03:45pm Sunday 12 July 2020

SickKids researchers unravel the cause of cystic fibrosis-related diabetes

Researchers at The Hospital for Sick Children (SickKids) have shown that the same biomarker that identifies CF at birth can predict which newborns are at greater risk for eventually developing diabetes, and that a major cause of this diabetes is prenatal damage to the pancreas. The study was published in the February 18 edition of Diabetes.

CF is a disease that affects the lungs and pancreas, among other organs. Newborn screening for CF consists of measuring the amount of a protein produced by the pancreas. In general, individuals with CF will have elevated levels of this protein and two mutations in the gene that causes CF, CFTR.  Those with severe mutations in CFTR will be unable to digest food properly within their first years of life; and 40 per cent of these individuals will go on to develop CF-related diabetes by the age of 40.

This new research finding suggests that clinicians will be able to use the protein levels at birth and the CFTR gene mutations to determine which individuals with CF should be monitored more closely for an earlier onset of diabetes.  Although the protein levels of newborns with CF are elevated above the normal population levels, within the elevated CF group those that have lower levels are at greater risk for developing diabetes earlier. Diabetes in individuals with CF negatively affects nutrition and lung function, and is associated with increased mortality.

David Soave, biostatistics graduate student at the University of Toronto, and Dr. Lisa Strug, senior author of the study and Senior Scientist in Child Health Evaluative Sciences at SickKids, along with their colleagues, used a statistical method to find a causal relationship between early damage to the exocrine pancreas, which is measured by levels of the protein, and a higher risk of CF-related diabetes among individuals with severe CFTR mutations.

“The earlier we can predict individuals at risk for more severe CF-associated disease, the more we can do by way of intervention and monitoring to ensure the best quality of life for the patient,” says Strug.

The casual relationship between early damage to the pancreas and an earlier onset of CF-related diabetes provides insights into potential therapeutic targets, explains Strug.  Medication that could promote ductal fluid flow and reduce or delay damage to the exocrine pancreas, could in turn delay the onset and reduce the risk of CF-related diabetes.

The Hospital for Sick Children (SickKids)

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