Diabetes as a Risk Factor in Atherosclerotic Cerebrovascular Disease

Stroke Characteristics in Diabetes

In both T1DM and T2DM, the commonest stroke phenotype is an ischemic stroke. The lacunar (small cerebral artery) subtype is consistently the most common, especially multiple lacunar strokes. Hemorrhagic strokes are six times less common, and subarachnoid hemorrhages are rare in this population. Although carotid and basilar artery occlusion are a complication of the heavy burden of atherosclerotic disease in DM, large-vessel infarcts are less common. In some studies A _1c is independently related to the severity of carotid occlusion as well as to macroalbuminuria. The incidence of transient ischemic attacks (TIAs) in DM is variably reported, though the majority find a low incidence. It is postulated that irreversible and permanent damage caused by hyperglycemic neuronal changes lead to strokes rather than TIAs. Ischemic strokes in the setting of hyperglycemia are at high risk for hemorrhagic transformation, especially with reperfusion therapy. Various BG cutoffs ranging over 150 mg/dL are reported to increase this risk. DM patients also have a high incidence of stroke mortality, early recurrence, and physical disability, especially with brain stem or cerebellar infarction.

Pathophysiology of Stroke in Diabetes and Hyperglycemia

Although classified as a macrovascular complication, DM causes both extracranial atherosclerotic and cortical microangiopathic changes. Carotid occlusion is common, especially in the elderly. Endothelial damage from subclinical inflammation of the vessel wall (high levels of interleukin [IL]-6, tumor necrosis factor [TNF], and TNF-α), oxidative stress increasing reactive oxygen species, lipoprotein oxidation, altered platelet aggregation, inhibition of fibrinolysis, and hypercoagulability are some vasculature features in DM. Prolonged hyperglycemia increases permanent glycosylation end products. Vessel wall reactivity to nitric oxide (NO) and free radical production is altered. The brain microvasculature is also damaged by hyalinosis and altered glucose oxidation, all these factors contributing to arterial damage.

An acute ischemic event is usually mitigated by collateral circulation. The irreversibly damaged central area is surrounded by the hypoperfused penumbra within which viable cells switch to anaerobic respiration. Early hyperglycemia is favorable to this process, but if perfusion is not restored, continued production and accumulation of lactate leads to cell death, enlarging the infarct. Initial use of intravenous insulin is reported to have multifactorial benefits that include stress hormone reduction and vessel wall relaxation, which lower blood pressure (BP).