Performance and patient acceptance of a commercially available beverage as compared to an oral glucose solution for oral glucose tolerance tests in cystic fibrosis (CF) patients who are screened for CF-related diabetes.

Cystic fibrosis (CF) is an incurable genetic disease that affects the pulmonary
system, digestive system, reproductive system and the sweat glands.
One of the common comorbidities in CF is pancreatic insufficiency (PI), it
affects 85% of the CF population. Pancreatic insufficiency expresses itself in
enzymatic deficiencies (exocrine insufficiency) and insulin deficiency
(endocrine insufficiency). The insulin deficiency in its turn can cause cystic
fibrosis related diabetes (CFRD) after a pre-diabetic state called impaired
glucose tolerance (IGT). CFRD is a unique form of diabetes and is extremely
common in CF patients, it is occurring in 40-50% of adult CF patients. CFRD
does not only affect patients nutritional status, it also leads to pulmonary
decline and earlier mortality as compared to patients without CFRD. Early
insulin therapy appears to revers some of the decline found with CFRD.
Therefore it is recommended to screen for CFRD yearly so it is caught in an
early stadium. For screening the oral glucose tolerance test (OGTT) or the
glucose challenge test is used. During the OGTT fasting patients have to drink
a 300 ml solution that contains 75 grams of glucose following an overnight
fast. The solution has to be finished in 15 minutes. Then the blood glucose
level is measured at 0 minutes and 120 minutes. CFRD is diagnosed when the
fasting glucose level is is higher or equal to 7mmol/L or the 120 minutes
glucose level is higher or equal to 11.1 mmol/L. IGT is diagnosed when the
glucose level after 120 minutes is > 7.8 mmol/L and <11.1 mmol/L.

The OGTT is perceived as uncomfortable by patients. The glucose solution makes
patients nauseous and can even cause vomiting. This leads to patients refusing
to undergo the OGTT and being diagnosed with CFRD in a later stadium. The
current AMC database for CF patients consisted in 2020 of 127 patients. Of 127
adult CF patients in Amsterdam UMC, 42 patients have known CFRD. Of the
remaining 85, 50 patients have exocrine pancreatic insufficiency for which they
take pancreatic enzyme suppletion. This group is most at risk to develop CFRD
or a disturbance in their glucose metabolism, so they would have the most
benefit from a yearly OGTT. However, only 19 (38%) of these patients underwent
an OGTT in 2020 and -although the reason for abstaining from this test is not
recorded, we know by experience that a percentage of these patients refuses to
be tested because they feel aversion against taking the glucose solution. In
2019 the database consisted of 121 patients, of which 78 have no known CFRD yet
and 48 of these have exocrine pancreatic insufficiency for which they take
pancreatic enzyme suppletion. Again only 19 (40%) of those patients underwent
an OGTT.

Therefore, to increase patients adherence in yearly screening for CFRD using
the OGTT, for this study the glucose solution is substituted with a
commercially available beverage (AA-drink). The hypothesis is that results of
this *AATT* will be comparable to the standard OGTT with respect to diagnosing
CFRD and IGT. Furthermore we believe that the *AATT* will be better tolerated
by this patient group leading to an increase in patient adherence to our yearly
CRFD screening.

Primary Objective: To compare the performance of a glucose tolerance test
(*AATT*) with a commercially available beverage to the results of the
conventional OGTT with respect to diagnosing IGT and CFRD in patients with CF.
Secondary Objective(s): To compare patient satisfaction using a prespecified
scoring system for the *AATT* as compared to the conventional OGTT.

The study will have the set-up of a randomized cross-over trial.
Participants will be patients diagnosed with CF from the outpatient clinic from
the Amsterdam UMC - location AMC. The study consists of 2 visits; one visit
patients will undergo the standard OGTT, the other visit patients will undergo
the OGTT substituting the glucose solution with a commercially available
beverage, AA-drink (united soft drinks, the Netherlands) (AATT).
Tests will be performed at the AMC and will take up a proximally 2.5 hours per
visit.
Participants will be patients diagnosed with CF from the outpatient clinic from
the AMC. Patients have to be at least 18 years old and both women and men will
be included. For this study patients will be divided in two subsets of CF
patients; those who are not diagnosed with CFRD yet and those already diagnosed
with CFRD or a disturbed glucose tolerance. Since we approach patients that
already have to come to the hospital to do their yearly screening using the
OGTT for the first group, they only have to visit 1 extra time to undergo the
AATT. The second group will have to come to the hospital 2 times, first for the
OGTT and the second time for the AATT. In both groups the visits need to be at
least 2 weeks apart. For both visits patients will have to be fasting before
they undergo either the OGTT or the AATT. The fasting starts at 22:00 the
evening before the test. Patients who are using insulin will be asked to not
inject any short-acting insulin after 23:59 the evening before the test.
Patients will present at the hospital at 08.30. An I.V. cannula will be placed
because blood samples have to be taken 5 times to determine the blood glucose
level at different time points. The use of the I.V. cannula will make the test
more comfortable for the patient. Patients will be randomly assorted to either
undergo the OGTT first and 2 weeks later the AAGTT or the other way around.
During one visit patients get to drink a 75 gram glucose solution (OGTT) of 300
ml in 15 minutes. Then their blood will be taken using the I.V. cannula at 0
minutes, 30 minutes, 60 minutes, 90 minutes and 120 minutes to determine the
glucose levels.
For the other visit the study set up is the same, the only difference is that
patients get to drink 500ml of AA-drink (AATT) instead of the glucose solution.
Patients will have to finish this in 15 minutes as well. How long it takes them
to drink the sports drink will be monitored to see if it is easy to do in 15
minutes.
During the test patients will be asked to score the glucose solution or the
sports drink using a visual analogue scale. The points patients will have to
score the beverages on are: overall satisfaction (very dissatisfied - very
satisfied), taste (really bad - really good), ease of drinking (very difficult
- very easy) and side effects after drinking (e.g. nauseousness, stomach ache)
(very little - a lot).

For the group that is already diagnosed with CFRD there is no personal direct
benefit with participation in this study. However, there is a possibility of
future comfort for other patients who have to undergo an OGTT. For the group
that is not diagnosed with CFRD there is a personal benefit because they still
have to get screened yearly.
The study consists of minor risks for the patients. Phlebitis is a possible
risk due to the I.V. and hyperglycaemia is a possible risk for the patients who
have to stop their short-acting insulin.
The study only takes 2 weeks for a patient and for the group that already has
to do the annual screening for CFRD it only takes 1 extra visit to the
hospital.