The main focus of our research is the development of a closed-loop system for glucose control in people with type 1 diabetes. After having demonstrated the safety and efficacy of overnight closed-loop insulin delivery, we are extending the evaluation of closed-loop to the daytime. Meal-related insulin dosing can be challenging and prandial insulin overdosing can be associated with the occurrence of postprandial hypoglycaemia, thus representing a confounding factor of hypoglycaemia free glucose control during the day. A further investigation is needed to evaluate alternative strategies for prandial insulin dosing. We will study eight adolescents with type 1 diabetes during closed-loop insulin delivery combined with either standard or reduced insulin doses with the meals, in a randomised crossover design. Stable glucose isotopes will be administered to collect data for modelling of glucose turnover around the meals, during daily activities and overnight.

The information provided by the use of glucose isotopes would be very helpful to increase our understanding of the physiology of glucose turnover and to facilitate the development of an improved control algorithm. Ultimately this study will help with the development of a closed-loop system to match insulin infusions to change in glucose levels in real life conditions.

Inclusion Criteria:

• The subject is between 12 and 18 years of age (inclusive).
• The subject has had type 1 diabetes, as defined by WHO for at least 1 year or is confirmed C-peptide negative.
• The subject will have been on insulin pump user for at least 3 months, with good knowledge of insulin self-adjustment.
• HbA1c ≤ 12 % based on analysis from central laboratory

Exclusion Criteria:

• Non-type 1 diabetes mellitus including those secondary to chronic disease
• Any other physical or psychological disease likely to interfere with the normal conduct of the study and interpretation of the study results
• Current treatment with drugs known to interfere with glucose metabolism such as systemic corticosteroids, non-selective beta-blockers and MAO inhibitors
• Known or suspected allergy against insulin
• Subjects with clinical significant nephropathy, neuropathy or proliferative retinopathy as judged by the clinician
• Total daily insulin dose >= 2 IU/kg
• Post-menarchal girls who are pregnant or intending to become pregnant or are breastfeeding
• Any coexisting cardiac and respiratory condition