Glucose-responsive insulin and glucagon delivery (dual-hormone artificial pancreas) in adults with type 1 diabetes: a randomized crossover controlled trial.
BACKGROUND
Most patients with type 1 diabetes do not achieve their glycemic targets. We aimed to assess the efficacy of glucose-responsive insulin and glucagon closed-loop delivery for controlling glucose levels in adults with type 1 diabetes.


METHODS
We conducted a randomized crossover trial involving 15 adults with type 1 diabetes, comparing standard insulin-pump therapy with dual-hormone, closed-loop delivery. Patients were admitted twice to a clinical research facility and received, in random order, both treatments. Each 15-hour visit (from 1600 to 0700) included an evening exercise session, followed by a medium-sized meal, a bedtime snack and an overnight stay. During visits that involved closed-loop delivery, basal insulin and glucagon miniboluses were delivered according to recommendations based on glucose sensor readings and a predictive dosing algorithm at 10-minute intervals. During visits involving standard insulin-pump therapy (control visits), patients used conventional treatment.


RESULTS
Dual-hormone closed-loop delivery increased the percentage of time for which patients' plasma glucose levels were in the target range (median 70.7% [interquartile range (IQR) 46.1%-88.4%] for closed-loop delivery v. 57.3% [IQR 25.2%-71.8%] for control, p = 0.003) and decreased the percentage of time for which plasma glucose levels were in the low range (bottom of target range [< 4.0 mmol/L], 0.0% [IQR 0.0%-3.0%] for closed-loop delivery v. 10.2% [IQR 0.0%-13.0%] for control, p = 0.01; hypoglycemia threshold [< 3.3 mmol/L], 0.0% [IQR 0.0%-0.0%] for closed-loop delivery v. 2.8% [IQR 0.0%-5.9%] for control, p = 0.006). Eight participants (53%) had at least 1 hypoglycemic event (plasma glucose < 3.0 mmol/L) during standard treatment, compared with just 1 participant (7%) during closed-loop treatment (p = 0.02).


CONCLUSIONS
Dual-hormone, closed-loop delivery guided by advanced algorithms improved short-term glucose control and reduced the risk of hypoglycemia in a group of 15 adults with type 1 diabetes.


BACKGROUND
ClinicalTrials.gov, no. NCT01297946.
Institut de Recherches Cliniques de Montréal, Montréal, Que. ahmad.haidar@mail.mcgill
Ahmad
A
Haidar
Laurent
L
Legault
Maryse
M
Dallaire
Ammar
A
Alkhateeb
Adèle
A
Coriati
Virginie
V
Messier
Peiyao
P
Cheng
Maude
M
Millette
Benoit
B
Boulet
Rémi
R
Rabasa-Lhoret
D000328:Adult; D000465:Algorithms; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D018592:Cross-Over Studies; D003661:Decision Support Techniques; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005934:Glucagon / Q000008:administration & dosage* / Q000627:therapeutic use; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D015918:Infusion Pumps, Implantable; D061267:Insulin Aspart / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D007332:Insulin Infusion Systems; D008297:Male; D019397:Pancreas, Artificial; D012044:Regression Analysis; D016896:Treatment Outcome
D015415:Biomarkers; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D005934:Glucagon; D061267:Insulin Aspart