Type 1 diabetes related to immune checkpoint inhibitors

Tachibana, Megumi; Imagawa, Akihisa

doi:10.1016/j.beem.2022.101657

Cited by 12 publications

(6 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The global prevalence of ICI-T1DM is approximately 1–1.8% ( 17 – 20 ). ICI-T1DM is characterized by an intermediate onset that is between acute-onset and fulminant T1DM, according to the speed of loss of β cells ( 21 , 22 ). Therefore, ICI-T1DM may have a different pathogenesis from that of acute-onset or fulminant T1DM.…”

Section: Discussionmentioning

confidence: 99%

Case report: Strong GAD antibody positivity and type 1 diabetes-HLA-susceptible haplotype-DRB104:05-DQB104:01 in a Japanese patient with immune checkpoint inhibitor-induced type 1 diabetes

Yabuki,

Hirai,

Moriya

et al. 2024

Front. Endocrinol.

View full text Add to dashboard Cite

Immune checkpoint inhibitors (ICIs) are widely used in cancer treatment; however, they can lead to immune-related adverse events, including immune checkpoint inhibitor-induced type 1 diabetes mellitus (ICI-T1DM). While fulminant T1DM is common in East Asia, ICI-T1DM has predominantly been reported in Western countries. In this report, we present the case of a 66-year-old Japanese man with type 2 diabetes mellitus undergoing dialysis for diabetic nephropathy. The patient was diagnosed with left upper lobe lung cancer, and treatment with nivolumab and ipilimumab was initiated. After 48 days, the patient experienced impaired consciousness and difficulty moving. His blood glucose levels were 815 mg/dL, and metabolic acidosis was detected, leading to a diagnosis of diabetic ketoacidosis. The patient was subsequently treated with continuous intravenous insulin. However, his C-peptide levels rapidly depleted, and new-onset ICI-T1DM was diagnosed. Although most Japanese patients with ICI-T1DM test negative for glutamic acid decarboxylase (GAD) antibodies, this case exhibited a strong positivity. Thus, we reviewed the literature on 15 similar Japanese cases, revealing a mean HbA1c level at onset of 8.7% and a mean time from ICI administration to onset of 9.7 weeks, which was shorter than that in GAD-negative cases. Moreover, human leukocyte antigen typing revealed five cases of DRB1*04:05-DQB1*04:01, including the present case, and one case of DRB1*09:01-DQB1*03:03, both of which were susceptible to T1DM haplotypes. These findings suggest that GAD antibody positivity may be associated with acute onset and disease progression in some cases of Japanese patients with ICI-T1DM. Given that the prediction of new-onset ICI-T1DM is challenging, monitoring GAD antibody levels might be useful. However, further studies with large sample sizes and validation across different racial and ethnic populations are warranted.

show abstract

Section: Discussionmentioning

confidence: 99%

Case report: Strong GAD antibody positivity and type 1 diabetes-HLA-susceptible haplotype-DRB104:05-DQB104:01 in a Japanese patient with immune checkpoint inhibitor-induced type 1 diabetes

Yabuki,

Hirai,

Moriya

et al. 2024

Front. Endocrinol.

View full text Add to dashboard Cite

show abstract

“…ICI-associated diabetes mellitus, relatively rare, has an estimated incidence of 3.5% ( 93 ) and can become extremely severe, leading to irreversible damage to beta cells and even death if not recognized and appropriately managed in time. The precise mechanism of ICI-related diabetes is unknown.…”

Section: Common Iraesmentioning

confidence: 99%

Immune-related adverse events of immune checkpoint inhibitors: a review

Yin

Han

et al. 2023

Front. Immunol.

View full text Add to dashboard Cite

Since the first Immune Checkpoint Inhibitor was developed, tumor immunotherapy has entered a new era, and the response rate and survival rate of many cancers have also been improved. Despite the success of immune checkpoint inhibitors, resistance limits the number of patients who can achieve a lasting response, and immune-related adverse events complicate treatment. The mechanism of immune-related adverse events (irAEs) is unclear. We summarize and discuss the mechanisms of action of immune checkpoint inhibitors, the different types of immune-related adverse events and their possible mechanisms, and describe possible strategies and targets for prevention and therapeutic interventions to mitigate them.

show abstract

“…In the past decade, the number of reported ICI-T1DM cases has consistently and significantly increased [ 47 , 54 - 60 ]. Generally, the incidence rate of T1DM following ICI administration is expected to be 1% [ 59 , 61 , 62 ].…”

Section: Epidemiology Clinical Characteristics and Current Guidelines...mentioning

confidence: 99%

“…The rapid onset of this disease causes fulminant presentation, including diabetic ketoacidosis (DKA), in 40% to 76% of the affected patients [ 47 , 59 , 64 , 65 , 67 - 69 ]. Majority of the patients report overt insulin insufficiency and low C-peptide levels (0.3 ng/mL in 63.4% of patients) [ 54 ]. Anti-glutamic acid decarboxylase autoantibodies were detected in 43% (positive total islet autoantibody was observed in 20% to 71% of patients) of patients and increased pancreatic enzyme in some [ 54 ].…”

Section: Epidemiology Clinical Characteristics and Current Guidelines...mentioning

confidence: 99%

“…Majority of the patients report overt insulin insufficiency and low C-peptide levels (0.3 ng/mL in 63.4% of patients) [ 54 ]. Anti-glutamic acid decarboxylase autoantibodies were detected in 43% (positive total islet autoantibody was observed in 20% to 71% of patients) of patients and increased pancreatic enzyme in some [ 54 ]. In most cases, insulin deficiency is irreversible; thus, majority of the patients eventually need lifelong insulin therapy [ 47 , 59 , 67 ].…”

Section: Epidemiology Clinical Characteristics and Current Guidelines...mentioning

confidence: 99%

See 1 more Smart Citation

Immune-Checkpoint Inhibitors-Induced Type 1 Diabetes Mellitus: From Its Molecular Mechanisms to Clinical Practice

Cho

Jung

2023

Diabetes Metab J

View full text Add to dashboard Cite

With the increasing use of immune-checkpoint inhibitors (ICIs), such as anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and anti-programmed cell death-1 (PD-1), for the treatment of malignancies, cases of ICI-induced type 1 diabetes mellitus (ICI-T1DM) have been reported globally. This review focuses on the features and pathogenesis of this disease. T1DM is an immune-related adverse event that occurs following the administration of anti-PD-1 or anti-programmed death ligand-1 (PDL1) alone or in combination with anti-CTLA-4. More than half of the reported cases presented as abrupt-onset diabetic ketoacidosis. The primary mechanism of ICI-T1DM is T-cell stimulation, which results from the loss of interaction between PD-1 and PD-L1 in pancreatic islet. The similarities and differences between ICI-T1DM and classical T1DM may provide insights into this disease entity. ICI-T1DM is a rare but often life-threatening medical emergency that healthcare professionals and patients need to be aware of. Early detection of and screening for this disease is imperative. At present, the only known treatment for ICI-T1DM is insulin injection. Further research into the mechanisms and risk factors associated with ICI-T1DM development may contribute to a better understanding of this disease entity and the identification of possible preventive strategies.

show abstract

Type 1 diabetes related to immune checkpoint inhibitors

Cited by 12 publications

References 27 publications

Case report: Strong GAD antibody positivity and type 1 diabetes-HLA-susceptible haplotype-DRB104:05-DQB104:01 in a Japanese patient with immune checkpoint inhibitor-induced type 1 diabetes

Case report: Strong GAD antibody positivity and type 1 diabetes-HLA-susceptible haplotype-DRB104:05-DQB104:01 in a Japanese patient with immune checkpoint inhibitor-induced type 1 diabetes

Immune-related adverse events of immune checkpoint inhibitors: a review

Immune-Checkpoint Inhibitors-Induced Type 1 Diabetes Mellitus: From Its Molecular Mechanisms to Clinical Practice

Contact Info

Product

Resources

About

Type 1 diabetes related to immune checkpoint inhibitors

Cited by 12 publications

References 27 publications

Case report: Strong GAD antibody positivity and type 1 diabetes-HLA-susceptible haplotype-DRB1*04:05-DQB1*04:01 in a Japanese patient with immune checkpoint inhibitor-induced type 1 diabetes

Case report: Strong GAD antibody positivity and type 1 diabetes-HLA-susceptible haplotype-DRB1*04:05-DQB1*04:01 in a Japanese patient with immune checkpoint inhibitor-induced type 1 diabetes

Immune-related adverse events of immune checkpoint inhibitors: a review

Immune-Checkpoint Inhibitors-Induced Type 1 Diabetes Mellitus: From Its Molecular Mechanisms to Clinical Practice

Contact Info

Product

Resources

About

Case report: Strong GAD antibody positivity and type 1 diabetes-HLA-susceptible haplotype-DRB104:05-DQB104:01 in a Japanese patient with immune checkpoint inhibitor-induced type 1 diabetes

Case report: Strong GAD antibody positivity and type 1 diabetes-HLA-susceptible haplotype-DRB104:05-DQB104:01 in a Japanese patient with immune checkpoint inhibitor-induced type 1 diabetes