A randomized controlled trial comparing the impact of continuous subcutaneous insulin infusion (CSII) therapy and multiple daily injection (MDI) regimens upon indices of behaviour, cognition and glycaemia in children and adolescents with type 1 diabetes.

INTERVENTION: Continuous subcutaneous insulin infusion (CSII) (also known as Insulin pump therapy) ‐ this is a commonly employed means of intensive insulin therapy and routine clinical practices in the management of patients on CSII will be employed in this study. CSII uses a mechanical device to continuously deliver insulin subcutaneously with additional patient activated 'boluses' being administered intermittently over the course of the day to cover food and to correct hyperglycaemia. Insulin delivery settings for participants in this study will be individualised and adjusted based on blood glucose levels as is routine clinical practice. All participants in this study will be recruited from the waiting list for commencement of CSII at their diabetes centre. This means they will already have been assessed as being suitable and willing candidates for CSII. At baseline, all participants in this study will be using multiple daily injections of insulin, giving individualised doses as prescribed by their diabetes team. Following baseline investigations, participants will be randomly assigned (1:1) to either commence CSII (the intervention group) or continue on multiple daily injections of insulin (the control / comparator group) for the 4 month study period. Those assigned to CSII will be started on this modality within one month of randomisation and continue on CSII thereafter. Commencement of CSII will follow standard practices at the diabetes centres involved in the study ‐ this involves 1.5 days of intensive education around the pronciples of CSII and its use. Thereafter, patients will have standard diabetes care, which comprises routine outpatient assessemtns (3‐4 monthly as is standard) and intermittent patient‐initiated contact with the diabetes team to adjust insulin delivery settings. After 4 months of their assigned therapy, all participants will have repeat investigations. Participants in the MDI group will thereafter be commenced on CSII (since all were recruited from the CSII waiting list and therefore this was their intention). CONDITION: Type 1 diabetes PRIMARY OUTCOME: Parental report of behaviour on the Behaviour Assessment System for Children‐ Second Edition (BASC‐2) questionnaire SECONDARY OUTCOME: Cognitive assessments. ; ; Cognitive assessments will comprise the standardised and commonly used cognitive tests listed below. These will be administered at baseline and end of study (by a trained research psychologist). ; Alternative versions will be used at each time point to eliminate any bias from 'practise‐effects'. ; ; Vocabulary will be assessed using: Vocabulary measure from Wechsler Intelligence Scale for Children's Fourth Edition(WISC‐1V) and an alternate version from the Wechsler Abbreviated Scale of Intelligence (WASI). ; Perceptual reasoning will be assessed using: Block design (WISC‐IV) and an alternative version from WASI. ; Immediate attention span will be assessed using: Digit span subtest (WISC‐IV). Alternative version from Children's Memory Scale (CMS). ; Selective attention, divided attention and sustained attention will be assessed using TEA‐Ch. TEA‐Ch is a standardised test of attention, with different subtests from the overall test measuring different aspects of attention e.g sustained attention, divided attention etc. Alternative versions are available within this test instrument. ; Cognitive flexibility will be assessed using the Contingency Naming test. ; Concept formation will be assessed using the Verbal fluency test of the Delis‐Kaplan Executive Function System (DKEFS). ; Organisation will be assessed using the Rey complex figure. ; Working memory will be assessed using Letter number sequencing from WISC‐IV. ; ; ; Indices assessed will include: ; New learning will be assessed using Paired associative learning. Glycated haemoglobin (HbA1c). This will be recorded at baseline and at the end of study by capillary blood sampling. Measurement will be by High Performance Liquid Chromatography using the Bio‐Rad D‐10TM Haemoglobin Testing System (Bio‐Rad Laboratories Inc., Hercules, CA, USA). A 5 microlitre capillary blood sample is required to perform the analysis. Normal (non‐diabetic) reference range for HbA1c assessed using this method is quoted at 4.5‐5.7%. Indices of glycaemia as calculated using data collected over a 6 day period of continuous glucose monitoring (CGM). ; The continuous glucose monitoring system uses a glucose oxidase sensor that is inserted subcutaneously and records interstitial glucose levels every 5 minutes for up to 6 days. The wearer does not have access to the data in real‐time as they can only be downloaded from the device at the end of the 6 day period. Each participant will wear a CGM device for 6 days at baseline (prior to randomisation) and again at the end of the 4 month trial period. ; Percent time in target range (4.0‐10.0 mmol/l) ; Percent time in hyperglycaemic range (>10.0 mmol/l) ; Percent time in hypoglycaemic range (<4.0 mmol/l) ; Glycaemic variation as measured by continuous overlapping net glycaemic action CONGA). ; ; Percent time in various glycaemic categories (target, hyperglycaemic, or hypoglycaemic) will be assessed by calculating the sum of the time in minutes spent in each range over the 6 day trace as a percentage of the total time recorded. ; ; ; Glycaemic variation will be assessed using CONGA, a measurement tool specifically designed by statisticians and clinicians at the Royal Children's Hospital Melbourne to assess the variation of CGM‐derived data over various time intervals (e.g 1 hour, 4 hours etc). This measurement is described in detail in the following reference: ; A novel approach to continuous glucose analysis utilizing glycemic variation. ; Diabetes Technol Ther. 2005 Apr;7(2):253‐63. ; McDonnell CM, Donath SM, Vidmar SI, Werther GA, Cameron FJ. Parental, self and teacher report of internalising behaviour Self‐report and teacher‐report of externalising behaviour INCLUSION CRITERIA: Youth aged 9‐15.5 years with type 1 diabetes mellitus. Most children younger than 9 are unable or unwilling to use an MDI regimen, as this involves a lunchtime injection of insulin at school, which can be practically difficult for young children. Sixteen is the older end of the validated age range for the selected cognitive tests employed; therefore adolescents recruited at 15.5y will still be <16y at the end of study. Naïve to CSII therapy Currently using MDI regimen for at least 1 month duration Previously assessed as suitable for CSII (by their own diabetes physician and care team) and already on the waiting list to commence CSII at their institution. This inclusion criterion is necessary as not all youth will be willing or deemed suitable to commence CSII (e.g. if not performing self monitoring of blood glucose levels at least 4 times / day). Have access to an insulin pump device through private health insurance, self‐pay