Clinical course of the syndrome of autoantibodies to the insulin receptor (type B insulin resistance)

Autoantibodies to the cell surface receptors represent an important mechanism of endocrine disease. we studied the natural history of the disease caused by autoantibodies to the insulin receptor. We evaluated 24 patients (M/F: 4/20; age of presentation: 10-68 yr) with this disease between January 1973 and December 2000. Twenty-one patients (88%) were African American. Acanthosis nigricans (+/-:21/3) and hyperandrogenism in females (7/20 patients) were common. All but 1 patient displayed nonspecific "autoimmune" features. Systemic lupus erythematosus (SLE) (n = 11) was the most common underlying syndrome. Thirteen of 24 patients had proteinuria, most commonly associated with lupus nephritis (n = 7). Three of 24 patients presented with spontaneous hypoglycemia. The remaining 21 patients (80%) presented with hyperglycemia and major weight loss (up to 120 lb within 5 mo). Long-term follow-up information is available for 18 of the 21 patients presenting with hyperglycemia. After a prolonged period of hyperglycemia (3-21 mo), spontaneous hypoglycemia ensued in 3 of the patients. Patients presenting with hyperglycemia received high doses of insulin for therapy (mean dose, 5,100 IU/day). The autoantibody disappeared spontaneously in 7 of 18 patients within 11-48 months (mean, 30 mo). Twelve remaining patients received various immunosuppressive regimens (steroids, cyclophosphamide, and cyclosporine). After 6-54 months of diabetes, 6 of these patients remitted within 6 weeks of immunotherapy. The remaining 6 patients received similar immunotherapy protocols, but did not go into remission despite 21-228 months (mean, 100 mo) of follow-up. None of the agents appeared more likely to induce remission. Another striking feature was the high rate of mortality: 13 of 24 patients (54%) died at 56 ± 12 years. Eight of the 13 deaths occurred in patients who went into remission. Three patients who had presented with hyperglycemia and then developed hypoglycemia died from complications of hypoglycemia. Type B insulin resistance is a heterogeneous metabolic syndrome seen predominantly in female African-American patients with a high association with SLE. About one-third of patients remit spontaneously. Immunotherapy did not have a significant impact on duration of diabetes. There is a high rate of mortality even in patients who entered remission, and a switch from hyperglycemia to hypoglycemia is an indicator of poor prognosis.