Artificial beta-cell: clinical experience toward an implantable closed-loop insulin delivery system.
OBJECTIVE
Restoration of long-term normal blood glucose control in diabetic patients supports the elaboration of an artificial beta cell. The possibility of implantation of the three crucial components of such a system (insulin delivery device, glucose sensor and controller) is analyzed.


METHODS
The Long-Term Sensor System project, aiming at a fully implantable artificial beta cell, assessed the feasibility of glucose control by the combined implantation of a pump for peritoneal insulin delivery and a central intravenous glucose sensor close to the right atrium, connected via a subcutaneous lead. It was initiated in 10 Type 1 diabetic patients in our clinic from 2000. Data obtained during this experience are reviewed and confronted to reported closed-loop trials using other approaches.


RESULTS
No significant complication related to prolonged implantation of intravenous sensors occurred and the combined implants were well tolerated. Glucose measurement by the intravenous sensors correlated well with meter values (r=0.83-0.93, with a mean absolute deviation of 16.5%) and accuracy has been sustained for an average duration of 9 months. Uploading of pump electronics by algorithms designed for closed-loop insulin delivery allowed in-patient 48 hour-trials aiming at automated glucose control. Glucose control was similar to that reported by investigations combining subcutaneous sensors to wearable pumps for subcutaneous insulin infusion. The benefits of more physiological insulin kinetics due to intra-peritoneal delivery have been hampered by the slow response time of intravenous sensors.


CONCLUSIONS
Although the concept of a fully implantable artificial beta cell has been validated as feasible, the limited performance in achieving glucose control requests improvements in the sensor structure to increase its longevity and decrease sensor delay.
Renard
E
E
Endocrinology Department, Lapeyronie Hospital, Montpellier, France. e-renard@chu-montpellier.fr
Costalat
G
G
Chevassus
H
H
Bringer
J
J
D002986:Clinical Trials as Topic; D003920:Diabetes Mellitus / Q000188:drug therapy*; D006801:Humans; D007328:Insulin / Q000008:administration & dosage / Q000627:therapeutic use*; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D019397:Pancreas, Artificial; D019736:Prostheses and Implants; D015203:Reproducibility of Results
D007328:Insulin