Evaluation of the Effect of Gain on the Meal Response of an Automated Closed-Loop Insulin Delivery System

  1. Antonios E. Panteleon,
  2. Mikhail Loutseiko,
  3. Garry M. Steil and
  4. Kerstin Rebrin
  1. From Medtronic MiniMed, Northridge, California
  1. Address correspondence and reprint requests to Garry Steil, PhD, Medtronic MiniMed, 18000 Devonshire Rd., Northridge, CA 91325. E-mail: garry.steil{at}


A continuous closed-loop insulin delivery system using subcutaneous insulin delivery was evaluated in eight diabetic canines. Continuous glucose profiles were obtained by extrapolation of blood glucose measurements. Insulin delivery rate was calculated, using a model of β-cell insulin secretion, and delivered with a Medtronic MiniMed subcutaneous infusion pump. The model acts like a classic proportional-integral-derivative controller, delivering insulin in proportion to glucose above target, history of past glucose values, and glucose rate of change. For each dog, a proportional gain was set relative to the open-loop total daily dose (TDD) of insulin. Additional gains based on 0.5 × TDD and 1.5 × TDD were also evaluated (gain dose response). Control was initiated 4 h before the meal with a target of 6.7 mmol/l. At the time of the meal, glucose was similar for all three gains (6.0 ± 0.3, 5.2 ± 0.3, and 4.9 ± 0.5 mmol/l for 0.5 × TDD, TDD, and 1.5 × TDD, respectively; P > 0.05) with near-target values restored at the end of experiments (8.2 ± 0.9, 6.0 ± 0.6, and 6.0 ± 0.5, respectively). The peak postprandial glucose level decreased significantly with increasing gain (12.1 ± 0.6, 9.6 ± 1.0, and 8.5 ± 0.6 mmol/l, respectively; P < 0.05). The data demonstrate that closed-loop insulin delivery using the subcutaneous site can provide stable glycemic control within a range of gain.


  • The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Accepted March 30, 2006.
    • Received October 15, 2005.
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