Comparison of Closed-loop Operation After Morning Meal With and Without Carbohydrate Counting (CLASS02)

• Percentage of postprandial time of plasma glucose concentrations spent in the high range (above 10.0 mmol/l). [ Time Frame: 0-300 min ] [ Designated as safety issue: No ]
• Mean plasma glucose concentration.
• Total insulin delivery
• Total glucagon delivery
• Plasma glucose concentration and incremental plasma glucose concentration at 2 hours postmeal
• Postprandial peak and incremental postprandial peak of plasma glucose concentration
• Percentage of time of plasma glucose concentrations spent in target range. Target range is defined to be between 4.0 and 10.0 mmol/l for 150 minutes postmeal and between 4.0 and 8.0 mmol/l afterwards
• Percentage of postprandial time of plasma glucose concentrations spent in the low range (below 4.0mmol/l) [ Time Frame: 0-300min ]

Closed-loop strategy is composed of three components: glucose sensor to read glucose levels, insulin pump to infuse insulin and a dosing mathematical algorithm to decide on the required insulin dosage based on the sensor's readings. A dual-hormone closed-loop system would regulate glucose levels through the infusion of two hormones: insulin and glucagon.

The main goal of this project is to assess whether a dual-hormone closed-loop strategy would alleviate the burden of carbohydrate counting from patients with type 1 diabetes (T1D) without a significant degradation in post-meal glucose control.

Each patient will be admitted twice to a clinical research facility. In one visit, patients will eat a morning meal accompanied with a matching insulin bolus (depending on the carbohydrate content of the meal) and glucose levels will be subsequently regulated using dual-hormone closed-loop system. In the other visit, patients will eat the same meal but will inject only a partial insulin bolus (not depending on carbohydrate content of the meal) and the remaining needed insulin will be delivered based on glucose sensor excursions as part of closed-loop operation. If post-meal glucose levels were indifferent between the two visits, then this would suggest that carbohydrate counting may not be necessary during closed-loop operation as the closed-loop system will give any remaining insulin needed to cover the glucose absorbed from the meal. Twelve subjects will be enrolled in this study.

• Active Comparator: CHO-independent partial insulin bolus with closed-loop
  Intervention: Device: Dual Hormone closed-loop system
• Active Comparator: CHO-dependent full insulin bolus combined with closed-loop
  Intervention: Device: Dual Hormone closed-loop system

Inclusion Criteria:

• Males and females ≥ 18 and ≤ 65 years of old.
• Clinical diagnosis of type 1 diabetes for at least one year. The diagnosis of type 1 diabetes is based on the investigator's judgment and medical history (e.g. history of acido-ketosis, etc.); C peptide level and antibody determinations are not needed.
• The subject will have been on insulin pump therapy for at least 3 months.
• Last (less than 3 months) HbA1c ≤ 12%.

Exclusion Criteria:

• Clinically significant nephropathy, neuropathy (especially clinically significant gastroparesis) or retinopathy as judged by the investigator.
• Recent (< 3 months) acute macrovascular event e.g. acute coronary syndrome or cardiac surgery.
• Pregnancy.

• Severe hypoglycemic episode within two weeks of screening.

  • Medication likely to affect with the interpretation of the results: Prandase, Victoza, Byetta and Symlin

• Known or suspected allergy to the trial products or meal contents.
• Other serious medical illness likely to interfere with study participation or with the ability to complete the trial by the judgment of the investigator.
• Failure to comply with team's recommendations (e.g. not willing to eat snack, not willing to change pump parameters, etc).
• Unreliable carbohydrate counting
• Problems with venous access

• McGill University
• Montreal Children's Hospital