Study protocol for a randomised open-label clinical trial examining the safety and efficacy of the Android Artificial Pancreas System (AAPS) with advanced bolus-free features in adults with type 1 diabetes: the 'CLOSE IT' (Closed Loop Open SourcE In Type 1 diabetes) trial.

INTRODUCTION: Multiple automated insulin delivery (AID) systems have become commercially available following randomised controlled trials demonstrating benefits in people with type 1 diabetes (T1D). However, their real-world utility may be undermined by user-associated burdens, including the need to carbohydrate count and deliver manual insulin boluses. There is an important need for a 'fully automated closed loop' (FCL) AID system, without manual mealtime boluses. The (Closed Loop Open SourcE In Type 1 diabetes) trial is a randomised trial comparing an FCL AID system to the same system used as a hybrid closed loop (HCL) in people with T1D, in an outpatient setting over an extended time frame. METHODS AND ANALYSIS: Randomised, open-label, parallel, non-inferiority trial comparing the Android Artificial Pancreas System (AAPS) AID algorithm used as FCL to the same algorithm used as HCL. Seventy-five participants aged 18-70 will be randomised (1:1) to one of two treatment arms for 12 weeks: (a) FCL-participants will be advised not to bolus for meals and (b) HCL-participants will use the AAPS AID algorithm as HCL with announced meals. The primary outcome is the percentage of time in target sensor glucose range (3.9-10.0 mmol/L). Secondary outcomes include other glycaemic metrics, safety, psychosocial factors, platform performance and user dietary factors. Twenty FCL arm participants will participate in a 4-week extension phase comparing glycaemic and dietary outcomes using NovoRapid (insulin aspart) to Fiasp (insulin aspart and niacinamide). ETHICS AND DISSEMINATION: Approvals are by the Alfred Health Ethics Committee (615/22) (Australia) and Health and Disability Ethics Committees (2022 FULL 13832) (New Zealand). Each participant will provide written informed consent. Data protection and confidentiality will be ensured. Study results will be disseminated by publications, conferences and patient advocacy groups. TRIAL REGISTRATION NUMBERS: ACTRN12622001400752 and ACTRN12622001401741.

Study protocol: glycaemic outcomes in people with type 2 diabetes initiating continuous glucose monitoring: the 2GO-CGM study.

Purpose: Improving glycaemic control in type 2 diabetes (T2D) is essential to reducing social and health-economic burden of diabetes-related complications. Continuous glucose monitoring (CGM) has been established as beneficial in improving glycaemic control and reducing hypoglycaemia in people with type 1 diabetes, however data in T2D is limited. This study has been designed to assess the effect of initiating real-time CGM (rtCGM) on glycaemic control in a high-risk population of adults with T2D. Secondary objectives are to assess the cost-effectiveness and safety of rtCGM, and the effects of rtCGM on diet/lifestyle and the burden of diabetic complications, including cardiovascular risk. Methods: This multicentre randomised controlled trial (RCT) will be conducted at three sites in New Zealand (Waikato, Christchurch and Dunedin). Eighty adults with T2D on insulin with suboptimal glycaemic control (HbA1c > 8.0% or 64 mmol/mol) will be randomised 1:1 to rtCGM or routine care with self-monitoring of blood glucose levels (SMBG) for three months. This intervention phase will be followed by a three-month continuation phase where SMBG group crossover to use rtCGM. Participants will then be invited to join the extension phase with continued use of rtCGM for a further 12 months. During the extension phase, both groups will independently titrate their insulin under the remote supervision of prescribing diabetes nurse specialists following an insulin titration algorithm. The primary outcome of the study is time in target glucose range (3.9-10 mmol/L or 70-180 mg/dL; TIR). Secondary outcomes include CGM metrics as per consensus statement recommendations, and HbA1c. Additional planned analyses include cardiovascular risk profile, incremental cost-effectiveness analyses, dietary patterns, and qualitative analyses. Trial registration number: The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12621000889853) on 8 July 2021 and the World Health Organisation International Clinical Trial Registry Platform (Universal Trial Number U1111-1264-5822).

The effect on satiety of ingesting isosweet and isoenergetic sucrose- and isomaltulose-sweetened beverages: a randomised crossover trial.

Generating feelings of satiety may be important in maintaining weight control. It has been hypothesised that the circulating concentration of glucose is a major determinant of satiety, yet the relationship between postprandial glycaemia and satiety is inconclusive. Our aim was to assess satiety following ingestion of beverages differing in glycaemic index (GI) containing either 50 g of sucrose (GI 65) or isomaltulose (PalatinoseTM) (GI 32). The beverages were matched for sweetness using a triangle sensory test. Seventy-seven participants were randomised to the order in which they received each beverage, 2 weeks apart. A standard lunch was given at 12.00 hours. Satiety was measured using 100-mm visual analogue scales (VAS) administered at 14.00 hours (baseline) and at 30, 60, 90, 120, 150 and 180 min after ingesting the beverage. Weighed diet records were kept from 17.00 to 24.00 hours. Mean differences for isomaltulose compared with sucrose AUC VAS were 'How hungry do you feel?' 109 (95 % CI -443, 661) mm × min; 'How satisfied do you feel?' 29 (95 % CI -569, 627) mm × min; 'How full do you feel?' -91 (95 % CI -725, 544) mm × min and 'How much do you think you can eat?' 300 (95 % CI -318, 919) mm × min. There was no between-treatment difference in satiety question responses or in dietary energy intake -291 (95 % CI -845, 267) kJ over the remainder of the day. In this experiment, feelings of satiety were independent of the GI of the test beverages. Any differences in satiety found between foods chosen on the basis of GI could be attributable to food properties other than the glycaemic-inducing potential of the food.

Cognitive Performance Following Ingestion of Glucose-Fructose Sweeteners That Impart Different Postprandial Glycaemic Responses: A Randomised Control Trial.

We aimed to investigate the isolated effect of glycaemia on cognitive test performance by using beverages sweetened with two different glucose-fructose disaccharides, sucrose and isomaltulose. In a randomised crossover design, 70 healthy adults received a low-glycaemic-index (GI) isomaltulose and sucralose beverage (GI 32) and a high-GI sucrose beverage (GI 65) on two occasions that were separated by two weeks. Following beverage ingestion, declarative memory and immediate word recall were examined at 30, 80 and 130 min. At 140 min, executive function was tested. To confirm that the glycaemic response of the test beverages matched published GI estimates, a subsample (n = 12) of the cognitive testing population (n = 70) underwent glycaemic response testing on different test days. A significantly lower value of mean (95% CI) blood glucose concentration incremental area under the curve (iAUC) was found for isomaltulose, in comparison to the blood glucose concentration iAUC value for sucrose, the difference corresponding to -44 mmol/L∙min (-70, -18), p = 0.003. The mean (95% CI) difference in numbers of correct answers or words recalled between beverages at 30, 80 and 130 min were 0.1 (-0.2, 0.5), -0.3 (-0.8, 0.2) and 0.0 (-0.5, 0.5) for declarative memory, and -0.5 (-1.4, 0.3), 0.4 (-0.4, 1.3) and -0.4 (-1.1, 0.4) for immediate free word recall. At 140 min, the mean difference in the trail-making test between beverages was -0.3 sec (-6.9, 6.3). None of these differences were statistically or clinically significant. In summary, cognitive performance was unaffected by different glycaemic responses to beverages during the postprandial period of 140 min.