Investigating the Incretin Effect in Cystic Fibrosis

A standard 2-hour oral glucose tolerance test where fasted patients (10hours overnight) consume a 75g glucose solution \& have glucose levels recorded up to every 30 mins for 2hours

A 4-hour version of the oral glucose tolerance test where fasted patients (10hours overnight) consume a 50g of glucose solution \& have glucose levels recorded up to every 5mins as well pancreatic and incretin responses at 10 fixed time points.

A glucose drip will be infused at a variable rate that recreates the individual subjects blood glucose values obtained during their 4-hour modified oral glucose tolerance test. This test will therefore last 4-hours and again subjects will be fasted (10hours overnight) at the time of the test. The same blood tests will be performed at the same time points as the modified glucose tolerance test

An intravenous glucose infusion will be infused at a rate that maintains blood glucose at a level of 180-216mg/dL (10-12 mmol/l) (hyperglycemic clamp). After 60mins an infusion of GLP-1 will be commenced at a rate of 0.25pmol/kg/min for 60mins and then continued at a rate of 1.2pmol/kg/min for a further 60mins. Subjects will be blinded to what infusion they are receiving.

An intravenous glucose infusion will be infused at a rate that maintains blood glucose at a level of 180-216mg/dL (10-12 mmol/l) (hyperglycemic clamp). After 60mins an infusion of GIP will be commenced at a rate of 1pmol/kg/min for 60mins and then continued at a rate of 4pmol/kg/min for a further 60mins. Subjects will be blinded to what infusion they are receiving.

"An intravenous glucose infusion will be infused at a rate that maintains blood glucose at a level of 180-216mg/dL (10-12 mmol/l) (hyperglycemic clamp).~After 60mins an infusion of normal saline will be commenced as a placebo infusion. It will be infused at a rate so that the total volume of fluid is similar to that infused during the other two hyperglycemic clamp interventions. Subjects will be blinded to what infusion they are receiving."

A standardised liquid meal (carbohydrate-rich) containing approximately 500kcal would be administered to patients who had fasted overnight (10hrs). Over the next 4hours bloods would be sampled at 10 fixed time points to measure features of the incretin response to this type of meal.

A standardised liquid meal (fat-rich) containing approximately 500kcal would be administered to patients who had fasted overnight (10hrs). Over the next 4hours bloods would be sampled at 10 fixed time points to measure features of the incretin response to this type of meal.

A standardised liquid meal (mixed) containing approximately 500kcal would be administered to patients who had fasted overnight (10hrs). Over the next 4hours bloods would be sampled at 10 fixed time points to measure features of the incretin response to this type of meal.

Continuous glucose monitoring entails wearing a small portable device, usually on the upper arm, for a period of three days. The device uses a small plastic tube to record the glucose level from interstitial fluid \& every minute wirelessly transmits this information to a base unit to enable a very accurate estimate of average blood sugar control to be defined.