Symposium ArticleDiabetes and Stroke: Epidemiology, Pathophysiology, Pharmaceuticals and Outcomes☆,☆☆
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.
References (40)
- et al.
Risk factors for ischaemic and intracerebral haemorrhagic stroke in 22 countries (the INTERSTROKE study): a case-control study
Lancet
(2010) - et al.
Diabetic and non-diabetic subjects with ischemic stroke: differences, subtype distribution and outcome
Nutr Metab Cardiovasc Dis
(2008) - et al.
Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial
Lancet
(2005) - et al.
Forecasting the future of cardiovascular disease in the United States: a policy statement from the American Heart Association
Circulation
(2011) - et al.
Diabetes mellitus and ischemic stroke in the young: clinical features and long-term prognosis
Neurology
(2011) Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies
Lancet
(2010)- et al.
Probability of stroke: a risk profile from the Framingham Study
Stroke
(1991) - et al.
Diabetes mellitus: a risk factor for ischemic stroke in a large biracial population
Stroke
(2013) - et al.
Diabetes mellitus and risk of stroke and its subtypes among Japanese: the Japan public health center study
Stroke
(2011) - et al.
Type 2 diabetes and risk of non-embolic ischaemic stroke in Japanese men and women
Diabetologia
(2004)
Short-term predictors of incident stroke in older adults. The Cardiovascular Health Study
Stroke
Stroke patterns, etiology, and prognosis in patients with diabetes mellitus
Neurology
Prospective study of type 1 and type 2 diabetes and risk of stroke subtypes: the Nurses׳ Health Study
Diabetes Care
Effect of pre-diabetes on future risk of stroke: meta-analysis
Br Med J
Perfusion deficit parallels exacerbation of cerebral ischemia/reperfusion injury in hyperglycemic rats
J Cereb Blood Flow Metab
Is hyperglycaemia an independent predictor of poor outcome after acute stroke? Results of a long-term follow up study
Br Med J
Acute hyperglycemia and acute hyperinsulinemia decrease plasma fibrinolytic activity and increase plasminogen activator inhibitor type 1 in the rat
Acta Diabetol
Admission glucose level and clinical outcomes in the NINDS rt-PA Stroke Trial
Neurology
Higher fasting glucose next day after intravenous thrombolysis is independently associated with poor outcome in acute ischemic stroke
J Stroke Cerebrovasc Dis
Long-term postischemic stroke mortality in diabetes: a veteran cohort analysis
Stroke
Cited by (357)
Association between galectin-3 and the prognosis of patients with stroke: A meta-analysis of observational studies
2024, Nutrition, Metabolism and Cardiovascular DiseasesAssociation of thyroid hormone sensitivity index with stroke in patients with coronary artery disease
2024, Journal of Stroke and Cerebrovascular DiseasesStress hyperglycemia increases short-term mortality in acute ischemic stroke patients after mechanical thrombectomy
2024, Diabetology and Metabolic Syndrome
- ☆
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.