Bio-medical Ontologies Maintenance and Change Management

296 M. Fernandez, M. Villasana, and D. Streja
obtained [14]. A summary of the limitations of each input model and the proposed
improvements is as follows [14]:
• The rate of glucose absorption model could be oversimplified. For glucose loads
different from 45 or 89 g, we took as valid the curve that corresponds to the load
closest in value to these [14] (e.g., if the actual glucose load was 15 g then the
curve obtained for 45 g was chosen as the rate of appearance). This approximation
would introduce unavoidable errors until better estimates could be obtained.
For this reason, a more recent model presented by Lehmann and Deutsch [16] is
being included in the present work instead.
• The insulin absorption model could be too simple to describe the data under
study [14]. A recent publication by Willinska and coworkers [19] shows that a
model like Shichiri’s model underestimates the post meal peak of plasma insulin,
whilst improvement in the model fit was enhanced when two absorption
channels were included. This latter model has been used in the present study in
substitution to Shichiri’s model.
These new input models are of superior quality in terms of data fitting and it is
expected that they will help to improve the ability of the minimal model in following
the experimental data.
2 Data
Glucose data collection was achieved through a continuous glucose monitoring sensor
(CGMS, Medtronic MiniMed, Northridge, CA). This technology allows 5 min
timed testing of interstitial glucose. The instrument is periodically calibrated using
patient’s plasma glucose and the data are transformed to accurately and timely
reflect patient’s serum glucose. The instrument’s precision has been tested for concentrations
ranging from 40 to 400 mg/dL.
Nine patients with longstanding Type I diabetes (C peptide negative) being controlled
subcutaneously by an insulin pump participated in the trial. After appropriate
instructions, the CGMS was inserted into the subcutaneous abdominal fat tissue
and calibrated over a 60 min period, as per standard Medtronic MiniMed operating
guidelines. The patients were monitored for 72 hours. At the time of the instructions
the patients were asked to record the time of administration of subcutaneous insulin,
the insulin bolus injections and basal rates and the amount of carbohydrate ingested.
All patients were previously instructed in evaluating the quantity of carbohydrates
and administered fast acting insulin.
After 5 days the patients returned, and the data was downloaded into the computer.
Time series were obtained of interstitial glucose every five minutes, along
with the times at which the patient recorded events such as: bolus insulin injection
times and amounts, glucose ingestion and approximate loads, and the times of exercise
initiation. The glucose data was transformed in serum glucose values with
Medtronic-Minimed software version 3.0.
Subsequently, data windows of 300 min each were extracted from the time series
upon the initiation of a meal. If the patient indicated food ingestion or more than two