In the total population, stroke is the fifth most common cause of death and the leading neurological cause of long-term disability in the United States, accounting in 2011 for $34 billion in health care costs. With the advent of sensitive brain imaging techniques, it is common to observe magnetic resonance imaging evidence of subclinical vascular brain injury, such as covert brain infarcts (CBI) and white matter hyperintensities (WMH). In an unselected sample of persons age >65 years without a history of clinical events, 10%–15% had CBI and 95% had WMH. The subclinical findings do not cause abrupt clinical symptoms but are often associated with cognitive decline and with an increased risk of subsequent stroke. Therefore, the clinical and public health burden of cerebrovascular disease is far greater than that of overt clinical disease. This burden is higher in persons with diabetes. Diabetes, a risk equivalent for cardiovascular disease, has been recognized as one of the major risk factors for stroke and subclinical vascular brain injury, such as CBI, WMH, and vascular cognitive impairment.
Stroke is clinically defined as an acute-onset focal neurological deficit persisting for more than 24 hours. About 85% of all strokes are ischemic, and the other 15% are hemorrhagic. Ischemic stroke is caused by an abrupt blockage of the artery, either by an embolus from the heart or from a more proximal artery, or from an in situ thrombus growing to occlude a cerebral artery affected by an atherosclerotic plaque, leading to an acute blockage of blood supply to the brain. Hemorrhagic stroke can result in accumulation of blood in the substrate of the brain, which is called intracerebral hemorrhage, in the cerebrospinal fluid around the brain, or in the cerebrospinal fluid spaces within the brain.
The etiology of stroke in persons with diabetes is comparable to the etiologies in other populations. However, multiple underlying pathophysiological processes in diabetes lead to a high prevalence of small vessel and/or large vessel atherosclerosis in persons with diabetes. Persons with diabetes have about twice the risk for stroke, particularly of ischemic stroke. Diabetic individuals after stroke have about a 25% reduction in a favorable outcome, such as being able to function independently in activities of daily living, and are more likely to die from the stroke. Those who survive are more likely to have recurrent strokes and to develop vascular cognitive impairment than persons without diabetes.
Diabetes is more common in nonwhite populations, and stroke risk has been assessed in various racial/ethnic subgroups. Diabetes is at least as important a risk factor for stroke in blacks, Japanese Americans, and Native Americans as it is in whites, with a 40%–100% higher risk in racial/ethnic minorities.
Coexistence of various risk factors, such as hypertension and hyperlipidemia, and concomitant coronary or peripheral vascular disease are common problems in persons with type 2 diabetes and are also independent risk factors for stroke and its serious complications. Impaired glucose tolerance and the metabolic syndrome, as well as microalbuminuria, are other stroke risk factors in persons with diabetes, with the metabolic syndrome increasing risk by 20%–40% and microalbuminuria increasing risk by approximately 80%.
Strict control of hyperglycemia has not been shown to reduce stroke incidence in persons with diabetes. Vigorous management of primary disease (diabetes) and careful identification and treatment of the concomitant vascular risk factors, especially hypertension, along with lifestyle modifications remain the fundamental approach for stroke prevention in this vulnerable population. Statins and low-dose aspirin may also be beneficial in preventing stroke or attenuating its adverse impact. Studies of oral hypoglycemic drugs and peroxisome proliferator-activated receptor-gamma (PPAR-γ) inhibitors have not, so far, shown a convincing effect on altering stroke risk among persons with diabetes.