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From the Departments of Internal Medicine (Drs. Kernan, Inzucchi, Viscoli, Bravata, and Horwitz), Neurology (Dr. Brass), and Epidemiology & Public Health (Drs. Brass and Horwitz), Yale University School of Medicine; and Veterans Affairs Connecticut Healthcare System (Drs. Brass and Bravata), New Haven, CT.
Address correspondence and reprint requests to Dr. Walter N. Kernan, Department of Medicine, Yale University School of Medicine, P.O. Box 208025, New Haven, CT 06520-8025; e-mail: walter.kernan{at}yale.edu
Background and purpose: Resistance to insulin-mediated glucose uptake by peripheral tissues is a cardinal defect in type 2 diabetes mellitus. Insulin resistance is also common among nondiabetic individuals, and may be an important risk factor for stroke in both populations. The authors review the definition, epidemiology, and treatment of insulin resistance.
Methods: The authors searched Medline (1977–2001) and reviewed bibliographies to identify pertinent English-language publications.
Results: Insulin resistance is present in most patients with type 2 diabetes. It is also common among elderly persons, certain ethnic groups, and persons with hypertension, obesity, physical deconditioning, and vascular disease. The principal pathophysiologic defect is impaired intracellular signaling in muscle tissue leading to defective glycogen synthesis. Insulin resistance is associated with numerous metabolic, hematologic, and cellular events that promote atherosclerosis and coagulation. The association between insulin resistance and risk for stroke has been examined in four case-control studies and five prospective observational cohort studies. Six of the nine studies are methodologically sound and provide evidence that insulin resistance is associated with risk for stroke.
Conclusion: Insulin resistance may be a prevalent risk factor for stroke. New drugs can safely reduce insulin resistance and may have a role in stroke prevention.
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