DAVID C KLONOFF, MD

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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

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GLUCOSE SENSORS IN ACHIEVING TARGET A1C
AUGUST 13, 2005 KEYSTONE RESORT
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San Francisco
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Mills Health Center San Mateo, California
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Spring, 1999
Vol. 1, No. 1
ISSN 1520-9156
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A SENSOR IS A DEVICE THAT DETECTS OR SENSES A
SIGNAL AND CAN MEASURE GLUCOSE INTERMITTENTLY IN
BLOOD OR CONTINUOUSLY IN ISF
DEFINITION
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Three Waves of Technology in Diabetes Monitoring
(1) Urine Testing
(2) Intermittent Blood Glucose Testing
(3) Continuous Glucose Monitoring
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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

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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)
n378
A1c ()
0 2 4 6 8
10 12
SMBG Tests per Day
Davidson et al. Diabetes 2004 53 (Suppl 2) A101
378 T1DM INSULIN PUMP USERS
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SMBG FREQUENCY CORRELATES WITH A1C ADJUSTED FOR
DEMOGRAPHIC VARIABLES
A1c ()
For full adherence D A1C 1.0 in T1 DM 0.6 in
T2 DM P lt .0001
No r values calculated
Karter et al. Am J Med 2001 1111-9
24,312 Kaiser Northern Calif adults (95 T2 / 5
T1)
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SMBG FREQUENCY CORRELATES WITH A1C ADJUSTED FOR
DEMOGRAPHIC VARIABLES
For each additional SMBG per day - A1c fell by
0.3
A1c ()
For full adherence D A1C 1.0 in T1 DM 0.6 in
T2 DM P lt .0001
No r values calculated
Karter et al. Am J Med 2001 1111-9
24,312 Kaiser Northern Calif adults (95 T2 / 5
T1)
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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
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THE DiGEMtrial PROTOCOL
A 12-MONTH RCT IN T2DM TO DETERMINE THE EFFECT OF
3 STRATEGIES OF SMBG ON CONTROL
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450 T2DM PATIENTS ON OHAs OR DIET
CONTROL Rx Q 3 MO A1c WITH NP INTERPRETATION
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SMBG WITH ADJUSTMENTS IN Rx PER NP ONLY
STUDY TO REPORT IN 2007
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SMBG WITH ADJUSTMENTS IN Rx PER SUBJECT OR NP
BMC Fam Pract 6 25 2005
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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

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CONTINUOUS GLUCOSE MONITORING
OUTLINE

• Purpose
• Technologies
• Target Populations
• Accuracy
• Clinical Indications
• Outcomes
• Future Trends

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CONTINUOUS GLUCOSE MONITORING
OUTLINE

• Purpose
• Technologies
• Target Populations
• Accuracy
• Clinical Indications
• Outcomes
• Future Trends

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PURPOSE OF CONTINUOUS GLUCOSE MONITORING
To obtain maximal information about shifting
blood glucose levels throughout the day to
make the best treatment decisions
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CONTINUOUS GLUCOSE MONITORING
OUTLINE

• Purpose
• Technologies
• Target Populations
• Accuracy
• Clinical Indications
• Outcomes
• Future Trends

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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)

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CONTINUOUS GLUCOSE MONITORING SYSTEM GOLD (CGMS
GOLD)
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CGMS GOLD - CONTINUOUS GLUCOSE MONITORING
SYSTEM
GLUCOSE SENSOR
MONITOR

• COM-STATION TO DOWNLOAD DATA

SENSERTER
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MEDTRONIC MINIMED GUARDIAN AND GUARDIAN RT
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MEDTRONIC MINIMED GUARDIAN
COMPONENTS
Sensor Transmitter Monitor Alarm (50 db)
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GLUCOWATCH G2 BIOGRAPHER
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TIME GLUCOSE TREND
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MENARINI GLUCODAY
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GLUCODAY CONTINUOUS GLUCOSE MONITOR
ITALY
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ABBOTT LABORATORIES FREESTYLE NAVIGATOR
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Abbott Laboratories FreeStyle Navigator Continuou
s 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
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DEPLOYMENT OF THE NAVIGATOR
1
2
Attach Sensor Mount to Skin
Press to Insert Sensor
3
4
3
Attach Transmitter to Sensor Mount
Data is Transmitted to Receiver
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DEXCOM SHORT-TERM CONTINUOUS GLUCOSE MONITORING
SYSTEM (STS)
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CONTINUOUS GLUCOSE MONITORING
OUTLINE

• Purpose
• Technologies
• Target Populations
• Accuracy
• Clinical Indications
• Outcomes
• Problems

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A TOOL FOR DETERMINING ACCURACY IN AN
EXPERIMENTAL BLOOD GLUCOSE MONITOR
RELATIVE ABSOLUTE DIFFERENCE (RAD)
x
I EXPERIMENTAL BG REFERENCE BG I
1 REFERENCE BG
100
RAD IS EXPRESSED AS A PERCENTAGE
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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
DirecNet Diabetes Technol Ther 2005 7109-114
200 children with T1DM in an outpatient setting
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A TOOL FOR DETERMINING ACCURACY IN AN
EXPERIMENTAL BLOOD GLUCOSE MONITOR
INTERNATIONAL ORGANIZATION FOR STANDARDIZATION
(ISO) CRITERIA

• Ref BG gt 75 mg/dl Sensor BG /- 20
• Ref BG lt 75 mg/dl Sensor BG /- 15 mg/dl
• Data expressed as of pairs meeting above
  criteria

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ISO ACCURACY OF CONTINUOUS BG MONITORS
One Touch Ultra
CGMS Gold
GW2B
of Values Meeting ISO Criteria
Reference Glucose Values (mg/dl)
DirecNet Diabetes Technol Ther 2003 5 781-789
and 791-800
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EIGHT-POINT TESTING VS CGMS TO EVALUATE CONTROL
IN T1DM
EIGHT-POINT TESTING ADVANTAGES
CGMS MONITOR ADVANTAGES
JCEM 2005 90 3387-3391
Children with T1DM n 200

• Similar Mean BGs
  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

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CONTINUOUS GLUCOSE MONITORING
OUTLINE

• Purpose
• Technologies
• Target Populations
• Accuracy
• Clinical Indications
• Outcomes
• Future Trends

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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

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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 ? to improve adherence

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ELEMENTS OF THERAPY THAT CAN BE ADJUSTED WITH CGM
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• Increase dose of mealtime insulin (1 of 8)
• 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
• Refer to ? to improve adherence

Type
Sabbah et al Diabetes 2000 49 (Suppl 1)
A393 Kaufman et al Diabetes Care 2001 24
2430-2434
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CONTINUOUS GLUCOSE MONITORING
OUTLINE

• Purpose
• Technologies
• Target Populations
• Accuracy
• Clinical Indications
• Outcomes
• Future Trends

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OUTCOMES TRIALS OF CGM STUDY DESIGNS AND
ENDPOINTS

• Six RCTs 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

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IMPROVED BG CONTROL WITH REAL TIME CONTINUOUS
GLUCOSE MONITORING USING AN IMPLANTED SENSOR
BLINDED TESTING vs REAL TIME ACCESS Time spent
Hypoglycemic (lt 55 mg/dl) Decreased 47 Time
spent Hyperglycemic (gt 241 mg/dl ) Decreased
25
10 8 6 4 2 0
BLINDED TESTING
REAL TIME ACCESS
Time Spent (hrs/day)
40 - 55 56 - 80 81 140
141 240 241 - 400
Glucose Range (mg/dl)
Diabetes Care. 200427734-8
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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
7440-447
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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
7440-447
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CONTINUOUS GLUCOSE MONITORING
OUTLINE

• Purpose
• Technologies
• Target Populations
• Accuracy
• Clinical Indications
• Outcomes
• Future Trends

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MEDTRONIC MINIMED PARADIGM SENSOR AUGMENTED
SYSTEM
CONTINUOUS REAL TIME SENSOR
TRANSMITTER
COMBINED MONITOR AND INSULIN PUMP
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MONITOR
SENSOR
SUTURES
CABLE
Diabetes Technol Ther 2002 4 305-312
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J Feline Med Surg 2005 7 53-62
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J Feline Med Surg 2005 7 53-62
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J Feline Med Surg 2005 7 53-62
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J Feline Med Surg 2005 7 53-62
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J Feline Med Surg 2005 7 53-62
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J Feline Med Surg 2005 7 53-62
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CONTINUOUS GLUCOSE MONITORING MEANS MORE BLOOD
GLUCOSE DATA
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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