Unravelling the developmental origins of cystic fibrosis-related diabetes.

Cystic fibrosis (CF)-related diabetes (CFRD) is a growing and evolving concern for people living with cystic fibrosis. As its own unique clinical entity, there is an urgent need to better understand this complex health challenge to improve the quality of life for people with CF. Unfortunately, many aspects of CFRD pathophysiology and pathogenesis remain unclear, resulting in a disparity in the standard of care provided. An emerging body of evidence supports that CFRD may have developmental origins, as people with CF present with pancreatic pathology and glucose abnormalities as early as in utero. This therefore suggests that the CF transmembrane conductance regulator (CFTR) gene mutations that cause CF may impair pancreatic organogenesis, thus leading to CFRD. This review consequently aims to summarise the existing evidence that may support a fundamentally vital role of CFTR in the development of the pancreas. From aspects of the endocrine and exocrine pancreas to scrutinising the broader islet microenvironment, the many constituents at play in pancreatic organogenesis are highlighted. Unravelling the deeper complexities of CFRD pathogenesis will not only clarify existing knowledge gaps but may transform the way future care is provided.