Investigating the Incretin Effect in Cystic Fibrosis
Investigating the Incretin Effect in Cystic Fibrosis
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.
Inclusion Criteria:

 -  Cystic fibrosis as diagnosed by EITHER Cystic fibrosis transmembrane conductance
 regulator (CFTR) mutation on genotyping OR Positive sweat test (Chloride ≥60mmol/L
 after pilocarpine iontophoresis) AND Clinical features in keeping with a diagnosis of
 Cystic Fibrosis

 -  Clinically stable for at least 4 weeks without inpatient or outpatient treatment for
 an infective exacerbation - including antibiotics (other than long-term prophylactic
 therapy) or steroids

 Exclusion Criteria:

 -  Active Pregnancy or <12 months Post-partum

 -  Clinically unstable patients

 -  Patients on long-term steroids

 -  Patients with known gastroparesis or previous surgery to the gastrointestinal tract
 (including vagotomy)

 -  History of organ transplant or planned organ transplant awaited

 -  Non-CF related diabetes (e.g. Type 1 or 2 Diabetes Mellitus)

 -  Active malignancy

 -  Clinically significant derangements in haematological or biochemical indices

 -  Clinical symptoms of malabsorption (frequent bowel motions/passing of undigested
 foodstuffs or steatorrhoea)

 -  Known difficult venous access

 -  Use of bile acid sequestrants in the previous 4 weeks