1. Six Sensor CGM Array- Which do you trust?
Data from subject D2
Joseph

2. Non-Closed Loop Insulin Administration Approaches
A. Types- MD judgment, paper protocols, order-entry systems, computerized algorithms
B. No adjustment for insulin sensitivity (Portland, PID computer protocols)-
may take longer to goal #
C. Adjusts for Insulin Sensitivity- Yale, U. Wash, Glucommander- faster but > risk hypoglycemia
Ideally, want BOTH : faster, without hypoglycemia ;
ULTIMATELY ALL SUFFER FROM HUMAN INTERFACE ISSUES
SO COMPUTERIZED ALGORITHMS IN CLOSED-LOOP CGMS DATA MAY BE SAFEST, LEAST RESOURCE INTENSIVE, APPROACH
Ideally, adjustable goal - ‘dial-in’ to fit sensor issues, different ICU’s, types of patients, different ICU directors!
Steil,g., ICY insulin Delivery Algorithms, J. Diabetes Sci Technol 3:125,2009

3. Efficiency, nurse compliance
Computerized Algorithms to Regulate Glucose in ICU- Potential to Compensate for Imperfect Sensors
Patient safety
Efficiency, nurse compliance
Decrease workload, reduce cognitive failure
Improve control, decrease hypoglycemia
Proportional Integrative Derivative-
Proportional- absolute deviation, # vs. goal,
Integral – trends leads to ‘basal’ insulin
Derivative- rate of change- leads to ‘correction factor’
Model Predictive Control- uses multiple variables to model the
behavior of glu/ ins in ICU-
potential for less variability- but if don’t include an
important variable, can be ‘off the track’
Hoekstra Critical Care 2009,13:223

4. Computerized Glucose Regulation in the ICU
PID advantage
in hospital where
multiple variables
May apply that are not
in MPC model !!!
Or use MPC to
monitor PID result,
to supervise/
detect possible
sensor failure/
Detect change in patient
condition

5. Hospital Closed Loop discrete PID algorithm
From the Stanford PICU study. Data shows example control achieved using reference blood glucose (BG) readings and discrete PID insulin infusion. Generation 4 sensor performance shown in blue (2006 ADA).

6. Mathematical Modeling to predict glycemia in ICU in order to Test Insulin Infusion Algorithms
eMPC

7. Methods- Sites of Delivery;
(1) multiple daily (subcutaneous) insulin injection (MDII)
(2) continuous subcutaneous insulin infusion (CSII) ,better
but not rapid enough effects for sudden changes seen in critical care
(3) intravenous insulin infusion (IVII), best for critical care
Drawbacks = obstruction of insulin infusion catheter, phlebitis, catheter related infection
(4) continuous intraperitoneal insulin infusion (CIPII)- physiologic, but too many issues
Control is inferior to IVII in cases of high BG variability, eg: critical care
Not suitable with abdominal diseases including peritonitis and abdominal surgery.
Catheter-related complications (e.g., occlusions, aggregation of insulin, local infections)
Production of anti-insulin antibodies.
High cost
Meds to be delivered
Glucose/ Insulin/ Glucagon-
? Incretin, Pramlintide
Hoshino, J Artif Organs (2009) 12:141–149

8. So, Given CGMS in ICU SETTING IS STILL HAMPERED BY
1. Relative Inaccuracy of sensors
2. Site/ Sensor Issues
3. Changing Insulin Sensitivity
4. Human Interface Issues
One can have
ALGORITHM ADJUST FOR THESE VARIABLES , but, knowing error rates, ADJUST GOAL to AVOID HYPOGLYCEMIA

9. Hyperinsulinemic-Normoglycemic Clamp Technique in Cardiac Surgery
70 non-DM
40 DM
Target mM
(This is a low range,
~65-110
Insulin 5mu/kg/min;
d20, varying rates
Hypoglycemia
] <60 [
Sato, Nutrition, 2010

10. Set algorithm 120mg% (6.6 mM), to avoid Hypoglycemia eg: Compensate for Imperfect Sensors, Clinical variables- ePID, External Closed-Loop Clinical Study
9/12/2018 9:00 PM
Aggregate Closed-Loop Results vs. Normal Glucose Tolerant Profile
(UCLA Clinical trial, n = 10 T1DM, n = 18 NGT)
Dial-up range one wishes!!
Diabetes 2006; 55(12): 3344–3350.

11. JDRF Potential Pathway to an Artificial Pancreas From Safety/ Regulary point of View1 2
Hypo/Hyper
Minimizer 3
Very Low Glucose a
Insulin Off Pump
Hypoglycemia
Minimizer
START
Fully Automated
Insulin +
Anti-insulin
Closed Loop 6
Fully Automated
Insulin
Closed Loop 5
Automated
Basal / Hybrid
Closed Loop 4
END

12. How to Speed up? 12

13. Work Forward to Achieve Ideal
Process- Where Do We Go From Here? Closed- Loop Continuous Monitoring In Critical Care --Back to the Future--
SAFETY IS OVERRIDING PRINCIPLE- Aim for lowest glucose possible without hypoglycemia (<80
Need Now- ROI exists-
Live with what we have now- adjusting algorithms to current sensor limitations-
Adjust DESIGN and USAGE of Imperfect Tools until IDEAL available
Work Forward to Achieve Ideal

14. The Ultimate Goal: Full Normalization of Glycemia
9/12/2018 9:00 PM
The Ultimate Goal: Full Normalization of Glycemia
Medtronic Diabetes has a goal of working toward the development of an artificial pancreas. We have two versions of a closed-loop system under development and clinical testing. An external system using the subcutaneous glucose sensor working in combination with the external pump, and a fully implanted system utilizing a long-term chronically implanted vascular sensor with our implanted insulin pump which provides intraperitoneal insulin delivery.
THANK YOU!!
Diabetes 2004; 53(5): 1201–1207.