title: Feasibility of closed-loop insulin delivery in type 2 diabetes: a randomized controlled study.
abstract: OBJECTIVE
  Closed-loop insulin delivery offers a promising treatment option, but to date, it has only been evaluated in type 1 diabetes. Our aim was to evaluate the feasibility of fully closed-loop subcutaneous insulin delivery in insulin-naïve patients with type 2 diabetes.
  
  
  METHODS
  Twelve subjects (seven males, age 57.2 years, BMI 30.5 kg/m2) with noninsulin-treated type 2 diabetes (HbA1c 8.4% [68 mmol/mol], diabetes duration 7.6 years) underwent two 24-h visits (closed-loop and control) in a randomized crossover design. During closed-loop visits, the subjects' routine diabetes therapy was replaced with model predictive control algorithm-driven subcutaneous insulin pump delivery based on real-time continuous glucose monitoring. Meals were unannounced, and no additional insulin was administered for carbohydrates consumed. During control visits, the usual diabetes regimen was continued (metformin 92%, sulfonylureas 58%, dipeptidyl peptidase-4 inhibitors 33%). On both visits, subjects consumed matched 50- to 80-g carbohydrate meals and optional 15-g carbohydrate snacks and remained largely sedentary. Plasma glucose measurements evaluated closed-loop performance.
  
  
  RESULTS
  Compared with conventional therapy, 24 h of closed-loop insulin delivery increased overall the median time in target plasma glucose (3.9-8.0 mmol/L) from 24 to 40% (P = 0.016), despite sensor under-reading by a median of 1.2 mmol/L. The benefit of the closed-loop system was more prominent overnight, with greater time in target glucose (median 78 vs. 35%; P = 0.041) and less time in hyperglycemia (22 vs. 65%; P = 0.041). There was no hypoglycemia during either intervention.
  
  
  CONCLUSIONS
  A closed-loop system without meal announcement and using subcutaneous insulin delivery in insulin-naïve patients with type 2 diabetes appears feasible and safe. Improvement in postprandial glucose control may require further optimization of system performance.
authors.affiliation: Corresponding author: Roman Hovorka, rh347@cam.ac.uk.
authors.forename: Kavita
authors.initials: K
authors.lastname: Kumareswaran
authors.forename: Hood
authors.initials: H
authors.lastname: Thabit
authors.forename: Lalantha
authors.initials: L
authors.lastname: Leelarathna
authors.forename: Karen
authors.initials: K
authors.lastname: Caldwell
authors.forename: Daniela
authors.initials: D
authors.lastname: Elleri
authors.forename: Janet M
authors.initials: JM
authors.lastname: Allen
authors.forename: Marianna
authors.initials: M
authors.lastname: Nodale
authors.forename: Malgorzata E
authors.initials: ME
authors.lastname: Wilinska
authors.forename: Mark L
authors.initials: ML
authors.lastname: Evans
authors.forename: Roman
authors.initials: R
authors.lastname: Hovorka
mesh_terms: D000328:Adult; D000368:Aged; D000465:Algorithms; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004040:Dietary Carbohydrates / Q000494:pharmacology; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D007328:Insulin / Q000008:administration & dosage* / Q000627:therapeutic use*; D007332:Insulin Infusion Systems; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D013453:Sulfonylurea Compounds / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D004040:Dietary Carbohydrates; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D007328:Insulin; D013453:Sulfonylurea Compounds; D008687:Metformin