Symposium Article
Diabetes and Stroke: Epidemiology, Pathophysiology, Pharmaceuticals and Outcomes,☆☆

https://doi.org/10.1016/j.amjms.2016.01.011Get rights and content

Abstract

There has been a significant increase in obesity rates worldwide with the corresponding surge in diabetes. Diabetes causes various microvascular and macrovascular changes often culminating in major clinical complications, 1 of which, is stroke. Although gains have been made over the last 2 decades in reducing the burden of stroke, the recent rise in rates of diabetes threatens to reverse these advances. Of the several mechanistic stroke subtypes, individuals with diabetes are especially susceptible to the consequences of cerebral small vessel diseases. Hyperglycemia confers greater risk of stroke occurrence. This increased risk is often seen in individuals with diabetes and is associated with poorer clinical outcomes (including higher mortality), especially following ischemic stroke. Improving stroke outcomes in individuals with diabetes requires prompt and persistent implementation of evidence-based medical therapies as well as adoption of beneficial lifestyle practices.

Introduction

Cardiovascular diseases (CVD), including stroke, are major healthcare issues in both developing and developed countries with deleterious effects at individual, family and societal levels. Between 2010 and 2030, the estimated total direct medical costs would escalate from $273–$818 billion in the United States alone.1

Major modifiable risk factors for stroke include hypertension, diabetes, smoking and dyslipidemia. Diabetes is a well-established risk factor for stroke. It can cause pathologic changes in blood vessels at various locations and can lead to stroke if cerebral vessels are directly affected. Additionally, mortality is higher and poststroke outcomes are poorer in patients with stroke with uncontrolled glucose levels. Whether tight control of hyperglycemia is associated with better outcomes in acute stroke phase needs to be further investigated in Phase III clinical trials. Controlling diabetes and other associated risk factors are effective ways to prevent initial strokes as well as stroke recurrence.

In this narrative article, we review the epidemiology linking diabetes and stroke; the pathophysiology of diabetes and stroke patterns and outcomes in individuals with diabetes. Additionally, we summarize the influence of hyperglycemia on poststroke outcomes and management of hyperglycemia during the acute phase of stroke. Finally, we review stroke prevention strategies for individuals with diabetes.

Section snippets

Epidemiology

An estimated 285 million individuals worldwide suffered diabetes during 2010, and the number is projected to increase to 439 million worldwide by 2030.1 This global increase includes a 69% increase in adults with diabetes in developing countries and a corresponding 20% increase in developed countries. This dramatic increase in the prevalence of type II diabetes is likely attributable to the increase in the prevalence of obesity. The metabolic syndrome is believed to affect at least 1 in 5

Pathophysiology

There are several possible mechanisms wherein diabetes leads to stroke. These include vascular endothelial dysfunction, increased early-age arterial stiffness, systemic inflammation and thickening of the capillary basal membrane. Abnormalities in early left ventricular diastolic filling are commonly seen in type II diabetes. The proposed mechanisms of congestive heart failure in type II diabetes include microvascular disease, metabolic derangements, interstitial fibrosis, hypertension and

Stroke Patterns in Diabetes

Uncontrolled diabetes puts subjects at risk for both ischemic and hemorrhagic strokes. There are specific clinical patterns of ischemic stroke in individuals with diabetes. For example, individuals with diabetes are more likely to have limb weakness and dysarthria as signs of lacunar cerebral infarction when compared with those without diabetes. In the Lausanne Stroke Registry between 1983 and 2002, patients with diabetes had higher relative prevalence of subcortical infarction and lower

Hyperglycemia and its Management

Hyperglycemia is a common phenomenon presented in the early acute stroke phase. It may be related to nonfasting state and stress reaction with impaired glucose metabolism. Stroke triggers generalized stress reaction involving the activation of the hypothalamic-pituitary-adrenal axis, which subsequently leads to increased levels of serum glucocorticoids, activation of the sympathetic autonomic nervous system and increased catecholamine release. Increased levels of stress hormones raise rates of

Stroke Prevention

No major clinical trials have examined specific stroke prevention strategies in individuals with diabetes. Evidence is scarce in secondary stroke prevention. Most available data are based on studies focusing on primary stroke prevention.

For an average of 6.5 years of intensive diabetes therapy (INT) in type I diabetes of Diabetes Control and Complications Trial (DCCT) and the Epidemiology of Diabetes Interventions and Complications (EDIC) study, former INT-reduced aggregate CVD risk by 42% (95%

Conclusions

Diabetes is an important modifiable risk factor for stroke, especially ischemic strokes. Hyperglycemia during the acute stroke phase is associated with poor outcomes in both ischemic and hemorrhagic strokes. It needs to be actively corrected but optimal management remains unknown. Aggressive glucose control through lifestyle change or medications and modification of other associated risk factors (such as BP and dyslipidemia) are critical steps toward effective stroke prevention.

Acknowledgment

We would like to thank Dr. James Sawers for his generous comments and edits to this article.

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    Grant support was provided from National Institute of Health, United States, grant (P20GM109040) and American Heart Association, United States, grant (14SDG1829003) (to WF). Grant support was also provided from National Institute of Health, United States, grants (NS079179 and NS094033) (to BO).

    ☆☆

    The authors have no conflicts of interest to disclose.

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