Type B insulin resistance syndrome: a systematic review

ABSTRACT A literature review on the clinical, laboratory, and treatment features of type B insulin resistance syndrome (TBIRS). Data from PubMed, the Virtual Health Library and Cochrane database were selected and analyzed using the REDCap application and R statistical program. From 182 papers, 65 were selected, which assessed 119 clinical cases, 76.5% in females and 42.9% in African-Americans, with an average age of 44 years. A common feature of TBIRS is co-occurrence of autoimmune diseases, such as systemic lupus erythematosus (most frequently reported). Hyperglycemia of difficult control was the mostly reported condition. Tests for anti-insulin receptor antibodies were positive in 44.2% of the cases. Disease management comprised fractional diet, insulin therapy (maximum dose given was 57 600 IU/day), plasmapheresis and immunosuppression with several classes of drugs, mainly glucocorticoids. Remission occurred in 69.7% of cases, in 30.3% of these spontaneously. The mortality rate was 15.38%. There was an inverse relationship between anti-insulin antibodies and remission (p = 0.033); and a positive correlation between combined immunosuppressive therapy and remission (p = 0.002). Relapse occurred in 7.6% of the cases. This rare syndrome has difficult-to-control diabetes, even with high doses of insulin, and it is usually associated with autoimmune diseases. Therapeutic advances using immunomodulatory therapy have led to significant improvements in the rate of remission.

Autoimmune Hypoglycemia in a Patient with Characterization of Insulin Receptor Autoantibodies

BACKGROUND: Type B insulin resistance syndrome is a manifestation of autoantibodies to the insulin receptor that results in severe hyperglycemia and acanthosis nigricans. However, the mechanisms by which these autoantibodies induce hypoglycemia are largely unknown. In this paper, we report the case of patient with type B insulin resistance syndrome who presented with frequent severe fasting hypoglycemia and acanthosis nigricans. METHODS: To evaluate the mechanism of hypoglycemia, we measured the inhibition of insulin binding to erythrocytes and IM9 lymphocytes in a sample of the patient's dialyzed serum before and after immunosuppressive therapy. RESULTS: In the patient's pre-treatment serum IgG, the binding of 125I-insulin to erythrocytes was markedly inhibited in a dose-dependent manner until the cold insulin level reached 10-9 mol/L. We also observed dose-dependent inhibition of insulin binding to IM9 lymphocytes, which reached approximately 82% inhibition and persisted even when diluted 1:20. After treatment with glucocorticoids, insulin-erythrocyte binding activity returned to between 70% and 80% of normal, while the inhibition of insulin-lymphocyte binding was reduced by 17%. CONCLUSION: We treated a patient with type B insulin resistance syndrome showing recurrent fasting hypoglycemia with steroids and azathioprine. We characterized the patient's insulin receptor antibodies by measuring the inhibition of insulin binding.

A Case of the Type B Insulin Resistance Syndrome with Chronic Hepatitis B

Type B insulin resistance syndrome is rare autoimmune disease that is characterized by various abnormalities of glycemic homeostasis, from hyperglycemia caused by extreme insulin resistance to fasting hypoglycemia. It can combine with other autoimmune diseases, most commonly systemic lupus erythematosus. It usually occurs in women and accompanies acanthosis nigricans, hyperandrogenism, and, in many cases, ovary dysfunction. The diagnosis of type B insulin resistance syndrome is based largely on the presence of insulin receptor autoantibodies and hyperglycemia, or hypoglycemia and hyperinsulinemia. In some cases, patients with the type B insulin resistance have been successfully treated with immunosuppressive therapy and plasmapheresis. We experienced type B insulin resistance syndrome in a patient with chronic hepatitis B and used only plasmapheresis for treatment. The immunosuppressive therapy was omitted due to the state of activation of chronic hepatitis B. We present this case with a review of relevant literature.

A case of adult nesidioblastosis mimicking an insulinoma and autoimmune hypoglycemia / 대한내과학회지

Hyperinsulinemic hypoglycemia in the absence of exogenous insulin use is caused by disorders such as insulinoma, diffuse beta-cell hyperplasia/nesidioblastosis, and autoimmune hypoglycemia. Nesidioblastosis is a rare cause of hypoglycemia in adults, accounting for 0.5~7.0% of organic hyperinsulinemia cases. Although pancreatic resection is considered the best treatment modality for curing nesidioblastosis, there is no consensus regarding the indications for and extent of the surgery due to its high risk and complication rate. A 75-year-old woman presented with an altered mental state, a mass suspected of being an insulinoma, and insulin receptor antibodies. The patient underwent surgery because of recurrent life-threatening hypoglycemia. Postoperative pathology of her pancreas revealed nesidioblastosis.

Clinical Characteristics in Korean Patients with Insulin Receptor Antibody Positive Acanthosis Nigricans / 대한내분비학회지

BACKGROUND: Insulin resistance syndrome shows extreme insulin resistance and is associated with acanthosis nigricans. We can differentiate it into type A insulin resistance that has insulin receptor defect, and type B insulin resistance due to insulin receptor autoantibody. Type B insulin resistance was firstly described by Kahn in 1976. It was often found in adult female and showed autoimmune characteristics. As clinical characteristics, there are hyperglycemia, hypoglycemia, hyperinsulinemia, extreme insulin resistance and acanthosis nigricans. METHODS: We investigated 17 insulin receptor autoantibody positive cases and 8 cases of normal control who had visited Wonju Christian Hospital from October 1994 to December 1995. Among insulin receptor autoantibody positive subject, male was 4 cases and female 13 cases. Their mean age was 42.2. We compared patients who had insulin receptor antibody positive acanthosis nigricans(IRA) with normal controls. IRA patients were 6 cases(35.3%) of nomal glucose tolerance, 11 cases(64.7%) of abnormal glucose tolerance including overt diabetes mellitus. RESULTS: The 11 cases(64.7%) among IRA patrents were obese and 13 cases(76.5%) had hyperininsulinemia. In IRA patients, mean serum insulin concentration during oral glucose tolerance test was 202.1mU/mL and it was greater than 46.3 of normal controls. Insulin sensitivity in 1.79mg/L * mM * xmU * min normal controls was higher than 0.74mg/L * mM * min of IRA patients. CONCLUSION: IRA patients showed abnormal glucose tolerance including overt diabetes millitus, severe insulin resistance, hyperinsulinemia and obesity.