title: Blood glucose control in type 1 diabetes with a bihormonal bionic endocrine pancreas.
abstract: OBJECTIVE
  To test whether safe and effective glycemic control could be achieved in type 1 diabetes using a bihormonal bionic endocrine pancreas driven by a continuous glucose monitor in experiments lasting more than two days and including six high-carbohydrate meals and exercise as challenges to glycemic control.
  
  
  METHODS
  Six subjects with type 1 diabetes and no endogenous insulin secretion participated in two 51-h experiments. Blood glucose was managed with a bionic endocrine pancreas controlling subcutaneous delivery of insulin and glucagon with insulin pumps. A partial meal-priming bolus of insulin (0.035 units/kg/meal, then 0.05 units/kg/meal in repeat experiments) was administered at the beginning of each meal (on average 78 ± 12 g of carbohydrates per meal were consumed). Plasma glucose (PG) control was evaluated with a reference quality measurement on venous blood every 15 min.
  
  
  RESULTS
  The overall mean PG was 158 mg/dL, with 68% of PG values in the range of 70-180 mg/dL. There were no significant differences in mean PG between larger and smaller meal-priming bolus experiments. Hypoglycemia (PG <70 mg/dL) was rare, with eight incidents during 576 h of closed-loop control (0.7% of total time). During 192 h of nighttime control, mean PG was 123 mg/dL, with 93% of PG values in the range of 70-180 mg/dL and only one episode of mild hypoglycemia (minimum PG 62 mg/dL).
  
  
  CONCLUSIONS
  A bihormonal bionic endocrine pancreas achieved excellent glycemic control with minimal hypoglycemia over the course of two days of continuous use despite high-carbohydrate meals and exercise. A trial testing a wearable version of the system under free-living conditions is justified.
authors.affiliation: Diabetes Unit and Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Russell
authors.forename: Firas H
authors.initials: FH
authors.lastname: El-Khatib
authors.forename: David M
authors.initials: DM
authors.lastname: Nathan
authors.forename: Kendra L
authors.initials: KL
authors.lastname: Magyar
authors.forename: John
authors.initials: J
authors.lastname: Jiang
authors.forename: Edward R
authors.initials: ER
authors.lastname: Damiano
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000187:drug effects*; D015190:Blood Glucose Self-Monitoring; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D005934:Glucagon / Q000627:therapeutic use; D006801:Humans; D007003:Hypoglycemia / Q000097:blood / Q000188:drug therapy / Q000378:metabolism; D007328:Insulin / Q000627:therapeutic use; D007515:Islets of Langerhans / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D007328:Insulin; D005934:Glucagon