Investigating the Incretin Effect in Cystic Fibrosis
Status:
Completed
Trial end date:
2015-07-01
Target enrollment:
Participant gender:
Summary
Most Cystic fibrosis (CF) patients now commonly live well into adulthood, this means they are
progressively accumulating damage to the insulin-secreting cells inside their pancreas. This
explains why most adult patients have some degree of abnormal sugar regulation & rates of
diabetes rise significantly with age. CF related diabetes is categorically different from
other types of diabetes & its development is serious as it heralds a faster decline in lung
function & a reduced life expectancy.
The hallmark of abnormal sugar handling in CF is high glucose levels after meals as the
damaged pancreas responds abnormally slowly. Over 70% of the initial response of a healthy
pancreas is induced, not by glucose alone, but by hormones released from the bowel known as
incretins. We want to establish whether incretins are important in blood sugar handling in CF
as specific drugs that enhance their effect are now available.
The study hypothesis is that the incretin system will function normally in patients with
Cystic Fibrosis. To show this we will measure how much insulin secretion is dependant on
incretin hormones in CF patients by comparing levels after a sugary drink test and then an
intravenous glucose drip test (run at a rate that mimics the blood sugar levels obtained
during the first test to make it a fair comparison ) - as incretins will only be produced in
the first test when the sugar passes through the bowel any extra insulin produced will be due
to these hormones. To detect resistance to the incretin hormones we will separately measure
responses to direct infusions of the hormones themselves. We will explore which components of
meals cause incretin hormone release from the bowel wall by measuring blood levels after
different types of meals are consumed. Finally we will measure levels of the enzyme that
breaks down the incretin hormones (DPP-4) to know if they are deactivated more quickly in
people with CF. By describing the incretin system in CF we will considerably improve our
understanding of this important condition as well as potentially highlighting new ways to
treat it.
Details
Lead Sponsor:
Liverpool Heart and Chest Hospital NHS Foundation Trust