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

2020 ◽  
Vol 200 (2) ◽  
pp. 131-140 ◽  
Author(s):  
Z. Quandt ◽  
A. Young ◽  
M. Anderson
Keyword(s):  
Diabetes Mellitus ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Autoimmune Diabetes

A Systematic Review of Cases of Diabetes Mellitus following Immune Checkpoint Inhibitor Therapy for Cancer

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 204-LB ◽  
Author(s):  
KARA R. MIZOKAMI-STOUT ◽  
ROMA GIANCHANDANI ◽  
MARK MACEACHERN ◽  
RAVI M. IYENGAR ◽  
SARAH YENTZ ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Systematic Review ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Inhibitor Therapy ◽  
Checkpoint Inhibitor Therapy

scholarly journals Durvalumab-induced diabetic ketoacidosis followed by hypothyroidism

2019 ◽  
Vol 2019 ◽  
Author(s):  
Shivani Patel ◽  
Venessa Chin ◽  
Jerry R Greenfield
Keyword(s):  
Diabetic Ketoacidosis ◽  
Thyroid Function ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Reference Range ◽  
Checkpoint Inhibitor ◽  
Autoimmune Diabetes ◽  
Inhibitor Therapy ◽  
Thyroid Function Tests ◽  
Checkpoint Inhibitor Therapy

Summary Durvalumab is a programmed cell death ligand 1 inhibitor, which is now approved in Australia for use in non-small-cell lung and urothelial cancers. Autoimmune diabetes is a rare immune-related adverse effect associated with the use of immune checkpoint inhibitor therapy. It is now being increasingly described reflecting the wider use of immune checkpoint inhibitor therapy. We report the case of a 49-year-old female who presented with polyuria, polydipsia and weight loss, 3 months following the commencement of durvalumab. On admission, she was in severe diabetic ketoacidosis with venous glucose: 20.1 mmol/L, pH: 7.14, bicarbonate 11.2 mmol/L and serum beta hydroxybutyrate: >8.0 mmol/L. She had no personal or family history of diabetes or autoimmune disease. Her HbA1c was 7.8% and her glutamic acid decarboxylase (GAD) antibodies were mildly elevated at 2.2 mU/L (reference range: <2 mU/L) with negative zinc transporter 8 (ZnT8) and islet cell (ICA) antibodies. Her fasting C-peptide was low at 86 pmol/L (reference range: 200–1200) with a corresponding serum glucose of 21.9 mmol/L. She was promptly stabilised with an insulin infusion in intensive care and discharged on basal bolus insulin. Durvalumab was recommenced once her glycaemic control had stabilised. Thyroid function tests at the time of admission were within normal limits with negative thyroid autoantibodies. Four weeks post discharge, repeat thyroid function tests revealed hypothyroidism, with an elevated thyroid-stimulating hormone (TSH) at 6.39 mIU/L (reference range: 0.40–4.80) and low free T4: 5.9 pmol/L (reference range: 8.0–16.0). These findings persisted with repeat testing despite an absence of clinical symptoms. Treatment with levothyroxine was commenced after excluding adrenal insufficiency (early morning cortisol: 339 nmol/L) and hypophysitis (normal pituitary on MRI). Learning points: Durvalumab use is rarely associated with fulminant autoimmune diabetes, presenting with severe DKA. Multiple endocrinopathies can co-exist with the use of a single immune checkpoint inhibitors; thus, patients should be regularly monitored. Regular blood glucose levels should be performed on routine pathology on all patients on immune checkpoint inhibitor. Clinician awareness of immunotherapy-related diabetes needs to increase in an attempt to detect hyperglycaemia early and prevent DKA.

scholarly journals Coexistence of Immune Checkpoint Inhibitor-Induced Autoimmune Diabetes and Pancreatitis

2021 ◽  
Vol 12 ◽  
Author(s):  
Amy L. Zhang ◽  
Fang Wang ◽  
Lee-Shing Chang ◽  
Marie E. McDonnell ◽  
Le Min
Keyword(s):  
Diabetic Ketoacidosis ◽  
Median Time ◽  
Clinical Features ◽  
Glucose Level ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Autoimmune Diabetes ◽  
Newly Diagnosed ◽  
C Peptide

Autoimmune diabetes is a rare but severe endocrine toxicity induced by immune checkpoint inhibitor (ICI) treatment. It is unclear if ICI causes selective islet toxicity or non-selective pancreas toxicity. We analyzed 11 patients treated with ICI who developed ICI-related autoimmune diabetes. Eight patients had lipase and/or amylase tested on the same day of diagnosis of autoimmune diabetes. Among them, 75% (6/8) had normal lipase and 100% (6/6) had normal amylase. There was no correlation between glucose level at onset and biochemical pancreatitis. We characterized the clinical features of ICI-induced autoimmune diabetes. Fifty-five percent (6/11) of patients tested positive for GAD65 autoantibodies, and 55% (6/11) developed diabetic ketoacidosis at manifestation of hyperglycemia. In all 11 patients, C-peptide levels were low in the presence of hyperglycemia. ICI-induced thyroiditis was found in 64% (7/11), of which 36% (4/11) were newly diagnosed with thyroiditis while the remaining 27% (3/11) had pre-existing hypothyroidism followed by ICI-induced thyroiditis. Additionally, 27% (3/11), developed ICI-induced hypophysitis. Thyroiditis and autoimmune diabetes coexisted in all patients with ICI-induced hypophysitis. The median time from ICI treatment to the onset of autoimmune diabetes was 11 weeks. Our data suggest that few patients had coexistent ICI-induced autoimmune diabetes and pancreatitis, suggesting ICI mainly caused selective islet toxicity.

scholarly journals Immune Checkpoint Inhibitor-Associated Diabetes Mellitus: A Single-Institution Experience

2020 ◽  
Author(s):  
David J. Byun ◽  
Rebecca Braunstein ◽  
Jessica Flynn ◽  
Junting Zheng ◽  
Robert A. Lefkowitz ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Case Series ◽  
Retrospective Chart Review ◽  
Single Institution ◽  
Pancreatic Atrophy ◽  
Gad65 Autoantibodies ◽  
Design And Methods

<b>OBJECTIVE</b> <p>To characterize immune checkpoint inhibitor-associated diabetes mellitus (ICI-DM) in a single-institution case series. </p> <p><b>DESIGN AND METHODS</b></p> <p>Retrospective chart review of 18 patients with new-onset ICI-DM following anti-PD-1/anti-PD-L1 therapy for advanced carcinomas.</p> <p><b>RESULTS</b></p> <p>9/18 patients had diabetic ketoacidosis (median glucose: 27.92mmol/L; median glucose before presentation: 6.35mmol/L). Median C-peptide at ICI-DM diagnosis was low, and declined during follow-up. Median anti-PD-1/anti-PD-L1 duration before ICI-DM was 3.65 months (range 0.56-12.23). Time to ICI-DM onset was a median 1.4 months/3 ICI cycles and 6 months/10 cycles in those positive and negative for GAD65 autoantibodies, respectively. Time to ICI-DM onset was a median 2.5 months/3 ICI cycles and 4.8 months/8 cycles after anti-PD-L1 or anti-PD-1 therapy, respectively. Significant pancreatic atrophy was seen radiographically.</p> <p><b>CONCLUSIONS</b></p> <p>ICI-DM presents abruptly, appears irreversible, is characterized by pancreatic atrophy, and may <a>occur both earlier following PD-L1 blockade compared to PD-1 inhibition </a>and in those who have positive GAD65 autoantibodies.</p>

A case series of immune checkpoint inhibitor induced diabetes mellitus (ICI-DM).

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. e22080-e22080
Author(s):  
Venessa H Tsang ◽  
Roderick J Clifton-Bligh ◽  
Georgina V. Long ◽  
Alexander David Guminski ◽  
Alexander M. Menzies
Keyword(s):  
Diabetes Mellitus ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Case Series

scholarly journals Combined immune checkpoint inhibitor therapy with nivolumab and ipilimumab causing acute-onset type 1 diabetes mellitus following a single administration: two case reports

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Marco Zezza ◽  
Christophe Kosinski ◽  
Carine Mekoguem ◽  
Laura Marino ◽  
Haithem Chtioui ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Acute Onset ◽  
Single Administration

Abstract Background The use of immune checkpoint inhibitor (ICI) therapy is becoming a standard of care for several cancers. Monoclonal antibodies targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death protein 1 (PD-1) or its ligand (PD-L1) cause a broad spectrum of autoimmune adverse events. ICI-induced type 1 diabetes mellitus (T1DM) is extremely rare (< 1%) but potentially life-threatening. It appears to be more common with PD-1 blockade (or combination immunotherapy) than with anti-CTLA-4 therapy, often during the first three to six months of therapy. Cases presentation We report an acute onset T1DM with severe inaugural diabetic ketoacidosis (DKA) and remarkably elevated Glutamic Acid Decarboxylase antibody (GADA) titres following a single administration of combined ICI therapy with nivolumab (anti-PD-1) and ipilimumab (anti-CTLA-4) in two adult patients with advanced metastatic melanoma. In these cases, the time to diabetes onset was remarkably short (two and five weeks), and one presented with fulminous T1DM in a previous long-standing type 2 diabetes mellitus. Conclusions Oncological patients treated with combination therapy of anti-PD-1 and anti-CTLA-4 can develop a particular pattern of T1DM, with very rapid onset within a few weeks after starting ICI therapy, even in the presence of an existing type 2 diabetes. ICI-induced T1DM is a medical emergency in presence of severe inaugural DKA and requires a collaboration between specialists and primary care physicians, as well as patient education, for early diagnosis and supportive care.

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