also, of innovative lation defectsJ 5° It has been found that geneticity and practical importance, high-resolution B-mode ulsignificantly influences some risk factors more than trasonography (in comparison to other noninvasive environmental factors, lsl methods) 177-182makes it possible to directly visualize Hyperglycemia and increased brain glucose exacer- both luminal and vessel wall features, with the early bates cerebral damage during and after global isch- detection of extracranial and intracranial carotid athemia. 152-159An increased blood glucose level is likely erosclerotic alterations. to enhance the deteriorated neurologic outcome in unACKNOWLEDGMENT treated diabetic patients after resuscitation as a result of cardiac arrest, ls3 The determination of plasma or This work was partly supported by the Nordisk Insulin blood glucose levels in acutely insulin-treated, nor- Fund. 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