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Immune-Related Adverse Events for Endocrine Toxicities - Diabetes Mellitus

Grades severity of hyperglycemia secondary to immune checkpoint inhibitor therapy.

Use in adult patients with signs and symptoms of new or worsening hyperglycemia that developed while on treatment with immune checkpoint inhibitors.

Criteria

Result:

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Advice

  • Monitor patients for hyperglycemia or other signs and symptoms of new or worsening diabetes mellitus, at baseline and with each treatment cycle during induction for 12 weeks, then every 3 to 6 weeks.

  • Consider a patient’s medical background, exposure history, and risk factors for identification of diabetes mellitus type.

  • If type 1 diabetes mellitus is suspected diagnostic work up should include anion gap and urine ketones etc. Anti–glutamic acid decarboxylase, anti–islet cell, or anti–insulin antibodies, insulin and C-peptide levels can assist in the diagnosis.

Management

For all patients where an IRAE diagnosis is being considered, it is always recommended to involve the specialist or team prescribing the immune checkpoint therapy. 

Grade 1:

  1. May continue ICPi with close clinical follow-up and laboratory evaluation.

  2. Consider oral medications for those with new-onset type 2 diabetes mellitus.

  3. Screen for T1DM if appropriate (i.e. acute onset with prior normal values or clinical concern for ketosis).

Grade 2:

  1. May hold ICPi until serum glucose is controlled. 

  2. For worsening control in type 2 diabetes mellitus, titrate oral therapy consider insulin.

  3. Administer insulin for type 1 diabetes mellitus or for patients whose diagnosis in question. 

  4. Obtain urgent endocrine (preferred) or internal medicine consultation for patients with type 1 diabetes mellitus. 

  5. Admission for patients with type 1 diabetes mellitus if ketoacidosis signs are present.

Grade 3-4:

  1. Hold ICPi until toxicity recovers to grade ≤1.

  2. Obtain urgent endocrine consultation.

  3. Initiate insulin therapy.

  4. Admit if there is concern for developing diabetic ketoacidosis, if the patient is symptomatic, if the patient with new onset type 1 diabetes mellitus is unable to see endocrinology.

Critical Actions

Distinguishing type 1 diabetes mellitus from type 2 diabetes mellitus is necessary. 

New onset hyperglycemia in a patient without risk factors of type 2 diabetes mellitus should raise concern for type 1 diabetes mellitus.

Insulin is the treatment of choice for any patient where the diagnosis is in question.

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