Optimizing diabetes treatment strategies in complex comorbidity

PROJECT SUMMARY/ABSTRACT Breast cancer (BC) survivors are the largest cancer survivor group (~4 million in the US) given improvements in screening and long-term BC survival. While BC progression is a concern in this group, many BC survivors die of comorbid illness. Specifically, type 2 diabetes (T2DM) is a major comorbidity (prevalence 20%) associated with increased morbidity and mortality in BC survivors. Thus, optimizing T2DM treatment can have a major beneficial impact in clinical outcomes. However, data regarding the optimal T2DM treatment strategies in BC survivors, particularly taking into account novel T2DM drugs, is limited. The harm/benefit ratio of different T2DM treatment approaches is likely significantly different for BC survivors due to an increased risk of T2DM complications (particularly cardiovascular disease [CVD] in setting of cardiotoxic BC treatments), unique harms from T2DM treatments, higher competing risks of death from BC, and differences in baseline QOL. To address this knowledge gap, I plan to develop and validate a simulation model to recapitulate the natural history, management, and outcomes of T2DM in BC survivors (Aim 1). I then will determine the most effective T2DM treatment strategy (according to age, stage, primary BC therapy, BC recurrence, CVD) in terms of glycemic control intensity (intensive vs. moderate) and first-line drugs (metformin, SGTL2i, GLP1ra vs. SGTL2i/GLP1ra combined) for Stage II-III BC survivors 2) (Aim 2). I am an endocrinologist and my career goal is to optimize diabetes care for cancer survivors and other understudied populations with complex comorbidity using innovative simulation modeling approaches. My proposed training plan focuses on the following domains: 1) Advanced statistical and epidemiological methods (quality of life, longitudinal data, and missing data imputation); 2) Simulation modeling and translation into practice; and 3) Leadership in research and career development (scientific communication, grant writing, etc.). I have assembled an interdisciplinary experienced mentorship team with expertise in diabetes, cancer survivorship epidemiology, biostatistics, and simulation modeling. I will complete my training at the Icahn School of Medicine at Mount Sinai, a national leader in research and one of the top 20 medical schools for research in the country. I have a mentorship team committed to the success of my proposal and my development into a competitive researcher for R-level grants