Insulin-Resistant Diabetes with Insulin Receptor Autoantibodies in a Male Patient Without Acanghosis Nigricans

Abstract

A 51-yr-old, nonobese, male patient presented with hyperglycemia and a recent 40-pound weight loss. Severe insulin resistance was documented in studies in which high amounts of insulin were infused using the Biostator GCIIS. Diabetic control was finally achieved with subcutaneous injections of 470 U of insulin per day. Positive laboratory findings included a mild pancytopenia, elevated erythrocyte sedimentation rate, decreased C3 and properdin, and increased IgA. Antinuclear or other autoantibodies were not present. Insulin antibody levels were within the range usually present in insulin-treated diabetic patients. Acanthosis nigricans was not present. Incubation of the patient's serum with IM-9 lymphoblastoid cells revealed that an insulin receptor antibody was present in a serum dilution of 1:80. Insulin-resistant diabetes mediated by insulin receptor antibodies may present in patients with immunologic findings but without overt dermatologic stigmata.

Insulin binding sites in various segments of the rabbit nephron.

“…A14-'251-insulin was chosen because it is stable, has a high specific activity, and its binding characteristics and biologic properties are similar to native insulin (9). These experimental conditions were found by us to be optimal for insulin binding to tubular cell membranes and to minimize insulin degradation during incubation (6 (10,11). Tubules were incubated for 60 min at 22°C in 2 Ml of undiluted serum from the patients and from a normal control.…”

Mechanism of Hyperglycemia and Response to Treatment with an Inhibitor of Fatty Acid Oxidation in a Patient with Insulin Resistance due to Antiinsulin Receptor Antibodies*

“…Approximately 25 patients with insulin resistance due to antiinsulin receptor antibodies have been reported (1)(2)(3)(4)(5)(6)(7). The presence of antiinsulin receptor antibodies was suggested by virtually complete absence of insulin binding to the patient's monocytes, erythrocytes, and adipocytes.…”

“…Intuitively, therapy aimed at decreasing the titer or affinity of the antireceptor antibody would be the logical approach, but the results of immunosuppressive therapy have been disappointing, with clinical benefit occurring in only a minority of patients (1)(2)(3)(4)(5)(6)(7)(15)(16)(17). Since insulin has no hypoglycemic effect in many of these patients, any successful hypoglycemic agent presumably would need to act through a pathway not involving the insulin receptor.…”

“…(J Clin Endocrinol Metab 59: 658,1984) S PONTANEOUS autoantibodies directed against the insulin receptor are associated with both hypoglycemia and insulin resistance in man (1)(2)(3)(4)(5)(6), indicating that these antibodies can function as either insulin agonists or antagonists (2,(7)(8)(9)(10)(11). Although patients with antiinsulin receptor antibodies may have only mild glucose intolerance, more marked hyperglycemia also occurs (1)(2)(3)(4)(5). The mechanism responsible for the hyperglycemia is not known.…”

A connective tissue disease complicated by insulin resistance due to receptor antibodies: Report of a case with high titer nuclear ribonucleoprotein antibodies

“…As reported, 3 patients had arthritis or arthralgias, 2 had Raynaud's phenomenon, 1 had multisystem progressive systemic sclerosis, 3 had features suggesting glomerulonephritis, 6 had leukopenia (less than 3400 WBC/mm3), 8 had hypergammaglobulinemia, 4 had circulating rheumatoid factors, and 5 had hypocomplementemia. In 1 case each the only connective tissue disease manifestations (other than ANA) were laboratory abnormalities consisting of proteinuria and hypocomplementemia (1,2); leukopenia, hypergammaglobulinemia, and a positive rheumatoid factor test (7); and leukopenia and hypocomplementemia (9). Sjogren's syndrome was diagnosed in 2 cases (3,4), but evidence supporting the diagnosis was not reported; painless salivary gland enlargement was reported in 2 additional patients (1,2,5,6).…”