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Review
. 2023 Oct 20:14:1226231.
doi: 10.3389/fendo.2023.1226231. eCollection 2023.

Case Report: Insulin hypersensitivity in youth with type 1 diabetes

Einas H Alkhatib  1 , Jody B Grundman  1 , Anna M Adamusiak  2 , Melena D Bellin  2   3 , Joel P Brooks  4 , Kevin S Buckley  5 , Erin M Janssen  6 , Maleewan Kitcharoensakkul  7 , Kyle P McNerney  8 , Thea L Pfeifer  9 , Brooke I Polk  7 , Brynn E Marks  10
Affiliations
Review

Case Report: Insulin hypersensitivity in youth with type 1 diabetes

Einas H Alkhatib et al. Front Endocrinol (Lausanne). .

Abstract

Objective: Immediate type I, type III, and delayed type IV hypersensitivity reactions to insulin are rare, but potentially serious complications of exogenous insulin administration required for the treatment of type 1 diabetes (T1D).

Methods: We present four cases of insulin hypersensitivity reactions occurring in youth with T1D and a literature review of this topic.

Results: Insulin hypersensitivity reactions included types I, III, and IV with presentations ranging from localized urticaria, erythematous nodules, and eczematous plaques to anaphylaxis with respiratory distress. Reactions occurred in youth with newly diagnosed T1D and in those with long-standing T1D who were using both injection and insulin pump therapy. Multidisciplinary care involving pediatric endocrinology and allergy/immunology utilizing trials of many adjunct therapies yielded minimal improvement. Despite the use of various treatments, including antihistamines, topical therapies, immunosuppressant medications, desensitization trials, and intravenous immune globulin, cutaneous reactions, elevated hemoglobin A1c levels, and negative effects on quality of life remain persistent challenges. One patient became one of the youngest pancreas transplant recipients in the world at age 12 years due to uncontrollable symptoms and intolerable adverse effects of attempted therapies.

Conclusion: Although rare, insulin hypersensitivity reactions negatively affect glycemic control and quality of life. These cases demonstrate the varying severity and presentation of insulin hypersensitivity reactions along with the limited success of various treatment approaches. Given the life-sustaining nature of insulin therapy, further studies are needed to better understand the underlying pathophysiology of insulin hypersensitivity and to develop targeted treatment approaches.

Keywords: insulin allergy; insulin hypersensitivity; pancreas transplant; pediatrics; type 1 diabetes.

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Conflict of interest statement

JBG has research support from the American Diabetes Association 7-21-PDFHD-09 and research supplies from Dexcom. MDB has research support from Dexcom and Viacyte and advisory board involvement for Ariel Precision Medicine, Insulet, and Vertex. BEM has received investigator-initiated research funding from Dexcom, Tandem Diabetes Care, Inc, and Digostics. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
(A–F) Patients (A–D) hypersensitivity reactions.
Figure 2
Figure 2
Flowchart of insulin allergy testing and management.
Figure 3
Figure 3
Insulin hypersensitivity treatments and immunologic mechanisms of actions.
See this image and copyright information in PMC

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