DAVID C KLONOFF, MD
Medical Director
Dorothy L. and James E. Frank
Diabetes Research Institute of
Mills-Peninsula Health Services
Clinical Professor of Medicine, UCSF
GLUCOSE
SENSORS
IN ACHIEVING
TARGET A1C
AUGUST 13, 2005
KEYSTONE RESORT
San Francisco
Mills Health Center
San Mateo, California
Spring, 1999
Vol. 1, No. 1
ISSN 1520-9156
A SENSOR
IS A DEVICE THAT
DETECTS OR SENSES
A SIGNAL AND CAN
MEASURE GLUCOSE
INTERMITTENTLY IN BLOOD
OR CONTINUOUSLY IN ISF
Three Waves of Technology
in Diabetes Monitoring
(1)
Urine
Testing
(2)
Intermittent
Blood Glucose
Testing
(3)
Continuous
Glucose
Monitoring
INTERMITTENT BLOOD GLUCOSE
SENSORS IN ACHIEVING TARGET A1C
CURRENT STATUS
 Improves control in T1DM and
insulin-treated T2DM
 Generally does not improve
control in T2DM on diet or OHAs
 Prevents severe hypos in all pts
 Works best if pts know to respond
A1c (%)
ASSOCIATION BETWEEN FREQUENCY
OF SMBG TESTING AND A1c IN T1DM
10
9.5
9
8.5
8
7.5
7
6.5
6
5.5
5
A1c = 5.99 + 5.32 / ([number of glucose tests per day] + 1.39)
n=378
0
2
4
6
8
10
12
SMBG Tests per Day
378 T1DM INSULIN PUMP USERS
Davidson et al. Diabetes 2004; 53 (Suppl 2): A101
A1c (%)
SMBG FREQUENCY CORRELATES WITH A1C
ADJUSTED FOR DEMOGRAPHIC VARIABLES
For full adherence
D A1C =
1.0% in T1 DM
0.6% in T2 DM
P < .0001
No r values calculated 24,312 Kaiser Northern Calif adults (95% T2 / 5% T1) Karter et al. Am J Med 2001: 111:1-9
SMBG FREQUENCY CORRELATES WITH A1C
ADJUSTED FOR DEMOGRAPHIC VARIABLES
A1c (%)
For each additional SMBG per day - A1c fell by 0.3%
For full adherence
D A1C =
1.0% in T1 DM
0.6% in T2 DM
P < .0001
No r values calculated 24,312 Kaiser Northern Calif adults (95% T2 / 5% T1) Karter et al. Am J Med 2001: 111:1-9
July 2005
● Volume 22
● Pages 200-206
SELFMONITORING OF BLOOD GLUCOSE IN NON-INSULIN-TREATED DIABETIC PATIENTS:
A LONGITUDINAL EVALUATION OF ITS IMPACT ON METABOLIC CONTROL
M. Franciosi, F. Pellegrini, G. De Berardis, M. Belfiglio, B. Di Nardo, S. Greenfield,
S. H. Kaplan, M. C. E. Rossi, M. Sacco, G. Tognoni, M. Valentini and A. Nicolucci for
The QuED Study Group quality of care and outcomes in Type 2 diabetes
1896 T2DM non-insulin-treated patients followed for 3 years
Freq of SMBG did not predict better control
but did predict fewer hypoglycemic episodes
THE DiGEMtrial PROTOCOL
A 12-MONTH RCT IN T2DM TO DETERMINE THE
EFFECT OF 3 STRATEGIES OF SMBG ON CONTROL
450 T2DM
PATIENTS
ON OHAs
OR DIET
STUDY TO
REPORT
IN 2007
1
CONTROL Rx: Q 3 MO A1c
WITH NP INTERPRETATION
2
SMBG WITH ADJUSTMENTS
IN Rx PER NP ONLY
3
SMBG WITH ADJUSTMENTS
IN Rx PER SUBJECT OR NP
BMC Fam Pract 6: 25; 2005
CONTINUOUS GLUCOSE SENSORS
IN ACHIEVING TARGET A1C
CURRENT STATUS
 Provides around-the-clock info on
absolute BG values and trends
 Five products now approved and
two are being evaluated by the FDA
 Greater accuracy needed
 Reimbursement is inconsistent
CONTINUOUS
GLUCOSE MONITORING
OUTLINE
 Purpose
 Technologies
 Target Populations
 Accuracy
 Clinical Indications
 Outcomes
 Future Trends
CONTINUOUS
GLUCOSE MONITORING
OUTLINE
 Purpose
 Technologies
 Target Populations
 Accuracy
 Clinical Indications
 Outcomes
 Future Trends
PURPOSE OF
CONTINUOUS GLUCOSE
MONITORING
To obtain maximal information
about shifting blood glucose levels
throughout the day to make
the best treatment decisions
CONTINUOUS
GLUCOSE MONITORING
OUTLINE
 Purpose
 Technologies
 Target Populations
 Accuracy
 Clinical Indications
 Outcomes
 Future Trends
CONTINUOUS GLUCOSE
MEASUREMENT DEVICES
APPROVED PRODUCTS IN US & EUROPE
 Continuous Glucose Monitoring




System Gold (CGMS Gold)
Guardian
Guardian RT * (Europe only)
GlucoWatch® G2 Biographer
GlucoDay * (Europe only)
CONTINUOUS
GLUCOSE
MONITORING
SYSTEM GOLD
(CGMS GOLD)
CGMS GOLD - CONTINUOUS GLUCOSE
MONITORING SYSTEM
GLUCOSE
SENSOR
MONITOR
COM-STATION TO
DOWNLOAD
DATA
SENSERTER
MEDTRONIC
MINIMED
GUARDIAN AND
GUARDIAN RT
MEDTRONIC MINIMED GUARDIAN
COMPONENTS
Sensor
Transmitter
Monitor
Alarm (50 db)
®
GLUCOWATCH
G2 BIOGRAPHER
TIME
GLUCOSE
TREND
MENARINI
GLUCODAY
GLUCODAY
CONTINUOUS GLUCOSE MONITOR
ITALY
ABBOTT
LABORATORIES
FREESTYLE
NAVIGATOR
Abbott Laboratories
FreeStyle Navigator™
Continuous
Glucose Monitor
FEATURES
1 Enzyme-tipped SC catheter
2 Wireless transmission to
monitor up to 10 ft away
3 Reads Q 1 min in real time
4 Sensor lasts 3 days
DEPLOYMENT OF THE NAVIGATOR
1
2
Press to Insert Sensor
Attach Sensor Mount to Skin
3
Attach Transmitter to Sensor Mount
4
Data is Transmitted to Receiver
DEXCOM
SHORT-TERM
CONTINUOUS
GLUCOSE
MONITORING
SYSTEM (STS)
CONTINUOUS
GLUCOSE MONITORING
OUTLINE
 Purpose
 Technologies
 Target Populations
 Accuracy
 Clinical Indications
 Outcomes
 Problems
A TOOL FOR DETERMINING
ACCURACY IN AN EXPERIMENTAL
BLOOD GLUCOSE MONITOR
RELATIVE ABSOLUTE DIFFERENCE (RAD) =
I EXPERIMENTAL BG – REFERENCE BG I x
REFERENCE BG
RAD IS EXPRESSED AS A PERCENTAGE
1
100
CONTINUOUS
GLUCOSE MONITORING
ACCURACY STUDIES BY DIRECNET
 RAD of CGMS 19%
 RAD of CGMS Gold 11% & 12%
 RAD of GW2B 16%
91 and 89 children with T1DM in a CRC setting DirecNet: Diabetes Technol Ther 2003; 5: 781-789 and 791-800
200 children with T1DM in an outpatient setting DirecNet: Diabetes Technol Ther 2005; 7:109-114
A TOOL FOR DETERMINING
ACCURACY IN AN EXPERIMENTAL
BLOOD GLUCOSE MONITOR
INTERNATIONAL ORGANIZATION
FOR STANDARDIZATION (ISO) CRITERIA
 Ref BG > 75 mg/dl: Sensor BG +/- 20%
 Ref BG < 75 mg/dl: Sensor BG +/- 15 mg/dl
 Data expressed as % of pairs meeting above criteria
% of Values Meeting ISO Criteria
ISO ACCURACY OF CONTINUOUS BG MONITORS
One Touch Ultra
CGMS Gold
GW2B
Reference Glucose Values (mg/dl)
DirecNet: Diabetes Technol Ther 2003; 5: 781-789 and 791-800
EIGHT-POINT TESTING VS CGMS TO
EVALUATE CONTROL IN T1DM
EIGHT-POINT TESTING
ADVANTAGES
 Similar Mean BGs:




CGMS MONITOR
ADVANTAGES
Children with T1DM n = 200 JCEM 2005; 90: 3387-3391
188 mg/dl
183 mg/dl
Mean noc BG: 199 mg/dl 174 mg/dl
? ↑ specificity low BG
? ↓ specificity low BG
Similar BG / A1c ratios:
23 mg/dl per 1% A1c
19/mg/dl per 1% A1c
2-hr PP ∆BG PM: 2-hr PP ∆BG PM: +
Compliance (72h): 10%
Compliance Median: 70h
CONTINUOUS
GLUCOSE MONITORING
OUTLINE
 Purpose
 Technologies
 Target Populations
 Accuracy
 Clinical Indications
 Outcomes
 Future Trends
SITUATIONS REQUIRING DETAILED
INFO ABOUT GLUCOSE FLUCTUATIONS
CLINICAL INDICATIONS TO USE CGM
 Assess impact of an adjustment in
therapy to improve control
 Achieve tighter control without causing
hypoglycemia (e.g. peds DM, GDM, ICU)
 Diagnose / prevent hypoglycemia during
sleep or hypoglycemia unawareness
 Quantify the response in clinical trials
ELEMENTS OF THERAPY THAT
CAN BE ADJUSTED WITH CGM
 Type or dose of mealtime insulin
 Type or dose of basal insulin
 Treatment of High or Low BG
 Insulin: Glucose ratio for High BGs
 Insulin: CH2O ratio at mealtime
 Carbohydrate composition of diet
 Discount in short-acting ins for exercise
 HS regimen because of dawn phenom
 Target pre- or post- prandial BG
 Refer to Ψ to improve adherence
ELEMENTS OF THERAPY THAT
CAN BE ADJUSTED WITH CGM
 Increase
dose of mealtime insulin (#1 of 8)
I
 Type of basal insulin .
(#1 of 9)
 Treatment of High or Low BG
 Insulin: Glucose ratio for High BGs
 Insulin: CH2O ratio at mealtime
 Carbohydrate composition of diet
 Discount in short-acting ins for exercise
 HS regimen because of dawn phenom
 Target pre- or post- prandial BG
Sabbah et al: Diabetes 2000; 49 (Suppl 1): A393
 Refer to Ψ to
improve
adherence
Kaufman et al: Diabetes Care 2001; 24: 2430-2434
CONTINUOUS
GLUCOSE MONITORING
OUTLINE
 Purpose
 Technologies
 Target Populations
 Accuracy
 Clinical Indications
 Outcomes
 Future Trends
OUTCOMES TRIALS OF CGM:
STUDY DESIGNS AND ENDPOINTS
 Six RCT’s: two showed SS ↓ in A1c,
three showed NSS ↓ in A1c and one
showed no ↓ in A1c but did show a
SS ↓ in duration of hypo episodes
 Five nonrandomized uncontrolled trials:
all five showed a SS ↓ in A1c
 One nonrandomized uncontrolled trial
using ↓ and ↑ excursions as an endpoint
showed reduced excursions of both
IMPROVED BG CONTROL
WITH REAL TIME
CONTINUOUS GLUCOSE
MONITORING USING AN
IMPLANTED SENSOR
Time Spent (hrs/day)
10
8
6
BLINDED TESTING
REAL TIME ACCESS
2
40 - 55
56 - 80
Time spent
Hypoglycemic
(< 55 mg/dl)
Decreased 47%
Time spent
Hyperglycemic
(> 241 mg/dl )
Decreased 25%
4
0
BLINDED TESTING vs
REAL TIME ACCESS
81 – 140
141 – 240
Glucose Range (mg/dl)
241 - 400
Diabetes Care. 2004;27:734-8
SUMMARY
20 T1DM subjects at Stanford
and Barbara Davis Center
wore 1-2 GlucoWatch GW2Bs
240 total alarms in 24 hours
(180 during sleep) for:
a) BG ≤ 70 mg/dl
b) expected hypo within 20 min
c) BG ≥ 300 mg/dl
Subjects awoke to:
29% of individual alarms
66% of alarm events
100% of true hypo events
DirecNet: Diabetes Technol Ther June 2005; 7:440-447
SUMMARY
20 T1DM subjects at Stanford
and Barbara Davis Center
wore 1-2 GlucoWatch GW2Bs
240 total alarms in 24 hours
(180 during sleep) for:
a) BG ≤ 70 mg/dl
b) expected hypo within 20 min
c) BG ≥ 300 mg/dl
Subjects awoke to:
29% of individual alarms
66% of alarm events
100% of true hypo events
DirecNet: Diabetes Technol Ther June 2005; 7:440-447
CONTINUOUS
GLUCOSE MONITORING
OUTLINE
 Purpose
 Technologies
 Target Populations
 Accuracy
 Clinical Indications
 Outcomes
 Future Trends
MEDTRONIC
MINIMED
PARADIGM
SENSOR
AUGMENTED
SYSTEM
CONTINUOUS
REAL TIME SENSOR
TRANSMITTER
COMBINED
MONITOR AND
INSULIN PUMP
MONITOR
SENSOR
SUTURES
CABLE
Diabetes Technol Ther 2002; 4: 305-312
J Feline Med Surg 2005; 7: 53-62
J Feline Med Surg 2005; 7: 53-62
J Feline Med Surg 2005; 7: 53-62
J Feline Med Surg 2005; 7: 53-62
J Feline Med Surg 2005; 7: 53-62
J Feline Med Surg 2005; 7: 53-62
CONTINUOUS
GLUCOSE MONITORING
MEANS MORE
BLOOD GLUCOSE DATA
CONTINUOUS GLUCOSE SENSORS
IN ACHIEVING TARGET A1C
CONCLUSIONS
 Provides maximal information for
making treatment decisions
 Multiple methods are effective
 Technology will be a routine part
of intensive treatment regimens
 In the future a continuous sensor
will control an artificial pancreas