Diabetes Technology and Insulin Therapy by Uq3Kz6

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									Diabetes Technology
         and
   Insulin Therapy
Bruce W. Bode, MD, FACE
Atlanta Diabetes Associates
      Atlanta, Georgia
Case 1: New Onset Diabetes

• 45-year-old male lawyer presents with
  “polys” and weight loss
• Sees internist who recommends metformin
  (blood glucose 500, urine ketones small,
  BMI 26)
• The lawyer does some internet reading and
  seeks a second opinion from diabetes
  specialist who was a high school classmate
  he has not seen for 27 years
Case 1: New Onset Diabetes

• What type of diabetes does he have?
   a) Type 1
   b) Type 1.5
   c) LADA
   d) Type 2
   e) a, b or c
Case 1: New Onset Diabetes
(cont’d)
• What is your best diagnostic tests to
  determine the type of diabetes?
   a) Islet cell antibody panel (ICA, anti-GAD)
   b) Serum C-peptide
   c) Genetic Typing
   d) Other tests?
LADA: Detection and
Impact of GAD Antibodies
• GAD: Glutamic acid decarboxylase
• Other antibodies
     — ICA, IA2, insulin autoantibodies
• 7% of the patients screened in the Treat to
  Target Study had GAD antibodies
• 95% of patients in the UKPDS who were
  anti-GAD or anti-ICA required insulin within
  6 years

UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1997;350:1288-1293.
Shimada A et al. Ann N Y Acad Sci. 2003;1005:378-386.
   Progression of Type 1 Diabetes
                       Precipitating Event

                   Genetic
                                      Antibody
                predisposition
                                                        Progressive loss
                                                        of insulin release
                 Normal insulin
                    release                                  Overt diabetes
                                                   Glucose
Beta cell
                                                   normal
 mass                                                        C-peptide
                                                             present

                                                                         No C-peptide
                                                                         present




                                     Age (y)
    Adapted from: Atkinson. Lancet. 2002;358:221-229.
Diabetes: New Cases
Diagnosed Annually in the US



Number




                                         Age Group

1999 – 2001 National Health Survey Estimates Projected to 2002,
Centers for Disease Control and Prevention, National Diabetes Fact Sheet.
Case 1: New Onset Diabetes

• Sees me the following AM
  (BG 514, urine ketones small)
• I concur with him that he has type 1 diabetes and
  metformin is not the treatment, insulin is
• What is your initial treatment?
   a) IV insulin
   b) Basal/bolus therapy with MDI
   c) Premixed
   d) Insulin pump therapy
Options in Insulin Therapy for
Type 1 Diabetes
• Current
  — Multiple injections
  — Insulin pump (CSII)
Case 1: New Onset Diabetes
(cont’d)
• He asks about insulin pump therapy instead
  of multiple injections
• I hospitalize him and tell him I will get back
  to him the following AM
    DCCT Absolute Risk of Retinopathy:
    Conventional vs Intensive Insulin Therapy
         • At the same A1C level, intensive insulin therapy provides a greater
           risk reduction of the development of retinopathy
                                    Development of Retinopathy
                    Conventional Therapy                    Intensive Therapy
        24                                     24
                             11% 10%
        20        Mean A1C                9%   20

 Rate 16                                            16
per 100
patient- 12                                         12
 years                                                            Mean A1C
                                              8%
         8                                          8                                     9%

                                              7%                                          8%
         4                                          4                                     7%
                                                                                          6%
         0                                          0
              0   1   2   3   4   5   6   7 8 9        0 1 2      3   4   5   6   7   8   9
                                          Time during study (y)
 DCCT Research Group. Diabetes. 1995;44:968–983.
    Does Intensive Diabetes Therapy
    Preserve Beta Cell Function?
                   1.0
                   0.9
                   0.8
    Patient        0.7
  probability      0.6
                   0.5
of maintaining
C-peptide > 2.0    0.4
                   0.3                                         Intensive therapy
                   0.2
                   0.1                     Conventional
                                             therapy
                   0.0
                         0        1         2        3        4          5         6
                                        Years Post Enrollment
                         Number of evaluated patients in each treatment group
        Intensive        108      131       80       53       32         8         2
     Conventional        165      150       63       32       22         3         0

     Adapted from: DCCT Study Group: Ann Intern Med. 1998;128:517-523.
 The Physiological Insulin Profile
             Short-lived, rapidly generated
          70    prandial insulin peaks
                                                             Normal free insulin levels
          60                                                 from genuine data (mean)

          50
Insulin 40
 (mU/L)
          30                                               Low, steady, basal
                                                             insulin profile
          20

          10

           0
           0600    0900      1200   1500    1800    2100   2400   0300   0600

                 Breakfast    Lunch        Dinner



  Adapted from Polonsky, et al. 1988.
    Basal/Bolus Treatment Program with
    Rapid-acting and Long-acting Analogs

             Breakfast     Lunch            Dinner
                     Aspart,     Aspart,       Aspart,
                      Lispro      Lispro        Lispro
                        or          or            or
Plasma               Glulisine   Glulisine     Glulisine
insulin


                                                              Glargine
                                                                 or
                                                              Detemir

      4:00    8:00       12:00      16:00       20:00      24:00   4:00   8:00
                                      Time
Insulin Predictability of Basal
Insulin

             Pumps
         Gold Standard          Detemir

                                    27%             Glargine
                                                      46%      NPH
               Intrasubject Variability
                                                               59%




Lepore M, et al. Diabetes. 2000;49:2142-2148.
Heise TC, et al. Diabetes. 2003;52(suppl 1):A121.
 Duration of Effectiveness
                  sc insulin                             N=20 T1DM
          220                                            Mean ± SEM

          200


          180                                          NPH
Glucose                                                              Ultralente
 mg/dl
          160
                                                                     Glargine
          140

                                                              CSII
          120

                        0        4       8        12     16     20       24
                                       Time (hours)
  Lepore M, et al. Diabetes. 2000;49:2142-2148.
Insulin Treatment in Type 2 Diabetes
 •   Basal Treatment (NPH, Glargine, or Detemir)
     Start 10U and titrate; will need ~0.5U/kg;
     will lower A1C 1.5 to 2 points
 •   Bolus Treatment Premeal
     Start at 3-5U premeal and titrate;
     will lower A1C 2 plus points
 •   Premixed Therapy
     Start at 5U BID and titrate; will need ~0.8U/kg;
     will lower A1C 2 plus points
 •   Basal Bolus Therapy
Case 1: New Onset Diabetes

•   If you decided on MDI, how do you
    determine his starting doses of insulin?
    a) Based on trial and error
    b) Based on BMI
    c) Based on weight
    d) Let the CDE decide
Starting Basal/Bolus Therapy

• Starting insulin dose is based on weight
   — 0.2 x wgt. in lbs. or 0.5 x wgt. in kg
• Bolus dose (aspart/lispro) = 20% of starting
  dose at each meal
• Basal dose (glargine/NPH) = 40% of starting
  dose at bedtime
 Starting MDI in 180-lb Person

• Starting dose = 0.2 x 180 lb
   — 0.2 x 180 = 36 units
• Bolus dose = 20% of starting dose at each meal
   — 20% of 36 units = 7 units ac (tid)
• Basal dose = 40% of starting dose at bedtime
   — 40% of 36 units = 14 units at HS
Correction Bolus (Supplement)

• Must determine how much glucose is lowered by
  1 unit of short- or rapid-acting insulin
• This number is known as the correction factor (CF)
• Use the 1700 rule to estimate the CF
• CF = 1700 divided by the total daily dose (TDD)
   — Ex: if TDD = 36 units, then CF = 1700/36 = ~50
   — Meaning 1 unit will lower the BG ~50 mg/dl
Correction Bolus Formula

           Current BG - Ideal BG
        Glucose Correction Factor
• Example:
  — Current BG:                   220 mg/dl
  — Ideal BG:                     100 mg/dl
  — Glucose Correction Factor:      50 mg/dl


                220 – 100 =2.4u
                   50
Insulin Pens
 The first insulin pen was developed by NovoNordisk in
 1926 but not launched until 1985. Since then, numerous
 pens, both disposable and reusable, have been
 developed adding to accuracy in dosing and
 convenience to insulin injection therapy.


  Disposable Lilly Pen




                             Novo Reusable Pen with   Aventis Reusable Pen with
Disposable NovoNordisk Pen
                               disposable cartridge      disposable cartridge
Options to MDI

• A Simpler Regimen
• Insulin Pump
• Premixed BID (DM 2 only)
Variable Basal Rate: CSII Program

                    Breakfast    Lunch           Dinner
Plasma insulin




                        Bolus Bolus                 Bolus


                                                              Basal infusion

             4:00    8:00       12:00    16:00        20:00   24:00   4:00   8:00
                                           Time
Summary: The Benefits of CSII in
Mimicking Normal Physiology
• Nocturnal variability
   — Covering the dawn phenomenon
• Exercise-related changes
   — Reducing basal insulin to normalize glucose
• Normal eating patterns
   — Multiple boluses; dual bolus
• Complex carbohydrates and dietary fat
   — Covering delayed carbohydrate absorption
Metabolic Advantages with CSII

• Improved glycemic control
• Better pharmacokinetic delivery of insulin
   — Less hypoglycemia than NPH based therapy
   — Less insulin required
• Improved quality of life
Insulin Delivery Therapy at End of
DCCT

          Pump 42%



  Unknown 2%

                                        MDI 56%



DCCT. Diabetes Care. 1995;18:361-376.
      CSII vs MDI with Glargine in Adults
     • Insulin aspart (CSII) vs insulin aspart / glargine
       (MDI)
                                                                IAsp + Glarg
                                         IAsp CSII
                                                                     MDI
                                        IAsp + Glarg              IAsp CSII
                                            MDI
                   Run-in (1 week)         Period 1 (5 weeks)      Period 2 (5
         weeks)


  • 100 patients with type 1 on CSII at entry
  • A1C <9%
  • Efficacy: A1C, fructosamine, 8-point BG profile, glucose
    exposure (CGMS)
  • Safety: frequency of hypoglycemia, AEs

Bode, et al. Diabetes 52,(Suppl 1), 2003 Abstract 438.
     CSII vs MDI in 100 DM 1 Patients
               200
                                                                          CSII (n=93)
                                                                          MDI (n=91)
               180

Self-monitored
      BG      160
    (mg/dL)
               140


               120


               100
                        BB      AB      BL     AL      BD        AD Midnight 3 AM

                                             Mean ± 2 SEM

     Bode BW, et al. Diabetes. 2003;52(suppl 1). Abstract 438.
  CSII vs MDI with Glargine in
  Children
      Randomized, Parallel-group, 16 week study


           Injection                  CSII (aspart) n=16
            therapy
                                 MDI (aspart/glargine) n=16
                                      16 Week treatment period

Subjects at baseline
          Age: 8-19 yr (mean 12.7 ± 2.7)
          Type 1 DM > 1 yr duration
          Standard insulin therapy (2-3 injections/day)

Doyle EA, et al. Diabetes Care 2004; 27: 1554
  16 Week Comparison of MDI using
  Glargine versus CSII: Children
                           P < 0.05
                                                       P < .001




                                                CSII

                                                MDI




Doyle EA, et al. Diabetes Care 2004; 27: 1554
    CSII versus MDI in Type 2 Diabetes
14 Center Randomized Parallel Group Study

                            Insulin aspart in CSII (n = 66)
       Screen:
    DM 2 >2 years     Target FBG 80-120
On insulin >6 months
                     Insulin aspart/NPH in MDI (n = 61)
     A1C > 7.5%;
      Stop OHA
                        Dose          Maintenance
                     adjustmen          period
                          t

                      Week 0         Week 8           Week 24


Raskin et al. Diabetes Care 26(9): 2598-2603, 2003
    CSII versus MDI in Type 2 Diabetes
14 Center Randomized Parallel Group Study




 A1C




 Raskin et al. Diabetes Care 26(9): 2598-2603, 2003
 CSII vs MDI in DM 2 Patients
                                                       CSII        MDI
Less pain
Fewer social limitations
Preference
Advocacy
Less hassle
Less life interference
General satisfaction
Flexibility
Convenience
Less burden

                   -5         0       5           10   15     20     25      30     35
                           Change in scores (raw units) from baseline to endpoint

  Testa et al. Diabetes. 2001;50(suppl 2):1781.
CSII vs MDI in Older Adults with Type 2 DM
2 Center Randomized Parallel Group Study

                        Insulin lispro in CSII (n = 48)
      Screen:
       DM 2
     On insulin
                       Insulin lispro/glargine in MDI (n = 50)
     Age > 60yo
     Stop OHA
                                    Dose
                                 adjustment

                  Week 0                          Week 52


Herman W et al, Poster 504-P, ADA 2005
CSII vs MDI in Older Adults with Type 2 DM 2
  Center Randomized Parallel Group Study




A1C




  Herman W et al, Poster 504-P, ADA 2005
Case 1: New Onset Diabetes

• I see patient in the AM and tell him that 8 out
  of 10 patients polled yesterday would have
  started CSII at onset if offered the choice
• Dr. Pozzilli, an expert in DM 1 prevention,
  also recommended CSII at onset if it was
  him or a close relative
• Patient opted for CSII
Case 1: New Onset Diabetes on
CSII: A1C Results




               A1C
Case 1: New Onset Diabetes on
CSII
• Patient extremely satisfied with his care
• C-peptide 0.9 to 0.8 at 1 year, 0.5 to 0.7 at 3
  years
• Does not understand why everyone is not
  on CSII with optimal control
Current Pump Therapy Indications

• Need to normalize blood glucose (BG)
   — A1C > 6.5%
   — Glycemic excursions
• Hypoglycemia or hypoglycemia
  unawareness
• Need for a flexible insulin regimen
US Pump Usage: Total Patients
Using Insulin Pumps




                       Industry estimates
Current Continuation Rate: Continuous
Subcutaneous Insulin Infusion (CSII)

 Continued 97%




                                                  Discontinued 3%
              N = 165
              Average duration = 3.6 years
              Average discontinuation <1%/y


Bode BW, et al. Diabetes. 1998;47(suppl 1):392.
     Smart Insulin Pumps




Photograph reproduced with permission of manufacturer.
Smart Pumps
Bolus Calculator: Meter-Entered



                             Paradigm 512™


            Paradigm Link™


• Monitor sends BG value to pump or patient dials in
  BG value
• Enter carbohydrate intake into pump
• “Bolus Calculator” calculates suggested dose
Bolus Calculator Set Up
Screen

 Calculator: On
 Carb Units: Grams
 Carb Ratios: 10
 BG Units:     mg/dl
 Sensitivity: 40
 BG Target: 80-100
 Active Insulin Time: 5 hours
Pump Infusion Sets: Perpendicular
vs Oblique
• Perpendicular (Sof-set™,
  Quick-set™, Ultraflex™)
   — Easier insertion
   — Prone to kink


• Oblique (Silhouette™,
  Tender™, Comfort™)
   — More difficult insertion
   — Less kinking
Disposable Patch Pumps
CSII:
Factors Affecting A1C
• Monitoring
      — A1C = 8.3 - (0.21 x BG per day)




Bode BW, et al. Diabetes. 1999;48(suppl 1):264.
Bode BW, et al. Diabetes Care. 2002;25:439.
Increased SMBG Testing
Frequency Lowers A1C

          Atlanta Diabetes Associates study:
          378 patients sorted from a database of 591
          Pumps=MM 511 or earlier
          BG Target=100
          C peptide <0.1
CSII:
Factors Affecting A1C (cont’d)
• Monitoring
      — A1C = 8.3 - (0.21 x BG per day)
• Recording 7.4 vs 7.8
• Diet practiced
      — CHO: 7.2
      — Fixed: 7.5
      — WAG: 8.0
• Insulin type (aspart, glulisine)

Bode BW, et al. Diabetes.1999;48(suppl 1):264.
Bode BW, et al. Diabetes Care. 2002;25:439.
Pump Formulas For Adults

• Total Daily Dose of Insulin (TDD)
      — Weight (kg) x 0.5
• Carbohydrate / Insulin Ratio (CIR)
      — CIR in grams = 6 x Body Weight (kg) / TDD
•    Correction Factor (CF)
      — CF = 1700 / TDD
•    Basal Insulin
      — Basal = 0.48 x TDD



Davidson et al. Diabetes Tech Therap. April 2003.
Initial Adult Dosage: Calculations

• Starting doses
      — Based on pre-pump total daily dose (TDD)
              • Reduce TDD by 25% to 30% for pump TDD
      — Calculated based on weight
              • 0.5 x weight in kg (0.24 x wgt in lbs)




Bode BW, et al. Diabetes. 1999;48(suppl 1):84.
Bell D, Ovalle F. Endocr Pract. 2000;6:357-360.
Crawford LM. Endocr Pract. 2000;6:239-243.
Target BG Ranges for CSII

• Normal awareness to hypoglycemia
     — Preprandial                  70 - 140 mg/dL
     — Postprandial <160 mg/dL
• Individually set for each patient




Bode BW. Medical Management of Type 1 Diabetes. 4th ed. ADA; 2004.
Fanelli CG, et al. Diabetologia. 1994;37:1265-1276.
Jovanovich L. Am J Obstet Gynecol. 1991;164:103-111.
Target BG Ranges for CSII

• Hypoglycemic unawareness
     — Preprandial:                     100 - 160 mg/dL
• Pregnant
     — Preprandial:                     60 - 90 mg/dL
     — 1 hr postprandial:                         <120 mg/dL
• Individually set for each patient


Bode BW. Medical Management of Type 1 Diabetes. 4th ed. ADA;2004.
Fanelli CG, et al. Diabetologia. 1994;37:1265-1276.
Jovanovich L. Am J Obstet Gynecol. 1991;164:103-111.
Initial Adult Dosage: Calculations

• Basal rate
   — 45% to 50% of pump TDD
   — Divide total basal by 24 hours to decide on
     hourly basal
   — Start with only 1 basal rate
   — See how it goes before adding basals
Basal Dose Adjustment Overnight

• Rule of 30:
   — Check BG
        • Bedtime
        • 12 AM
        • 3 AM
        • 6 AM
   — Adjust overnight basal if readings
     vary >30 mg/dL
Basal Dose Adjustment Overnight

• Adults often need an increase in basal rate
  in the “dawn” hours (4 AM to 9 AM)
• Children often need an increase in basal
  rate earlier starting at 10 PM to 2 AM
Variable Basal Rate: Adults

                   Breakfast    Lunch           Dinner
Plasma insulin




                      Bolus Bolus                  Bolus


                                                             Basal infusion

            4:00   8:00        12:00    16:00        20:00   24:00   4:00   8:00
                                         Time
Variable Basal Rate: Children

                   Breakfast    Lunch           Dinner
Plasma insulin




                      Bolus Bolus                  Bolus

                                                             Basal infusion



            4:00   8:00        12:00    16:00        20:00   24:00   4:00   8:00
                                         Time
Basal Dose Adjustment Daytime

• Rule of 30:
   — Check BG
       • Before usual mealtime
       • Skip meal
       • Every 2 hrs (for 6 hrs)
   — Adjust daytime basal if readings vary
     >30 mg/dL
Bolus Dose Calculations

• Meal (food) Bolus Method 1
  — Test BG before meal
  — Give predetermined insulin dose for
    predetermined CHO content
  — Test BG after meal
  — Goal <60 mg/dl rise postmeal or
    <160 mg/dL
Estimating the Carbohydrate to
Insulin Ratio (CIR)
• Individually determined
      — CIR = (2.8 x wgt in lbs) ÷ TDD
              or
      — CIR = (6 x wgt in kg) ÷ TDD
      — Anywhere from 5 to 25 g CHO is covered by
        1 unit of insulin




Davidson et al. Diabetes Tech Therap. April 2003.
Pump Follow-up Procedures
• Monitor, record, and report glucoses
     — Premeal and postmeal
     — Overnight (periodically)
• Contact as needed
     — Phone, fax, e-mail
• Office visits
     — First infusion set change
     — 1-2 weeks later with RD, RN, or MD and PRN
     — Quarterly visits once stable

Bode BW. Medical Management of Type 1 Diabetes. 4th ed. ADA; 2004.
Avoiding DKA

•   BG is greater than 250 mg/dL:
     — Take correction dose
     — Check for ketones
     — Recheck in 60 minutes
             • If coming down, leave alone
             • If not, take a shot and change the site
• There is no increase in DKA occurrence with pumps


Adapted from Fredrickson L, et al. Optimal Pumping: A Guide to Good Health with Diabetes.
Medtronic MiniMed, Inc.; 1998.
Plotnick L, et al. Diabetes Care. 2003;26:1142-1146.
Avoiding Hypoglycemia

• Frequent blood glucose monitoring
• Occasional 3 AM checks
• Consider readjusting glycemic goals for
  hypoglycemic unawareness
• Bolus frequency
     — Utilize Bolus Wizard calculator
     — Utilize technology to avoid over bolus


Adapted from Fredrickson L, et al. Optimal Pumping: A Guide to Good Health with Diabetes.
Medtronic MiniMed, Inc.; 1998.
If A1C Is Not at Goal
Must look at:
• SMBG frequency and         • Infusion site areas
  recording
                                — Are they in areas of
• Diet practiced                  lipohypertrophy?

   — Do they know what       • Other factors:
     they are eating?           — Fear of low BG
   — Do they bolus for all      — Overtreatment of low
     food and snacks?             BG
If on Smart Pumps and Not at Goal

• Postmeal too high
  — Lower CIR (Carb-to-Insulin Ratio)
• All BGs too high
  — Lower target and/or change CF (ISF)
• Fasting or premeal too high
  — Increase basal
Do Smart Pumps Enable Others to
Go to CSII?
• YES
• All patients with diabetes not at goal are
  candidates for Insulin Pump Therapy
   — Type 1 any age
   — Type 2
   — Diabetes in pregnancy
For This System to Work

• It is critical that the target, basal doses,
  correction doses, and carbohydrate ratios
  are accurate
• Understanding how to match carbohydrate
  amounts with insulin is critical
• If the target is set too high (>110 mg/dL),
  glucoses will run too high.
  Normal target is 100 mg/dL and for
  pregnancy 80 mg/dL is safe
If A1C Is Not at Goal and
No Reason Identified
• Place on a continuous glucose monitoring
  system
  Continuous Monitoring Systems



                                                     DexCom
                        Abbott Navigator

Cygnus Glucowatch




                                                 Pendragon Medical
                    Medtronic MiniMed CGMS


Menarini GlucoDay

                                      Guardian
Missed Postprandial Hyperglycemia
With Fingersticks

                                 400
 Glucose Concentration (mg/dL)




                                 350

                                 300

                                 250

                                 200

                                 150

                                 100

                                 50

                                  0
                                  12:00 AM   4:00 AM   8:00 AM    12:00 PM   4:00 PM   8:00 PM

                                                                 Time
Missed Postprandial Hyperglycemia
With Fingersticks
Sensor-Augmented Insulin Pump
System
   External Open-Loop

                        Patients are expected to make
                        immediate therapy adjustments
                        based upon real-time continuous
                        glucose readings displayed every 5
                        minutes and by viewing a graph with
                        3-hour and 24-hour glucose trends.*


                        *Not yet approved by the FDA or
                        European Health Authorities
Sensor Augmented Pump*

  — Receives sensor glucose values
    every 5 minutes
  — Receives meter value to
    automatically calibrate sensor
  — Displays current glucose value,
    trend graph, hypo and hyper
    glycemia alerts
                        Meter BG
                                                 Sensor BG




      Download         Download
      Sensor, Meter,   Sensor, Meter,   Dummy Pump
      & Pump Data      & Pump Data
      only in office
  Sensor Augmented Pump Therapy
  A Pilot Study



                             CSII                     CSII
                          Sensor CSII             Sensor CSII

    Run-in   (1 week)        Period 1 (12 weeks) Period 2 (12 weeks)



• 20 patients with type 1 on CSII for at least 1 year
• A1C >6.5%; SMBG ≥4 per day
• Efficacy: A1C (mean and % <7), BG mean, glucose exposure (CGMS)
• Safety: frequency of hypoglycemia, AEs
Case 1:

J.B is a 50 yo teacher with DM 1 since age
14, on CSII for 18 years, A1C 8.1.

Has Hypoglycemia Unawareness with need
for secondary help by wife once a month.

Enters a real-time open loop sensor
augmented pump trial
               Case 1:
JB, 50 yo male, DM 1 age 14, TDD 38,
Basal 0.7, ICR 1:12, Target 100; CF 42
                                                                   Glucose Sensor Profile: 29-Sep-04




                                  350

                                                                           2.8U
                                  300        Breakfast
                                                5U
                                  250
  Glucose Concentration (mg/dL)




                                                                                                             Sensor Value (BG)
                                                                   Lunch                          Supper
                                                                                                            Paired Meter Value
                                  200                                                                       Meter Value
                                                                    3U                              5U      Sensor On
                                                                                                            Sensor Off
                                  150                                                                       Upper Limit
                                                                                                            Lower Limit
                                                                                                            Init Packet
                                  100



                                  50         2 Glucose
                                               Tabs
                                    0
                                  12:00 AM   4:00 AM     8:00 AM       12:00 PM      4:00 PM      8:00 PM
                                                                         Time
                                                          Case 1:
                                           JB, 50 yo male, DM 1 age 14, TDD 38,
                                           Basal 0.7, ICR 1:12, Target 100; CF 42
                                                                  Glucose Sensor Profile: 01-Oct-04
                                      Another Day
                                350


                                                                                                7.4U
                                300


                                                                         No bolus
                                250
                                             Breakfast 63g;
Glucose Concentration (mg/dL)




                                                                                                                Sensor Value (BG)
                                             Took 5.1U                                                         Paired Meter Value
                                200                                                                            Meter Value
                                                                                                               Sensor On
                                                                                                               Sensor Off
                                150                                                                            Upper Limit
                                                                                                               Lower Limit
                                                                                                               Init Packet
                                100


                                                                 Lunch 60 g; 5U                   Supper Out
                                50
                                                                                                  ?50g 4U
                                 0
                                12:00 AM     4:00 AM   8:00 AM        12:00 PM      4:00 PM      8:00 PM
                                                                        Time
Case 1 JB Modal Day Graph
                                                                                                                                 13-Sep-04
                                                                         Glucose Sensor Profile                                  14-Sep-04
                                                                              Modal Day
                                                                                                                                 15-Sep-04
                                                                                                                                 16-Sep-04
                                600                                                                                              17-Sep-04
                                                                                                                                 18-Sep-04
                                                                                                                                 19-Sep-04
                                                                                                                                 20-Sep-04
                                500                                                                                              21-Sep-04
                                                                                                                                 22-Sep-04
                                                                                                                                 23-Sep-04
                                                                                                                                 24-Sep-04
Glucose Concentration (mg/dL)




                                400
                                                                                                                                 25-Sep-04
                                                                                                                                 26-Sep-04
                                                                                                                                 27-Sep-04
                                                                                                                                 28-Sep-04
                                300
                                                                                                                                 29-Sep-04
                                                                                                                                 30-Sep-04
                                                                                                                                 1-Oct-04
                                                                                                                                 2-Oct-04
                                200
                                                                                                                                 3-Oct-04
                                                                                                                                 4-Oct-04
                                                                                                                                 5-Oct-04
                                                                                                                                 6-Oct-04
                                100
                                                                                                                                 7-Oct-04
                                                                                                                                 8-Oct-04
                                                                                                                                 9-Oct-04
                                 0                                                                                               10-Oct-04
                                12:00 AM   3:00 AM   6:00 AM   9:00 AM     12:00 PM     3:00 PM   6:00 PM   9:00 PM   12:00 AM   11-Oct-04
                                                                            Time                                                 12-Oct-04
                                                                                                                                 15-Oct-04
                                                                                                                                 16-Oct-04
Case 2:
MB. is a 49 yo mother with DM 1 since age
21, on CSII for 22 years,
with A1C 8.1.

Labile BG values on 4.6 tests/day.
Works part-time.
History of low BG spells needing help.

Enters a real-time open loop sensor
augmented pump trial
                                            Case 2: MB, 49 yo female,
                                           History of Labile BG and Lows
                                                                                                              Glucose Sensor Profile: 13-Dec-04


                                                                                                                Glucose Sensor Profile: 13-Dec-04

                                450
                                       TDD = 47 U                              450
                                                                                                                                          2U
                                400
                                       2 U per Carb
                                                                               400

                                350    Basal 61%
                                                                               350
Glucose Concentration (mg/dL)




                                                                                                                                                                                       Sensor Value (BG)
                                               Glucose Concentration (mg/dL)




                                300                                                                                                                         Sensor Value (BG)
                                            4U                                 300
                                                                                                                                                            Meter Value                Meter Value
                                                                                                         OU                                                 Sensor On                  Sensor On
                                250                                            250
                                                                                                                                2 Carb                      Sensor Off
                                                                                                                                                            Paired Meter Value
                                                                                                                                                                                       Sensor Off
                                                                                                                                                                                       Paired Meter Value
                                200
                                                                               200                                                2U                        Sensor Limit (Above 400)
                                                                                                                                                            Sensor Limit (Below 40)
                                                                                                                                                                                       Sensor Limit (Above 400)
                                                                                                                                                            Start Up                   Sensor Limit (Below 40)

                                             0U                                150                        1 Carb                                            Meter Value (Over 450)     Start Up
                                150                                                                                                                                                    Meter Value (Over 450)
                                           2 Carb                              100                         OU
                                100
                                                                               50


                                50                                              0
                                                                               12:00 AM   4:00 AM   8:00 AM      12:00 PM      4:00 PM       8:00 PM
                                      Basal 1.2 U/h                                                                Time
                                 0
                                12:00 AM    4:00 AM                                       8:00 AM              12:00 PM                  4:00 PM       8:00 PM
                                                                                                                 Time
      Case 4: MB, 49 yo female,
     History of Labile BG and Lows
Changes made:
1. Decreased Basal by 1.0 U/h
2. Increased CIR to 2.2 U per Carb
3. A1C dropped to 7.3% at 3 months
                       Case 5
• 16-year-old girl with T1DM for 7 years
                      Problems: Too low breakfast dose;
• HbA1c: 9.1%         Increased meal carb on 10/24
   Why the Majority Reached Goal

• They wore it 90% of the time
• They were long term patients in my
  practice on CSII for years
• They looked at it 10 to 20 times per day
• They made changes with my help by
  looking at trends and patterns
CSII versus Sensor Augmented CSII
(7 Center Study)

                         CSII (715 model) ~70
    Screen:
  DM 1 on CSII
  A1C > 7.5%;
                        Sensor Augmented CSII ~70
SMBG ≥ 4 per day
   Age 12-80
                             Download via
                               CareLink

                   Week 2
               Week 0         Week 13           Week 26 Week 52

Efficacy: A1C (mean and % <7), BG mean, glucose exposure (CGMS)
E
Safety: frequency of hypoglycemia, AEs
f
Vision Toward the Artificial
Pancreas
       External Closed-Loop                            Implanted Closed-Loop




*This product concept not yet submitted to the FDA for commercialization.
Predicted Times

• Glucose Sensors
  — Alarm sensor (72 hr) 2004
  — Guardian RT (72 hr) 2005
  — Replace fingersticks 2006
• Semi-closed loop 2007-2008
• Implantable 2007-2008
Summary

• Insulin remains the most powerful agent
  we have to control diabetes
• When used appropriately in a basal/bolus
  format, near-normal glycemia can be
  achieved
• Newer insulins and insulin delivery devices
  along with glucose sensors will
  revolutionize our care of diabetes
Questions

• For a copy or viewing of these slides, go to:




           www.adaendo.com

								
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