None listed
Conditions
Brief summary
Gut emptying is of central importance to blood glucose levels after meals and is a major determinant of overall blood glucose control in diabetes. Blood glucose levels and insulin release after meals are also influenced by secretion of hormones from the gut in response to a meal. The gut hormones stimulate insulin secretion in response to raised blood glucose levels. However fat, rather than carbohydrate may be the most potent stimulus for gut hormone release. We aim to measure the effect of gut emptying and gut hormone release on high blood glucose levels in youth with cystic fibrosis (CF). We will determine whether the adequate replacement of pancreatic enzymes improves blood glucose levels after meals in youth with CF. Our findings for gut hormone release will inform investigation of potential therapies, eg. free fatty acid therapy, to prime gut hormone release to reduce the impact of high blood glucose levels on the complications associated with CF. Hypothesis : In young people with CF i) Gut emptying of a high fat/carbohydrate meal will be abnormally rapid. ii) Abnormal emptying will be associated with high blood glucose levels after a meal and reduced gut hormone secretion and insulin responses. iii) These abnormal responses will be normalised by pancreatic enzyme supplementation.
Interventions
CF subjects will have 2 study days on which they will consume a high fat/ carbohydrate pancake at approximately 8.30am after fasting from both solids and liquids from 10pm the previous evening. The study days will be separated by at least 24 hours so no residual 13C Na-octanoate is present at the time of the second study.
The pancake in the CF group will either be: (1) with pancreatic enzymes [1 generic capsule filled with 50,000U lipase] or (2) placebo without pancreatic enzyme replacement [
CF subjects will have 2 study days on which they will consume a high fat/ carbohydrate pancake at approximately 8.30am after fasting from both solids and liquids from 10pm the previous evening. The study days will be separated by at least 24 hours so no residual 13C Na-octanoate is present at the time of the second study. The pancake in the CF group will either be: (1) with pancreatic enzymes [1 generic capsule filled with 50,000U lipase] or (2) placebo without pancreatic enzyme replacement [1 generic capsule filled with microcellulose prepared by the pharmacy]. Pancreatic enzyme replacement In the CF group the enzyme replacement will be double blinded and the order of the studies (one with and one without enzyme replacement) will be randomised. The capsules will be given by a medication cup so that any difference in weight and feel can’t be distinguished. Creon Forte/placebo capsules will be provided on the day of the study and will be taken at the start of the meal by the CF subjects. Insulin administration CF subjects who are normally on insulin will administer their ultrashort insulin analog (novorapid) before the ingestion of the meal at time -15minutes, via subcutaneous injection or an insulin pump. Pancake Each subject will consume the pancake within 5min. t = 0 is defined as the time of meal completion. The standard pancake (70g of Green’s (Trademark) Pancake and Pikelet Mix mixed with 100mL water and cooked with 10g butter; total of 13.5 g fat, 44.2g of carbohydrate, 252 Calories) will be modified to increase the fat content to 40g by replacing some of the H2O with polyunsaturated oil. This represents the high fat diet prescribed to CF subjects and will maximize the effect of pancreatic enzymes. After consuming the pancake CF subjects will undergo a gastric emptying breath test and measurement of incretin hormones over 4 hours.
Sponsors
Adelaide University
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Treatment
Masking
Blinded (masking used)
Eligibility
Sex/Gender
All
Age
10 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
16 subjects with cystic fibrosis (CF) with exocrine pancreatic insufficiency and taking pancreatic enzymes. CF related diabetes will be defined as those with diabetes detected on an oral glucose tolerance test (WHO definition); CF without diabetes will be defined as those with a normal glucose tolerance test in the previous 12 months. 16 healthy control subjects without clinically significant systemic disease, and BMI <95th centile will be recruited and will be matched for age to the CF subjects.
Exclusion criteria
Exclusion criteria CF subjects: severe pulmonary disease (FEV1<30% predicted), significant liver disease (Child-Pugh score >6), previous gastrointestinal surgery (apart from uncomplicated appendicectomy), requirement for medications that could affect gastrointestinal motility (eg erythromycin, SSRIs), pregnancy or lactation Exclusion criteria controls: previous gastrointestinal surgery (apart from uncomplicated appendicectomy), requirement for medications that could affect gastrointestinal motility (eg erythromycin, SSRIs), pregnancy or lactation.
Outcome results
None listed