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Immune checkpoint inhibitors: an emerging cause of insulin-dependent diabetes
Anupam Kotwal1, Candace Haddox2, Matthew Block3
1Division of Endocrinology, Diabetes, Metabolism and Nutrition, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
Objective:
Insulin-dependent diabetes can occur with immune checkpoint inhibitor (ICI) therapy. We aimed to characterize the frequency, natural history and potential predictors of ICI-induced diabetes.
Research Design And Methods:
We reviewed 1444 patients treated with ICIs over 6 years at our cancer center, and from the 1163 patients who received programmed cell death protein 1 (PD-1) inhibitors, we identified 21 such cases, 12 of which developed new-onset insulin-dependent diabetes and 9 experienced worsening of pre-existing type 2 diabetes.
Results:
ICI-induced diabetes occurred most frequently with pembrolizumab (2.2%) compared with nivolumab (1%) and ipilimumab (0%). The median age was 61 years, and body mass index was 31 kg/m2, which are both higher than expected for spontaneous type 1 diabetes. Other immune-related adverse events occurred in 62%, the most common being immune mediated thyroid disease. New-onset insulin-dependent diabetes developed after a median of four cycles or 5 months; 67% presented with diabetic ketoacidosis and 83% with low or undetectable C-peptide. Autoantibodies were elevated in 5/7 (71%) at the time of new-onset diabetes. Diabetes did not resolve during a median follow-up of 1 year.
Conclusions:
PD-1 inhibitors can lead to insulin deficiency presenting as new-onset diabetes or worsening of pre-existing type 2 diabetes, with a frequency of 1.8 %. The underlying mechanism appears similar to spontaneous type 1 diabetes but there is a faster progression to severe insulin deficiency. Better characterization of ICI-induced diabetes will improve patient care and enhance our understanding of immune-mediated diabetes.
Insights
Immune checkpoint inhibitors (ICIs) can cause new-onset or worsening diabetes. This study found a 1.8% frequency of ICI-induced diabetes, often presenting as severe insulin deficiency, requiring careful patient monitoring.
Area of Science:
- Endocrinology
- Oncology
- Immunology
Background:
- Immune checkpoint inhibitors (ICIs) are increasingly used in cancer therapy.
- Insulin-dependent diabetes mellitus (IDDM) is a potential adverse effect of ICI therapy.
- Characterizing ICI-induced diabetes is crucial for patient management and understanding of immune-mediated diseases.
Purpose of the Study:
- To determine the frequency, clinical course, and predictors of ICI-induced diabetes.
- To differentiate ICI-induced diabetes from spontaneous diabetes.
- To inform clinical practice regarding the management of diabetes in patients receiving ICIs.
Main Methods:
- Retrospective review of 1444 patients treated with ICIs over 6 years.
- Identification and analysis of 1163 patients receiving programmed cell death protein 1 (PD-1) inhibitors.
- Detailed clinical data collection including demographics, diabetes presentation, and outcomes.
Main Results:
- ICI-induced diabetes occurred in 1.8% of patients receiving PD-1 inhibitors.
- Pembrolizumab was associated with a higher frequency (2.2%) compared to nivolumab (1%) and ipilimumab (0%).
- Patients often presented with diabetic ketoacidosis and low C-peptide levels, indicating severe insulin deficiency; diabetes was persistent.
Conclusions:
- PD-1 inhibitors can cause insulin deficiency, manifesting as new-onset or worsened diabetes.
- The mechanism resembles type 1 diabetes but progresses more rapidly to severe insulin deficiency.
- Further research into ICI-induced diabetes will enhance patient care and understanding of immune-mediated diabetes.
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