Unravelling Checkpoint Inhibitor Associated Autoimmune Diabetes: From Bench to Bedside

Wu, Linda; Tsang, Venessa; Sasson, Sarah C.; Menzies, Alexander M.; Carlino, Matteo S.; Brown, David A.; Clifton‐Bligh, Roderick; Gunton, Jenny E.

doi:10.3389/fendo.2021.764138

“…The time from ICI treatment initiation to diagnosis of DM-ICIs was heterogeneous, with a mean of 15.8 weeks, a minimum of 3.6 weeks, and a maximum of 45 weeks. These data are consistent with those reported in major published cohorts, where a mean of 9 weeks to diagnosis was observed, with atypical cases ranging from a few days after the first administration of ICIs until years after completion of treatment [8,21].…”

Section: Discussionsupporting

confidence: 91%

“…Based on this mechanism, a C-peptide measurement below 0.6 nmol/L has been proposed as a diagnostic criterion for DM-ICIs by most authors [8,[12][13][14]. However, this cutoff point differs from that proposed by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) in their consensus document for the diagnosis of T1DM, where a random C-peptide value (measured within 5 hours after meal) of <0.6 nmol/L (without concomitant hypoglycaemia or long fasting period) is considered suggestive of insulinopenic DM [16].…”

Section: Discussionmentioning

confidence: 99%

“…The following criteria were used to diagnose cases of DM-ICIs: (1) diagnosis of diabetes after receiving the first course of treatment with ICIs, (2) onset with an episode of acute hyperglycaemia ≥ 200 mg/dL or glycated hemoglobin ðHbA1cÞ ≥ 6:5% (taking into account that in case of sudden presentation, HbA1c may not be elevated at the time of diagnosis), (3) demonstration of β-cell destruction as evidenced by a result < 0:6 nmol/L in a random 5 h postprandial Cpeptide measurement (as it has been suggested by the ADA-EASD consensus report for the management of T1DM) [8,16].…”

Section: Methodsmentioning

confidence: 99%

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Flash Glucose Monitoring and Diabetes Mellitus Induced by Immune Checkpoint Inhibitors: An Approach to Clinical Practice

Vera-Gómez

¹

,

Piñar-Gutiérrez

²

,

Guerrero-Vázquez

³

et al. 2022

Journal of Diabetes Research

4

1

0

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Objectives. The aim of this study is to investigate in depth diabetes mellitus associated with immune checkpoint inhibitors (DM-ICIs) by analysing a case series. We also evaluated the clinical impact of flash glucose monitoring (FGM) systems in the management of this entity. Methods. We conducted an observational cohort study of DM-ICIs diagnosed in two hospitals in Seville (Spain). Patients with a new diagnosis of diabetes mellitus (DM) or with sudden worsening of preexisting DM after starting treatment with ICIs, with a random 5 hour-postprandial C-peptide value of <0.6 nmol/L and without possibility of subsequent withdrawal of insulin treatment, were included. Results. A total of 7 cases were identified, mostly males ( n = 6 ; 85.7%), with a mean age of 64.9 years. The mean glycated hemoglobin (HbA1c) upon diagnosis was 8.1%, with diabetic ketoacidosis (DKA) observed in 6 cases (85.7%). Subcutaneous flash glucose monitoring (FGM) systems were used in six cases, with a mean follow-up period of 42.7 weeks. During the first 90 days of use, mean average glucose was 167.5 mg/dL, with a coefficient of variation (CV) of 34.6%. The mean time in the range 70-180 mg/dL (TIR) was 59.7%, with a mean time above range (TAR) 181-250 mg/dL of 27.8% and a mean TAR > 250 mg / dL of 10.2%. The mean time below range (TBR) 54-69 mg/dL was 2%, while the mean TBR < 54 mg / dL was 0.3%. The mean glucose management indicator (GMI) was 7.3%. No significant differences were observed in FGM values for the following 90 days of follow-up. A progressive improvement in all parameters of glycaemic control was observed between the first month of FGM use and the sixth month of FGM use. Of note, there was a decrease in mean CV (40.6% to 34.1%, p = 0.25 ), mean TAR 181-250 (30.3% to 26%, p = 0.49 ), mean TAR > 250 mg / dL (16.3% to 7.7%, p = 0.09 ), mean TBR 54-69 mg/dL (5.2% to 2%, p = 0.16 ), and mean TBR < 54 mg / dL (1.8% to 0.2%, p = 0.31 ), along with an increase in mean values of TIR 70-180 mg/dL (46.5% to 60.5%, p = 0.09 ). The lack of statistical significance in the differences observed in the mean FGM values over the follow-up period may be related to the small sample size. Conclusion. DM-ICI is recognised by a state of sudden-onset insulinopenia, often associated with DKA. The use of FGM systems may be a valid option for the effective management of DM-ICIs and for the prevention of severe hyperglycaemic and hypoglycaemic episodes in this condition.

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“…Nivolumab-induced autoimmune diabetes mellitus is another rare adverse event. Type I diabetes mellitus (T1DM) is diagnosed by the occurrence of hyperglycemia with evidence of autoimmunity and insulin insufficiency; 90% of patients test positive for islet autoantibodies at some point during treatment [10].…”

Section: Discussionmentioning

confidence: 99%

“…Nivolumab-induced autoimmune diabetes mellitus is another rare adverse event. Type I diabetes mellitus (T1DM) is diagnosed by the occurrence of hyperglycemia with evidence of autoimmunity and insulin insufficiency; 90% of patients test positive for islet autoantibodies at some point during treatment [ 10 ]. Patients with drug reactions with eosinophilia and systemic symptoms (DRESS) are at risk for autoimmune disorders such as T1DM, thyroiditis, and systemic lupus erythematosus (SLE).…”

Section: Discussionmentioning

confidence: 99%

Rare Adverse Events Related to Nivolumab, an Immune Checkpoint Inhibitor: A Case Series

Ganta¹,

Alnabwani²,

Keating³

et al. 2022

Cureus

4

0

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Immune checkpoint inhibitors are a novel class of immunotherapy drugs that have improved the prognosis of melanoma, renal cell carcinoma, non-small cell lung cancer, urothelial carcinoma, and various other solid tumors. Nivolumab is an immune checkpoint inhibitor that acts by inhibiting programmed death. Its use is associated with significant immune-related adverse events, such as pneumonitis, thyroiditis, hepatitis, pruritus, vitiligo, and diarrhea. However, adrenal insufficiency and checkpoint inhibitor-related autoimmune diabetes mellitus are extremely rare adverse events related to nivolumab treatment. Here, we are highlighting cases of adrenal insufficiency and diabetes inspidus as a result of nivolumab. These rare adverse events in our case series are to raise awareness that this medication also may be the cause for this illness among oncologists, endocrinologists, internists, and other clinicians.

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

Guo,

Xiao

2024

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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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Unravelling Checkpoint Inhibitor Associated Autoimmune Diabetes: From Bench to Bedside

Cited by 33 publications

References 131 publications

Flash Glucose Monitoring and Diabetes Mellitus Induced by Immune Checkpoint Inhibitors: An Approach to Clinical Practice

Flash Glucose Monitoring and Diabetes Mellitus Induced by Immune Checkpoint Inhibitors: An Approach to Clinical Practice

Rare Adverse Events Related to Nivolumab, an Immune Checkpoint Inhibitor: A Case Series

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

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