Continuous glucose monitoring system used to establish medication management protocol for the safe use of a 2-day intermittent energy restriction (5:2 diet) in type 2 diabetes mellitus.

A randomised controlled trial will be conducted to test two medication protocols; fixed and adjusted (see below). Based on the binomial data (number of hypo/hyperglycaemic events after 2 weeks of treatment in our pilot trial), a sample size of 40 participants who are already experiencing hypoglycaemic events will be required to demonstrate superiority. We aim to recruit 50 participants in case of dropouts. Participants with a BMI>27 and medication controlled T2DM, both oral hypoglycaemic agents (OHA) likely to cause hypoglycaemia (sulphonylureas) and insulin, will attend the clinic at baseline to have their continuous glucose monitoring system (CGMS) sensor installed and baseline HbA1c measured. The sensor has a 5mm flexible filament that is inserted, subcutaneously, into the back of the upper arm, (there may be a small amount of discomfort). The sensor starts recording blood glucose levels 1 hour after insertion. HbA1c will be measured using a point of care machine which requires finger prick blood only. Participants will then be asked to follow their usual diet for 2 weeks, recording their intake (weighed diet record) and using the monitor to store continuous glucose data. (The electronic monitor records and stores BGLs from the sensor electrode. Participants will be required to scan their sensor every 6-8 hours to record continuous data). The data will allow us to establish the regularity of extreme levels and the number of events; hypoglycaemic events <4mmol/L and/or hyperglycaemia events >10mmol/L. Participants will then attend the clinic for a second visit (after 2 weeks) to have their original sensor removed and the data analysed. If the participant experiences 1 or more hypoglycaemic events they will be eligible to continue into the intervention phase. Eligible participants will attend for a third visit to have a new sensor installed and to start the intervention, 2 weeks of 2-day IER treatment (500-600kcals/day) (non-consecutive) with their specific medication protocol; randomised 1:1 to either fixed or adjusted medication treatment groups. A Dietitian with 5+ years clinical experience and an Endocrinologist with 10+ years clinical experience will be conducting the research (providing dietary advice, including a written IER treatment booklet designed for this study with diet details and delivering the medication protocol). During the intervention period, participants will continue to record dietary intake and use the monitor to store continuous glucose data. Participants will be asked to keep their diet on habitual eating days similar to the previous fortnights intake. Participants will then attend the clinic for their final visit at the end of their 2-week period to have their sensor removed. We will then analyse the intervention CGMS data to see if glucose control improved (reduced number of events) due to the adjusted medication protocol. Participants will be asked to keep their exercise levels stable during the 4-5 week trial, pedometers will be provided. Adjusted protocol is based on the number of glycaemic events during the participants 2 week usual/normal diet. One or more hypoglycaemic events over 2 weeks then follow the fixed protocol 1 level greater restriction than appropriate. E.G: If HbA1c is >=7% then the participant should follow the <7% fixed protocol (see details in fixed protocol below). Four or more events over 2 weeks then follow protocol 1 level less restriction than appropriate. E.G: If HbA1c is <7% then the participant should follow the >=7-<8% fixed protocol (see details in fixed protocol below). Hypoglycaemia takes priority. Note: if participants experience no hypo or hyper glycaemic events over 2 weeks they will follow the fixed protocol for their HbA1c level. Fixed protocol. Our fixed protocol requires discontinuation of sulphonylureas as well as insulin if baseline HbA1c is <7%. If >=7 but <8% then sulphonylureas are discontinued on intermittent energy days only and long acting insulin the night before the intermittent energy day. If HbA1c is >=8% but <10% then all medications are discontinued on intermittent energy days only. If HbA1c is >= 10% but <12% then sulphonylureas remain unchanged, short active insulin is discontinued and long acting insulin is reduced by 10% on intermittent energy days only. If >=12% then short acting insulin is discontinued on intermittent energy days only.