Continuous Glucose Monitoring System (CGMS) by zwk61917

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									  Continuous Glucose
Monitoring System (CGMS)
           Chien-Wen Chou MD
  Division of Endocrinology & Metabolism
          Chi-Mei Medical Center
               30 June 2006
 Continuous Glucose Monitoring
            System
• A continuous glucose monitoring system (CGMS)
  is an FDA-approved device that records glucose
  levels throughout the day and night.
• only approved device -- Medtronic's MiniMed
  device-can provide up to 288 glucose
  measurements every 24 hours.
• The system is used to measure an average
  blood glucose for up to 3 days, while the person
  with diabetes continues daily activities at home
 How Does the Device Work? (1)
• First, a tiny glucose-sensing device called a
  "sensor" is inserted just under the skin of your
  abdomen.
• Tape is used to hold it in place.
• The sensor measures the level of glucose in the
  tissue every 10 seconds and sends the
  information via a wire to a pager-sized device
  called a "monitor" that you attach to a belt or the
  waistline of your pants.
• The system automatically records an average
  glucose value every 5 minutes for up to 72 hours.
 How Does the Device Work? (2)
• Results of at least four finger stick blood glucose
  readings taken with a standard glucose meter and taken
  at different times each day are entered into the monitor
  for calibration.
• Any insulin taken, exercise engaged in, and meals or
  snacks consumed are both entered into a paper-based
  "diary" and recorded into the monitor (by pushing a
  button to mark the time of the meals, medication,
  exercise, and other special event you wish to record).
• After 3 days, the sensor is removed at the doctor's office
  and the information stored in the CGMS is downloaded
  into a computer.
• The information will be presented as graphs or charts
  that can help reveal patterns of glucose fluctuations.
    When Is the Device Used?
• The CGMS is not intended for day-to-day monitoring or
  long-term self-care and it is not a replacement for
  standard blood glucose monitoring.
• The main advantage of continuous glucose monitoring is
  that it can help identify fluctuations and trends that would
  otherwise go unnoticed with standard HbA1c tests and
  intermittent finger stick measurements.
• For example, the device can capture dangerously low
  overnight blood glucose levels which often go undetected,
  reveal high blood sugar levels between meals, show early
  morning spikes in blood sugar, evaluate how diet and
  exercise affect blood sugars, or provide up to a 72-hour
  complete review of the effects of changes
• Continuous monitoring is reimbursed by Medicare and
  covered by many private insurance plans
  Continuous Glucose
       Monitoring
Roadmap for 21st century
    diabetes therapy
    David C. Klonoff, MD, FACP
 Diabetes Care 28:1231-1239, 2005
               Purposes
• provides information about the direction,
  magnitude, duration, frequency, and
  causes of fluctuations in blood glucose
  levels.
• provides much greater insight into glucose
  levels throughout the day.
• help identify and prevent unwanted
  periods of hypo- and hyperglycemia.
              Technologies (1)
• Five CGMs have been approved by the U.S. Food and
  Drug Administration (FDA) for use in the U.S. or carry CE
  marking for use in Europe.
• Continuous Glucose Monitoring System Gold (CGMS
  Gold; Medtronic MiniMed, Northridge, CA)
• GlucoWatch G2 Biographer (GW2B; Cygnus, Redwood
  City, CA)
• Guardian Telemetered Glucose Monitoring System
  (Medtronic MiniMed)
• GlucoDay (A. Menarini Diagnostics, Florence, Italy)
• Pendra (Pendragon Medical, Zurich, Switzerland)
• FreeStyle Navigator Continuous Glucose Monitor (Abbott
  Laboratories, Alameda, CA) -- premarket approval
  application has been submitted to the FDA
                 Technologies (2)
• minimal invasiveness through continuous measurement of interstitial
  fluid (ISF) or with the
• noninvasive method of applying electromagnetic radiation through
  the skin to blood vessels in the body.
• bringing a sensor into contact with ISF include inserting an indwelling
  sensor subcutaneously (into the abdominal wall or arm) to measure
  ISF in situ or harvesting this fluid by various mechanisms that
  compromise the skin barrier and delivering the fluid to an external
  sensor
• After a warm-up period of up to 2 h and a device-specific calibration
  process, each device’s sensor will provide a blood glucose reading
  every 1–10 min for up to 72 h with the minimally invasive technology
  and up to 3 months with the noninvasive technology.
• Results are available to the patient in real time or retrospectively.
• Every manufacturer of a CGM produces at least one model that
  sounds an alarm if the glucose level falls outside of a preset
  euglycemic range.
             Target Populations
• The ideal time to calibrate is either after fasting or at least
  3 h postprandially, but not right after exercise or when the
  blood glucose level is likely to be rising or falling.
• Without such calibration, continuous readings may be
  inaccurate.
• Currently available CGMs that provide real-time readings
  should not be used to make therapeutic decisions, such
  as whether to dose insulin or eat, because they are not
  sufficiently accurate.
• Instead, an abnormal reading should prompt a finger-
  stick blood glucose measurement whose value can be
  acted upon.
• Patients require a thorough training program to calibrate
  and operate a CGM.
                    Accuracy (1)
• A real-time CGM can be programmed to sound an alarm
  for readings below or above a target range
• The most important use of an alarm is to detect
  unsuspected hypoglycemia (such as during sleep) so that
  glucose can be administered to prevent brain damage.
• There is a trade-off between an alarm’s sensitivity and
  specificity.
• In general, if the alarm is set to sound at a lower level than
  the hypoglycemic threshold, then the specificity will be
  good but the sensitivity may be poor.
• If the alarm is set to sound at a glucose level higher than
  the hypoglycemic threshold, then the sensitivity will be
  good but the specificity may be poor.
• The greater accuracy a continuous monitor can provide,
  the less of a trade-off is necessary
                        Accuracy (2)
•   The Diabetes Research in Children Network (DirecNet) is a U.S. network of
    five clinical centers and a coordinating center dedicated to researching
    glucose monitoring technology in children with type 1 diabetes
•   The network’s investigators, the DirecNet Study Group, assessed the
    accuracy of the first- and second-generation CGMS and the GW2B in
    children with type 1 diabetes in concurrently published studies
•   The second-generation CGMS Gold, compared with the first-generation
    CGMS, had a lower median relative absolute difference (RAD) between
    CGMS glucose and reference serum glucose paired values (11 and 19%,
    respectively)
•   For the GW2B, the median RAD between GW2B glucose and reference
    serum glucose paired values was 16%
•   Similar RAD values of 21% have been reported for the first-generation
    CGMS by Kubiak et al.
•   RAD values of 12.8% and 12.8–15.7% have been reported for the second-
    generation CGMS Gold system by Goldberg et al. and Guerci et al.
    respectively.
                         Accuracy (3)
•   The DirecNet Study Group found the CGMS Gold system, which is the
    second generation of CGMS technology, as well as the GW2B, which is the
    second generation of GlucoWatch technology, to have inversely
    proportional sensitivity and specificity rates during hypoglycemia in children
    and adolescents with type 1 diabetes.
•   A series of alarm settings were selected for a reference blood glucose of 60
    mg/dl.
•   For CGMS Gold, the settings with sensitivity and specificity were 60 mg/dl,
    49 and 42%; 80 mg/dl, 84 and 36%; 100 mg/dl, 100 and 25%; and 120
    mg/dl, 100 and 16%.
•   With the GW2B, the settings were 60 mg/dl, 23 and 49%; 80 mg/dl, 59 and
    33%; 100 mg/dl, 84 and 20%; and 120 mg/dl, 92 and 15%.
•   The authors concluded, "These data show that the GW2B and the CGMS
    do not reliably detect hypoglycemia.
•   Both of these devices perform better at higher glucose levels, suggesting
    that they may be more useful in reducing HbA1c levels than in detecting
    hypoglycemia"
                           Accuracy (4)
•   The International Organization for Standardization (ISO) standards for accuracy of
    point blood glucose tests require that a sensor blood glucose value be within 15 mg/dl
    of reference for a reference value 75 mg/dl and within 20% of reference for a
    reference value >75 mg/dl.
•   Sensor accuracy by this definition is expressed as the percentage of data pairs
    meeting these requirements.
•   The DirecNet group found that for hypoglycemic blood glucose levels (determined by
    a reference blood glucose monitor, the OneTouch Ultra), the CGMS Gold met the
    ISO standards in only 48% of readings and the GW2B met these standards in only
    32% of readings
•   The percentage of data points attaining ISO accuracy standards climbed as the blood
    glucose level rose, topping out for the highest segment of reference blood glucose
    levels (i.e., blood glucose values 240 mg/dl).
•   In this glycemic category, the CGMS Gold and GW2B, respectively, met ISO
    accuracy for 81 and 67% of data points.
•   In a separate series of 15 healthy nondiabetic children undergoing continuous
    glucose monitoring over 24 h, the DirecNet Group reported that the median absolute
    difference in concentrations for the GW2B was 13 mg/dl and for the CGMS was 17
    mg/dl.
•   Furthermore, 30% of the values from the GW2B and 42% of the values from the
    CGMS deviated by >20 mg/dl from the reference value
         Clinical Indications (1)
• when adjusting therapy
• quantifying the response in a trial of a diabetes therapy
• assessing the impact of lifestyle modifications on
  glycemic control
• monitoring conditions where tighter control without
  hypoglycemia is sought (e.g., gestational diabetes,
  pediatric diabetes, in the intensive care unit)
• diagnosing and then preventing hypoglycemia (e.g.,
  during sleep, with hypoglycemia unawareness)
• diagnosing and preventing postprandial hypoglycemia.
• facilitate adjustments in therapy to improve control (most
  important use)
           Clinical Indications (2)
• Specific therapeutic adjustments include changing from regular to a
  synthetic ultrashort-acting insulin analog at mealtime, changing from
  NPH to a synthetic ultralong-acting insulin once or twice per day,
  increasing or decreasing the mealtime insulin bolus dosage,
  increasing or decreasing the basal insulin rate, altering the treatment
  of intermittent hypoglycemia or hyperglycemia, changing the insulin-
  to-glucose correction algorithm for premeal hyperglycemia, changing
  the insulin-to-carbohydrate ratio at mealtime, changing the method for
  counting carbohydrates, changing the carbohydrate composition of
  the diet, changing the discount in short-acting insulin dosage for
  exercise, changing the nighttime regimen because of the dawn
  phenomenon, changing the target preprandial or postprandial blood
  glucose values, or before referring a patient for psychological
  counseling to improve adherence to the treatment regimen.
• The most frequent therapy adjustment by Sabbah et al.(out of eight
  adjustments) was to increase the mealtime bolus dosage.
• The most frequent therapy adjustment by Kaufman et al.(out of nine
  adjustments) was to modify the type of basal long-acting insulin.
Advances in Glucose Monitoring
• As recently as July 2003, the FDA approved the first wireless
  combination system, consisting of a glucose monitor and an
  "intelligent" insulin pump (co-developed by Medtronic MiniMed and
  Becton, Dickinson and Company).
• The next phase of advances will allow insulin pumps to not only
  simply recommend proper insulin dosages, but actually automatically
  deliver them.
• More recently, in August 2005, Medtronic has expanded its CGMS
  line and announced FDA approval of its newest device, called the
  Guardian RT.
• This system works just like the MiniMed device but instead, displays
  the "real-time" glucose levels every five minutes. This information
  alerts the patient immediately to glucose levels that are too high or
  low, allowing for adjustments in therapy
   Light Waves Instead of Finger
              Pricks
• Several companies are developing non-invasive glucose monitoring
  devices that rely on light waves.
• The monitors shine infrared (or near-infrared) light onto the skin of
  the patient's forearm and analyse the light that is reflected back to
  determine the concentration of glucose in the tissue.
• The company Sensys has made progress in developing a
  commercial, portable version of an infrared monitor.
• Their latest model, the Sensys Medical Glucose Tracking System is
  about the size of a computer tower and is over 90% accurate.
• CME Telemetrix has developed a product called GlucoNIR, a non-
  invasive infrared system which may also be able to non-invasively
  measure HbA1c.
• Animas is developing an implantable version of an infrared optical
  sensor, intended to be implanted in the body for up to 5 years, but
  the device is not expected to be available until 2005.
A Glucose-Monitoring Skin Patch
• SpectRx and Abbott Laboratories are developing
  a continuous glucose monitor which will be worn
  as a skin patch.
• This monitor would measure glucose levels in
  interstitial fluid, collected through microscopic
  holes created by a laser in the dead outer layer
  of skin, and measured through glucose oxidase
  reaction/electrical current generation in a patch
  containing a glucose sensor.
• This device is currently being assessed in
  human trials in adults and children.
    Glucose-Sensing Contact Lens
•   Researchers at the University of Texas and Ciba Vision are developing
    glucose sensing contact lenses which are designed to be used in
    conjunction with a palm-sized light source.
•   The contact lens is made using a meshwork that traps fluorescent molecules
    inside the lens.
•   The patient inserts the contact lenses in the usual way, holds the light device
    up to the eye and activates it, sending a small burst of glowing light into the
    contact lens.
•   The fluorescent molecules in the lens bind to and react with the glucose in
    the user’s tears.
•   The device reads the wavelength of the fluorescence reflected from the
    contact lens and translates the reading into a measure of the glucose.
•   Higher levels of fluorescence mean higher levels of glucose.
•   There is a seven-minute delay before a hand-held device stores the glucose
    data.
•   This device also includes an alarm that signals a patient if the glucose levels
    rise too quickly.
•   Clinical trials are underway.
                  A Smart Tattoo
• A collaboration between Texas A&M University and Penn State
  University is developing a "smart tattoo" that could provide accurate
  blood glucose readings.
• Polyethylene glycol beads coated with fluorescent molecules are
  injected beneath the skin surface and interact with the interstitial
  fluid.
• In low glucose, the tattoo is highly fluorescent.
• In high glucose, the fluorescence beads are displaced by glucose
  binding and the overall fluorescence of the tattoo decreases.
• Fluorescence can be read by a detection light.
• Preliminary data in tattooed rats have yielded promising results.

								
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