Opposing Effects of Glucose on Stroke and Reperfusion Injury

Robbins, Nathaniel M.; Swanson, Raymond A.

doi:10.1161/strokeaha.114.004889

Cited by 123 publications

(112 citation statements)

References 49 publications

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“…Especially in ischemic stroke patients, day‐long duration of hyperglycemia had a strong association with higher risk of the outcome in the hours after acute stroke, accelerating brain damage 22. Elevation of blood glucose levels caused activation of the coagulant system, suppression of the fibrinolytic system, and production of free radicals 26, 28, 29, 30, 31. This elevation may also lead to acidosis, excitatory amino acids, and injury to the blood–brain barrier, which cause ischemic brain damage in animal models and expand ischemic lesions volumetrically 1, 23, 25, 32.…”

Section: Discussionmentioning

confidence: 99%

Outcome Prediction in Acute Stroke Patients by Continuous Glucose Monitoring

Wada

Yoshimura

Inoue

et al. 2018

JAHA

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BackgroundThe purpose of this study was to examine the relationships between glucose parameters obtained by continuous glucose monitoring and clinical outcomes in acute stroke patients.Methods and ResultsConsecutive patients with acute ischemic stroke or intracerebral hemorrhage within 24 hours after onset were included. A continuous glucose monitoring device (iPro2) was attached for the initial 72 hours after emergent admission. Eight glucose parameters were obtained from continuous glucose monitoring: maximum, minimum, mean, and SD of blood glucose levels, as well as area under the curve more than 8 mmol/L of blood glucose, distribution time more than 8 mmol/L of blood glucose, coefficient of variation (%CV), and presence of time less than 4 mmol/L over 72 hours. The primary outcome measure was death or dependency at 3 months (modified Rankin Scale score ≥3). One hundred patients with acute ischemic stroke (n=58) or intracerebral hemorrhage (n=42) were included. Blood glucose levels varied between 5.2±1.4 and 11.4±3.2 mmol/L over 72 hours, with area under the curve more than 8 mmol/L of blood glucose of 0.7±1.4 min×mmol/L, distribution time more than 8 mmol/L of blood glucose of 31.7±32.7%, coefficient of variation of 15.5±5.4%, and presence of hypoglycemia in 20% of overall patients. Mean glucose level (adjusted odds ratio, 1.60, 95% confidence interval, 1.12–2.28/1 mmol/L), area under the curve more than 8 mmol/L of blood glucose (2.13, 1.12–4.02/1 min×mmol/L), and distribution time more than 8 mmol/L of blood glucose (1.25, 1.05–1.50/10%) were related to death or dependency for overall patients, as well as for acute ischemic stroke patients (2.05, 1.15–3.65; 2.38, 1.04–5.44; 1.85, 1.10–3.10, respectively).ConclusionsHigh mean glucose levels, distribution time more than 8 mmol/L of blood glucose, and areas under the curve more than 8 mmol/L of blood glucose during the initial 72 hours of acute stroke were associated with death or dependency at 3 months.

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Section: Discussionmentioning

confidence: 99%

Outcome Prediction in Acute Stroke Patients by Continuous Glucose Monitoring

Wada

Yoshimura

Inoue

et al. 2018

JAHA

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“…However, in lacunar infarction that involves the occlusion of a deep penetrating vessel, hyperglycemia decreases neurological functional deficits without affecting, or even decreasing, subcortical infarction volume 134, 135. These effects are widely attributed to an intact BBB, which prevents entry of neurotoxins and inflammatory factors into the ischemic brain, and poor collateral circulation in the subcortical areas, which makes glucose levels inconsequential 135, 136. In normoglycemic rats subject to stroke, the ischemic border zone exhibits an increased glucose utilization rate with damage to neurons, while in hyperglycemic rats subject to stroke, normal glucose metabolism and structurally intact neurons were observed in the ischemic border zone 133.…”

Section: Hyperglycemia In Patients With Acute Strokementioning

confidence: 99%

“…Such neuroprotection after stroke in hyperglycemic conditions may be attributable to inhibition of the metabolically demanding, spontaneous, recurrent, and transient increases in extracellular potassium in the cortical ischemic border zone that is observed under normoglycemic stroke conditions 134. In fact, the very high energy demands imposed by the spreading depression near ischemic core regions may be fueled under high glucose conditions 136. Persistent hyperglycemia after stroke is an independent determinant of infarct expansion via recruiting the ischemic penumbra and leads to worse functional outcome,137 hence treatment strategies to normalize glucose levels after stroke are necessary.…”

Section: Hyperglycemia In Patients With Acute Strokementioning

confidence: 99%

Blood–Brain Barrier Disruption, Vascular Impairment, and Ischemia/Reperfusion Damage in Diabetic Stroke

Venkat

Chopp

Chen

2017

JAHA

117

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“…5 It is unclear exactly how hyperglycaemia causes worse outcomes in acute stroke. 6 Hyperglycaemia related acidosis is a proposed mechanism.…”

Section: The Impact Of Hyperglycaemia On Strokementioning

confidence: 99%

“…Based on these definitions, hyperglycaemia is found at presentation in 30-60% of all stroke patients. 5 Research has shown that acute hyperglycaemia in stroke contributes to worse functional outcomes, longer hospital admission and higher mortality. 6 There is uncertainty about what level of blood glucose contributes to unfavourable outcomes.…”

Section: Introductionmentioning

confidence: 99%

Stroke and diabetes: a dangerous liaison

et al. 2016

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Ischaemic stroke is a major cause of disability and death and the incidence rate of ischaemic stroke is doubled in patients who have diabetes. Admission hyperglycaemia in acute stroke patients is associated with higher mortality, longer hospital stay and worse functional outcome. However, it remains unclear whether hyperglycaemia is in fact a marker of stroke severity or whether hyperglycaemia directly contributes to brain damage. Potential mechanisms of hyperglycaemia related brain damage in stroke include acidosis, oxidative stress and reperfusion injury. Evidence suggests a potential benefit of treatment of hyperglycaemia with insulin in acute stroke patients but the potential for morbidity caused hypoglycaemia should be considered. The American Heart Association/American Stroke Association guidelines recommend maintaining the blood glucose level in the range 7.8-10 mmol/L during acute stroke hospitalisation whilst the European Stroke Organization guideline recommends lowering the blood glucose with insulin to below 10 mmol/L. More research is needed to explore the impact of admission hyperglycaemia and hypoglycaemia on stroke outcomes and the role of other glucose lowering therapies. Br J Diabetes 2016;16:114-118

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Opposing Effects of Glucose on Stroke and Reperfusion Injury

Cited by 123 publications

References 49 publications

Outcome Prediction in Acute Stroke Patients by Continuous Glucose Monitoring

Outcome Prediction in Acute Stroke Patients by Continuous Glucose Monitoring

Blood–Brain Barrier Disruption, Vascular Impairment, and Ischemia/Reperfusion Damage in Diabetic Stroke

Stroke and diabetes: a dangerous liaison

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