Immune checkpoint inhibitors: an emerging cause of insulin-dependent diabetes

Kotwal, Anupam; Haddox, Candace L.; Block, Matthew S.; Kudva, Yogish C.

doi:10.1136/bmjdrc-2018-000591

Cited by 171 publications

(213 citation statements)

References 23 publications

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“…As overall awareness of CPI‐DM increases, presentation in DKA may be decreasing due to earlier recognition and intervention . CPI‐DM can occur despite pre‐existing T2DM, but it is exceptionally difficult to differentiate CPI‐DM from exacerbation of underlying T2DM unless the pre‐existing T2DM is well controlled without insulin . Despite marked hyperglycemia at diagnosis (at times more than 1000 mg/dL), hemoglobin A1c (HbA1c) levels are usually only mildly elevated at presentation (7·6–8·0% ), which supports the acuity of this disease .…”

Section: Case Definition and Natural Historymentioning

confidence: 99%

“…The length of time from CPI initiation to onset of CPI‐DM is highly variable. It occurs within days of the first treatment cycle to years following treatment initiation . Median time to diagnosis is between 7 and 17 weeks .…”

Section: Case Definition and Natural Historymentioning

confidence: 99%

“…The demographics of CPI‐DM cases probably reflect the demographics of patients receiving CPIs (Table ). The average age is in the 60s and there is a slight male predominance . Non‐Hispanic Caucasians are the major race/ethnicity affected with CPI‐DM, but a meaningful minority of Asians are affected (15–25% ).…”

Section: Clinical Attributes and Epidemiologymentioning

confidence: 99%

“…In CPI‐DM, as in type I diabetes mellitus (T1DM), steroids appear to both fail to reverse β cell dysfunction and worsen insulin resistance. Because of the high morbidity associated with diabetes, CPI‐DM is of particular clinical concern despite its rarity, with estimates between 0·2 and 1·4% of CPI‐treated patients. As CPIs are increasingly used in lower stage cancers, including adjuvant settings and in complex therapeutic combinations, it is imperative to understand the risk of an adverse effect with such a high impact on quality of life.…”

Section: Introductionmentioning

confidence: 99%

“…In this review, we describe the key features of CPI‐DM and consider their utility in providing mechanistic understanding in the context of CPI‐DM, irAEs and general islet autoimmunity. To describe the key characteristics of CPI‐DM, we use a growing body of literature that includes a recent review by De Filette and colleagues that summarizes 91 case reports, institution specific case–series that include an additional independent 53 cases [27 from University of California San Francisco (UCSF) and Yale (five of which were included in De Filette et al ’s case summary) , 21 from Mayo Clinic and 10 from Melanoma Institute Australia )] and a recent analysis of the World Health Organization (WHO) pharmacovigilance database , which approaches CPI‐DM from a global perspective and has fewer patient‐specific details. Together, these papers encompass the current understanding of CPI‐DM from a clinical perspective.…”

Section: Introductionmentioning

confidence: 99%

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Immune checkpoint inhibitor diabetes mellitus: a novel form of autoimmune diabetes

Quandt

Young

Anderson

2020

Clinical and Experimental Immunology

125

105

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Autoimmune diabetes mellitus is a rare but significant side effect of treatment with immune checkpoint inhibitors. Immune checkpoint inhibitorinduced diabetes mellitus (CPI-DM) is characterized by acute onset of dramatic hyperglycemia with severe insulin deficiency and occurrence following exposure to programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitors rather than cytotoxic T lymphocyteassociated antigen 4 (CTLA-4) inhibitors. As a growing number of patients undergo immunotherapy, further understanding of the characteristics of CPI-DM patients is needed for improved prognostic and diagnostic application in order to reduce overall morbidity for this already at-risk population. Additionally, understanding of the features and mechanisms of CPI-DM may contribute to understanding mechanisms of spontaneous type I diabetes mellitus (T1DM). Here, we summarize the clinical features of CPI-DM and interrogate the genetic and cellular mechanisms that may contribute to the disease, as well as the clinical challenges for predicting and treating these patients as increasing cancer immunotherapies reach clinical utility.

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Section: Case Definition and Natural Historymentioning

confidence: 99%

Section: Case Definition and Natural Historymentioning

confidence: 99%

Section: Clinical Attributes and Epidemiologymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Immune checkpoint inhibitor diabetes mellitus: a novel form of autoimmune diabetes

Quandt

Young

Anderson

2020

Clinical and Experimental Immunology

125

105

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Identification of Immune Checkpoint Inhibitor–Induced Diabetes

Ruiz-Esteves,

Shank,

Deutsch

et al. 2024

JAMA Oncol

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ImportanceImmune checkpoint inhibitors (ICIs) have revolutionized cancer care; however, accompanying immune-related adverse events (irAEs) confer substantial morbidity and occasional mortality. Life-threatening irAEs may require permanent cessation of ICI, even in patients with positive tumor response. Therefore, it is imperative to comprehensively define the spectrum of irAEs to aid individualized decision-making around the initiation of ICI therapy.ObjectiveTo define incidence, risk factors, and clinical spectrum of an irreversible and life-threatening irAE: ICI-induced diabetes.Design, Setting, and ParticipantsThis cohort study, conducted at an academic integrated health care system examined 14 328 adult patients treated with ICIs, including 64 patients who developed ICI-induced diabetes, from July 2010 to January 2022. The data were analyzed from 2022 to 2023. Cases of ICI-induced diabetes were manually confirmed; detailed clinical phenotyping was performed at diagnosis and 1-year follow-up. For 862 patients, genotyping data were available, and polygenic risk for type 1 diabetes was determined.Main Outcomes and MeasuresFor ICI-induced diabetes cases and controls, demographic characteristics, comorbidities, tumor category, and ICI category were compared. Among ICI-induced diabetes cases, markers of glycemic physiology were examined at diagnosis and 1-year follow-up. For patients with available genotyping, a published type 1 diabetes polygenic score (T1D GRS2) was calculated.ResultsOf 14 328 participants, 6571 (45.9%) were women, and the median (range) age was 66 (8-106) years. The prevalence of ICI-induced diabetes among ICI-treated patients was 0.45% (64 of 14 328), with an incidence of 124.8 per 100 000 person-years. Preexisting type 2 diabetes (odds ratio [OR], 5.91; 95% CI, 3.34-10.45) and treatment with combination ICI (OR, 2.57; 95% CI, 1.44-4.59) were significant clinical risk factors of ICI-induced diabetes. T1D GRS2 was associated with ICI-induced diabetes risk, with an OR of 4.4 (95% CI, 1.8-10.5) for patients in the top decile of T1D GRS2, demonstrating a genetic association between spontaneous autoimmunity and irAEs. Patients with ICI-induced diabetes were in 3 distinct phenotypic categories based on autoantibodies and residual pancreatic function, with varying severity of initial presentation.Conclusions and RelevanceThe results of this analysis of 14 328 ICI-treated patients followed up from ICI initiation determined the incidence, risk factors and clinical spectrum of ICI-induced diabetes. Widespread implementation of this approach across organ-specific irAEs may enhance diagnosis and management of these conditions, and this becomes especially pertinent as ICI treatment rapidly expands to treat a wide spectrum of cancers and is used at earlier stages of treatment.

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Guideline for the Management of Diabetes Mellitus in the Elderly in China (2024 Edition)

Guo,

Xiao

2024

Aging Medicine

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With the deepening of aging in China, the prevalence of diabetes in older people has increased noticeably, and standardized diabetes management is critical for improving clinical outcomes of diabetes in older people. In 2021, the National Center of Gerontology, Chinese Society of Geriatrics, and Diabetes Professional Committee of Chinese Aging Well Association organized experts to write the first guideline for diabetes diagnosis and treatment in older people in China, the Guideline for the Management of Diabetes Mellitus in the Elderly in China (2021 Edition). The guideline emphasizes that older patients with diabetes are a highly heterogeneous group requiring comprehensive assessment and stratified and individualized management strategies. The guideline proposes simple treatments and de‐intensified treatment strategies for older patients with diabetes. This edition of the guideline provides clinicians with practical and operable clinical guidance, thus greatly contributing to the comprehensive and full‐cycle standardized management of older patients with diabetes in China and promoting the extensive development of clinical and basic research on diabetes in older people and related fields. In the past 3 years, evidence‐based medicine for older patients with diabetes and related fields has further advanced, and new treatment concepts, drugs, and technologies have been developed. The guideline editorial committee promptly updated the first edition of the guideline and compiled the Guideline for the Management of Diabetes Mellitus in the Elderly in China (2024 Edition). More precise management paths for older patients with diabetes are proposed, for achieving continued standardization of the management of older Chinese patients with diabetes and improving their clinical outcomes.

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Immune checkpoint inhibitors: an emerging cause of insulin-dependent diabetes

Cited by 171 publications

References 23 publications

Immune checkpoint inhibitor diabetes mellitus: a novel form of autoimmune diabetes

Immune checkpoint inhibitor diabetes mellitus: a novel form of autoimmune diabetes

Identification of Immune Checkpoint Inhibitor–Induced Diabetes

Guideline for the Management of Diabetes Mellitus in the Elderly in China (2024 Edition)

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