Objective
The objective of this grant is to determine cancer and therapy specific risk factors for cancer immunotherapy induced diabetes, assess glucose variability while on cancer immunotherapy, integrate risk prediction into our clinical care in the oncology clinic and pilot an approach for closer monitoring of patients.
Background Rationale
A new form of cancer treatment called immunotherapy has emerged in the last ten to fifteen years. Immunotherapy harnesses the power of the immune system against cancer cells, but causes autoimmune side effects that are very different from the side effects of prior chemotherapy approaches. In particular, a novel form of autoimmune diabetes occurs. This form of diabetes is clinically very similar to type 1 diabetes with strong genetic overlap. Despite this genetic overlap, there are lower rates of the autoantibodies that can usually help identify type 1 diabetes. By studying this form of provoked diabetes, we will pinpoint triggers and immune phenomena that precede overt diabetes after autoimmune provocation. Given the rarity but high morbidity of cancer immunotherapy induced diabetes, to improve patient care and clinical research, we must improve our prediction and monitoring for this disease. This will contribute to our understanding of the natural history of type 1 diabetes.
Description of Project
Cancer immunotherapy induced diabetes is a form of autoimmune diabetes similar to type 1 diabetes. The development of autoimmune diabetes while on cancer therapy is challenging for patients and providers alike. we need to better understand who gets this complication by risk factor studies. We then need to apply these predictions to clinical practice to be able to identify patients as they develop diabetes, and therefore finding a window for possible successful intervention to attenuate its course.
Anticipated Outcome
In the near term, identification of predictive risk factors and glucose variability will narrow the number of patients for whom to offer close surveillance for hyperglycemia, to consider alternative approaches to cancer care (so long as they are adequate), and to include in prospective translational interrogation of immune changes occurring from exposure to cancer immunotherapy. In the longer term, this risk prediction for autoimmune diabetes will be integrated with the preventive immunomodulation being carried out in conventional type 1 diabetes, so that a patient at high risk of cancer immunotherapy induced diabetes will be afforded the opportunity to avoid this life-long side effect and so that we can better explain the mechanistic triggers that move the non-cancer patient from early stage stage type 1 diabetes to late stage diabetes. Specifically, we will identify which cancer types and treatment types have the highest incidence of cancer immunotherapy induced diabetes, we will integrate autoantibody and genetic testing into the clinic, and we will identify changes in glucose variability subjects at average risk for diabetes and high risk for diabetes.
Relevance to T1D
Cancer immunotherapy induced diabetes is a targeted autoimmune attack on the beta cell provoked by known immunological triggers, i.e. the cancer treatment. Clinically, this appears most similar to type 1 diabetes. Cancer immunotherapy induced autoimmune diabetes offers a window into the stepwise breaks in the body’s native ability to protect “self” from the immune system and therefore sheds light on how this might occur in type 1 diabetes. By identifying the risk factors and developing monitoring techniques, we will be able to at a minimum improve clinical care in these cancer patients, but also build towards being able to prevent or attenuate this form of diabetes, and gain required samples to understand the exact changes in the immune system as this disease progresses. Research within these two forms of autoimmune diabetes is a symbiotic relationship- insights from one can certainly be employed by the other.