What Is Immunotherapy-Induced Diabetes?

Among patients with cancer, treatment with immunotherapies — a type of drug that helps to activate the immune system to fight cancer — can also result in unwanted attacks on healthy tissues known as autoimmune diseases, as an expert explained in an interview with CURE.

Dr. Melissa G,. Lechner, assistant professor of medicine in the division of endocrinology, diabetes and metabolism at the David Geffen School of Medicine, spoke with CURE about one of these side effects: immunotherapy-induced diabetes.

Lechner is the senior author of a study published in JCI Insight that identifies JAK inhibitors as a potential means of preventing and possibly reversing immune checkpoint inhibitor-induced type 1 diabetes.

Transcript

What should patients and clinicians know about the potential autoimmune side effects of immunotherapy, particularly how it can impact metabolic health, such as triggering diabetes?

Immunotherapies help activate the immune system to fight cancer. Because they activate the immune system, they can have unwanted attacks on healthy tissues that we think of as autoimmune disease, which can affect a number of different tissues. About two-thirds of patients get it. In particular, checkpoint inhibitor immunotherapy can cause diabetes, which is an accelerated form of autoimmune diabetes that happens in about 1% of patients who receive cancer immunotherapy.

I think our patients with cancer are obviously facing a lot of different comorbid health problems, and it's helpful to distinguish them. We certainly see a lot of patients who have diabetes from the type 2 insulin resistance form, but we also have a lot of patients who get these autoimmune side effects. I think it's also helpful to put it in context with spontaneous type 1 diabetes.

People are familiar with juvenile diabetes, or spontaneous type 1 diabetes, which is an autoimmune attack on the pancreas's insulin-producing cells that can happen over a period of months to years. In contrast, the immune checkpoint inhibitor form of autoimmune diabetes is an autoimmune attack. It similarly destroys all of the insulin-producing cells in the pancreas and leads to a complete dependence on multiple daily injections of insulin. However, in contrast to juvenile type 1 diabetes, it tends to progress over a period of weeks.

Patients very rapidly have high blood sugar, and it's so rapid and aggressive that about 80% to 90% of those patients will have diabetic ketoacidosis, which is a very severe form of hyperglycemia and insulin deficit that actually lands them in the intensive care unit at diagnosis. So, it's a very rapid form of the disease and is considered almost universally permanent. You have a very dangerous and debilitating diagnosis that is added to a patient with cancer's already challenging regimen in many cases.

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