Post on 06-Apr-2018
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Glucose Monitorsand Glucose
Sensing
Applications for the21st Century and Beyond
The Quest for the Closed Loop
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WhyGlucose Sensing??
More real time assessment
Ability to detecthypoglycemia andhyperglycemia atodd times
Better administration and correlation of insulindosagesless guessing
Mayuncover eating disorders and other issuesrelated to stress, diet and exercise
Patient compliance with monitoring an issue manydo not like to poke fingers or other sites so often.Pain and discomfort, lack of blood obtained, loststrips, etc.
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WhyGlucose Sensing??
Goal Closing the Loop
An artificialpancreas
Provide accurate and specific data to control glucoselevels many individuals keep blood glucoses higherthan optimal to avoidhypoglycemia
Fear ofhypoglycemia in the middle of the night notwaking up
Take the worry out of diabetes treatment Type 1patients in particular; parents, children andphysicians
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Optimal Conditions for GlucoseMeasurement
Immediate availabilityof results andmeasurements
High frequencyof measurements Measurements every2-5 minutes would be ideal
Ability to detect rapid rise or decline is necessity
Need quick signal stabilityafter initiation or
placement Stabilityoverprolongedperiod of time (>3
days necessary)
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Case for Glucose Sensing Recent
Studies
23 patients participated hospitalized andambulatory
Both Type 1 and Type 2 individuals Study lasted 72hours (key time limit)
75 capillarysamples were obtained
Microdialysis subcutaneous monitoring system used
microdialysis catheter; extracorporeal electrochemicalsensor
signal needed to be corrected for fluid transportation 31minutes (lag time)
Diabetes Care 24: 1696, 2001 Jungheim et al
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Results of Studyand Conclusions
Studies showed no limitations to patients activityandonlymild skin irritation
Difference between SCGM and capillaryglucose was~ 7-9 % over the full range (meter differences can beas much as 10 15 %)
Hypoglycemia was detected with SCGM but wasmissed 58-71% of the time byspot capillary
measurements. This despite 5-7 or moremeasurements per day
No decay in sensitivityover the 72hourperiod
SCGM could be useful in glucose control & therapy
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Glucose Monitor Development
Race for the Closed LoopSystem, Painless,
Continuous and the Gold
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Types of Monitors in Development
Minimally invasive interstitial devices
Transcutaneous optical devices
Electrochemical sensing devices
subcutaneous
Implantable
Implantable optical sensors
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Physiologyof Interstitial Fluid
Extracellular fluid and flows through thecapillarywalls
Glucose levels in interstitial fluid bloodglucose
Lag time could be ~ 10 to 20 minutes
Perspiration, oils and other environmental
factors (lotions, etc.) can dilute themeasurements and adverselyaffect theresults as sample size is small
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Interstitial Glucose Sensor
Glucowatch Biographer 2
Cygnus Corp: www.glucowatch.com
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Glucowatch Schematic
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Advantages and Limitations ofGlucowatch System
Non-invasive
Detects trends andpatternsin glucose levels
readings every10 minuteswith up to 6/hour = 72readings/monitoring session
Alertspatients to rapidschanges in glucose levels
Lesspainful??
Computer download capable ? Abilityto determine insulin
or medication adjustmens
2hour warm-up period
Calibration is needed witheach sensor use
Skin irritation with sensorand adhesive
Skipped readings possiblewith rapid changes intemperature,perspirationand if system is bumped or
dislodged If several readings in a row
are skipped, the systemmust be recalibrated
Advantages Limitations
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Use of Glucowatch Biographer 2
Intended for use in adults and children todetect trends andpatterns in glucose levels
To detect and assess hyperglycemic andhypoglycemicpatterns to help facilitateadjustments in therapy
To be used as an adjunctive device, tosupplement, not replace, information obtainedfrom traditional and standardhome glucosemonitoring devices!
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Glucowatch Biographer 2
Draws out interstitial fluid byreverse electroionophesis
Glucose interacts with Glucose Oxidase Membrane to formhydrogenperoxide which interacts with biosensorproducing low
electric current which is measured and analyzed Glucowatch 2
Cost $599 to $799
Rebates can save $200 to $300
Auto sensor
Disposable transdermalpad
Changed every14-15hours
~$4 each (2 needed) for each recording session
Concerns with calibration time, risk of infection and irritation
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Glucose Collection with the GlucoWatchG2Biographer Uses Reverse Iontophoresis
Only small compounds pass
through the skin.
No proteins (e.g., hemoglobin)in the extract
Glucose is collected at thecathode.
Interfering species (ascorbateand urate) collected at anode
The charge and size
exclusion properties ofreverse iontophoretic
extraction will lead to a very
clean sample.Cl-, (ascorbate, urate)
Na+, neutral species(i.e., glucose)
CATHODECATHODE ANODEANODE
Data on file, Cygnus Inc. 2002.
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The Automatic Monitoring Processwith the GlucoWatchG2 Biographer *
3 min glucose collection 7 min glucose measurement
107107mg/dLmg/dL
* Following a 2 hour warm-up and calibration
A RUNNING AVERAGE PROVIDES READINGS EVERY 10 MINUTESA RUNNING AVERAGE PROVIDES READINGS EVERY 10 MINUTES
InternalInternalmeasuremeasure
DisplayedDisplayedreadingreading
3 min3 min 7 min7 min 3 min3 min 7 min7 min 3 min3 min 7 min7 min 3 min3 min 7 min7 min
105105mg/dLmg/dL118118mg/dLmg/dL
127127mg/dLmg/dL
109109mg/dLmg/dL
101101mg/dLmg/dL
112112mg/dLmg/dL
3:10 pm3:10 pm 3:20 pm3:20 pm 3:30 pm3:30 pm 3:40 pm3:40 pmTIMETIME
Data on file, Cygnus Inc. 2002.
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0
50
100
150
200
250
300
350
400
0 100 200 300 400
One Touch Profile
BiographerReadings(mg/d
L)
E
D
B
B
E
C
A
C
D
2996 paired pointsSlope = 0.95, Intercept = 12.6 mg/dL, r = 0.80
GlucoWatchBiographerHome Study Clarke Error Grid Analysis
One TouchProfile* Glucose Readings (mg/dL)
ZONE
A
B
C
D
E
Biographer
Readings
60%
34%
1%
4%
0.1%
(A) Accurate. Biographer within 20% of finger-sticktest result (or both below 70 mg/dL)
(B) Acceptable. Difference greater than 20% butBiographer would not lead to baddecision
(C) Might cause an over-correction of normalglucose levels. Finger-stick blood glucose test
result in the normal range, but Biographer reading ishigh or low.
(D) Failure to detect a high or low glucose level.
Biographer reading in the normal range, but finger-
stick blood glucose test result is high or low
(E) Treatment error could occur. Biographerreading low when finger-stick blood glucose is high
or Biographer reading high when finger-stick is low.
Data on file, Cygnus Inc. 2002.* One TouchProfile Johnson andJohnson, New Brunswick New Jersey
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Studies of Glucowatch vs. Meters
Differences between interstitial fluid and bloodglucose
Time lag: 17.2 minutes 7 minutes with Glucowatch
Time lag: 13 minutes with most blood glucose meters
With glucose increasing, changes were less asmeasured byGlucowatch as compared with blood
With glucose decreasing, changes were greater as
measured byGlucowatch as compared with blood ormeters
Conclusion: possible false hyperglycemia and falsehypoglycemia if taken unilaterally
Kulcu et al:
ADA Meeting2002
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SpectRx Glucose Sensing System
Transdermal Biophotonic System
Fluid is collected through micropores
Laser system used on the outer layer of skin Measured in a patch which contains a glucose sensor
Clinical trials are ongoing
Is not FDA approved at this time
Still similar to Glucowatch in that itprovidesinformation on trends and not necessarily real-timefor treatment adjustments
SpectRx website: www.spectrx.com
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SpectRx Glucose Sensing System
Laserdevice on the skin surface
Patch with sensor system embedded
www.spectrx.com
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Preliminarydata with SpectRx ISFSystem
www.spectrx.com
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Preliminarydata with SpectRx ISFSystem
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Pendragon Glucose Sensing System
Uses electromagneticwaves
Attached to lowerforearm similar to theGlucowatch
Performsmeasurements every
minute but averagingoccurs
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Pendragon Glucose Sensing System
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Recent Studywith PENDRA
15 individuals without diabetes
Changes in microcirculation of the arms resulted invarying glucose values
Temperature changes, other environmental issueshad to address via a complex calibration procedure
Conclusions: Need to fix device appropriately to arm to avoid
possible variations Needs extensive physician and patient training to
operate
Needs further studies prior to any extensive use in theclinical setting
Diabetes Technologyand Therapeutics 6:435, 2004
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Electrochemical Glucose Sensors
CGMS
TGMS
DexC
O
M
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Continuous Glucose MonitoringSystem--CGMS
Basic Premise: Glucose + Oxygen = Gluconic Acid +H2O2
Reaction is submitted to an electrical current which isproportional to the glucose concentration which is
measured
Enzymatic or Electrochemical Sensors are implantedin the subcutaneous tissue (under the skin)
Similar to the catheters used in insulin pump therapy
Short term use atpresent; reliability just 48 to 72hours
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Medtronic (MiniMed) CGMS System
Two Views of CGMS
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Mechanism of Action of CGMS
Enzymatic Reaction is measured by sensor in IF through skin
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CGMS System
Sensor is percutaneous an ~1mm in diameter
Measures an average glucose value every5minutes and is stored in the monitor
Hard wired system; worn externally
Requires calibration at 4-5 times per day, otherwisedata is not able to be downloaded
Able to enter events on the monitor to assist withinterpretation of results
3 dayuse onlyat this time Not real timerequires return to physician office for
download and interpretation
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CGMS System
Problems with encapsulation tissue which can causeerrors in data collection
Anything implanted in the bodyover time becomes
covered with a protein layer initially and then a collagenlike layer
Encapsulation tissue is to protect the body from foreignobjects which maybe perceived as harmful and to isolatethe object chemically (ie.broken port in pulmonary
artery) This chemical isolation could decrease the sensitivityand
response time of electrochemical subcutaneous systemssuch as CGMS
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CGMSCGMS ReproducibilityStudyReproducibilityStudyMetzger, M. et al: Diabetes Care 25:1185, July2002Metzger, M. et al: Diabetes Care 25:1185, July2002
Self monitoring of glucosesSelf monitoring of glucosesseveral times per day will leaveseveral times per day will leavegapsgaps large excursions canlarge excursions canoccur without patientoccur without patientknowledgeknowledge
Hypothesis:Hypothesis: to test theto test thereproducibility of the CGMS inreproducibility of the CGMS inrealreal--life settinglife setting
CGMS may be a tool that couldCGMS may be a tool that could
alleviate this difficultyalleviate this difficulty System measures glucoseSystem measures glucose
concentration every 5 minutesconcentration every 5 minutesfor a 72 hour periodfor a 72 hour period
Preliminary StudyPreliminary Study performedperformedin Type 2 patientsin Type 2 patients
~ 150 separate glucose tracings~ 150 separate glucose tracings
Included healthy volunteers andIncluded healthy volunteers andpatients on only metforminpatients on only metformin
Correlated with frequent bloodCorrelated with frequent bloodglucose measurementsglucose measurements
Noted exceeding high incidenceNoted exceeding high incidenceof hypoglycemic events with noof hypoglycemic events with nosymptoms andsymptoms and notnot confirmed byconfirmed bysimultaneous blood glucosesimultaneous blood glucosemeasurementsmeasurements
Correlation coefficientCorrelation coefficient r=0.74r=0.74
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CGMSCGMS ReproducibilityStudyReproducibilityStudyMetzger, M. et al: Diabetes Care 25:1185, July2002Metzger, M. et al: Diabetes Care 25:1185, July2002
Real Life Study was undertaken to determine accuracyReal Life Study was undertaken to determine accuracy
and reproducibility of tracings utilizing the CGMS deviceand reproducibility of tracings utilizing the CGMS device
11 patients involved in the study11 patients involved in the study 6 had Type 1 diabetes6 had Type 1 diabetes
3 had Type 2 diabetes3 had Type 2 diabetes
2 healthy volunteers with no history of DM2 healthy volunteers with no history of DM
10 male, 1 female10 male, 1 female Placed on two glucose sensor devices simultaneously for aPlaced on two glucose sensor devices simultaneously for a
3 day period with usual normal activity3 day period with usual normal activity
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CGMSCGMS ReproducibilityStudyReproducibilityStudyMetzger, M. et al: Diabetes Care 25:1185, July2002Metzger, M. et al: Diabetes Care 25:1185, July2002
ProtocolProtocol Sensors were attached according to theSensors were attached according to themanufacturers instructionsmanufacturers instructions
Sensors were placed in the abdominal SQ tissue 4Sensors were placed in the abdominal SQ tissue 4--5 cm to5 cm to
the right or left of the umbilicusthe right or left of the umbilicus
Calibration and Initialization were performed and 1 hourCalibration and Initialization were performed and 1 hourwas elapsed before first capillary glucosewas elapsed before first capillary glucose
Meal times were recordedMeal times were recorded
Capillary glucoses were done immediately post meals,Capillary glucoses were done immediately post meals,during the night and early AMduring the night and early AM
Capillary glucoses were entered into the monitor within 5Capillary glucoses were entered into the monitor within 5minutes of determinationminutes of determination
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CGMSCGMS ReproducibilityStudyReproducibilityStudyMetzger, M. et al: Diabetes Care 25:1185, July2002EAMetzger, M. et al: Diabetes Care 25:1185, July2002EA
Download was done upon completion and analysis wasDownload was done upon completion and analysis wasperformed immediatelyperformed immediately
Anonymity was preservedAnonymity was preserved
Each day was divided into 8 time intervals according toEach day was divided into 8 time intervals according tothe meal times of the patientthe meal times of the patient
Classifications:Classifications:
A:A: SatisfactorySatisfactory
B:B: if all glucose values are between 80if all glucose values are between 80 150150 C:C: glucose > 150 during >1 hr., too lowglucose > 150 during >1 hr., too low
D:D: glucose < 70 during >30 minutes or impossible to evaluate dueglucose < 70 during >30 minutes or impossible to evaluate dueto technical reasonsto technical reasons
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CGMSCGMS ReproducibilityStudyReproducibilityStudyMetzger, M. et al: Diabetes Care 25:1185, July2002Metzger, M. et al: Diabetes Care 25:1185, July2002
D Classification was further subclassified:D Classification was further subclassified:
D1:D1:Low concordance between sensor and glucometer r < 0.8 orLow concordance between sensor and glucometer r < 0.8 or
the difference is too high (28%)the difference is too high (28%)
D2:D2:Insufficient number of meter glucose values entered forInsufficient number of meter glucose values entered for
calibrationcalibration
D3:D3: Strong midnight shift: usual sensor glucose values postStrong midnight shift: usual sensor glucose values post
midnight. Usually secondary to insufficient number of calibrationmidnight. Usually secondary to insufficient number of calibration
values.values.
Evaluations were analyzed by two different observersEvaluations were analyzed by two different observers
independently and concordance rates wereindependently and concordance rates were
determineddetermined
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CGMSCGMS ReproducibilityStudyReproducibilityStudy
Metzger, M. et al: Diabetes Care 25:1185, July2002Metzger, M. et al: Diabetes Care 25:1185, July2002
MeanMean sensor not recording glucose valuessensor not recording glucose values 46 classified in the D group and not46 classified in the D group and not use of sensor: 60.4use of sensor: 60.4 16.916.9
hours each patienthours each patient
432 single time intervals were initially evaluated432 single time intervals were initially evaluated 78 (18%) were discarded for technical reasons78 (18%) were discarded for technical reasons
32 due to interpretable32 due to interpretable
139 paired sets of data were available for sensor139 paired sets of data were available for sensor--sensorsensorcomparison.comparison.
92 from Type 1 patients92 from Type 1 patients
30 from Type 2 patients30 from Type 2 patients
17 from non17 from non--diabetes volunteersdiabetes volunteers
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CGMSCGMS ReproducibilityStudyReproducibilityStudy
Metzger, M. et al: Diabetes Care 25:1185, July2002Metzger, M. et al: Diabetes Care 25:1185, July2002
Concordance was seen in only 65% of the timeConcordance was seen in only 65% of the timeperiodsperiods
25% noted glucose levels too high in one sensor25% noted glucose levels too high in one sensor
and satisfactory in the otherand satisfactory in the other 9% noted glucose levels too low with satisfactory9% noted glucose levels too low with satisfactory
levels in the otherlevels in the other
1 case noted: sensor 1 showed hyperglycemia,1 case noted: sensor 1 showed hyperglycemia,
sensor 2 showed hypoglycemiasensor 2 showed hypoglycemia No difference between patients with DM and nonNo difference between patients with DM and non
DMDM
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CGMSCGMS ReproducibilityStudyReproducibilityStudy
Metzger, M. et al: Diabetes Care 25:1185, July2002Metzger, M. et al: Diabetes Care 25:1185, July2002
Conclusions:Conclusions:
Accuracy and reproducibility is lower thanAccuracy and reproducibility is lower than
previously thoughtpreviously thoughtDifferences were greatest between the 125 andDifferences were greatest between the 125 and
225 mg/dl range225 mg/dl range most important area inmost important area intreatment of patients with diabetes mellitustreatment of patients with diabetes mellitus
Correlation between two simultaneous sensorsCorrelation between two simultaneous sensorswas lower than that of capillary vs. sensor (r =was lower than that of capillary vs. sensor (r =0.84 vs. 0.90)0.84 vs. 0.90)
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CGMSCGMS ReproducibilityStudyReproducibilityStudy
Metzger, M. et al: Diabetes Care 25:1185, July2002Metzger, M. et al: Diabetes Care 25:1185, July2002
Conclusions:Conclusions:
35% clinically important discrepancies between35% clinically important discrepancies between
two simultaneous sensor tracingstwo simultaneous sensor tracings
Could result in incorrect clinical advice in 17%Could result in incorrect clinical advice in 17%
of patient casesof patient cases
@@
RESULTS OBTAINED IN REAL LIFERESULTS OBTAINED IN REAL LIFESITUATIONS MUST BE INTERPRETED INSITUATIONS MUST BE INTERPRETED IN
INDIVIDUAL CLINICAL TERMSINDIVIDUAL CLINICAL TERMS
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CGMSCGMS ReproducibilityStudyReproducibilityStudy
Metzger, M. et al: Diabetes Care 25:1185, July2002Metzger, M. et al: Diabetes Care 25:1185, July2002
Development of a reliable device for continuousDevelopment of a reliable device for continuous
glucose monitoring is of outmost importance inglucose monitoring is of outmost importance in
the treatment of diabetesthe treatment of diabetes Future endeavors in this area must be rigorouslyFuture endeavors in this area must be rigorously
evaluated in real life situations before releaseevaluated in real life situations before release
to the general publicto the general public
Rebuttal from MedtronicRebuttal from Medtronic concerns in the aboveconcerns in the above
study: software used was earlier version, devicestudy: software used was earlier version, device
was used for more than planned or approvedwas used for more than planned or approved
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Additional StudiesAdditional Studies----20032003
Armstrong and King: ADA Meeting 2003
11 subjects: 2 No Diabetes, 6 Type 1, 3 Type 2
Measured Glucoses with 1 Touch Ultra 7 times per day Wore 2 sensors (CGMS) concurrently for 3 days
Mean Sensor life: 67 hours
Used updated software
Found accuracy with newer software ~94% Most of differences between modalities within 10%
Sensor-sensor differences less than previous study
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Rebuttal to Metzger FindingsRebuttal to Metzger Findings
Expectations did not coincide with CGMS intended use
Study did not use Clarke error grid but was one ofsubjective assessment
Study did use updated software (Solutions 3.0)
Results are similar to those reported in the post-marketing studies (Diabetes Technology andTherapeutics, 2000)
CGMS is intended to supplement, not replace, bloodglucose information using standard monitoring devices
CGMS, when used with home monitoring devices andHbA1C values can help optimize clinical management
Mastrototaro and Gross; Diabetes Care 26:256 2003
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Rebuttal to Metzger FindingsRebuttal to Metzger Findings
Solutions 3.0 software resolves most of the 18% rate of
technical problems encountered in the study
Correction of the midnight shiftImprovement in the accuracy and reproducibility of
the downloads
Improvement in the agreement between sensor and
meter values
Mastrototaro and Gross; Diabetes Care 26:256 2003
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Rebuttal to Metzger FindingsRebuttal to Metzger Findings
CONCLUSIONS:
Results should be weighed against the
encouraging results and conclusions fromprevious and evolving reports and research
Appears that this is a work in progress andshould not be utilized as the sole clinical
indicator! should not be used at present as theonly source for change in treatment regimens
-Speakers judgment after reviewing literature
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Sample CGMS Reports
Daily Report of Blood Glucoses
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Sample CGMS Reports
Modal Time Reports Can be varied individually
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Sample CGMS Reports
Composite 3 day report for comparison
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Additional Studies Involving Children
Accuracyof Glucowatch 2 system and CGMS indetectinghypoglycemia
Multi-center study
Involved the Children in Diabetes ResearchNetwork
91 children enrolled
Ages 3-17
Patients were enrolled in a CRC-clinical researchcenter for 24 hours
Diabetes Care 27:722-726 2004
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Glucowatch 2 vs. CGMS
Patients used CGMS and Glucowatch 2 during eachadmission
1/3 patients started CGMS 48hours prior toadmission
1/3 patients started CGMS 24 hours prior toadmission
1/3 patients started CGMS on the dayof admission
Eachpatient used 2 sensors for the G-watch 2 duringthe study 2hour overlap
1 TouchUltra meter used as calibration and control
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Glucowatch 2 vs. CGMS
Samples: everyhour during the dayevery30 minutes during the night
Hypoglycemia induction test: samples obtained every5 minutes for 90 minutes
Adjustment of values for lag time: time involved insampling the interstitial fluid measuring glucose ascompared with blood
Glucowatch 2 Biographer 17.5 minutes
CGMS 2.5 minutes
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Glucowatch 2 vs. CGMS
Glucowatch 2
Biographer
~ 23 % of valueswere withinreference rangewhen glucoses were< 60 mg%
51% false alarmswere detected withuse
CGMSSystem
Both modified and
original sensorsnoted < 50%detection withinreference range (36and 48 %)
58% to 60% falsealarms weredetected with use
Results of Study
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StudyConclusions
Neither Glucowatch 2 nor CGMS is accurate in reportingglucose values in the hypoglycemic range
Accuracyof both devices is better when reference glucose
levels are >100 mg/dl
Neither device is appropriate at this time for real timedetection
Both systems are more likely to be of value in adjusting
bolus and basal insulin doses in patients with consistentlyelevated glucoses and A1C levels
The accuracyof these earlygeneration sensors is similarto the earlygeneration meters (circa 1970s-early 1980s)
M difi d H U f CGMS
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Modified Home Use of CGMSGuardian System
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Guardian Home System
Sensor can be set to alarm at certain levels bothhigh and low
Monitor can be placed up to 6 feet away; does not
have to be worn Monitor can store up to 21 days of data
Can be downloaded to personal computer
Still needs calibration similar to CGMS system
Alerts or alarms need to be verified with finger stickglucose
Cost is not set atpresent (~ $800- $1500 anticipated)
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Anticipated Sample Guardian Report
www.minimed.com
Reports similar to CGMSSystem
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Paradigm 522 System PatientUse
Consists of Glucose Sensor, Radio Transmitter andPump receiver
Abstractpresented at ADA 2004 (Orlando)
9 Patients involved; Ages 10-21, Type 1 DM
Used CSII
Did 4 Blood Glucoses/dayvia HGM
Wore 7 sensors during the 3 week trial
A1C levels decreased 0.3% Glucoses decreased average 20 mg%
Work in progress; Not available yet!!!
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Implantable Subcutaneous Systems
Enzyme electrode system
Electrochemical device
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DexCom Subcutaneous Sensor System
Implantable Sensordevice Pager monitoring system
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DexCom Subcutaneous Sensor System
Special bioprotective layerprevents foreign bodyreaction with sensor
Can measure glucoses ranging from 40 mg/dl to700 mg/dl (2.2-38.9 mmol/L)
Recalibration every20 days
160 180 day lifespan for sensor
Still need to do HGM 2-3 times/day to initiateglucose algorithm
Easily implanted in subcutaneous tissue
Can be accomplished as outpatientprocedure
Diabetes Care 27:734, 2004EndocrinologyClinics NA 33:175, 2004
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Therasense Navigator System
Interstitial System Wireless system Needs calibration 1-2
times per day Readings every1-2
minutes conceptualized High and low glucose
alarms to be
incorporated Currentlyexperimental Companynot
distributing info at thistime
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Near Infrared Spectroscopy
Non-invasive techniques
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Sensys Medical Systems
EndocrinologyClinics ofNA 33: 163-173 2004
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Sensys Medical Systems
Measures glucose non-invasively via NIRspectroscopy
Device weighs less than 1.5pounds
Fiber-optichead secured to the forearm Still needs HGM for calibration
Various components such as sweat, fat, etc. caninterfere with efficacy
Can use either volar or dorsal aspects of the forearm Uses a rechargeable battery
Studies ongoing withpatient use
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Open-flow Microperfusion Systems
ADICOL Project-Disetronic/Roche
Advanced Insulin Infusion with aControl Loop
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ADICOL Project Disetronic /Roche
Inserted into thesubcutaneous adiposetissue
Double lumen catheter
Acquires glucosereadings every30minutes
Goal subcutaneousglucose sensing/insulindeliverysystem
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ADICOL Project Disetronic /Roche
Large bore catheter
Readings only
every 30 minutes
Small study sample
with patient use
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Infrared Spectroscopy
Animas CorporationContinuous GlucoseMonitoring System
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Infrared Spectroscopy
Infrared light is absorbed bymolecules
Each molecule has its own spectra (absorptioncharacteristic)similar to its own footprint
Theoretically-bymeasuring the absorbed light vs.wavelength, one could delineate the species andconcentration
In reality this is difficult
Water absorbs most IR light
Blood scatters light
Different species overlap in their spectra or footprint
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Sketch of Animas Sensor
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ImplantedExtravascular Sensor Head
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Early Animas Sensor Head
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C l i ( 2 94) b i l
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0
50100
150
200
250300
350
400
450
0 50 100 150 200 250 300 350 400 450
Concentration (mg/dl)Determined by Glucometer
C
oncentr
ation(m
g/dl),
usin
g
O
pticalM
ean
Correlation (r2=.94) between optical
and conventional means (500 people)
I i M t i D
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0
50
100
150
200
250
300
350
Time
Glu
coseConcentration(mg/dl)
In vivo Measurements in Dog:
Glucometer and Sensor Head vs. Time
Glucometer
Sensor
A i C i S
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Animas Continuous System
Has designed and built short term prototype anddemonstrated stability in animals
Need to miniaturize system Laser diodes under development
Telemetry developed
Electronics being modified and mostlydeveloped
Clinical trials in humans projected to start 2005 or
2006. Projected as earlyPhase 2 studies withsites to be determined. No pediatricpatients tobe involved!
Advantages of
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Advantages of
Animas Monitor
y Provides continuous reading of blood glucose withoutpatient intervention
y Measures glucose in bloodas opposed to some other body
fluid, e.g. interstitial fluid, ocular fluid
y The encapsulation/ fibrin tissue has no effect on monitoraccuracy
y Provides direct access to blood, obviating loss and
interference associated with light transmission through
intervening tissues.
y Sensor stays implanted for at least 5 years, limited by
battery life. No percutaneous wires or cables are utilized.
What is the Goal of These
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What is the Goal of TheseTechnologies?
Development of a ClosedLoop System TheArtificial Pancreas
*Put the Endocrinologist intoEarlyor PermanentRetirement
Have We Achieved
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Have We Achieved
Goal???
Not Yet!!
Wh t H B A li h d?
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What Has Been Accomplished?
New Technology to determine patterns and facilitatechanges in therapy
Prototypes for long term glucose monitoring
More awareness bypatients and families regardingthe importance of intensive therapyand tight controlof blood glucoses
Consumer driven research for an artificialpancreas
More physicians are implementing intensive therapywith technology now available to compliment thetreatment
Fi l Th ht
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Final Thoughts
No system atpresent is appropriate for a closed loopsystem
No system developed atpresent can replace the
finger stick monitor for real time glucose valuesand treatment decisions
Presently, there are 50+ companies or individualsattempting to develop a continuous glucosemonitoring system
EVENTUALLY, THAT DAYWILLARRIVE!!WHEN, ONEONLYKNOWS!