Investigation of Appropriate Timing of Additional Insulin Dosing for Fat and Protein in Children With Type 1 Diabetes Using Multiple Daily Injections

The study design is a repeated measures study involving the provision of a standard high protein/high fat evening test meal on 3 different evenings within a 7-day period in the same study subject. The children/adolescents will be instructed to give an insulin dose for the carbohydrate before the meal (calculated using their optimal insulin to carbohydrate (ICR) - 20%). In addition they will have an additional dose for the fat and protein content either before (together with the dose for the carbohydrate in the meal [control meal]), 1 hour after, or 2 hours after the meal. These will be carried out in a random order in each subject. Continuous glucose monitoring (CGM) will be carried out for the whole 7 day period. Questionnaires will assess the acceptability to young people and their parents of the extra insulin doses.

After an initial contact in the clinic, and provision of patient information leaflets, the research nurse or dietitian will telephone the patient and family after a week to answer any questions they may have about the study. If they are keen to participate, an appointment will be arranged for consent and to commence the study (Visit 1).

At Visit 1 the investigators will obtain informed consent and commence a week-long run-in period for participants to optimise insulin to carbohydrate ratio at the evening meal. During this week subjects will be requested to test capillary blood glucose (BG) levels at 7 points throughout the day (pre-meals, 2 hrs after meals and bed). They will be asked to eat a fat and protein free meal on one of these days. If necessary, adjustments to the insulin to carbohydrate ratio (ICR) or long-acting insulin doses will be made over the telephone by an experienced member of their clinical team. This is to decrease the likelihood of a correction bolus for a high BG level being required at the evening meal during the study week.

At the end of the run-in week, participants will then attend the outpatient clinic or day care ward research facility at the Oxford Children's Hospital or the Horton Hospital outpatient clinic in Banbury or the Royal Berkshire Hospital in Reading (Visit 2). At this visit, the subcutaneous glucose sensor will be inserted by the research nurse and children and young people and their families will be trained on its use prior to the study commencing. CGM records glucose levels every 5 minutes over 7 days and thus provides much more information than routine capillary BG testing. It also alarms to alert patients of high and low glucose levels. Children and young people will also record their BG levels from routine finger pricks, pre-prandially and before bed and on waking in the morning.

Also at Visit 2, the study dietitian will review BG readings and food diary from the previous week and optimise ICR doses of rapid acting insulin. This ratio will then be used to calculate insulin doses for the study meals. On three evenings over the next 7 days, the children will eat a standard high protein/high fat meal. The evenings will not be set, but will depend on the child and family schedule. The child and family will be able to choose which days during the study period on which they complete the study meals but will be advised to avoid days when the participant has undertaken lots of exercise, has had frequent hypoglycaemic episodes or has been unwell.