The PILGRIM study: in silico modeling of a predictive low glucose management system and feasibility in youth with type 1 diabetes during exercise.
BACKGROUND
Predictive low glucose management (PLGM) may help prevent hypoglycemia by stopping insulin pump delivery based on predicted sensor glucose values.


METHODS
Hypoglycemic challenges were simulated using the Food and Drug Administration-accepted glucose simulator with 100 virtual patients. PLGM was then tested with a system composed of a Paradigm(®) insulin pump (Medtronic, Northridge, CA), an Enlite™ glucose sensor (Medtronic), and a BlackBerry(®) (Waterloo, ON, Canada)-based controller. Subjects (n=22) on continuous subcutaneous insulin infusion (five females, 17 males; median [range] age, 15 [range, 14-20] years; median [range] diabetes duration, 7 [2-14] years; median [range] glycated hemoglobin, 8.0% [6.7-10.4%]) exercised until the PLGM system suspended insulin delivery or until the reference blood glucose value (HemoCue(®); HemoCue GmbH, Großostheim, Germany) reached the predictive suspension threshold setting.


RESULTS
PLGM reduced hypoglycemia (<70 mg/dL) in silico by 26.7% compared with no insulin suspension, as opposed to a 5.3% reduction in hypoglycemia with use of low glucose suspend (LGS). The median duration of hypoglycemia (time spent <70 mg/dL) with PLGM was significantly less than with LGS (58 min vs. 101 min, respectively; P<0.001). In the clinical trial the hypoglycemic threshold during exercise was reached in 73% of the patients, and hypoglycemia was prevented in 80% of the successful experiments. The mean (±SD) sensor glucose at predictive suspension was 92±7 mg/dL, resulting in a postsuspension nadir (by HemoCue) of 77±22 mg/dL. The suspension lasted for 90±35 (range, 30-120) min, resulting in a sensor glucose level at insulin resumption of 97±19 mg/dL.


CONCLUSIONS
In silico modeling and early feasibility data demonstrate that PLGM may further reduce the severity of hypoglycemia beyond that already established for algorithms that use a threshold-based suspension.
1 Children's Hospital on the Bult , Hannover, Germany .
Thomas
T
Danne
Christiana
C
Tsioli
Olga
O
Kordonouri
Sarah
S
Blaesig
Kerstin
K
Remus
Anirban
A
Roy
Barry
B
Keenan
Scott W
SW
Lee
Francine R
FR
Kaufman
D000293:Adolescent; D015374:Biosensing Techniques; D001786:Blood Glucose / Q000378:metabolism*; D003198:Computer Simulation; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology; D015444:Exercise; D005240:Feasibility Studies; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced* / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D007328:Insulin / Q000008:administration & dosage / Q000009:adverse effects*; D007332:Insulin Infusion Systems / Q000009:adverse effects*; D008297:Male; D018670:Monitoring, Ambulatory; D055815:Young Adult
D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; C517652:hemoglobin A1c protein, human