Fully integrated artificial pancreas in type 1 diabetes: modular closed-loop glucose control maintains near normoglycemia.
Integrated closed-loop control (CLC), combining continuous glucose monitoring (CGM) with insulin pump (continuous subcutaneous insulin infusion [CSII]), known as artificial pancreas, can help optimize glycemic control in diabetes. We present a fundamental modular concept for CLC design, illustrated by clinical studies involving 11 adolescents and 27 adults at the Universities of Virginia, Padova, and Montpellier. We tested two modular CLC constructs: standard control to range (sCTR), designed to augment pump plus CGM by preventing extreme glucose excursions; and enhanced control to range (eCTR), designed to truly optimize control within near normoglycemia of 3.9-10 mmol/L. The CLC system was fully integrated using automated data transfer CGM→algorithm→CSII. All studies used randomized crossover design comparing CSII versus CLC during identical 22-h hospitalizations including meals, overnight rest, and 30-min exercise. sCTR increased significantly the time in near normoglycemia from 61 to 74%, simultaneously reducing hypoglycemia 2.7-fold. eCTR improved mean blood glucose from 7.73 to 6.68 mmol/L without increasing hypoglycemia, achieved 97% in near normoglycemia and 77% in tight glycemic control, and reduced variability overnight. In conclusion, sCTR and eCTR represent sequential steps toward automated CLC, preventing extremes (sCTR) and further optimizing control (eCTR). This approach inspires compelling new concepts: modular assembly, sequential deployment, testing, and clinical acceptance of custom-built CLC systems tailored to individual patient needs.
University of Virginia, Center for Diabetes Technology, Charlottesville, Virginia, USA. mb6nt@virginia.edu
Marc
M
Breton
Anne
A
Farret
Daniela
D
Bruttomesso
Stacey
S
Anderson
Lalo
L
Magni
Stephen
S
Patek
Chiara
C
Dalla Man
Jerome
J
Place
Susan
S
Demartini
Simone
S
Del Favero
Chiara
C
Toffanin
Colleen
C
Hughes-Karvetski
Eyal
E
Dassau
Howard
H
Zisser
Francis J
FJ
Doyle
Giuseppe
G
De Nicolao
Angelo
A
Avogaro
Claudio
C
Cobelli
Eric
E
Renard
Boris
B
Kovatchev
D000293:Adolescent; D000328:Adult; D000465:Algorithms; D001331:Automation; D001786:Blood Glucose / Q000378:metabolism*; D003198:Computer Simulation; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007332:Insulin Infusion Systems; D008875:Middle Aged; D019397:Pancreas, Artificial
D001786:Blood Glucose; D007004:Hypoglycemic Agents