Diabetes and Stroke: What Are the Connections?

Abstract

Stroke is a major cause of death and long-term disability worldwide. Diabetes is associated with an increased risk of cardiovascular complications, including stroke. People with diabetes have a 1.5-2 times higher risk of stroke compared with people without diabetes, with risk increasing with diabetes duration. These risks may also differ according to sex, with a greater risk observed among women versus men. Several mechanisms associated with diabetes lead to stroke, including large artery atherosclerosis, cerebral small vessel disease, and cardiac embolism. Hyperglycemia confers increased risk for worse outcomes in people presenting with acute ischemic stroke, compared with people with normal glycemia. Moreover, people with diabetes may have poorer post-stroke outcomes and higher risk of stroke recurrence than those without diabetes. Appropriate management of diabetes and other vascular risk factors may improve stroke outcomes and reduce the risk for recurrent stroke. Secondary stroke prevention guidelines recommend screening for diabetes following a stroke. The diabetes medications pioglitazone and glucagon-like peptide-1 receptor agonists have demonstrated protection against stroke in randomized controlled trials; this protective effect is believed to be independent of glycemic control. Neurologists are often involved in the management of modifiable risk factors for stroke (including hypertension, hyperlipidemia, and atrial fibrillation), but less often in the direct management of diabetes. This review provides an overview of the relationships between diabetes and stroke, including epidemiology, pathophysiology, post-stroke outcomes, and treatments for people with stroke and diabetes. This should aid neurologists in diabetes-related decision-making when treating people with acute or recurrent stroke.

Keywords: Diabetes mellitus; Hyperglycemia; Outcome assessment; Risk; Stroke.

Figure 1.

Risk of stroke in people with diabetes compared with those without diabetes (studies between 2010 and 2022 with N>1,000). B, both; CI, confidence interval; F, females; H, hemorrhagic; HR, hazard ratio; I, ischemic; IRR, incidence risk ratio; M, males; NR, not reported; RR, relative risk. ^*No P value available.

Figure 2.

Potential pathophysiological mechanisms wherein diabetes leads to (ischemic) stroke.

Figure 3.

Therapies available for treatment of people with diabetes according to their effect on reduction of stroke risk [55, 65-67]. Data shown for each drug class are for overall risk of stroke relative to placebo, from Benn et al [55]. CI, confidence interval; DPP-4is, dipeptidyl peptidase-4 inhibitors; GLP-1 RA, glucagon-like peptide-1 receptor agonist; SGLT-2is, sodium-glucose cotransporter-2 inhibitors; RR, relative risk. ^*Glucose-lowering agent has shown evidence of improvement in stroke risk when analyzed at individual level within drug class, within meta-analyses or post hoc studies mainly utilizing data from cardiovascular outcome trials in which stroke formed part of the primary outcome; ^†Lacks statistical evidence of an effect on stroke risk.