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GLUCOWATCHGLUCOWATCH®® G2™ G2™

BIOGRAPHERBIOGRAPHERH. PETER CHASE, MDH. PETER CHASE, MD

I)I) INTRODUCTIONINTRODUCTION

II)II) ACCURACY DATAACCURACY DATA

III)III) HOME PILOT TRIALHOME PILOT TRIAL

IV)IV) DIRECNET STUDY GROUPDIRECNET STUDY GROUP

V)V) SUMMARYSUMMARY

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GlucoWatchGlucoWatch®® G2™ G2™ BiographerBiographer

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GlucoWatchGlucoWatch®® G2 G2™™ Biographer Biographer (GW2B)(GW2B)

• Measures interstitial glucose extracted by reverse iontophoresis

• Requires a single calibration value following the 2-hour warm-up period

• Glucose readings every 10 minutes for 13 hours

• Values range from 40 to 400 mg/dL

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GlucoWatch G2 BiographerGlucoWatch G2 Biographer

INTRODUCTIONINTRODUCTION

i) Second generation model (i) Second generation model (G2B)G2B)

ii) Warm-up 2 hours ii) Warm-up 2 hours enter BG value enter BG value

iii) Reverse iontophoresis: AAA batteryiii) Reverse iontophoresis: AAA battery

iv)iv) Pulls interstitial fluid (including glucose) Pulls interstitial fluid (including glucose) into gel discs in Auto Sensorinto gel discs in Auto Sensor

v) Readings as often as every 10 min for up v) Readings as often as every 10 min for up to 13 hrs (max = 76 readings; Ave = 55)to 13 hrs (max = 76 readings; Ave = 55)

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INTRO: INTRO: G2BG2B

vi) Numerous data integrity checks are vi) Numerous data integrity checks are performed that monitor environmental performed that monitor environmental factors (temperature, sweating), sensor factors (temperature, sweating), sensor function, and performance. If the reading function, and performance. If the reading fails the data integrity checks, it is skipped fails the data integrity checks, it is skipped because the value may be incorrect.because the value may be incorrect.

vii) The G2 Biographer averages the reading vii) The G2 Biographer averages the reading obtained in the most recent cycle with the obtained in the most recent cycle with the reading obtained in the previous 10 minute reading obtained in the previous 10 minute cycle.cycle.

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The Automatic Monitoring Process

* 3 min glucose collection † 7 min glucose measurement

TIME

INTERNAL MEASURE

DISPLAYED READING

TIME

DURATION †7min*3 min

127 mg/dl 109 mg/dl 101 mg/dl 90 mg/dl

3:40 pm 118 mg/dl

3:20 pm 3:30 pm 3:40 pm 3:50 pm 4:00pm

3:20 pm 3:30 pm 3:40 pm 3:50 pm 4:00pm

4:00 pm 96 mg/dl

3:50 pm 105 mg/dl

Glucose readings continue

to be averaged

and displayed every 10 minutes

†7min*3 min †7min*3 min †7min*3 min

A “running average” provides readings every 10 minutes

TIME

INTERNAL MEASURE

DISPLAYED READING

TIME

DURATION

TIME

INTERNAL MEASURE

DISPLAYED READING

TIME

DURATION †7min*3 min †7min*3 min

127 mg/dl 109 mg/dl 101 mg/dl 90 mg/dl

3:40 pm 118 mg/dl

3:20 pm 3:30 pm 3:40 pm 3:50 pm 4:00pm

3:20 pm 3:30 pm 3:40 pm 3:50 pm 4:00pm

4:00 pm 96 mg/dl

3:50 pm 105 mg/dl

Glucose readings continue

to be averaged

and displayed every 10 minutes

†7min*3 min †7min*3 min †7min*3 min †7min*3 min †7min*3 min †7min*3 min

A “running average” provides readings every 10 minutes

Following a 2 Hour Warm-up and Calibration

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INTRO: G2BINTRO: G2B

vii) Alarms for: vii) Alarms for:

• • Hypo/hyper-glycemia (level set by user)Hypo/hyper-glycemia (level set by user)

• • Pending low in next 10-20 minutesPending low in next 10-20 minutes

• • Low or drop 30 minutes prior to Low or drop 30 minutes prior to detection detection of sweatof sweat

viii) Up or down arrows with change of 9mg/dlviii) Up or down arrows with change of 9mg/dl

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INTRO: INTRO: G2B: Major uses:G2B: Major uses:

i) Nocturnal hypoglycemiai) Nocturnal hypoglycemia

ii) Postprandial hyperglycemiaii) Postprandial hyperglycemia

iii) Hypoglycemic unawarenessiii) Hypoglycemic unawareness

iv) Gestational diabetesiv) Gestational diabetes

v) Type 2 diabetesv) Type 2 diabetes

vi) Other (e.g. Glycogen Storage Dis.)vi) Other (e.g. Glycogen Storage Dis.)

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GG2B: Positives:2B: Positives:

i)i) Detection of lows – particularly Detection of lows – particularly during the nightduring the night

ii)ii) Making aware of post-prandial highsMaking aware of post-prandial highs

iii)iii) “ “Watchdog” effectWatchdog” effect

iv)iv) Detecting “patterns”Detecting “patterns”

v)v) e-mailing data to MD or RNe-mailing data to MD or RN

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INTRO: GINTRO: G2B:Negatives:2B:Negatives:

i)i) Skipped readings with sweatingSkipped readings with sweating

ii)ii) Not always awakening for alarmNot always awakening for alarm

iii)iii) Not waterproofNot waterproof

iv)iv) Skin itching, blisters, (remove sensor with Skin itching, blisters, (remove sensor with UnisolveUnisolve®) (adults > youth)®) (adults > youth)

v)v) Won’t take first calibration (6%) due to Won’t take first calibration (6%) due to sweat, rapid BG change, weak signalsweat, rapid BG change, weak signal

vi)vi) Other skipped readingsOther skipped readings

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Side EffectsSide Effects

• No serious skin reactions

• No other problems

Moderate Irritationexample

Mild Irritationexample

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GlucoWatch FunctionGlucoWatch Function• Sensor calibration

– 1st attempt 94%– 2nd attempt 2%– Failed 4%

• Sensor lifespan*– ≥14.5 hours (Full) 81%– 10.0 to 14.5 hours 3%– 6.0 to 10.0 hours 6%– <6.0 hours 10%

• Of 14,232 possible GW2B measurements– 17% were skipped

• Excludes sensors stopped early for logistical reasons.

DirecNet Data

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Analyzer FeaturesAnalyzer FeaturesAnalyzer FeaturesAnalyzer Features

Analyzer alert settings

may differ from

Biographer settings Biographer DOWN alerts

Trend arrows not shown on Analyzer screen

220 mg/dL

160 mg/dL

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Part II: ACCURACY STUDIES Part II: ACCURACY STUDIES IN CHILDRENIN CHILDREN

1)1) Eastman RC, Chase HP, Buckingham B, Eastman RC, Chase HP, Buckingham B, et al. Pediatric Diabetes 3:127, 2002et al. Pediatric Diabetes 3:127, 2002

i)i) Clinic settingClinic setting

ii)ii) 3 First GW Biographers/subject3 First GW Biographers/subject

iii)iii) Multiple wear sitesMultiple wear sites

iv)iv) Compared to HemoCueCompared to HemoCue®® meter meter

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ACCURACY STUDIES IN ACCURACY STUDIES IN CHILDRENCHILDREN

2)2) DirecNet Study GroupDirecNet Study Group

i)i) InpatientInpatient

ii) 2 – 4 Gii) 2 – 4 G2B2Bs/subjects/subject

iii) Upper and lower arm sitesiii) Upper and lower arm sites

iv) Compared to hospital lab BGiv) Compared to hospital lab BG

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ACCURACY STUDIES IN ACCURACY STUDIES IN CHILDRENCHILDREN

GWBGWB GG2B2B

(Pediatric Diabetes(Pediatric Diabetes)) (DirecNet(DirecNet))

SettingsSettings Clinic (14 Hr)Clinic (14 Hr) Inpatient (26 Hr)Inpatient (26 Hr)

No. YouthNo. Youth 66 (11.9 yrs) 66 (11.9 yrs) 89 (9.9 yrs) 89 (9.9 yrs)

SensorsSensors 198 198 285 285

Comparisons Comparisons 1313 1313 3,659 3,659

Skipped Readings: 14%Skipped Readings: 14% 17% 17%

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ACCURACY STUDIES IN ACCURACY STUDIES IN CHILDRENCHILDREN

GWBGWB GG2B2B(Pediatric Diabetes(Pediatric Diabetes)) ((DirecNet)DirecNet)

i)i) Mean Difference*Mean Difference* -17 mg/dl-17 mg/dl 2.1 mg/dl 2.1 mg/dl

ii)ii) Absolute Difference**Absolute Difference** 34 mg/dl34 mg/dl 30.8 mg/dl30.8 mg/dl

iii) MARD***iii) MARD*** 21% 21% 22% 22%

*Mean Difference = *Mean Difference = Sensor value – Lab valueSensor value – Lab value**Absolute Difference= Absolute value of difference**Absolute Difference= Absolute value of difference**MARD = **MARD = Mean Absolute Relative Difference =Mean Absolute Relative Difference =

Sensor value – lab valueSensor value – lab value x 100 x 100 lab valuelab value

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ACCURACY STUDIES IN ACCURACY STUDIES IN CHILDRENCHILDREN

GWBGWB GG2B2B

((Pediatric DiabetesPediatric Diabetes))((DirecNetDirecNet))

iv) Correlation Coef.iv) Correlation Coef. 0.82 0.82 0.86 0.86

v) Consensus Errorv) Consensus Error 97%97% 97% 97%

Grid (A + B)Grid (A + B)

vi) Paired Values vi) Paired Values 76%76% 74% 74%

within 20%within 20%

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ACCURACY STUDIES IN ACCURACY STUDIES IN CHILDREN:HYPOGLYCEMIACHILDREN:HYPOGLYCEMIA

Overnight Hypoglycemia (<70mg/dl)Overnight Hypoglycemia (<70mg/dl)

1)1) 18 episodes by G2B (DirecNet)18 episodes by G2B (DirecNet)

2) 10 episodes = Lab glucose matched2) 10 episodes = Lab glucose matched

8 episodes = not confirmed8 episodes = not confirmed

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0405BG-44

0534BG-54

13 yo on CSIIBasal rates had been erased Accidentally put in rates 12 hours off

True lows detected by alarm

4/7 4/8 4/9 4/10

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BG 177

13 yo on CSII withcorrect/new basal rates in placeHbA1c = 7.4%

4/12 4/13

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Part III: HOME PILOT STUDYPart III: HOME PILOT STUDY

Use of the GlucoWatch Biographer (GWB) in Use of the GlucoWatch Biographer (GWB) in Children with Type 1 Diabetes (T1DM) Children with Type 1 Diabetes (T1DM)

Chase HP, Roberts MD, Wightman C, Chase HP, Roberts MD, Wightman C, Klingensmith G, Garg SK, et al. Pediatrics Klingensmith G, Garg SK, et al. Pediatrics 111:790-794,2003.111:790-794,2003.

Objective: To determine the usefulness of the Objective: To determine the usefulness of the GWB for: 1) detection of hypoglycemia GWB for: 1) detection of hypoglycemia 2) improving glucose control in children and 2) improving glucose control in children and adolescents with T1DM in a home environment adolescents with T1DM in a home environment

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40 Randomized Study Subjects40 Randomized Study Subjects• Age 7-17 years; mean = 12.4 yrsAge 7-17 years; mean = 12.4 yrs• Type 1 diabetes 1 yr (mean = 6.3 yrs)Type 1 diabetes 1 yr (mean = 6.3 yrs)• HbA1c >8% on 2 occasions during prior 6 monthsHbA1c >8% on 2 occasions during prior 6 months• Absence of clinically significant disease or condition Absence of clinically significant disease or condition

that would interfere with participation in the trialthat would interfere with participation in the trial• No history of severe hypoglycemia for 6 months No history of severe hypoglycemia for 6 months

preceding entry into the trial (many had prior history preceding entry into the trial (many had prior history of severe hypoglycemia >6 months before study)of severe hypoglycemia >6 months before study)

• Willingness to be randomly assigned to standard care Willingness to be randomly assigned to standard care or standard care with Biographer monitoring 4 or standard care with Biographer monitoring 4 times/week times/week

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Study PlanStudy Plan

• Randomization to two treatment groupsRandomization to two treatment groups– standard care in the home environment standard care in the home environment – standard care in the home environment with standard care in the home environment with

GlucoWatch Biographer monitoringGlucoWatch Biographer monitoring• Biographer alerts set to 70 and 300 mg/dLBiographer alerts set to 70 and 300 mg/dL• Confirmation of alerts by conventional Confirmation of alerts by conventional

blood glucose monitoringblood glucose monitoring• Both groups: weekly review of SMBG Both groups: weekly review of SMBG

data (data (±GWB data) and a phone call from ±GWB data) and a phone call from HPCHPC

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Outcome MeasuresOutcome Measures

• HbA1c measured at baseline, and at 1 and 3 HbA1c measured at baseline, and at 1 and 3 months (DCA-2000)months (DCA-2000)

• Hypoglycemia events determined Hypoglycemia events determined

- Biographer alert = 70 mg/dl- Biographer alert = 70 mg/dl

- Hypoglycemic event = SMBG <70 mg/dl- Hypoglycemic event = SMBG <70 mg/dl

• SurveysSurveys– Fear of HypoglycemiaFear of Hypoglycemia– Quality of Life (DCCT)Quality of Life (DCCT)

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GWB: HOME USEGWB: HOME USE

WeekWeek 1-41-4 5-85-8 9-139-13

#Uses/wk#Uses/wk 4.1 4.1 3.7 3.7 3.0 3.0

%Hi BG* %Hi BG* 4.7 4.7 2.5 2.5 3.1 3.1

%Lo BG* %Lo BG* 14.214.2 16.616.6 16.5 16.5

*GWB readings*GWB readings

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Frequency of Hypoglycemia Frequency of Hypoglycemia Home Meter Blood Glucose Home Meter Blood Glucose << 70 mg/dL 70 mg/dL

0

0.5

1

1.5

2

2.5

3

3.5

Control Group Biographer GroupWhile Not Wearing

Biographer

Wearing Biographer

Eve

nts

/100

Per

son

Ho

urs

24 Hours6AM-10PM10PM-6AM

*

*

* p<0.05* p<0.05 versusversus controlcontrol

*

*

*

*

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Median HbA1c by Group vs. TimeMedian HbA1c by Group vs. Time

8.99.0

8.5 8.6

8.68.4

8.3 8.4

8.6

8.9

7

7.5

8

8.5

9

9.5

10

-1 0 1 2 3 4 5 6 7 8 9 10

Month of Study

HbA1C

Control

GW group

Randomized Trial Observation Phase

* p<0.05 versus control group

*

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Summary and ConclusionsSummary and Conclusions• Biographer use was well tolerated in the home Biographer use was well tolerated in the home

environmentenvironment• HbA1c was significantly lower (p<0.05) in the HbA1c was significantly lower (p<0.05) in the

Biographer treatment group compared to the control Biographer treatment group compared to the control group after 3 months of treatment group after 3 months of treatment

• Biographer users detected significantly more Biographer users detected significantly more hypoglycemia during the day and night than non-hypoglycemia during the day and night than non-usersusers

• The Biographer is useful for improving glucose The Biographer is useful for improving glucose control and detecting hypoglycemia in children and control and detecting hypoglycemia in children and adolescents with type 1 diabetesadolescents with type 1 diabetes

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Using DCCT data, a decline in HbA1c from 9.0 to 8.4 for 100 subjects for a lifetime would:

1) Prevent severe eye disease in 20 people

2) Prevent blindness in 6 people

3) Prevent gross kidney damage in 20 people (8 needing transplants)

4) Prevent 6 cases of neuropathy

Reduction in Complications: Eastman RC, Chase HP and Leptien AD

Pediatric Diabetes 4:82-86, 2003

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Slept through alarmsPicked up low at calibration

0733BG 138

2 GWB tracingsPre-teen girlIDDM x 5yrsPatient at slumber party

2008BG 56

4/18 4/194/150805BG 305

1059BG 259

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4/25 5/2

1736bg350

1511 Piano teacher gave candy but did not test

1357bg175

Pre-teen girlIDDM x 5yrs

0908bg245

1009bg45

Went to officeNo snack given

Low alarm at sametime as last week (1530)No bg test

1759bg215

1151bg80

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Part IV: DIRECNET STUDY Part IV: DIRECNET STUDY GROUPGROUP

DIDIabetes abetes REREsearch in search in CChildren hildren NETNETworkwork

i)i) NIH funded collaborative study group NIH funded collaborative study group (NICHD and NIDDK)(NICHD and NIDDK)

ii)ii) 5 Centers: Denver, Iowa, Nemours (FL), 5 Centers: Denver, Iowa, Nemours (FL), Stanford and Yale.Stanford and Yale.

+ Coordinating Center: = Jaeb Center for + Coordinating Center: = Jaeb Center for Health Research, Tampa, FLHealth Research, Tampa, FL

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DIRECNET STUDY GROUPDIRECNET STUDY GROUPiii)iii) Objective = to critically evaluate the Objective = to critically evaluate the

clinical usefulness of current and future clinical usefulness of current and future glucose sensors in youth with T1DM.glucose sensors in youth with T1DM.

iv)iv) Initial inpatient study= accuracy of G2B Initial inpatient study= accuracy of G2B and of CGMS. Abstracts #156 OR,and of CGMS. Abstracts #156 OR,

#432-P and #387-P .#432-P and #387-P .

v) Next study: Similar to the GWB Pilot v) Next study: Similar to the GWB Pilot Trial done in Denver, but with 200 Trial done in Denver, but with 200 children x 6 months. children x 6 months.

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Part V: SUMMARYPart V: SUMMARYPurpose of the GlucoWatch Biographer:Purpose of the GlucoWatch Biographer:

To detect trends and to track patterns in To detect trends and to track patterns in glucose levels as a supplement to SMBG (not to glucose levels as a supplement to SMBG (not to replace SMBG). replace SMBG).

ConclusionConclusion::

The level of accuracy is sufficient for detecting The level of accuracy is sufficient for detecting trends. Pilot data shows the GWB is useful for trends. Pilot data shows the GWB is useful for improving glycemic control and detecting improving glycemic control and detecting hypoglycemia in children and adolescents with hypoglycemia in children and adolescents with T1DM.T1DM.