Two types of fulminant type 1 diabetes mellitus: Immune checkpoint inhibitor‐related and conventional

Imagawa, Akihisa

doi:10.1111/jdi.13450

Cited by 8 publications

(7 citation statements)

References 10 publications

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“…[5] ICI-related FT1DM sometimes includes acute-onset T1DM and progresses less rapidly than conventional FT1DM. [6] The frequency of ICI-induced T1DM was reportedly 0.2%. [7] We have summarized 8 cases of MM with ICI-induced T1DM at our hospital between 2014 and 2021 (Table 1).…”

Section: Discussionmentioning

confidence: 99%

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Type 1 diabetes associated with immune checkpoint inhibitors for malignant melanoma: A case report and review of 8 cases

Ishiguro¹,

Ogata²,

Ohashi

et al. 2022

Medicine

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Advanced malignant melanoma (MM) is treated with immune checkpoint inhibitor (ICI) therapy, which often results in several immune-related adverse events. Fulminant type 1 diabetes mellitus (T1DM) is a rare, rapidly progressive, life-threatening disease. Here, we summarize 8 cases of MM with ICI-induced T1DM and describe one case that developed fulminant T1DM due to nivolumab therapy. We retrospectively reviewed patients treated with ICI from 2014 to 2021 at our hospital. The clinical features and risk factors of ICI-induced T1DM were discussed. ICIs were administered to 426 MM patients at our hospital. Among these, nivolumab was administered in 5 cases, pembrolizumab in 1 case, and the combination of nivolumab and ipilimumab in 2 cases. The frequency of ICI-associated T1DM was 1.88%. The mean glycated hemoglobin level at T1DM onset was 8.0 ± 1.0%. Of the patients, 75% were diagnosed with fulminant T1DM, 62.5% developed diabetic ketoacidosis, and 25% had glutamic acid decarboxylase (GAD) antibodies (an early predictive marker for T1DM). The mean interval between the first ICI administration and T1DM development was 201 ± 187 days. The mean duration of resumption was 13 ± 7 days. We should monitor for T1DM development following treatment with ICIs. ICI can be continued to be used to treat MM if insulin therapy successfully controls T1DM. A 67-year-old patient who received adjuvant nivolumab therapy developed fulminant T1DM and thyrotoxicosis 57 days later and tested positive for GAD antibodies. Subsequently, he developed hypophysitis and an isolated adrenocorticotropin deficiency. He continued receiving nivolumab along with self-injected insulin without developing recurrence.

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Section: Discussionmentioning

confidence: 99%

“…[ 5 ] ICI-related FT1DM sometimes includes acute-onset T1DM and progresses less rapidly than conventional FT1DM. [ 6 ] The frequency of ICI-induced T1DM was reportedly 0.2%. [ 7 ]…”

Section: Discussionmentioning

confidence: 99%

Type 1 diabetes associated with immune checkpoint inhibitors for malignant melanoma: A case report and review of 8 cases

Ishiguro¹,

Ogata²,

Ohashi

et al. 2022

Medicine

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“…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.

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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.

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“…From a treatment perspective, severe insulin deficiency and dysregulation of glucagon secretion put patients with type 1 diabetes at high risk of hyperglycemia and severe hypoglycemia. Advanced insulin formulation and delivery systems [43] , supplemented by continuous glucose monitoring devices [44] , had improved the safety and effectiveness of intensive insulin therapy, making early diagnosis of type 1 diabetes imperative to improve their prognosis [45,46] .…”

Section: Islet Autoimmunity and Type 1 Diabetesmentioning

confidence: 99%

“…The optimal cutoff value was 0.50 nmol/L for random CP, 0.42 nmol/L for fasting CP, and 0.60 nmol/L for stimulated CP [126] . Other researchers proposed using fasting plasma CP < 250 pmol/L with or without autoantibodies to indicate absolute or severe insulin deficiency [46] . In our prospective analysis, Chinese patients with type 2 diabetes who had GADA positivity and low CP had the fastest progression rate to insulin treatment with a high risk of severe hypoglycemia.…”

Section: Using Biogenetic Markers To Increase the Precision Of Diagno...mentioning

confidence: 99%

Multifaceted nature of young-onset diabetes - can genomic medicine improve the precision of diagnosis and management?

Chan,

Elaine,

Kong

et al. 2024

J Transl Genet Genom

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Young-onset type 2 diabetes (YOD), defined as diabetes diagnosis before age 40, has an aggressive clinical course with premature mortality, in part due to long disease duration and lack of evidence to guide diagnosis and management. Autoimmune type 1 diabetes, maturity-onset diabetes of the young (MODY), and latent autoimmune diabetes in adults (LADA) are subtypes of diabetes in young people, which, however, cannot fully explain their complex clinical course. Similarly, family members carrying the same rare genetic variant of monogenic diabetes can have different presentations and outcomes. Ancestral heterogeneity, ecological transition, inter-ethnic differences in genomic architecture, and variations in living environment, lifestyles, access to care, and timeliness of diagnosis and treatment can influence the age of diagnosis and exposure to these cardiometabolic-renal risk factors. Despite the wealth of literature on genetic associations with diabetes, the familial cosegregation of rare variants and their relevance to YOD remains uncertain. This perspective was motivated by decades of clinical observations and learnings from an ongoing randomized controlled trial that uses biogenetic markers to classify patients with YOD for improving outcomes. Apart from highlighting the need to use family-based studies to improve the precision of diagnosis, we discussed atypical causes for diabetic ketoacidosis and the importance of lifecourse and psychosocial-behavioral factors in patients with YOD. Apart from detailed clinical evaluation, we propose using plasma C peptide, homeostasis model of assessment (HOMA) indexes, autoantibodies, and polygenic risk scores to stratify risk, classify diabetes subtypes, and personalize treatment in YOD. To achieve these goals, we advocate changing the practice environment and team structure to enable physicians to use the insights they learn from patients and their family members to implement precision medicine and improve the outlook of these high-risk individuals.

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Two types of fulminant type 1 diabetes mellitus: Immune checkpoint inhibitor‐related and conventional

Cited by 8 publications

References 10 publications

Type 1 diabetes associated with immune checkpoint inhibitors for malignant melanoma: A case report and review of 8 cases

Type 1 diabetes associated with immune checkpoint inhibitors for malignant melanoma: A case report and review of 8 cases

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

Multifaceted nature of young-onset diabetes - can genomic medicine improve the precision of diagnosis and management?

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Two types of fulminant type 1 diabetes mellitus: Immune checkpoint inhibitor‐related and conventional

Cited by 8 publications

References 10 publications

Type 1 diabetes associated with immune checkpoint inhibitors for malignant melanoma: A case report and review of 8 cases

Type 1 diabetes associated with immune checkpoint inhibitors for malignant melanoma: A case report and review of 8 cases

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

Multifaceted nature of young-onset diabetes - can genomic medicine improve the precision of diagnosis and management?

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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