Glucose clamp algorithms and insulin time-action profiles.
BACKGROUND
Most current insulin pumps include an insulin-on-board (IOB) feature to help subjects avoid problems associated with "insulin stacking." In addition, many control algorithms proposed for a closed-loop artificial pancreas make use of IOB to reduce the probability of hypoglycemic events that often occur due to the integral action of the controller. The IOB curves are generated from the pharmacodynamic (time-activity profiles) actions of subcutaneous insulin, which are obtained from glycemic clamp studies.


METHODS
Glycemic clamp algorithms are reviewed and in silico studies are performed to analyze the effect of glucose meter bias and noise on glycemic control and the manipulated glucose infusion rates. The glucose infusion rates are used to obtain insulin time-activity profiles, which are then used to generate IOB curves.


RESULTS
A model-based, three-step-ahead controller is shown to be equivalent to a proportional-integral control algorithm with time-delay compensation. A systematic glucose meter bias of +6 mg/dl results in a decrease in the glucose area under the curve of 3% but no change in the IOB profiles.


CONCLUSIONS
Based on these preliminary simulation studies, a substantial amount of glucose meter bias and noise during a glycemic clamp can be tolerated with little net effect on the IOB curves. It is suggested that handheld glucose meters can therefore be used in clamp studies if the measurements are filtered (averaged) before processing by the control algorithm. Clinical studies are needed to confirm these preliminary results.
Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, New York 12180-3590, USA. bequette@rpi.edu
B Wayne
BW
Bequette
D000465:Algorithms; D001786:Blood Glucose / Q000187:drug effects*; D003198:Computer Simulation; D003920:Diabetes Mellitus / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D019719:Diagnostic Equipment; D004867:Equipment Design; D015309:Glucose Clamp Technique / Q000295:instrumentation; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D007328:Insulin / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D007332:Insulin Infusion Systems; D008954:Models, Biological; D019397:Pancreas, Artificial; D011237:Predictive Value of Tests; D015203:Reproducibility of Results
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin