Which medications can precipitate autoimmune type 1 diabetes?

Medications That Can Cause Type 1 Diabetes

Immune checkpoint inhibitors are the primary medication class that can precipitate autoimmune type 1 diabetes, and all healthcare professionals administering these agents must educate and monitor patients for this potentially life-threatening adverse effect. 1

Checkpoint Inhibitors: The Primary Culprit

Mechanism and Risk Profile

• Checkpoint inhibitors (used alone or in combination) can trigger checkpoint inhibitor-associated type 1 diabetes through immune-mediated destruction of pancreatic beta cells 1
• Risk cannot be predicted by family history or autoantibodies, making universal vigilance essential for all patients receiving these medications 1
• Patients may present with diabetic ketoacidosis (DKA) as the first manifestation, which can be life-threatening 1

Clinical Monitoring Requirements

• All healthcare professionals administering checkpoint inhibitors or caring for patients with current or past exposure must be mindful of this adverse effect 1
• Patients should be educated about symptoms of hyperglycemia and DKA before initiating therapy 1
• Even individuals with high-risk HLA haplotypes for type 1 diabetes can develop checkpoint inhibitor-associated type 1 diabetes 1

Chemical and Environmental Exposures

Endocrine-Disrupting Chemicals

• The Endocrine Society's 2015 scientific statement established relationships between endocrine-disrupting chemical exposures and diabetes 2
• These chemicals can interfere with hormone production, release, transport, metabolism, binding, action, or elimination 2
• They may act as hormone receptor agonists or antagonists, potentially triggering delayed onset of diabetes 2

Specific Chemical Exposures

• Arsenic exposure shows suggestive evidence for diabetes causation, with one meta-analysis demonstrating an odds ratio of 2.52 (95% CI 1.69-3.75) for type 2 diabetes in high-exposure populations 2
• Uranium exposure may contribute to diabetes through inflammatory mechanisms, particularly concerning in populations with already high diabetes prevalence 2

Important Clinical Caveats

Classification Challenges

• Standard diabetes classification systems acknowledge drug- or chemical-induced diabetes but note these may precipitate diabetes in individuals with pre-existing insulin resistance, making classification unclear 2
• Some patients may develop autoimmune type 1 diabetes, while others may develop insulin-deficient diabetes without autoimmune markers 1

Presentation Patterns

• 25-50% of patients with new-onset type 1 diabetes present with life-threatening DKA 1
• Adults may retain sufficient beta-cell function to prevent DKA for years, creating a delayed presentation pattern 1
• The rate of beta-cell destruction is highly variable, being rapid in some individuals and slow in others 1

Monitoring Strategy for High-Risk Patients

• Assess for inflammatory markers in populations with known toxic exposures to indicate immune perturbation 2
• Screen more aggressively for diabetic kidney disease in populations with known uranium or heavy metal exposures due to synergistic nephrotoxic effects 2
• Consider confounding by socioeconomic factors and other environmental exposures when evaluating chemical-diabetes relationships 2

Viral Triggers (Not Medications, But Relevant Context)

• SARS-CoV-2 infection has been associated with increased cases of hyperglycemia, DKA, and new diabetes, suggesting it can trigger or unmask type 1 diabetes 1
• Enteroviruses such as Coxsackievirus B have been associated with type 1 diabetes 1
• The cytokine storm associated with severe infections creates a highly inflammatory state that could contribute to beta-cell damage 1