Research in focus: CF-related diabetes - what have we found out and where next?
CF-related diabetes (CFRD) is a distinct form of diabetes unique to people with cystic fibrosis. The signs and symptoms of CFRD share similarities to both Type 1 and Type 2 diabetes, but CFRD is a distinct condition, with a different underlying cause. Exactly how CFRD develops on a cellular level isn’t fully understood and that’s why, in 2017, we awarded Professor James Shaw and colleagues a Cystic Fibrosis Trust Strategic Research Centre (SRC) grant of £750,000 over three years to find out. The programme of work is drawing to close and it has been a great success.
To understand the underlying cause of CFRD, researchers from four different countries within the SRC investigated how the pancreas works in people with CFRD in comparison to people with no health concerns. The pancreas has two jobs: to help us digest food and to keep the amount of sugar in the blood at the right level. The researchers investigated both of these jobs of the pancreas in their quest to understand the cause of CF-related diabetes.
What do we know about CF-related diabetes so far?
To help manage the levels of sugar in the blood, the pancreas releases the hormone insulin. In CFRD, the body can’t release enough insulin from where it is made in the pancreas, and the body also responds differently to the insulin that is released, which means that the sugar levels in the blood aren’t regulated properly. The researchers investigated what’s causing the production of insulin to stop. They looked at what’s happening in the insulin-producing cells and also what the trigger may be for these changes to happen.
The researchers found that the damage in CFRD is not due to the faulty CF protein in these cells, as these cells don’t make the CF protein in the first place. This is a really important finding as it has allowed them and other researchers in this field to eliminate studies into CF protein in insulin-producing cells from their investigations. This is also a call to action to researchers to look at the consequences of what’s happening in the rest of the pancreas to truly understand what’s causing CFRD.
What we still need to find out
The researchers identified stress signals from the digestive-juice-producing parts of the pancreas as a possible trigger for CFRD, but we don’t know enough about specifically which stress signals are involved, and the steps that lead up to the damage.
We have awarded a second three-year SRC grant of £750,000 to Professor Shaw to investigate this further. Professor Shaw and an international group of colleagues will look at how the signals move from the digestive-juice-producing parts of the pancreas to the insulin-producing cells; which signals cause the most damage and whether these signals can be measured in the blood of people with cystic fibrosis.
“We believe that CFRD is caused by signals from damage to the digestive-juice-producing part of the pancreas, which stop insulin-producing cells from working properly. Understanding more about these signals could lead to entirely new approaches to treating diabetes, avoiding the need for insulin injections”, explained Professor Shaw, Professor of Regenerative Medicine for Diabetes at the Institute of Cellular Medicine at Newcastle University; and Principal investigator of the SRC.
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