Risk Factors : Diabetes

Introduction

Diabetes is an endocrine disease with devastating vascular consequences . In the cerebrovasculature, accelerated atherosclerosis of the large vessels is believed to contribute to complications, such as stroke and transient ischemic attacks. There is growing body of evidence that microvascular disease also contributes to stroke and other neurological diseases including Alzheimer disease and vascular cognitive impairment . This chapter will summarize the epidemiological data on diabetes and cerebrovascular diseases with a focus on stroke and cognitive impairment and discuss the impact of diabetes-mediated pathological changes in cerebrovascular function and structure on stroke and cognitive impairment in preclinical models.

Diabetes and Stroke

Diabetic patients are at two- to sixfold increased risk of stroke, compared with their age-matched counterparts, and the highest relative risks occur in young patients with type 1 diabetes . As reviewed in 2012, determining the effect of glycemic control on stroke prevention has been challenging but evidence from multiple trials suggests that tight glycemic control reduces the risk of cerebrovascular disease and it takes many years of follow-up to demonstrate this benefit in patients . In addition to a higher risk, acute and long-term outcomes of stroke are also worse in patients with diabetes. Patients with diabetic ischemic stroke are at a twofold higher relative risk of 30-day mortality as well as long-term disability . Although there is a lack of evidence regarding optimal acute management of hyperglycemia after stroke, the American Heart Association recommends managing hyperglycemia to a target glucose level of <300 mg/dL and trials are ongoing to test the impact of glucose control in the acute stroke period. There is clear evidence that diabetes decreases the thrombolytic efficacy while increasing the risk of hemorrhagic transformation in patients receiving tissue plasminogen activator (rtPA), the only Food and Drug Administration–approved treatment for acute ischemic stroke . However, there are no guidelines with respect to the use of rtPA in diabetic patients.

The underlying reasons why diabetic patients suffer to a greater extent from acute ischemic stroke remain elusive. There is no clear evidence that diabetic patients present with larger cerebral infarctions. Indeed, the landmark Trial of Org 10172 in Acute Stroke Treatment (TOAST) showed that hyperglycemia worsened outcome in nonlacunar stroke but not in lacunar stroke . Evidence also suggests that lacunar infarcts resulting from occlusion of small penetrating arterioles are more common in diabetic patients . It also has to be noted that silent infarcts may be more common in diabetic patients, contributing to higher incidence of cognitive impairment . It is also unclear whether the duration and severity of preexisting diabetes is critical for acute stroke injury and recovery. A meta-analysis suggested that patients who present with hyperglycemia and no history of diabetes suffer the most from acute ischemic stroke .