scholarly journals Type B insulin resistance syndrome associated with connective tissue disease and psoriasis

2020 ◽  
Vol 2020 ◽  
Author(s):  
Agnieszka Łebkowska ◽  
Anna Krentowska ◽  
Agnieszka Adamska ◽  
Danuta Lipińska ◽  
Beata Piasecka ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Connective Tissue ◽  
Insulin Receptor ◽  
Connective Tissue Disease ◽  
Acanthosis Nigricans ◽  
Insulin Resistance Syndrome ◽  
List Type ◽  
Type B ◽  
Immunoprecipitation Assay ◽  
Severe Insulin Resistance

Summary Type B insulin resistance syndrome (TBIR) is characterised by the rapid onset of severe insulin resistance due to circulating anti-insulin receptor antibodies (AIRAs). Widespread acanthosis nigricans is normally seen, and co-occurrence with other autoimmune diseases is common. We report a 27-year-old Caucasian man with psoriasis and connective tissue disease who presented with unexplained rapid weight loss, severe acanthosis nigricans, and hyperglycaemia punctuated by fasting hypoglycaemia. Severe insulin resistance was confirmed by hyperinsulinaemic euglycaemic clamping, and immunoprecipitation assay demonstrated AIRAs, confirming TBIR. Treatment with corticosteroids, metformin and hydroxychloroquine allowed withdrawal of insulin therapy, with stabilisation of glycaemia and diminished signs of insulin resistance; however, morning fasting hypoglycaemic episodes persisted. Over three years of follow-up, metabolic control remained satisfactory on a regimen of metformin, hydroxychloroquine and methotrexate; however, psoriatic arthritis developed. This case illustrates TBIR as a rare but severe form of acquired insulin resistance and describes an effective multidisciplinary approach to treatment. Learning points: We describe an unusual case of type B insulin resistance syndrome (TBIR) in association with mixed connective tissue disease and psoriasis. Clinical evidence of severe insulin resistance was corroborated by euglycaemic hyperinsulinaemic clamp, and anti-insulin receptor autoantibodies were confirmed by immunoprecipitation assay. Treatment with metformin, hydroxychloroquine and methotrexate ameliorated extreme insulin resistance.

scholarly journals Successful remission of type B insulin resistance syndrome without rituximab in an elderly male

2020 ◽  
Vol 2020 ◽  
Author(s):  
Marcio José Concepción-Zavaleta ◽  
Sofía Pilar Ildefonso-Najarro ◽  
Esteban Alberto Plasencia-Dueñas ◽  
María Alejandra Quispe-Flores ◽  
Cristian David Armas-Flórez ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Autoimmune Disease ◽  
Insulin Receptor ◽  
Case Reports ◽  
Immunosuppressive Treatment ◽  
Insulin Resistance Syndrome ◽  
Response To Treatment ◽  
List Type ◽  
Type B ◽  
Severe Insulin Resistance

Summary Type B insulin resistance syndrome (TBIR) is a rare autoimmune disease caused by antibodies against the insulin receptor. It should be considered in patients with dysglycaemia and severe insulin resistance when other more common causes have been ruled out. We report a case of a 72-year-old male with a 4-year history of type 2 diabetes who presented with hypercatabolism, vitiligo, acanthosis nigricans, and hyperglycaemia resistant to massive doses of insulin (up to 1000 U/day). Detection of anti-insulin receptor antibodies confirmed TBIR. The patient received six pulses of methylprednisolone and daily treatment with cyclophosphamide for 6 months. Response to treatment was evident after the fourth pulse of methylprednisolone, as indicated by weight gain, decreased glycosylated haemoglobin and decreased requirement of exogenous insulin that was later discontinued due to episodes of hypoglycaemia. Remission was eventually achieved and the patient is currently asymptomatic, does not require insulin therapy, has normal glycaemia and is awaiting initiation of maintenance therapy with azathioprine. Thus, TBIR remitted without the use of rituximab. This case highlights the importance of diagnosis and treatment in a timely fashion, as well as the significance of clinical features, available laboratory findings and medication. Large controlled studies are required to standardise a therapeutic protocol, particularly in resource-constrained settings where access to rituximab is limited. Learning points: Type B insulin resistance syndrome is a rare autoimmune disorder that should be considered in patients with dysglycaemia, severe insulin resistance and a concomitant autoimmune disease. Serological confirmation of antibodies against the insulin receptor is not necessary in all cases due to the high associated mortality without timely treatment. Although there is no standardised immunosuppressive treatment, a protocol containing rituximab, cyclophosphamide and steroids has shown a significant reduction in previously reported mortality rates. The present case, reports successful remission in an atypical patient using cyclophosphamide and methylprednisolone, which is an effective therapy in countries in which rituximab is not covered by health insurance. When there is improvement in the hypercatabolic phase, the insulin dose should be reduced and/or discontinued to prevent hypoglycaemia; a mild postprandial hyperglycaemic state should be acceptable.

scholarly journals Insulin receptor autoantibody-mediated hypoglycemia in a woman with mixed connective tissue disease

2021 ◽  
Author(s):  
Max C Petersen ◽  
Jonah M Graves ◽  
Tony Yao ◽  
Lutz Schomburg ◽  
Waldemar B Minich ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Connective Tissue ◽  
Insulin Receptor ◽  
Connective Tissue Disease ◽  
Mixed Connective Tissue Disease ◽  
Severe Hypoglycemia ◽  
Systemic Autoimmune Disease ◽  
Antibody Testing ◽  
Severe Insulin Resistance ◽  
Receptor Antibody

Abstract Autoantibodies to the insulin receptor are rare and typically cause severe insulin resistance and hyperglycemia, a condition termed type B insulin resistance. Uncommonly, antibodies to the insulin receptor can cause hypoglycemia. We present the case of a woman who developed recurrent severe hypoglycemia and myopathy, was found to have insulin receptor autoantibodies and mixed connective tissue disease, and had resolution of hypoglycemia with immunosuppression. A 55-year-old woman with a history of obesity, hypertension, and prior hemorrhagic stroke presented with recurrent severe hypoglycemia. A diagnostic fast resulted in hypoinsulinemic hypoketotic hypoglycemia. Adrenal function was intact. Progressive myopathy had developed simultaneously with her hypoglycemia, and rheumatologic evaluation revealed mixed connective tissue disease. The plasma acylcarnitine profile was normal, extensive oncologic evaluation including IGF-2 measurement was unrevealing, and anti-insulin antibody testing was negative. Ultimately, anti-insulin receptor antibodies were found to be present. The patient was treated with glucocorticoids and rituximab. Eight weeks after initiation of immunosuppression, the insulin receptor antibody titer had decreased and hypoglycemia had resolved. Eight months after diagnosis, the patient remained free of severe hypoglycemia despite tapering of glucocorticoids to a near-physiologic dose. Though antibodies to the insulin receptor typically cause severe insulin resistance, this patient had no evidence of insulin resistance and instead presented with recurrent severe hypoglycemia, which responded to glucocorticoids and rituximab. The diagnosis of insulin receptor antibody-mediated hypoglycemia is rare but should be considered in patients with systemic autoimmune disease, including mixed connective tissue disease, in the appropriate clinical context.

scholarly journals A New Mutation of the INSR Gene in a 13-Year-Old Girl with Severe Insulin Resistance Syndrome in China

2021 ◽  
Vol 2021 ◽  
pp. 1-4
Author(s):  
Jing Jin ◽  
Xinxin Liang ◽  
Jie Wei ◽  
Lingling Xu
Keyword(s):  
Insulin Resistance ◽  
Insulin Receptor ◽  
Acanthosis Nigricans ◽  
Polycystic Ovary ◽  
Receptor Gene ◽  
Insulin Resistance Syndrome ◽  
Type A ◽  
Insulin Receptor Gene ◽  
Severe Insulin Resistance ◽  
Type A Insulin Resistance

Background. Mutations in insulin receptor genes can cause severe insulin resistance syndrome. Compared with Rabson-Mendenhall Syndrome and Donohue’s Syndrome, type A insulin resistance syndrome is generally not serious. The main manifestations in woman with type A insulin resistance syndrome are hyperinsulinemia, insulin resistance, acanthosis nigricans, hyperandrogenism, and polycystic ovary. Case Presentation. A 13-year-old girl (Han nationality) visited the hospital due to hairiness and acanthosis nigricans. Further examination revealed severe hyperinsulinemia, insulin resistance, elevated blood glucose, hyperandrogenism, and polycystic ovary. Analysis of the insulin receptor gene by sequencing showed the presence of a nucleotide change in intron 7 (c. 1610+1G > A). The mutation was a splicing mutation, which can obviously affect the mRNA splicing of the insulin receptor and cause its function loss. The patient was finally diagnosed with type A insulin resistance syndrome. After 2 months of metformin treatment, the patient had spontaneous menstrual cramps and significantly improved acanthosis nigricans and sex hormones. Conclusion. We report for the first time a new splicing mutation on the insulin receptor gene at the 7th intron (c.1610+1G > A), which leads to type A insulin resistance syndrome. In clinically suspected patients with polycystic ovary syndrome, if there are extremely high blood levels of insulin in the blood, genetic testing should be performed to detect insulin receptor gene mutation of type A insulin resistance syndrome.

Type B insulin resistance syndrome in a patient with connective tissue disease

2017 ◽  
Author(s):  
Agnieszka Lebkowska ◽  
Anna Krentowska ◽  
Agnieszka Adamska ◽  
Beata Piasecka ◽  
Danuta Lipinska ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Connective Tissue ◽  
Connective Tissue Disease ◽  
Insulin Resistance Syndrome ◽  
Type B

scholarly journals Two Novel Variants and One Previously Reported Variant in the Insulin Receptor Gene in Two Cases with Severe Insulin Resistance Syndrome

2020 ◽  
Vol 11 (2) ◽  
pp. 90-96
Author(s):  
Aydilek Dagdeviren Cakir ◽  
Said Saidov ◽  
Hande Turan ◽  
Serdar Ceylaner ◽  
Yavuz Özer ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Receptor ◽  
Receptor Gene ◽  
Insulin Resistance Syndrome ◽  
Insulin Receptor Gene ◽  
Severe Insulin Resistance ◽  
Novel Variants

scholarly journals SEVERE INSULIN RESISTANCE WITH DIABETIC KETOACIDOSIS AFTER BRENTUXIMAB TREATMENT

2020 ◽  
Vol 6 (2) ◽  
pp. e98-e100
Author(s):  
Janet M. Chiang ◽  
Andrew R. Lai ◽  
Mark Anderson ◽  
Robert J. Rushakoff
Keyword(s):  
Insulin Resistance ◽  
Insulin Receptor ◽  
Diabetic Ketoacidosis ◽  
Hodgkin Lymphoma ◽  
Cytokine Release ◽  
Type B ◽  
Severe Insulin Resistance ◽  
Intravenous Insulin ◽  
Previous Diagnosis

Objective: To increase awareness of unusual inflammatory and other responses including severe insulin resistance (IR) associated with the use of targeted immunotherapies such as brentuximab. Methods: We report the case of a man without any previous diagnosis of diabetes who developed diabetic ketoacidosis complicated by severe IR (unresponsive to >600 units of intravenous insulin per hour) after receiving brentuximab for Hodgkin lymphoma. Results: Autoantibodies to the insulin receptor were not detected in the patient's serum, thus excluding a diagnosis of type B IR. Conclusion: We hypothesize that brentuximab administration led to a rare reaction leading to systemic cytokine release with extreme IR in our patient.

scholarly journals Type B insulin resistance syndrome in a patient with type 1 diabetes

2020 ◽  
Vol 2020 ◽  
Author(s):  
Åke Sjöholm ◽  
Maria João Pereira ◽  
Thomas Nilsson ◽  
Torbjörn Linde ◽  
Petros Katsogiannos ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Receptor ◽  
Plasma Glucose ◽  
Insulin Resistance Syndrome ◽  
Autoimmune Disorder ◽  
Type B ◽  
Binding Assays ◽  
Considerable Difficulty ◽  
Remarkable Effect ◽  
Insulin Requirements

Summary Type B insulin resistance syndrome (TBIRS) is a very rare autoimmune disorder with polyclonal autoantibodies against the insulin receptor, resulting in severe and refractory hyperglycemia. Described here is a patient who within a few months after the onset of autoimmune type 1 diabetes increased her insulin requirements more than 20-fold; despite this she had considerable difficulty maintaining a plasma glucose value of <40–60 mmol/L (720–1100 mg/dL). On suspicion of TBIRS, the patient was started on tapering dose of glucocorticoids to overcome the autoimmune insulin receptor blockade, resulting in an immediate and pronounced effect. Within days, insulin requirements decreased by 80–90% and plasma glucose stabilized around 7–8 mmol/L (126–144 mg/dL). The presence of antibodies to the insulin receptor was detected by immunoprecipitation and binding assays. After a 4-month remission on low maintenance dose prednisolone, the patient relapsed, which required repeated plasmaphereses and immune column treatments with temporarily remarkable effect. Mixed and transient results were seen with rituximab, mycophenolic acid and bortezomib, but the glycemic status remained suboptimal. Lack of compliance and recurrent infections may have contributed to this. Learning points: Type B insulin resistance syndrome (TBIRS) is a very rare autoimmune disorder with acquired polyclonal autoantibodies against the insulin receptor, resulting in severe and refractory hyperglycemia. We describe here a young patient in whom, a few months after the onset of a regular autoimmune diabetes, insulin requirements in a short time increased more than 20-fold, but despite this, the plasma glucose level could be kept at <40–60 mmol/L only with considerable difficulty. Did this patient have TBIRS? On suspicion of TBIRS, the patient was started on tapering glucocorticoids to overcome the autoimmune insulin receptor blockade, resulting in an immediate and pronounced effect; within days insulin requirements decreased by 80–90% and plasma glucose stabilized around 7–8 mmol/L. The presence of antibodies to the insulin receptor was detected by immunoprecipitation and binding assays. After a 4-month remission on low maintenance dose prednisolone, the patient relapsed, which required repeated plasmaphereses with temporarily remarkable effect. TBIRS should be considered in diabetic patients whose glycemia and/or insulin requirements are inexplicably and dramatically increased.

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