Diabetes Technology and

Insulin Therapy

Bruce W. Bode, MD, FACE

Atlanta Diabetes AssociatesAtlanta, 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?

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

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

Progression of Type 1 Diabetes

Adapted from: Atkinson. Lancet. 2002;358:221-229.

Age (y)

Precipitating Event

Beta cell mass

Genetic predisposition

Normal insulin release

Glucose normal

Overt diabetes

No C-peptidepresent

Progressive loss of insulin release

C-peptidepresent

AntibodyAntibody

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

Age Group

Number

Diabetes: New Cases Diagnosed Annually in the US

0

100,000

200,000

300,000

400,000

500,000

600,000

700,000

20-39 40-59 60+

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

DCCT Research Group. Diabetes. 1995;44:968–983.

Conventional TherapyConventional Therapy Intensive TherapyIntensive Therapy

00

44

88

1212

1616

2020

2424

11 22 33 44 55 66 77 88 9900

Mean A1CMean A1C

10%10%

9%9%

8%8%

7%7%

RateRate per 100 per 100 patient-patient-yearsyears

Time during Time during study (y) (y)

00

44

88

1212

1616

2020

2424

11 22 33 44 55 66 77 88 9900

Mean A1CMean A1C

8%8%7%7%6%6%

11%11%

9%9%

Development of Retinopathy

Does Intensive Diabetes Therapy Preserve Beta Cell Function?

Adapted from: DCCT Study Group: Ann Intern Med. 1998;128:517-523.

0 1 2 3 4 5 6

0.00.10.20.30.40.50.60.70.80.9

1.0

Years Post Enrollment

Number of evaluated patients in each treatment group

IntensiveConventional

0

131 80 53 32 8 2108150 63 32 22 3 0165

Conventionaltherapy

Intensive therapy

Patient probability

of maintaining C-peptide > 2.0

The Physiological Insulin Profile

Adapted from Polonsky, et al. 1988.

10

20

30

Insulin (mU/L)

0

40

50

60

70Short-lived, rapidly generated

prandial insulin peaks

Low, steady, basalinsulin profile

Normal free insulin levelsfrom genuine data (mean)

0600 0900 1200 1500 1800 2100 2400 0300 0600

Breakfast Lunch Dinner

4:00 16:00 20:00 24:00 4:00

Breakfast Lunch Dinner

8:0012:008:00

Time

Glargineor

Detemir

Plasma insulin

Basal/Bolus Treatment Program with Rapid-acting and Long-acting Analogs

Aspart,Lispro

orGlulisine

Aspart,Lispro

orGlulisine

Aspart,Lispro

orGlulisine

Insulin Predictability of Basal Insulin

NPH

Glargine

Detemir

Pumps

46%

59%

27%

Gold Standard

Intrasubject Variability

Lepore M, et al. Diabetes. 2000;49:2142-2148.Heise TC, et al. Diabetes. 2003;52(suppl 1):A121.

Glargine

NPH

sc insulin N=20 T1DMMean ± SEM

Time (hours)

Ultralente

CSII

Glucose mg/dl

Lepore M, et al. Diabetes. 2000;49:2142-2148.

Duration of Effectiveness

220

200

180

160

140

120

0 4 8 12 16 20 24

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

• Example:

— Current BG: 220 mg/dl

— Ideal BG: 100 mg/dl

— Glucose Correction Factor: 50 mg/dl

Current BG - Ideal BGGlucose Correction Factor

220 – 10050

=2.4u

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

disposable cartridgeDisposable NovoNordisk Pen

Aventis Reusable Pen with

disposable cartridge

Options to MDI

• A Simpler Regimen

• Insulin Pump

• Premixed BID (DM 2 only)

4:00 16:00 20:00 24:00 4:00

Breakfast Lunch Dinner

8:0012:008:00

Time

Basal infusion

Bolus Bolus Bolus

Pla

sma

insu

lin

Variable Basal Rate: CSII Program

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

DCCT. Diabetes Care. 1995;18:361-376.

Insulin Delivery Therapy at End of DCCT

Pump 42%

MDI 56%

Unknown 2%

• Insulin aspart (CSII) vs insulin aspart / glargine (MDI)

Run-in (1 week) Period 1 (5 weeks) Period 2 (5 weeks)

IAsp CSII

IAsp CSII

IAsp + Glarg MDI

IAsp + Glarg MDI

CSII vs MDI with Glargine in Adults

Bode, et al. Diabetes 52,(Suppl 1), 2003 Abstract 438.

• 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

CSII vs MDI in 100 DM 1 Patients

Bode BW, et al. Diabetes. 2003;52(suppl 1). Abstract 438.

Mean ± 2 SEM

200

160

140

120

100

180

Self-monitored BG

(mg/dL)

BB AB BL AL BD AD Midnight 3 AM

CSII (n=93)

MDI (n=91)

CSII vs MDI with Glargine in Children

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

CSII (aspart) n=16

MDI (aspart/glargine) n=16

16 Week treatment period

Injectiontherapy

Randomized, Parallel-group, 16 week study

Doyle EA, et al. Diabetes Care 2004; 27: 1554

16 Week Comparison of MDI using Glargine versus CSII: Children

100

150

200

BF L D HS

Mean BG Levels (mg/dl)

16

26

16

6

05

1015202530

During Study After Study

Number of patients on each therapy

Doyle EA, et al. Diabetes Care 2004; 27: 1554

8.1

7.2

8.2 8.1

6.5

7

7.5

8

8.5

Pre Post

A1C Level (% )

P < 0.05P < .001

CSII

MDI

CSII versus MDI in Type 2 Diabetes14 Center Randomized Parallel Group Study

Dose adjustmen

t

Maintenance period

Week 0 Week 8 Week 24

Insulin aspart in CSII (n = 66)

Insulin aspart/NPH in MDI (n = 61)

Screen:

DM 2 >2 years

On insulin >6 months

A1C > 7.5%;

Stop OHA

Raskin et al. Diabetes Care 26(9): 2598-2603, 2003

Target FBG 80-120

CSII versus MDI in Type 2 Diabetes14 Center Randomized Parallel Group Study

8.28

7.6 7.5

6

6.5

7

7.5

8

8.5

9

Pump MDI

Baseline

24 weeks A1C

Raskin et al. Diabetes Care 26(9): 2598-2603, 2003

Change in scores (raw units) from baseline to endpoint

-5 0 5 10 15 20 25 30 35

Convenience

Less burden

Less hassle

Advocacy

Preference

General satisfaction

Flexibility

Less life interference

Less pain

Fewer social limitations

MDICSII

CSII vs MDI in DM 2 Patients

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

Dose adjustment

Week 0 Week 52

Insulin lispro in CSII (n = 48)

Insulin lispro/glargine in MDI (n = 50)

Screen:

DM 2

On insulin

Age > 60yo

Stop OHA

Herman W et al, Poster 504-P, ADA 2005

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

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

4.05.06.07.08.09.0

10.011.012.013.014.0

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

195,000

220,000

250,000

157,000

120,000

43,00035,00026,50020,000

15,00011,40087006600

60,000

81,000

0

50,000

100,000

150,000

200,000

250,000

US Pump Usage: Total Patients Using Insulin Pumps

Industry estimates

N = 165Average duration = 3.6 yearsAverage discontinuation <1%/y

Continued 97%

Discontinued 3%

Current Continuation Rate: Continuous Subcutaneous Insulin Infusion (CSII)

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

Photograph reproduced with permission of manufacturer.

Smart Insulin Pumps

Smart PumpsBolus Calculator: Meter-Entered

• Monitor sends BG value to pump or patient dials in BG value

• Enter carbohydrate intake into pump

• “Bolus Calculator” calculates suggested dose

Paradigm Link™

Paradigm 512™) ) ) ) ) ) ) ) ) )

) ) )

Calculator: OnCarb Units: GramsCarb Ratios: 10BG Units: mg/dlSensitivity: 40BG Target: 80-100Active Insulin Time: 5 hours

Bolus Calculator Set Up Screen

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.

4.0

5.0

6.0

7.0

8.0

9.0

10.0

11.0

12.0

0 2 4 6 8 10 12 14

SMBG Frequency (BG per day)

A1C

Increased SMBG Testing Frequency Lowers A1C

Atlanta Diabetes Associates study:378 patients sorted from a database of 591 Pumps=MM 511 or earlierBG Target=100C 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

4:00 16:00 20:00 24:00 4:00

Breakfast Lunch Dinner

8:0012:008:00

Time

Basal infusion

Bolus Bolus Bolus

Variable Basal Rate: AdultsP

lasm

a in

suli

n

Breakfast Lunch Dinner

Basal infusion

Bolus Bolus Bolus

Variable Basal Rate: ChildrenP

lasm

a in

suli

n

Time

4:00 16:00 20:00 24:00 4:00 8:0012:008:00

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.

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 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.

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

If A1C Is Not at Goal

• SMBG frequency and recording

• Diet practiced

— Do they know what they are eating?

— Do they bolus for all food and snacks?

• Infusion site areas

— Are they in areas of lipohypertrophy?

• Other factors:

— Fear of low BG

— Overtreatment of low BG

Must look at:

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

Cygnus Glucowatch

Menarini GlucoDay

Medtronic MiniMed CGMS

Guardian

DexCom

Pendragon Medical

Abbott Navigator

Missed Postprandial Hyperglycemia With Fingersticks

0

50

100

150

200

250

300

350

400

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

Time

Glu

co

se C

on

cen

tra

tio

n (

mg

/dL

)

Missed Postprandial Hyperglycemia With Fingersticks

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 Insulin Pump System

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

Sensor BGMeter BG

Download Sensor, Meter, & Pump Data

Download Sensor, Meter, & Pump Data only in office

Dummy Pump

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

Sensor CSII

CSII

Sensor CSII

CSII

Sensor Augmented Pump Therapy A Pilot Study

• 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

Breakfast5U

Lunch3U

2 GlucoseTabs

2.8U

Supper5U

Case 1: JB, 50 yo male, DM 1 age 14, TDD 38,Basal 0.7, ICR 1:12, Target 100; CF 42

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

0

50

100

150

200

250

300

350

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

Time

Glu

co

se

Co

nc

en

tra

tio

n (

mg

/dL

)

Sensor Value (BG)

Paired Meter Value

Meter Value

Sensor On

Sensor Off

Upper Limit

Lower Limit

Init Packet

Breakfast 63g; Took 5.1U

No bolus

Lunch 60 g; 5U Supper Out?50g 4U

7.4U

Another Day

Case 1 JB Modal Day Graph

Glucose Sensor ProfileModal Day

0

100

200

300

400

500

600

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

Time

Glu

co

se C

on

cen

trati

on

(m

g/d

L)

13-Sep-04

14-Sep-04

15-Sep-04

16-Sep-04

17-Sep-04

18-Sep-04

19-Sep-04

20-Sep-04

21-Sep-04

22-Sep-04

23-Sep-04

24-Sep-04

25-Sep-04

26-Sep-04

27-Sep-04

28-Sep-04

29-Sep-04

30-Sep-04

1-Oct-04

2-Oct-04

3-Oct-04

4-Oct-04

5-Oct-04

6-Oct-04

7-Oct-04

8-Oct-04

9-Oct-04

10-Oct-04

11-Oct-04

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

0

50

100

150

200

250

300

350

400

450

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

Time

Glu

cose

Con

cent

ratio

n (m

g/dL

) Sensor Value (BG)

Meter Value

Sensor On

Sensor Off

Paired Meter Value

Sensor Limit (Above 400)

Sensor Limit (Below 40)

Start Up

Meter Value (Over 450)

Glucose Sensor Profile: 13-Dec-04

0

50

100

150

200

250

300

350

400

450

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

Time

Glu

co

se C

on

cen

trati

on

(m

g/d

L)

Sensor Value (BG)

Meter Value

Sensor On

Sensor Off

Paired Meter Value

Sensor Limit (Above 400)

Sensor Limit (Below 40)

Start Up

Meter Value (Over 450)

Basal 1.2 U/h

TDD = 47 U2 U per CarbBasal 61%

4 U

0 U2 Carb

O U

1 CarbO U

2 Carb2 U

2 U

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 5Case 5• 16-year-old girl with T1DM for 7 years16-year-old girl with T1DM for 7 years• HbA1c: 9.1% HbA1c: 9.1%

0

50

100

150

200

250

300

350

400

12:00 AM 4:00 AM 8:00 AM 12:00 PM 4:00 PM 8:00 PM 12:00 AMTime

Glu

co

se

(m

g/d

L)

22-Oct-03 23-Oct-0324-Oct-03 25-Oct-03

Problems: Too low breakfast dose; Problems: Too low breakfast dose; Increased meal carb on 10/24Increased 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)

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Week 0 Week 13 Week 26

CSII (715 model) ~70

Sensor Augmented CSII ~70

Screen:

DM 1 on CSII

A1C > 7.5%;

SMBG ≥ 4 per day

Age 12-80

Week 52

Efficacy: A1C (mean and % <7), BG mean, glucose exposure (CGMS) Safety: frequency of hypoglycemia, AEs

Efficacy: A1C (mean and % <7), BG mean, glucose exposure (CGMS) Safety: frequency of hypoglycemia, AEs

Week 2

Vision Toward the Artificial Pancreas

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

Implanted Closed-LoopExternal Closed-Loop

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