Syndromes of autoimmunity and hypoglycemia. Autoantibodies directed against insulin and its receptor.
Humoral autoimmunity plays an important role in the pathogenesis of two forms of hypoglycemia. In one syndrome, antireceptor autoantibodies bind to the insulin receptor, mimic insulin action, and cause fasting hypoglycemia. In most patients with autoantibodies to the insulin receptor, there is other evidence of autoimmune disease as well. Interpretation of the standard tests used in evaluation of hypoglycemia may be confusing in these patients. For example, antireceptor antibodies may inhibit insulin binding, thereby inhibiting insulin clearance and elevating levels of plasma insulin. Nevertheless, because hypoglycemia suppresses beta-cell secretion, C-peptide levels are usually low. This constellation of data is consistent with surreptitious insulin injection. The most important laboratory test in the differential diagnosis is a direct assay for the presence of antibodies directed against the insulin receptor. Therapy with prednisone appears to alleviate the hypoglycemia rapidly, usually within 24 hours. This effect of prednisone appears to result from antagonism of the effects of antireceptor antibodies without actually lowering their titer. The natural history of this syndrome is that the antireceptor antibodies disappear and the syndrome resolves over a time course of several months to several years. In North America, the presence of anti-insulin antibodies in a hypoglycemic patient most commonly suggests that the patient has been immunized with exogenous insulin. However, some patients--especially in Japan--develop spontaneous autoantibodies directed against insulin. These antibodies can cause hypoglycemia, which is generally reactive in that it occurs several hours after a meal or a glucose challenge rather than in a fasting state. The most effective therapy is frequent small feedings and avoidance of large meals.
Taylor
S I
SI
National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland.
Barbetti
F
F
Accili
D
D
Roth
J
J
Gorden
P
P
D001323:Autoantibodies / Q000032:analysis / Q000276:immunology*; D001327:Autoimmune Diseases / Q000175:diagnosis / Q000276:immunology* / Q000628:therapy; D006801:Humans; D007003:Hypoglycemia / Q000209:etiology / Q000276:immunology* / Q000628:therapy; D007159:Immunologic Tests; D007330:Insulin Antibodies / Q000032:analysis / Q000276:immunology*; D011972:Receptor, Insulin / Q000276:immunology*; D013577:Syndrome
D001323:Autoantibodies; D007330:Insulin Antibodies; D011972:Receptor, Insulin