Transcript Nocturnal Hypoglycemia - Is it Safe To Go To Sleep? Bruce Buckingham, MD.

Nocturnal Hypoglycemia - Is
it Safe To Go To Sleep?
Bruce Buckingham, MD
Topics to be Covered
• Overview Of Hypoglycemia
• Real Time Monitoring With Hypoglycemic
Alarms
• Closing the Loop
– Stopping insulin delivery based on real-time
glucose sensors
HYPOGLYCEMIA
• 657 children followed for 3 years
• 8.5% had severe (seizure or coma) and
27% moderate (required assistance)
hypoglycemia
• < 6 y.o. = 40/100 patient yrs
• >6 y.o. = 17/100 patient yrs
• 75% of seizures occurred at night
DIABETES CARE 20:22, 1997
Causes of Hypoglyecmia
• Insulin
– NPH peaking in the middle of the night
– IM instead of SQ
– Hot tub
• Exercise
– Hypoglycemia can occur 6-12 hours post
exercise
• Missed snack
• Alcohol
Glucose Infusion Rate
sc insulin
N=20 T1DM
Mean ± SEM
4.0
20
3.0
Ultralente
2.0
16
CSII
12
8
1.0
µmol/kg/min
mg/kg/min
NPH
24
4
Glargine
0
0
0
4
8
12
Time (hours)
16
20
24
Lepore et al. Diabetes 2000;49:2142-8.
Concentrations [mlU/mL]
Intra-subject Variability
Insulin Glargine
3
2
2
4
1
6
8
Subject 2
Subject 3
Subject 7
Subject 9
Subject 14
Subject 18
Subject 19
Subject 22
Subject 28
Subject 34
Subject 35
0
3
2
2
4
1
6
8
0
Subject 27
3
2
2
4
1
6
8
0
-1
4
9
14
19
-124
4
9
14
19
-124
Time [h]
Visit 2
4
9
14
Visit 3
Scholtz et al. Diabetes 1999;48(suppl 1):A97. Abst 416; Study
1012
19
-1 24
4
9
14
19
24
Incidence of Hypoglycemia with
Overnight Discrete Glucose Monitoring
Study
Hypo
Testing
# of
nights
61
Porter 1997
<64
11PM,
2AM, 6 AM
DirecNet 2001
<60
DirecNet 2004
Sedentary Day
DirecNet 2004
Active Day
% low
37.8%
Q ½ hr
91
10%
< 60
q ½ hr
50
28%
< 60
q ½ hr
50
48%
Twenty-one Adults – Discrete Glucose
Measurements Q 15 Minutes Overnight
Snack
Glucose Values < 70
mg/dl
% of
% of Night
Patients
57
27
None
Snack = 26 gm CHO
43
15
Cornstarch Bar
52
21
Raju, JCEM Feb, 2006
Nocturnal Hypoglycemia
Effect of Bedtime Snacks
Raju, JCEM Feb, 2006
Effect of High Fat Bedtime Snack on
Nocturnal Hypoglycemia
DirecNet Pediatric Diabetes 2008
Effect of High Fat Bedtime snack on
Nocturnal Hypoglycemia
DirecNet Pediatric Diabetes 2008
14 y.o. male A1c = 6.6%,
Crew (rowing team) in PM
5/16/06
5/27/06
Camp Chinnock Study
Seizure
Courtesy of Dr. Kevin Kaiserman
Australian Patient
Norwegian Patient
17 yo Female, A1c 6.2
Daily Details 2-2-06
Seizure
17 yo Female, A1c 6.2, in Study 3 Months
Daily Detail 2-1-06
CGMS Gold Study in 19 Toddlers at
Stanford – Dr Laura Gandrud
Age
(year; mean, SD; range)
Male/Female
Pump/Injection
Duration of Diabetes
(year; mean, SD)
HbA1c (mean, SD)
History of seizure
4.8 ± 1.4
(1.6 to 6.8)
9/10
6/13
2.2 ± 1.4
8.0 ± 0.8%
1
Glucose Trends: CT
Post-breakfast
excursion
Nocturnal lows
Hypoglycemia Detection:
Meter v. Sensor
350
# of
Events
300
Meter glucose
250
Sensor glucose
311
200
150
100
136
130
50
5
0
Mild
Glucose <65 mg/dL
Severe
Glucose ≤ 40 mg/dL
All subjects had
sensor
hypoglycemia, 17
of 19 children had
severe sensor
hypoglycemia
Hypoglycemia: Duration
Duration: 42 ± 52 minutes
44 nights
(14%)
Duration:
30 ± 42
minutes
No Hypoglycemia
Mild Hypoglycemia
62 nights
(20%)
Severe Hypoglycemia
213 nights (67%)
319 nights total
JDRF RCT Nocturnal
Hypoglycemia
Poster at DTT, 2009
• 36,000 nights
– Guardian and Navigator
• 176 subjects
• Hypoglycemia = 2 consecutive CGM
readings ≤ 60 mg/dl
JDRF RCT Nocturnal
Hypoglycemia
• Hypoglycemia occurred during 8.5% of
nights
• Mean duration of hypoglycemia
= 81 minutes
• 47% of nights had at least 1 hour of
hypoglycemia
• 23% had at least 2 hours
• 11% had at least 3 hours
Severe Hypoglycemia Events in
JDRF CGS
Hypoglycemia event rate per 100 person-years
0-6 months
7-12 months
25.0
20.0
15.0
10.0
5.0
0.0
overall
(N=83)
baseline A1c >=7.0%
(N=49)
baseilne A1c <7.0%
(N=34)
≥ 1 Severe Hypo Event in Last 12m
T1D Exchange Data, Helmsley Foundation
Injection
Response of Subjects to Alarms
•
•
•
•
Clinical Research Center Study
28 subjects the type 1 diabetes
Ages 4-17
Videotaped using an infrared camera from
9 PM to 7 AM
• Videotapes were reviewed by two
reviewers to determine if subjects awoke
to an alarm and their response to the
alarm
160
Average of 1
hour
To Awaken to
Multiple Alarms
140
Blood Glucose (mg/dl)
120
≈50% False Positive
Alarm Rate
100
80
60
28% Response
40% Respond 28% Response To Subsequent
To Subsequent Alarms
To First Alarm
Alarms
40
20
0
9:00:00 PM
12:00:00 AM
3:00:00 AM
Time
6:00:00 AM
Sensor Glucose
Low Alarm
Prediced Low Alarm
70 mg/dl
INDIVIDUAL ALARMS
PATIENT FACTORS (1)
N
# of Alarms
# of Times
Awakened
OVERALL
AGE
20
180
53 (29%)
Age 4-6
Age 7-11
Age 12-18
GENDER
Male
5
7
8
Female
p-value
0.11
30
95
55
5 (17%)
19 (20%)
29 (53%)
0.75
8
12
65
115
25 (38%)
28 (24%)
Decreased Hypoglycemia with CGM
Use
Battelino, Diabetes Care, April, 2011
•
•
•
•
120 Children (45%) and Adults (55%)
A1c < 7.5% (mean 6.9%)
Doing 5 SMBG tests each day
Mean days of sensor wear/week:
Pediatrics=5.6, Adults=4.9
Decreased Hypoglycemia with CGM
Use
Battelino, Diabetes Care, April, 2011
Hypoglycemia is Dramatically
Reduced by Maintaining/Restoring
C-peptide Secretion
• At onset of diabetes – Honeymoon
• Pancreas Transplant
• Islet cell Transplant
Probability of maintaining C-peptide secretion in DCCTT
Intensive
Conventional
Ann Intern Med 1998;128:517-523
The Effect of C-Peptide Response on Long-Term
Complications and Hypoglycemia
Intensive Treatment
Group
Non
Responders responders
Retinopathy*
Nephropathy*
Severe
Hypoglycemia*
2.0
1.4
4.7
2.5
6.6
17.3
* Rate per 100 patient-years
Ann Intern Med 128:517-523, 1998
Conventional
Treatment Group
Responders
Non
responders
7.1
3.1
3.0
8.7
3.4
4.3
Hypoglycemia Unawareness
Blunted Adrenalin Response to
Hypoglycemia
Diabetes Care 32:1954-1959, 2009
• 30% of children 3-8 years old and 12-18 years
old failed to release adrenalin in response to
hypoglycemia
• Parents blinded to their child’s glucose level
failed to recognize hypoglycemia 71% of the
time
Improving Hypoglycemia
Unawareness with Real-Time CGM
Ly, Diabetes Care 34:50. 2011
•
•
•
•
•
11 adolescents 12-18 years old
Treated for 4 weeks
Each group to do 4-6 fingersticks each day
5 in standard group
6 in real-time CGM – low alarm set to 108
mg/dl (6 mmol/l)
1000
900
Standard Therapy
CGMS
800
* p=0.031
700
600
Percent
500
%
400
p=0.375
300
200
100
0
Baseline
After 4 weeks
Real Time Non-specific Nocturnal
Alarms
•
•
•
•
The dog barking
Sleep partner
Sleep Sentry
HypoMon
Sleep Sentry
• In Adults
– detects 66% of lows
– 66% false alarm rate
• In Pediatrics
– 192 alarms for 42 lows
– 3.6 false alarms for
each true low
Acta Med Scand 220:213, 1986;
Diabetes Care 6:597, 1983
Sleep Sentry
• 18 subjects with type 1 diabetes without
hypoglycemic unawareness
• 2 hour insulin infusion to a blood glucose
of <55 mg/dl
• 10/18 subjects (55%) alarmed when low
• 8/18 (45%) were non responders
• No difference in catecholamine levels, or
sense of diaphoresis between responders
and non-responders
Clarke, Diabetes Care 11:630,
1988
Target Product #1 – Very Low Glucose
Insulin-off Pump
BG – mM
Alarm warns that glucose has crossed pre-set threshold – if
no response, insulin delivery suspended for 2 hours
10
Alarm #1
Alarm #2 – no response
3.9
Insulin Off - two hours
3.0
Time
47
TYPE 1 DIABETES
Minimed Low Glucose Suspend
Mastrototaro DTT 11:S-37, 2009
• Paradigm Veo System –
– Available in almost all countries except the
US
• Integrates 2-hour autosuspend
• Hypoglycemic threshold set by user
49
Daily Summary report – Subject Remained in LGS for 2
Hours
270 mg/dl
180 mg/dl
90 mg/dl
Data on file at Medtronic. The Paradigm Veo insulin pump is not FDA approved, and therefore not commercially
available in the US.
50
Studies of Pump Interruption
Paper
Yr
N
At 2 Hours
Ketones
Glucose
Krzentowski
1983
8
Not elevated
Not elevated
Castillo
1996
15
0.3 mM
Not Elevated
Attia
1998
18
0.3 mM
↑ by 1-40
mg/dl
Orsini
2006
8
0.4 mM
↑ by 20 mg/dl
DirecNet
2006
49
< 0.4 mM
↑ by 10 mg/dl
What Do We Know About Low Glucose Suspend?
• Multiple Studies
• UK User Evaluation – Pratik Choudhary, M.D., 6 sites in UK
• Diabetes Care
• PVEO Study – Thomas Danne, M.D., 3 Sites in Germany
• Diabetes Care
• ADA Oral Presentation, 2011
• Sunday, June 26, 2011: 8:15 AM - 8:30 AM
• Data Mining of CareLink
• Pratik Agrawal, Brian Kannard, John Shin
• Journal of Diabetes Science and Technology
• ADA audio poster presentation Monday 12-1 PM, 0915-P
• In-Clinic Veo US Regulatory Study
• Almost Done
The Paradigm Veo insulin pump is not FDA approved, and therefore not commercially available in the US.
52
Data used for analysis Accepted for publication in JDST,
presented at multiple meetings, ADA 2011, DTS, ATTD
X54 launched in Dec 2009
CareLink Personal Database
278 users were selected
– Selection Criteria:
more than 3 months (90 days) of unique
sensor days
– Days Analysed: 28,401 patient-days
26,050 patient-day LGS ON
2,351 patient-days LGS OFF
The Paradigm Veo insulin pump is not FDA approved, and therefore not commercially available in the US.
53
LGS duration
11% of all LGS events run for full 2 hours
45% of all LGS events are cancelled by the users in < 5 minutes and
another 21% within 30 minutes
Fig. Distribution of duration of the LGS event
The Paradigm Veo insulin pump is not FDA approved, and therefore not commercially available in the US.
54
LGS events by time of day
67.7% of all LGS events occur during the day (8 am to 10 pm) and 10% occur at lunch
time (12 am to 2 pm)
During the day, 50% of LGS event are overridden in 5 minutes; 5.5% of LGS events
last 2 hours
Might be beneficial to set hourly LGS threshold settings – reduce nuisance alarms
during the day
Number of LGS events in each hour during the day Number of 2 hour long LGS events in each hour during the day
The Paradigm Veo insulin pump is not FDA approved, and therefore not commercially available in the US.
55
Effect of LGS on hypoglycemia
By means of %SG for individual users**
LGS Off
Reduction in severe
hypoglycemic blood glucose
levels is observed with LGS
LGS On
p
Mean
151.34
156.04
0.050
STD
60.07
54.84
0.028
%SG<50
1.33
0.92
0.001
%SG<60
3.58
2.63
0.140
%SG<70
6.73
5.48
0.433
%SG<80
11.39
10.05
0.866
Comparison of low sensor BG when LGS is OFF vs. ON
Percent time SG <= 50
Percent time SG <= 80
**”Characterization of the Low Glucose Suspend Feature of the Medtronic Paradigm Veo Insulin Pump and Events Preceding its Activation” .
To be presented by Dr. Fran Kaufman at the ADA conference 2011
The Paradigm Veo insulin pump is not FDA approved, and therefore not commercially available in the US.
56
Effect of LGS on hyperglycemia
By means of %SG for individual users**
Decrease in the severe
hypoglycemic blood glucose
levels not associated with
increase in severe
hyperglycemic glucose levels
LGS Off
LGS On
p
%SG>150
41.23
47.10
0.051
%SG>180
28.02
31.34
0.055
%SG>240
11.65
11.28
0.023
%SG>300
4.64
3.41
0.001
Comparison of high sensor BG when LGS is OFF vs. ON
Percent time SG >= 240
Percent time SG >= 300
**”Characterization of the Low Glucose Suspend Feature of the Medtronic Paradigm Veo Insulin Pump and Events Preceding its Activation” .
To be presented by Dr. Fran Kaufman at the ADA conference 2011, Poster session Monday 12-1 PM 0915-P
The Paradigm Veo insulin pump is not FDA approved, and therefore not commercially available in the US.
57
Sensor Response Following 2 hour Pump
Suspend
Trang Ly, Jennifer Nicholas, Elizabeth Davis, Timothy Jones
ADA Poster 404, 2011
•
•
•
•
•
•
25 subjects
Mean Age 17.5±1.8 years
Mean A1c = 7.7±0.1%
Wore the Veo Pump 1728 days
2320 LGS events
11% lasted the full 2 hours
– 74% of these were overnight
Sensor Response Following 2 hour Pump
Suspend
Trang Ly, Jennifer Nicholas, Elizabeth Davis, Timothy Jones
ADA Poster 404, 2011
• No DKA
• No severe hypoglycemia
• High Patient Satisfaction
– 85% choosing to continue to use the system after
the 6 month study
Sensor Response Following 2 hour Pump
Suspend
Trang Ly, Jennifer Nicholas, Elizabeth Davis, Timothy Jones
ADA Poster 404, 2011
• On 10 nights there were multiple pump
suspensions
• Average 4.2 hours
• Mean AM Glucose 256±25 mg/dl
• This represents 0.58% of sensor time
Sensor Response Following 2 hour Pump Suspend
Trang Ly, Jennifer Nicholas, Elizabeth Davis, Timothy Jones
ADA Poster 404, 2011
Target Product #2 – Hypo Minimizer
BG – mM
Reduction or suspension of insulin delivery to minimize time
below hypo threshold
10
Hypoglycemia Predicted,
insulin delivery suspended
3.9
3.0
Time
63
Preventing Nocturnal
Hypoglycemia with a Partial
Closed Loop System
Stanford:
B. Buckingham, Darrell Wilson, Fraser
Cameron, P. Clinton, Kimberly Caswell
Barbara Davis Center:
H. Peter Chase, Erin
Cobry, Victoria Gage
UCSB: Frank Doyle, Eyal Dassau
Rensselaer Polytechnic Institute:
Wayne
Bequette, Hyunjin Lee
Acknowledgments:
Juvenile Diabetes Research Foundation (JDRF) grants
# 22-2006-1107 and 22-2007-479
Ideal Alarm
• Can predict impending hyper and hypoglycemia
• Has reasonable sensitivity (80%) and few false
positives (20%)
• All parameters can be set by the patient
• Can be silenced and/or placed in a “vibrate”
mode
• Alarms can be sent to a remote receiver, i.e. to a
parents room
• Alarms can turn on a light or the child’s stereo
Sensor Communicating with Pump
to Prevent Nocturnal
Hypoglycemia
• To use continuous glucose monitoring to
detect impending episodes of nocturnal
hypoglycemia
• When hypoglycemia is predicted, the
insulin infusion pump will be suspended
until the sensor glucose is on an upward
trend and above 80 mg/dl
CL2-MW 9-3-08
3 Alarm, Threshold 80 mg/dl, Horizon 35 min
2.5
Controller Glucose
YSI
Basal Insulin
Serum Glucose (mg/dl)
140
2.0
120
100
1.5
80
1.0
60
40
0.5
20
0.0
0
100
200
300
400
Time in Minutes Beginning at 9:30 PM
500
600
Insulin Infusion Rate (u/hr)
160
CL2-SC 8-27
3 Alarm, Threshold 80 mg/dl, Horizon 35 min
180
160
3
Serum Glucose (mg/dl)
140
120
2
100
80
60
1
40
20
0
0
100
200
300
400
500
Time in Minutes Beginning at 9:30 PM
600
700
Insulin Infusion Rate (u/hr)
Controller Glucose
YSI
Basal Insulin
CL2 JM 8-2-08 1-13-09
3 Alarm, Threshold 80 mg/dl, Horizon 35 min
200
Controller Glucose
YSI
Basal Insulin
160
3
Glucose (mg/dl)
140
120
2
100
80
60
1
40
20
0
0
100
200
300
400
500
Time in Minutes Beginning at 9:30 PM
600
700
Insulin Infusion Rate (u/hr)
180
CL2 13 DA 1-9-09
2 Alarm, Threshold 80 mg/dl, Horizon 35 min
180
Controller Glucose
YSI
Basal Insulin
Glucose (mg/dl)
140
3
120
2
100
80
60
1
40
20
0
0
100
200
300
400
500
Time in Minutes Beginning at 8:45 PM
600
700
Insulin Infusion Rate (u/hr)
160
CL2 15 JB 1-13-09
2 Alarm, Threshold 80 mg/dl, Horizon 35 min
250
Controller Glucose
YSI
Basal Insulin
150
2
100
1
50
0
0
100
200
300
400
500
Time in Minutes Beginning at 8:55 PM
600
700
Insulin Infusion Rate (u/hr)
Glucose (mg/dl)
200
3
Outcome Using 3 alarms to Trigger
Pump Shut Off
First
Event of
Night
Success
Failure
7
3
Second
Third Event
Event of
of Night
Night
2
1
1
0
%
71%
29%
Predictors of Successful
Hypoglycemia Prevention
At time of Pump
Shut Off
Difference between
Navigator and YSI
glucose
(Mean ± SD)
Rate of Change
(Mean ± SD)
YSI Glucose at shut off
(Mean ± SD)
Success
(n= 31)
Failure
(n=8)
P
value
4±9
18 ± 10
0.001
-0.4 ± 0.3
-0. 65 ± 0.5
NS
97 ± 14
86 ± 17
NS
Rate Of Change Of Glucose Levels Following Pump Suspension To
Prevent Hypoglycemia
(mean ± SEM)
Rate of Change of Glucose (mg/dl-min)
0.8
Navigator
FreeStyle Glucose
0.6
0.4
0.2
0.0
-0.2
-0.4
-0.6
High
Basal
Insulin
-0.8
Pump Off
Usual Basal Insulin Infusion Rate
-1.0
0
50
100
150
Time From Pump Shut Off (Minutes)
200
250
Decreasing Nocturnal Hypoglycemia
Using Predictive Pump Shut-Off
• Inpatient setting to optimize predictive alarms
– Hypoglycemia prevented 75% of nights in 28
subjects
Mean
Median
Range
Length of Pump Peak Glucose Time to Peak
Shut-Off*
Post Shut Off Glucose
(min)
(mg/dl
(min)
130
165
100
90
56-390
155
105-275
95
55-170
* 21 Subjects with at least 180 minutes of observation time following pump
suspension, and no treatment for hypoglycemia
Main User Interface
Start Session Screen
Running
9:00:00 AM
8:00:00 AM
7:00:00 AM
6:00:00 AM
5:00:00 AM
4:00:00 AM
3:00:00 AM
2:00:00 AM
1:00:00 AM
12:00:00 AM
11:00:00 PM
10:00:00 PM
9:00:00 PM
8:00:00 PM
Glucose (mg/dL)
300
PSO2-003-0001
250
2.5
200
2
150
1.5
100
1
50
0.5
0
0
Basal Insulin (U/hr) and Ketones (mmol/L)
3
GlucoScout
Hypo
Thresh
CGMAlgo
YSI
Shutoff Cue
Basal Insulin
10:00:00 AM
9:00:00 AM
8:00:00 AM
7:00:00 AM
6:00:00 AM
5:00:00 AM
4:00:00 AM
3:00:00 AM
2:00:00 AM
1:00:00 AM
12:00:00 AM
11:00:00 PM
10:00:00 PM
9:00:00 PM
8:00:00 PM
Glucose (mg/dL)
300
PSO2-003-0002
250
2.5
200
2
150
1.5
100
1
50
0.5
0
0
Basal Insulin (U/hr) and Ketones (mmol/L)
3
GlucoScout
Hypo
Thresh
CGMAlgo
Fingerstick
Shutoff Cue
Basal
Insulin
9:00:00 AM
8:00:00 AM
7:00:00 AM
6:00:00 AM
5:00:00 AM
4:00:00 AM
3:00:00 AM
2:00:00 AM
1:00:00 AM
12:00:00 AM
11:00:00 PM
10:00:00 PM
9:00:00 PM
8:00:00 PM
Glucose (mg/dL)
PSO2-003-0003
250
2.5
200
2
150
1.5
100
1
50
0.5
0
0
Basal Insulin (U/hr) and Ketones (mmol/L)
300
3
Hypo
Thresh
CGMAlgo
YSI
Fingerstick
Shutoff Cue
GlucoScout
10:00:00 AM
9:00:00 AM
8:00:00 AM
7:00:00 AM
6:00:00 AM
5:00:00 AM
4:00:00 AM
3:00:00 AM
2:00:00 AM
1:00:00 AM
12:00:00 AM
11:00:00 PM
10:00:00 PM
9:00:00 PM
8:00:00 PM
Glucose (mg/dL)
PSO2-003-0006
250
2.5
200
2
150
1.5
100
1
50
0.5
0
0
Basal Insulin (U/hr) and Ketones (mmol/L)
300
3
GlucoScout
Hypo
Thresh
CGMAlgo
Shutoff Cue
Basal Insulin
Ketones
10:00:00 AM
9:00:00 AM
8:00:00 AM
7:00:00 AM
6:00:00 AM
5:00:00 AM
4:00:00 AM
3:00:00 AM
2:00:00 AM
1:00:00 AM
12:00:00 AM
11:00:00 PM
10:00:00 PM
9:00:00 PM
8:00:00 PM
Glucose (mg/dL)
PSO2-003-0007
250
3.5
3
200
2.5
150
2
100
1.5
1
50
0.5
0
0
Basal Insulin (U/hr) and Ketones (mmol/L)
300
4
GlucoScout
Hypo Thresh
CGMAlgo
Shutoff Cue
Basal Insulin
Ketones
10:00:00 AM
9:00:00 AM
8:00:00 AM
7:00:00 AM
6:00:00 AM
5:00:00 AM
4:00:00 AM
3:00:00 AM
2:00:00 AM
1:00:00 AM
12:00:00 AM
11:00:00 PM
10:00:00 PM
9:00:00 PM
8:00:00 PM
Glucose (mg/dL)
PSO2-003-0008
250
2.5
200
2
150
1.5
100
1
50
0.5
0
0
Basal Insulin (U/hr) and Ketones (mmol/L)
300
3
GlucoScout
Hypo
Thresh
CGMAlgo
YSI
Fingerstick
Shutoff Raw
Roman Hovorka Overnight Closed Loop
Studies at Cambridge
one night
closed-loop
VO2 max
assessment
0 weeks
one night
open-loop
randomisation
one night
open-loop
one night
closed-loop
plus 1 - 3 weeks
plus 1 - 3 weeks
Study night
both
closed-loop
CSIInights
night
night
Open-loop
Open-loop
Closed-loop
CGM
calibration
as requested
by device
15
min plasma
glucose
and 30 min
plasma insulin
standardised
2x20min
light meal
walking on
&
insulin bolus treadmill
55% VO2max
arrival
15:00 16:00
18:00 18:45
20:00
time of day (hh:mm)
08:00
CGM and Pump
•
•
Freestyle Navigator (Abbott Diabetes Care)
• Single sensor
Cozmo (Smiths Medical)
• Aspart insulin
Control algorithm
•
•
Model-predictive control algorithm
Linear Kalman filter with interacting multiple model
strategy
start of closed-loop
control
limit for
insulin infusion
insulin infusion
modulated every 15 min
Results
CGM [median (IQR)]
snack &
prandial
bolus
exercise
Closed loop
CSII
16
Glucose (mmol/L)
14
12
10
8
6
4
PG 2mmol/ll
study stopped
2
0
16:00 18:00
20:00
22:00
00:00
Time (h)
02:00
04:00
06:00
08:00
No rescue carbohydrates given
In Summary
• Real-time near-continuous glucose
sensors can detect nocturnal
hypoglycemia and awaken subjects
• Real-time sensors can be used to treat
predicted hypoglycemia
• Using current CGM sensors in a closed
loop would have a significant impact on
hemoglobin A1c levels