EXTREME INSULIN RESISTANCE IN ATAXIA TELANGIECTASIA - DEFECT IN AFFINITY OF INSULIN RECEPTORS

The syndrome of ataxia telangiectasia is associated with glucose intolerance and Insulin resistance. We examined the status of insulin receptors on circulating monocytes and on cultured fibroblasts from two siblings with ataxia telangiectasia and severe insulin resistance. 125I-insulin binding to monocytes of the two patients consistently demonstrated an 80 to 85 per cent decrease in receptor affinity. In contrast, the defect in receptor affinity was not expressed on the patients’ cultured fibroblasts or on monocytes or fibroblasts obtained from unaffected family members. Whole plasma and immunoglobulin-enriched fractions of plasma from the patients inhibited the normal binding of insulin to its receptors on cultured human lymphocytes (IM-9 line) and on human placental membranes. We conclude that the insulin resistance in the two siblings with ataxia telangiectasia was associated with defects in the affinity of the receptors for insulin, probably caused by circulating inhibitors of insulin binding. (N Engl J Med 298:1164–1171, 1978) ATAXIA telangiectasia, an autosomal recessive syndrome characterized by progressive cerebellar ataxia, telangiectasias and diverse abnormalities of the immune system, is often accompanied by glucose intolerance and insulin resistance.12 Schalch et al.12 reported that 10 out of 17 patients with ataxia telangiectasia (59 per cent) had hyperglycemia, usually associated with elevated levels of plasma insulin and resistance to the hypoglycemic effect of administered insulin. These patients had no other causes of insulin resistance, such as circulating antibodies to insulin, obesity, lipoatrophy, Cushing's disease or acromegaly. Recent studies have examined the interaction of insulin with its target-cell receptor in several clinical states. © 1978, Massachusetts Medical Society. All rights reserved.