Imaging of the Buffering Effect of Insulin Antibodies in the Autoimmune Hypoglycemic Syndrome1

Dozio, Nicoletta; Scavini, Marina; Beretta, Andrea; Sarugeri, Elena; Sartori, Stefano; Belloni, Cristina; Dosio, Flaviano; Savi, Annarita; Fazio, Ferruccio; Sodoyez, J. C.; Pozza, G.

doi:10.1210/jcem.83.2.4599

Cited by 23 publications

(7 citation statements)

References 38 publications

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“…The characteristics of anti-insulin antibodies have been thoroughly studied in IAS. It is evident that high-affinity insulin antibodies frequently induce insulin resistance, whereas the presence of low-affinity antibodies induce hypoglycaemia due to the dissociation of the high amount of insulin from the insulin–antibody complex (12) (13). However, in diabetes, only a few studies have focused on the characteristics of these antibodies (6).…”

Section: Discussionmentioning

confidence: 99%

Analytical and clinical challenges in a patient with concurrent type 1 diabetes, subcutaneous insulin resistance and insulin autoimmune syndrome

Jassam

Amin

Holland

et al. 2014

Endocrinology, Diabetes &Amp; Metabolism Case Reports

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SummaryA lean 15-year-old girl was diagnosed with type 1 diabetes based on symptomatic hyperglycaemia and positive anti-islet cell antibodies. Glycaemia was initially stabilised on twice-daily mixed insulin. After 11 months from the time of diagnosis, she complained of hyperglycaemia and ketosis alternating with hypoglycaemia. This progressively worsened until prolonged hospital admission was required for treatment of refractory hypoglycaemia. A high titre of anti-insulin antibodies was detected associated with a very low recovery of immunoreactive (free) insulin from plasma after precipitation with polyethylene glycol, suggesting the presence of insulin in bound complexes. Insulin autoimmune syndrome was diagnosed and metabolic fluctuations were initially managed supportively. However, due to poor glucose control, immunosuppressive therapy was initiated first with steroids and plasmapheresis and later with anti-CD20 antibody therapy (Rituximab). This treatment was associated with a gradual disappearance of anti-insulin antibodies and her underlying type 1 diabetes has subsequently been successfully managed with an insulin pump.Learning points Anti-insulin antibodies may result in low levels of free insulin.Polyclonal anti-insulin antibodies can interfere with the pharmacological action of administered insulin, resulting in hypoglycaemia and insulin resistance, due to varying affinities and capacities.In this patient, rituximab administration was associated with a gradual disappearance of anti-insulin antibodies.It is hypothesised that this patient had subcutaneous insulin resistance (SIR) caused by insulin capture at the tissue level, either by antibodies or by sequestration.A prolonged tissue resistance protocol may be more appropriate in patients with immune-mediated SIR syndrome.

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Section: Discussionmentioning

confidence: 99%

Analytical and clinical challenges in a patient with concurrent type 1 diabetes, subcutaneous insulin resistance and insulin autoimmune syndrome

Jassam

Amin

Holland

et al. 2014

Endocrinology, Diabetes &Amp; Metabolism Case Reports

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“…122 Plasmapheresis has been used in more severe cases, with the aim to lower IAA titer rapidly, thus preventing hypoglycemia. 113,123,124 Independently from the kind of therapeutic approach adopted, frequent glucose monitoring during the follow-up seems advisable. Continuous glucose monitoring (CGM) allows glucose measurement in the interstitial fluid with a frequency up to 5 mins, with the possibility of high and low glucose levels alarms and glucose trend information, that has been proven efficacious in diabetic patients in helping reducing HbA1c concentrations.…”

Section: Therapymentioning

confidence: 99%

<p>Insulin Autoimmune Syndrome (Hirata Disease): A Comprehensive Review Fifty Years After Its First Description</p>

Cappellani¹,

Macchia²,

Falorni³

et al. 2020

DMSO

114

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Insulin autoimmune syndrome (IAS), also named Hirata's disease, is a rare condition characterized by hypoglycemic episodes due to the presence of high titers of insulin autoantibodies (IAA). IAS is a form of immune-mediated hypoglycemia, which develops when a triggering factor (ie, a medication or a viral infection) acts on an underlying predisposing genetic background. IAS pathogenesis involves the formation of insulin-IAA complexes that induce glycemic alterations with a double-phase mechanism: IAA prevent insulin to bind its receptor in the postprandial phase, possibly resulting in mild hyperglycemia; thereafter, insulin is released from the complexes irrespective of blood glucose concentrations, thus inducing hypoglycemia. The diagnosis of IAS is challenging, requiring a careful workup aimed at excluding other causes of hyperinsulinemic hypoglycemia. The gold standard for the definitive diagnosis is the finding of IAA in a blood sample. Because IAS is frequently a self-remitting disease, its management mostly consists of supportive measures, such as dietary modifications, aimed at preventing the development of hypoglycemia. Pharmacological therapies may occasionally be necessary for patients presenting with severe manifestations of IAS. Available therapies may include drugs that reduce pancreatic insulin secretion (somatostatin analogues and diazoxide, for instance) and immunosuppressive agents (glucocorticoids, azathioprine and rituximab). The purpose of this review is to provide a comprehensive analysis of the disease, by describing the burden of knowledge that has been obtained in the 50 years following its first description, took in 1970, and by highlighting the points that are still unclear in its pathogenesis and management.

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“…In patients with this low-affinity/high-binding antibody, food-stimulated pancreatic insulin rapidly binds to insulin autoantibodies after eating, and this binding reduces insulin utilization by receptors in the liver and peripheral tissues, masking the biological activity of insulin and leading to postprandial hyperglycemia, which further stimulates insulin secretion from the pancreas [ 43 ]. Dozio et al[ 43 ] investigated the mechanism of hypoglycemia by performing 125I-labeled insulin scintigraphy in a patient with IAS. Following intravenous administration of 125I-labeled insulin, the patient showed sustained labeled insulin activity in the blood, with no uptake of labeled hormones in the liver or kidneys.…”

Section: Resultsmentioning

confidence: 99%

Insulin Autoimmune Syndrome: A Systematic Review

Lin

Chen

Ning

2023

International Journal of Endocrinology

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Insulin autoimmune syndrome (IAS) is a rare endocrine disorder characterized by recurrent episodes of severe hypoglycemia, markedly elevated serum insulin, and positive insulin autoantibodies. In recent years, various countries have reported it one after another. It can be seen that we must pay attention to this disease. The diagnosis of IAS is challenging, requiring a careful workup aimed at excluding other causes of hyperinsulinemic hypoglycemia. High levels of insulin autoantibodies are found in patients, and C-peptide is not parallel to insulin, which could be diagnostic. IAS is a self-limiting disease with a good prognosis. Its treatment mainly includes symptomatic supportive treatment, such as adjusting the diet and using acarbose and other drugs to delay the absorption of glucose to prevent hypoglycemia. For patients with severe symptoms, available treatments may include drugs that reduce pancreatic insulin secretion (such as somatostatin and diazoxide), immunosuppressants (glucocorticoids, zaprin, and rituximab), and even plasma exchange to remove autoantibodies from the body. This review provides a comprehensive analysis of the epidemiology, pathogenesis, clinical manifestations, diagnosis and identification, and monitoring and treatment management of IAS.

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Imaging of the Buffering Effect of Insulin Antibodies in the Autoimmune Hypoglycemic Syndrome1

Cited by 23 publications

References 38 publications

Analytical and clinical challenges in a patient with concurrent type 1 diabetes, subcutaneous insulin resistance and insulin autoimmune syndrome

Analytical and clinical challenges in a patient with concurrent type 1 diabetes, subcutaneous insulin resistance and insulin autoimmune syndrome

<p>Insulin Autoimmune Syndrome (Hirata Disease): A Comprehensive Review Fifty Years After Its First Description</p>

Insulin Autoimmune Syndrome: A Systematic Review

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