Recurrent Diabetic Ketoacidosis and Extreme Insulin Resistance Due to Anti-Insulin Antibodies: Response to Immunosuppression and Plasma Exchange

Ahmed, Maaz; Subbalaxmi, M.V.S; Anne, Beatrice; Deme, Swaroopa

doi:10.1089/dia.2020.0438

Cited by 5 publications

(7 citation statements)

References 14 publications

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“…Regarding insulin dosage requirements, the IA-positive group appeared to require slightly more insulin than the control group, despite there being no statistical difference, suggesting that IAs may not be associated with immune insulin resistance in the short-term, while the long-term effects must be determined by subsequent studies. Although it has been documented that patients with high IA levels may present with a rare syndrome of severe insulin resistance (requiring more than 200 U/d of insulin for at least two days) ( 9 , 27 ), the underlying causal mechanism remains unclear. Additional prospective treatment trials involving human and animal insulin, insulin analogs, and inhaled insulin trials have also shown no significant correlation between IA levels and insulin dose in insulin-naive and insulin-treated patients ( 5 , 7 , 28 ).…”

Section: Discussionmentioning

confidence: 99%

“…According to Fineberg et al (5), insulin antibodies (IAs) were still present in 40-60% of insulin-treated diabetics. Although previous studies showed no significant correlation between IAs and glucose control (6,7), IA-associated cases leading to severe clinical events, including insulin resistance (8), recurrent diabetic ketoacidosis (DKA) (9), or hypoglycemia (10), have continued to be reported. Recently, these events have garnered a resurgence of attention and have been defined as comprising exogenous insulin antibody syndrome (EIAS) (10,11).…”

Section: Introductionmentioning

confidence: 99%

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Association of subclass distribution of insulin antibody with glucose control in insulin-treated type 2 diabetes mellitus: a retrospective observational study

Chen

Yin

et al. 2023

Front. Endocrinol.

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ObjectiveTo examine the distribution and effects of the subclass of insulin antibodies on glucose control and side events in patients with type 2 diabetes treated with premixed insulin analog.MethodsA total of 516 patients treated with premixed insulin analog were sequentially enrolled from the First Affiliated Hospital of Nanjing Medical University from June 2016 to August 2020. Subclass-specific insulin antibodies (IAs) (IgG1-4, IgA, IgD, IgE, and IgM) were detected in IA-positive patients by electrochemiluminescence. We analyzed glucose control, serum insulin, and insulin-related events between IA-positive and IA-negative groups, as well as among patients with different IA subclasses.ResultsOverall, 98 of 516 subjects (19.0%) were positive for total IAs after premixed insulin analog therapy; of these participants, 92 had subclass IAs, and IgG-IA was the predominant subclass, followed by IgE-IA. IAs were associated with serum total insulin increase and local injection-site reactions but not glycemic control and hypoglycemia. In the subgroup analysis in patients with IA-positive, the IgE-IA and IA subclass numbers were more associated with increased serum total insulin levels. Additionally, IgE-IA might be correlated more strongly with local responses and weakly with hypoglycemia, while IgM-IA might be correlated more strongly with hypoglycemia.ConclusionWe concluded that IAs or IA subclasses might be associated with unfavorable events in patients receiving premixed insulin analog therapy, which can be used as an adjunctive monitoring indicator in clinical insulin trials.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Association of subclass distribution of insulin antibody with glucose control in insulin-treated type 2 diabetes mellitus: a retrospective observational study

Chen

Yin

et al. 2023

Front. Endocrinol.

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“…Therapies that have shown efficacy include withdrawal of insulin and utilization of oral agents in type 2 diabetes. However, with type 1 diabetes replacement of insulin with oral agents is not an option and the proven efficacious treatments are the use of glucocorticoids, plasmapheresis, and immunosuppressants [8][9][10][11][12]. However, there has never been a placebo controlled or randomized study to compare these options and a randomized study is made less likely to occur because of the rarity of this condition.…”

Section: Discussionmentioning

confidence: 99%

Development of Exogenous Insulin Antibody Syndrome in a Patient with Newly Diagnosed Type 1 Diabetes Successfully Treated with Oral Immunosuppressive Monotherapy

Jerkins

Bell

2021

Diabetes Ther

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Exogenous insulin antibody syndrome (EIAS), which rarely occurs in the patient with type 1 diabetes, results in antibody-induced insulin resistance, hyperglycemia, ketosis, ketoacidosis, and hypoglycemia when insulin is released from the saturated insulin antibodies. Recommended treatment regimens include glucocorticoids, immunosuppressants, and plasmapheresis. In the patient with type 1 diabetes, glucocorticoids may by inducing and/or worsening ketoacidosis be contraindicated. With immunosuppressants, various anecdotal treatment regimens have been reported. Currently the most commonly recommended regimen is intravenous immunosuppressive therapy in combination with oral immunosuppressants. Herein we describe a patient in whom oral immunosuppressant monotherapy with mycophenolate resulted in the cure of EIAS, thus avoiding the expense associated with intravenous immunosuppressant therapy and/ or hospitalization for plasmapheresis.

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“…Both TPE and IVIg have been utilized in the treatment of insulin-induced type III HSRs. TPE was effective in 3 cases, including ours, while IVIg's effectiveness varied, with an initial positive response reported in one case (4)(5)(6)(7)(8). Immunosuppressive agents targeting B and T cells, such as rituximab, methotrexate, azathioprine, and MMF, have yielded varying effectiveness results (Table 1).…”

Section: Sample Characteristicsmentioning

confidence: 93%

“…Infrequently, insulin hypersensitivity can arise from the formation of antigen-antibody immune complexes (ICs), resulting in type III HSRs. These reactions are often characterized by the development of painful subcutaneous nodules, commonly referred to as “Arthus’ reactions”, occurring at the insulin injection sites within 24 h of the subcutaneous injection ( 2 , 4 ).…”

Section: Introductionmentioning

confidence: 99%

A case report and systematic literature review: insulin-induced type III hypersensitivity reaction

Meredith,

Patel,

Huang

et al. 2024

Front. Allergy

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Insulin-induced type III hypersensitivity reactions (HSRs) are exceedingly rare and pose complex diagnostic and management challenges. We describe a case of a 43-year-old woman with type 1 diabetes mellitus (DM), severe insulin resistance, and subcutaneous nodules at injection sites, accompanied by elevated anti-insulin IgG autoantibodies. Treatment involved therapeutic plasma exchange (TPE) and intravenous immunoglobulin (IVIg) as bridge therapy, followed by long-term immunosuppression, which reduced autoantibody levels and improved insulin tolerance. Given the limited treatment guidelines, we conducted a comprehensive literature review, identifying 16 similar cases. Most patients were females with a median age of 36.5 years; 63% had type 1 DM, and 44% had concurrent insulin resistance (56% with elevated autoantibodies). Treatment approaches varied, with glucocorticoids used in 67% of cases. Patients with Type 1 DM were less responsive to steroids than those with type 1 DM, and had a more severe course. Of those patients with severe disease necessitating immunosuppression, 66% had poor responses or experienced relapses. The underlying mechanism of insulin-induced type III HSRs remains poorly understood. Immunosuppressive therapy reduces anti-insulin IgG autoantibodies, leading to short-term clinical improvement and improved insulin resistance, emphasizing their crucial role in the condition. However, the long-term efficacy of immunosuppression remains uncertain and necessitates continuous evaluation and further research.

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Recurrent Diabetic Ketoacidosis and Extreme Insulin Resistance Due to Anti-Insulin Antibodies: Response to Immunosuppression and Plasma Exchange

Cited by 5 publications

References 14 publications

Association of subclass distribution of insulin antibody with glucose control in insulin-treated type 2 diabetes mellitus: a retrospective observational study

Association of subclass distribution of insulin antibody with glucose control in insulin-treated type 2 diabetes mellitus: a retrospective observational study

Development of Exogenous Insulin Antibody Syndrome in a Patient with Newly Diagnosed Type 1 Diabetes Successfully Treated with Oral Immunosuppressive Monotherapy

A case report and systematic literature review: insulin-induced type III hypersensitivity reaction

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