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Cystic fibrosis-related diabetes (CFRD) is an increasingly prevalent condition, affecting about 19% of people with CF, and often poses significant health challenges. The primary defect underlying CFRD is the pancreatic beta cell's inability to secrete sufficient insulin to maintain normal blood glucose levels. Despite recent advances in our understanding of the pancreatic processes that may contribute to beta cell dysfunction, we have much to learn about why CFRD develops and how to prevent it. Additionally, as the CF population ages and undergoes pulmonary and nutritional improvements — alongside rising obesity rates — the landscape of CFRD is evolving. During plenary 2 of the North American Cystic Fibrosis Conference, speakers focused on recent advances and exciting new directions in basic science and clinical research in CFRD. Rebecca Hull-Meichle, PhD, gives us a view of the CF pancreas under a microscope, focusing on new insights into cellular mechanisms underlying CFRD and how these discoveries may one day be translated into potential therapies. Melissa Putman, MD, takes us through the changing landscape of CFRD in the post-modulator era, including emerging diabetes technologies, new treatment strategies, and redefining nutrition in an aging CF population. Livestreamed from NACFC 2024 in Boston, Massachusetts September 26, 2024. 00:00 | The Tipping Point: The Journey to Understand & Advance Research in CFRD 00:22 | CF Foundation President and CEO Michael Boyle, MD welcomes the audience to Plenary 2 00:55 | Recognizing the 2024 NACFC Honorary Co-Chairs 03:30 | Recognizing former CF Foundation Chief Medical Officer, Bruce Marshall, MD 11:27 | CF Foundation Senior Vice President of Clinical Research JP Clancy, MD and Senior Director of Research Katherine Tuggle, PhD introduce Plenary 2 16:20 | Rebecca Hull-Meichle, PhD gives a view of the CF pancreas under a microscope, focusing on new insights into cellular mechanisms underlying CFRD 16:55 | CF is a full-body disease 19:26 | Overview of the pancreas 20:55 | What is the role of CFTR in the pancreas? 24:09 | Exocrine and endocrine pancreas disease in CF 39:57 | CF islets show very high levels of inflammation 41:50 | Comprehensive analysis of the CF pancreas 43:10 | Summary of Rebecca’s talk 44:10 | Melissa Putman, MD discusses the clinical aspects and the changing face of CFRD 44:30 | What is CFRD and why is it a problem? 46:35 | Distinct challenges of CFRD 49:58 | How do we diagnose and treat CFRD? 54:45 | What is the only recommended treatment for people with CFRD? 56:04 | What is the impact of highly effective modulator therapy on CFRD? 59:15 | VIDEO: Alex and Emma share their experiences with CFRD 1:03:46 | How is the landscape changing for CF and CFRD? 1:07:32 | What is the iLet Bionic Pancreas? 1:11:00 | Rising rates of overweight/obesity 1:12:04 | Emerging non-insulin therapies in CF 1:20:14 | The future of CFRD: Shifting the tipping point