eMedicine Specialties > Neurology > Neuro-vascular Diseases

Metabolic Disease & Stroke: Hyperglycemia/Hypoglycemia

Author: Pitchaiah Mandava, MD, PhD, Assistant Professor, Department of Neurology, Baylor College of Medicine; Consulting Staff, Department of Neurology, Michael E DeBakey Veterans Affairs Medical Center
Coauthor(s): Thomas A Kent, MD, Professor, Department of Neurology, Baylor College of Medicine; Neurology Care Line Executive, Michael E DeBakey Veterans Affairs Medical Center
Contributor Information and Disclosures

Updated: Apr 4, 2006

Introduction

Background

This article primarily addresses effects of hyperglycemia and hypoglycemia in the setting of acute stroke. Preexisting hyperglycemia is found commonly in patients presenting with acute stroke, and hypoglycemia may present with focal symptoms mimicking acute stroke. The reader is referred to more definitive discourses about the general management of diabetes and other manifestations of hyperglycemia and hypoglycemia in the general neurologic and endocrinologic literature.

Hyperglycemia: Although confounded by other factors, such as severity of the infarct, hyperglycemia in the face of acute stroke worsens clinical outcome. Nondiabetic hyperglycemic ischemic stroke patients have a 3-fold higher 30-day mortality and diabetic patients have a 2-fold 30-day mortality (Capes, 2001). In several trials involving thrombolytic and anticoagulation therapy in patients with stroke, hyperglycemia appears to be an independent risk factor for worsened outcome. Hyperglycemia has been suggested as an independent risk factor in hemorrhagic conversion of the stroke after administration of thrombolytic therapy.

Hypoglycemia: Several case reports describe hypoglycemia mimicking acute stroke or symptoms of transient ischemic attack (TIA). Misdiagnosis and improper treatment could worsen the outcomes. Therefore, evaluation of glucose levels is recommended in patients presenting with symptoms suggestive of acute stroke, particularly prior to administration of recombinant tissue-type plasminogen activator (rtPA). Symptoms caused by hypoglycemia can occur suddenly and fluctuate, suggesting a vascular etiology.

Pathophysiology

Hyperglycemia

Diabetes mellitus is an independent risk factor for stroke and may be one of the factors causing strokes at younger ages in groups such as Hispanic Americans that have a relatively high incidence of diabetes. The mechanism is believed to be accelerated atherosclerosis, which can affect vessels in many distributions, including small and large vessels. Cardiac involvement may predispose to embolic strokes as well. In addition, patients with diabetes may have any of several lipid abnormalities. Elevated levels of triglycerides, low-density lipoproteins (LDL), and very low-density lipoproteins (VLDL), along with lower than normal levels of high-density lipoprotein (HDL), are common findings in the lipid profiles of patients with diabetes. The combined effect of these factors results in promotion of atherosclerosis and thrombosis.

The specific mechanism(s) by which hyperglycemia leads to poorer clinical outcome in patients receiving anticoagulants or thrombolytics is not known, although several have been proposed, including the following:

• In some vascular beds, hyperglycemia causes glycosylation and thereby interferes with protein and enzyme function, including those functions that regulate production of substances that cause vasodilation and cellular adhesion within the vasculature.
• Hyperglycemia results in the formation of advanced glycation end products that are toxic to endothelial cells, and production of free radicals from various sources may result in further vascular injury.

Hyperglycemia worsens outcome and increases rate of mortality from stroke. Two mechanisms have been postulated to explain the negative influence of hyperglycemia on outcome following stroke:

• Poorer reperfusion due to vascular injury
• Increased acidosis, perhaps from lactic acid, leading to further tissue injury

Both mechanisms have been supported by experimental data. Parsons et al (2002) used MRI and MR spectroscopy in patients with hyperglycemic stroke and report that the detrimental effect of hyperglycemia may be due to metabolic acidosis in the infracted brain parenchyma. However, earlier animal studies suggested that hyperglycemia has a detrimental effect on cerebral vascular tree (Kawai, 1997; Quast, 1997).

In some studies, hyperglycemia appears to be associated with a reduced incidence of primary intracerebral hemorrhage. However, risk of hemorrhagic conversion of strokes appears to increase after rtPA administration in patients with diabetes. This risk may be present even at moderate elevations of serum glucose level. Notably, moderate hyperglycemia is presently not an exclusion criterion for administration of rtPA in patients with acute stroke; the range of blood glucose for which rtPA treatment of patients with acute stroke is acceptable is 50-400 mg/dL.

Hypoglycemia

Low levels of glucose can result from the following:

• Overuse of oral hypoglycemic agents or insulin
• Overproduction of endogenous insulin, which may be a result of an insulinoma
• Medical illnesses such as sepsis, renal failure, and hepatic failure

Two different mechanisms have been suggested as the causes of hypoglycemia-related strokelike episodes, as follows:

• The brain uses glucose predominantly for oxidative metabolism. Different brain regions have different metabolic demands. The need for glucose is highest in the cerebral cortex and basal ganglia. The cerebellum and the subcortical white matter have less demand for this substrate. Focal deficits may be a result of asymmetric distribution of glucose transporters.
• Gold and Marshall suggest that coagulation defects may be the cause of strokelike episodes.

Frequency

International

Hyperglycemia: Hyperglycemia is reported to be present in 20-50% of patients incurring acute stroke. In many trials of thrombolytic agents, hyperglycemia occurred in about 20-30% of subjects.

Hypoglycemia: The Diabetes Control and Complications Trial (DCCT) found a 3-fold higher rate of severe hypoglycemia in the group that received intensive treatment for diabetes than in those who received conventional therapy. Patients in the group receiving intensive therapy required medical attention for hypoglycemia at an incidence of 62 episodes per 100 patient-years. Berkovic et al reported that hypoglycemia was the cause of symptoms mimicking acute stroke in 3 of a total of 1460 patients admitted to their stroke unit over a 5-year period.

Clinical

History

• Hyperglycemia and acute stroke
  • Patients may come to the attention of physicians because of preexisting diabetes mellitus.
  • Diabetes may be seen with other risk factors for stroke such as hypertension and hypercholesterolemia.
  • Hyperglycemia also may be seen in the setting of an acute stroke without a history of diabetes, presumably due to a sympathetic response to the infarct.
• Hypoglycemia and strokelike symptoms
  • Diabetes mellitus may have been diagnosed earlier, and recent changes in the doses of hypoglycemic agents and insulin may have been instituted.
  • Aggressively tight control, either patient driven or physician directed, may give rise to chronic hypoglycemia or recurrent episodes of hypoglycemia.
  • If factitious hypoglycemia is suspected, such behavior may have manifested earlier by similar episodes or other factitious behaviors.

Physical

• Signs and symptoms of acute stroke are covered in other articles (Stroke, Hemorrhagic; Stroke, Ischemic).
• Retinopathy, neuropathy, and peripheral vascular disease may be found in patients with long-standing diabetes.
• In the literature, signs of an acute stroke, such as hemiplegia, aphasia, and cortical blindness, have been reported with hypoglycemia.

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