Oncotarget: Rapid onset type 1 diabetes with anti-PD-1 directed therapy

October 09, 2020

Volume 11, Issue 28 of Oncotarget features "Rapid onset type 1 diabetes with anti-PD-1 directed therapy", by Yun et al. and reported that Type 1 diabetes is a rare immune-related adverse event caused by checkpoint inhibitors with serious risk for diabetic ketoacidosis.

Of the patients who received immunotherapy, 5 patients were found to have type 1 diabetes, all of whom presented with DKA requiring insulin at 20 to 972 days from their first anti-PD- 1 dose.

Four patients had new-onset diabetes with mean Hb A1c of 9.1% on DKA presentation and persistent elevations over time.

Two patients who tested positive for glutamic acid decarboxylase antibodies presented with DKA at 20 and 106 days from first anti-PD-1 administration whereas patients who were autoantibody negative had DKA more than a year later.

The case series suggests that monitoring glycemia in patients on PD-1 inhibitors is not predictive for diabetes occurrence.

Dr. Sandip Pravin Patel from The Division of Hematology-Oncology in the Department of Medicine at The University of California San Diego said, "Cancer immunotherapy has broadened in clinical use over the last decade with FDA approval for treatment of various malignancies including melanoma, non-small cell lung cancer (NSCLC), renal cell carcinoma, urothelial carcinoma, head, and neck carcinomas, cutaneous squamous cell cancer, microsatellite unstable tumors, and Hodgkin's lymphoma."

Autoimmune type 1 diabetes is generally associated with positive autoantibodies to islet proteins including glutamic acid decarboxylase, insulin, insulinoma-associated antigen-2, zinc transporter 8, and islet cells.

However, only a subset of patients who acquire type 1 diabetes is found to have autoantibodies and specific HLA alleles, making these biomarkers poor predictors of diabetes incidence.

Given the rarity of type 1 diabetes as an ir AE, the authors sought to characterize the real-world diagnosis, management, and sequelae of patients who developed this ir AE in the context of their immune checkpoint blockade.

This Oncotarget paper highlights the rapid kinetics of type 1 diabetes in patients on checkpoint inhibitors.

"This Oncotarget paper highlights the rapid kinetics of type 1 diabetes in patients on checkpoint inhibitors"

Type 1 diabetes presented as DKA for all patients in this series and all but one patient had a new diagnosis of diabetes, without antecedent laboratory or imaging findings.

The Patel Research Team concluded in their OncotargetResearch Paper that their case series illustrates the rare incidence of immunotherapy-induced type 1 diabetes and describes the rapid course of this disease in patients.

Regardless of whether or not patients remain on checkpoint inhibitors, those with immunotherapy-induced diabetes are at risk for hyperglycemia and recurrent DKA. Surveillance of glycemia or Hb A1c does not predict diabetes but does have a role after type 1 diabetes arises as glycemia fluctuates and elevated Hb A1c levels persist.

Furthermore, GAD antibodies are present in about half of patients who develop type 1 diabetes after immunotherapy, warranting additional investigations into whether this is all association and a marker of immune attack.

Given the absence of prescient laboratory or imaging findings in patients who develop type 1 diabetes on anti-PD-1 therapy, patients should be counseled on the symptoms of hyperglycemia which include polyuria, polydipsia, abdominal pain, nausea and emesis and seek medical attention immediately.
-end-
Sign up for free Altmetric alerts about this article

DOI - https://doi.org/10.18632/oncotarget.27665

Full text - https://www.oncotarget.com/article/27665/text/

Correspondence to - Sandip Pravin Patel - patel@ucsd.edu

Keywords - type 1 diabetes, diabetic ketoacidosis (DKA), immune-related adverse event (irAE), immunotherapy, PD-1 inhibitors

About Oncotarget

Oncotarget is a weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.

To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:

SoundCloud -https://soundcloud.com/oncotarget
Facebook -https://www.facebook.com/Oncotarget/
Twitter -https://twitter.com/oncotarget
LinkedIn -https://www.linkedin.com/company/oncotarget
Pinterest -https://www.pinterest.com/oncotarget/
Reddit -https://www.reddit.com/user/Oncotarget/

Oncotarget is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls

Media Contact
MEDIA@IMPACTJOURNALS.COM
18009220957x105

Impact Journals LLC

Related Diabetes Articles from Brightsurf:

New diabetes medication reduced heart event risk in those with diabetes and kidney disease
Sotagliflozin - a type of medication known as an SGLT2 inhibitor primarily prescribed for Type 2 diabetes - reduces the risk of adverse cardiovascular events for patients with diabetes and kidney disease.

Diabetes drug boosts survival in patients with type 2 diabetes and COVID-19 pneumonia
Sitagliptin, a drug to lower blood sugar in type 2 diabetes, also improves survival in diabetic patients hospitalized with COVID-19, suggests a multicenter observational study in Italy.

Making sense of diabetes
Throughout her 38-year nursing career, Laurel Despins has progressed from a bedside nurse to a clinical nurse specialist and has worked in medical, surgical and cardiac intensive care units.

Helping teens with type 1 diabetes improve diabetes control with MyDiaText
Adolescence is a difficult period of development, made more complex for those with Type 1 diabetes mellitus (T1DM).

Diabetes-in-a-dish model uncovers new insights into the cause of type 2 diabetes
Researchers have developed a novel 'disease-in-a-dish' model to study the basic molecular factors that lead to the development of type 2 diabetes, uncovering the potential existence of major signaling defects both inside and outside of the classical insulin signaling cascade, and providing new perspectives on the mechanisms behind insulin resistance in type 2 diabetes and possibly opportunities for the development of novel therapeutics for the disease.

Tele-diabetes to manage new-onset diabetes during COVID-19 pandemic
Two new case studies highlight the use of tele-diabetes to manage new-onset type 1 diabetes in an adult and an infant during the COVID-19 pandemic.

Genetic profile may predict type 2 diabetes risk among women with gestational diabetes
Women who go on to develop type 2 diabetes after having gestational, or pregnancy-related, diabetes are more likely to have particular genetic profiles, suggests an analysis by researchers at the National Institutes of Health and other institutions.

Maternal gestational diabetes linked to diabetes in children
Children and youth of mothers who had gestational diabetes during pregnancy are at increased risk of diabetes themselves, according to new research published in CMAJ (Canadian Medical Association Journal).

Two diabetes medications don't slow progression of type 2 diabetes in youth
In youth with impaired glucose tolerance or recent-onset type 2 diabetes, neither initial treatment with long-acting insulin followed by the drug metformin, nor metformin alone preserved the body's ability to make insulin, according to results published online June 25 in Diabetes Care.

People with diabetes visit the dentist less frequently despite link between diabetes, oral health
Adults with diabetes are less likely to visit the dentist than people with prediabetes or without diabetes, finds a new study led by researchers at NYU Rory Meyers College of Nursing and East Carolina University's Brody School of Medicine.

Read More: Diabetes News and Diabetes Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.