Insulin and SensorsWhere are we now and where

are we heading?

Bruce W. Bode, MD, FACE

Atlanta Diabetes Associates

Atlanta, Georgia

Maintain near normal glycemia Avoid short-term crisis Minimize long-term complications Improve the quality of life

0 12 24

Hours

Goals of Intensive Diabetes Therapy

Goals in Management of Diabetes

Pre-meal BG 4 to 8 mmol/l

Post-meal BG < 8 to 9 mmol/l

A1C < 6.5%

Blood Pressure < 130/80

LDL < 100 mg/dL; HDL > 45 mg/dL

Triglycerides < 150 mg/dL

Insulin

The most powerful agent we have

to control glucose

Options in Insulin Therapy for Type 1 Diabetes

Current

– Multiple injections

– Insulin pump (CSII)

Future

– Implant (artificial pancreas)

– Transplant (pancreas; islet cells)

Progression of Type 1 Diabetes

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

Age (y)

Precipitating Event

Be

ta-c

ell

ma

ss

Genetic predisposition

Normal insulin release

Glucose normal

Overt diabetes

No C-peptidepresent

Progressive loss of insulin release

C-peptidepresent

AntibodyAntibody

Type 2 Diabetes … A Progressive Disease

Over time, most patients will need insulin

to control glucose

A1C in the UKPDS

06

7

8

9

0 3 6 9 12 15

HbA

1c (

%)

Years from randomisation

Conventional

Intensive

6.2% upper limit of normal range

UKPDS: -Cell Function for the Patients Remaining on Diet for 6 Years

0

20

40

60

80

100

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

Years After Diagnosis

-C

ell F

un

ctio

n (

%

)

Adapted from UKPDS Group. Diabetes. 1995; 44:1249-1258.

N=376

Multiple factors may drive progressive decline of -cell function

-cell(genetic background)

Hyperglycaemia(glucose toxicity)

Proteinglycation

Amyloiddeposition

Insulin resistance

“lipotoxicity”elevated FFA,TG

Approach to Combination Oral Therapy

Intensifying of Oral Therapies

metformin &/or glitazone+

sulfonylurea/repaglinide&/or glucosidase inh

sulfonylurea/repaglinide&/or glucosidase inh

+metformin &/or glitazone

Continue

FPG < 6.7 mmol/l A1C < 7.0% FPG > 6.7 mmol/l A1C >7.0%

Add Insulin

Comparison of Human Insulins / Analogues

Insulin Onset of Duration ofpreparations action Peak action

Regular 30–60 min 2–4 h 6–10 h

Aspart/Lispro 5–15 min 1–2 h 4–6 h

NPH/Lente 1–2 h 4–8 h 10–20 h

Ultralente 2–4 h Unpredictable 16–20 h

Glargine 1–2 h Flat ~24 h

Dissociation & Absorption of Aspart

Insulin Aspart (NovoLog)

Regular Human Insulin

Peak Time = 80-120 min

Peak Time = 40-50 min

CapillaryMembrane

Su

bcu

tan

eou

s T

issu

eS

ub

cuta

neo

us

Tis

sue

400

350

300

250

200

150

100

MealSC injection

50

00 30 60

Time (min)90 120 180 210150 240

Regular Lispro

500450400350300250

150

50

200

100

00 50 100

Time (min)150 200 300250

Pla

sm

a i

ns

uli

n (

pm

ol/

L)

Pla

sm

a i

ns

uli

n (

pm

ol/

L)

MealSC injection

Heinemann, et al. Diabet Med. 1996;13:625–629; Mudaliar, et al. Diabetes Care. 1999;22:1501–1506.

Short-Acting Insulin AnalogsLispro and Aspart Plasma Insulin Profiles

Regular Aspart

Glucose Infusion Rate

n = 20 T1DMMean ± SEM

SC insulin

4.0

3.0

2.0

1.0

0

24

20

16

12

8

4

0

0 4 8 12 16 20 24Time (hours)

mg

/kg

/min

µm

ol/k

g/m

in

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

NPH

Ultralente

CSII

Glargine

Glargine

Plasma Glucose

Time (hours)

220

200

180

160

140

120

12

11

10

9

8

7

0 4 8 12 16 20 24

mg

/dL

mm

ol/L

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

n = 20 T1DMMean ± SEM

SC insulin

NPH

Ultralente

CSII

Overall Summary: Glargine

Insulin glargine has the following

clinical benefits

– Once-daily dosing because of its prolonged

duration of action and smooth, peakless time-

action profile (mean 23.5 hours)

– Comparable or better glycemic control (FBG)

– Lower risk of nocturnal hypoglycemic events

– Safety profile similar to that of human insulin

ANA-2155:Insulin aspart CSII vs. insulin aspart/glargine MDI Open-label, randomized, crossover, two-arm study of 10-week duration

Comparison of insulin aspart CSII vs. insulin aspart/glargine MDI

Subjects: n=100, type 1 patients on CSII at entry, HbA1c < 9%

Assessments

– Efficacy: HbA1c, fructosamine, 8-pt BG profile, glucose exposure ( CGMS)

– Safety: Freq. of hypoglycaemia, AEs

Run-in (1wk) Period 1 (5wks) Period 2 (5wks)

IAsp CSII

IAsp CSII

IAsp + Gar MDI

IAsp + Gar MDI

Aspart (CSII) vs Aspart/Insulin glargine (MDI)

8-Point Blood Glucose Profiles

Novo Nordisk, data on file (Study 2155/US)Mean ± 2 sem

200

160

140

120

100

180

Se

lf-M

on

ito

red

BG

(m

g/d

L)

BB AB BL AL BD AD Midnight 3am

CSII (n=93)

MDI (n=91)

n=63 in each treatment

0

500

1000

1500

2000

2500

3000

CSII MDI

p = 0.0027

Novo Nordisk, data on file (Study 2155/US)

Aspart (CSII) vs Aspart/Insulin glargine (MDI) Glucose Exposure During CGMS

Measurement of AUC(glu) ≥80 mg/dL during the 48-hour continuous glucose monitoring period

†

AUCglu (mg•hr/dL)

†

Aspart (CSII) vs Aspart/Insulin glargine (MDI) Serum Fructosamine

n=97

Novo Nordisk, data on file (Study 2155/US)

*p = 0.0001

CSII MDI0

100

200

300

400

means ± 2 sem

Fructosamine (μmol/L)

Aspart (CSII) vs Aspart/Insulin Glargine (MDI) Rate of Minor Hypoglycemia

Novo Nordisk, data on file (Study 2155/US)

Ep

iso

des

/ s

ub

jec

t / 5

we

eks

Total Daytime Nocturnal

CSII

MDI5

4

3

2

1

0

6

7p=0.21

p<0.01

p<0.01

Gly ThrGlu Phe Tyr Pro Lys Thr

Gly ThrGlu Phe Tyr Pro Lys Thr

23 24 25 26 27 28 29 30

Insulin

Detemir

(CH(CH22))44

NHNH

COCO

RR

Primary Structure of Lys(B29)-N--Tetradecanoyl, Des(B30)-Insulin

2626Brunner GA, et al. Exp Clin Endocrinol Diabetes. 2000;108:100-105.

Elapsed time (min)

0.0

0.5

1.0

1.5

2.0

-100 100 300 500 700 900 1100 1300 1500

Detemir-high

Detemir-low

Placebo

Glu

cose

infu

sio

n r

ate

(mg

/kg

/min

)

Insulin Detemir in Nondiabetic Subjects—Pharmacokinetics by Glucose Clamp

Lowers A1C as effectively Lowers FPG significantly more Provides significantly lower intra-subject variation of fasting

blood glucose (more predictable) Produces a smoother nocturnal glucose profile Causes a lower incidence of hypoglycaemia Associated with some weight loss Causes no safety concerns

Insulin detemir in comparison to NPH:

ConclusionsFrom Phase 2 and 3 Studies

4:004:00

2525

5050

7575

8:008:00 12:0012:00 16:0016:00 20:00 20:00 24:0024:00 4:004:00

BreakfastBreakfast LunchLunch DinnerDinner

Pla

sma

insu

lin

(P

lasm

a in

suli

n (µ U

/ml)

U

/ml)

TimeTime

8:008:00

Physiological Serum Insulin Secretion Profile

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

Breakfast Lunch Dinner

8:0012:008:00

Time

Glargineor

Detemir

Lispro Lispro Lispro

Aspart Aspart Aspartor oror

Pla

sma

insu

lin

Basal/Bolus Treatment Program withRapid-acting and Long-acting Analogs

The Basal/Bolus Insulin Concept

Basal insulin

– Suppresses glucose production between meals and overnight

– 40% to 50% of daily needs

Bolus insulin (mealtime)

– Limits hyperglycemia after meals

– Immediate rise and sharp peak at 1 hour

– 10% to 20% of total daily insulin requirement at each meal

Treatment to Target Study: NPH vs Glargine in DM2 patients on OHA

Add 10 units Basal insulin at bedtime (NPH or Glargine)

Continue current oral agents

Titrate insulin weekly to fasting BG < 5.5 mmol/l

- if 5.5-6.6 mmol/l, increase 0 to 2 units

- if 6.7-7.7 mmol/l, increase 4 units

- if 7.8-8.8 mmol/l, increase 6 units

- if 8.9-10.0 mmol/l, increase 8 units

Treatment to Target Study; A1C Decrease

8.6

7.5

7.16.9 7

6.5

7

7.5

8

8.5

9

0 5 10 15 20 25 30

Weeks in Study (N=691)

Mea

n H

bA

1c%

Advancing Basal/Bolus Insulin

Indicated when FBG acceptable but– A1C > 7% or > 6.5%

and/or– SMBG before dinner > 7.8 mmol/l

Insulin options– To glargine or NPH, add mealtime aspart /

lispro– To suppertime 70/30, add morning 70/30– Consider insulin pump therapy

Novo Nordisk devices in diabetes care

First pen (NovoPen 1) launched in 1985

Committed to developing one new insulin administration system per year.

Insulin Pens

Prefilled Syringe with Flexible Dosing

82%

2%

16%

Prefer FlexPen

Prefer Humalog pen

No preference

82% of DNEs Preferred FlexPen®

Source: Diabetes Nurse Educators In-Depth Study—Reactions to FlexPen.

Pen Preference Study

®

InDuo™ - IntegrationFeature

Combined insulin doser and blood glucose monitor

InDuo™ - Doser Remembers

Feature

Remembers amount of insulin delivered and time since last dose

Benefit

Helps people inject the right amount of insulin at the right time

Device Preference: InDuo vs Vial/Syringe/Meter

79%

21%

InDuo

Vial/Syringe

Bode et al, Diabetes June, 2003

Multicenter, Randomized, Cross-over Study of 125 DM 1 patients

Starting MDI

Starting insulin dose is based on weight

0.2 x wgt. in lbs. or 0.45 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 80 kg person

Starting dose = 0.45 x 80 kg

0.45 x 80 = 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

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 90 rule to estimate the CF

CF = 90 divided by the total daily dose (TDD)

ex: if TDD = 36 units, then CF = 90/36 = ~2.5

meaning 1 unit will lower the BG ~2.5 mmol/l

Correction Bolus Formula

Example:

–Current BG: 12 mmol/l

– Ideal BG: 5.5 mmol/l

–Glucose Correction Factor: 2.5

Current BG - Ideal BGGlucose Correction factor

12 – 5.5 2.5

= 2.6 units

Options to MDI

A Simpler Regimen

Insulin Pump

Premixed BID (DM 2 only)

4:004:00 16:0016:00 20:00 20:00 24:0024:00 4:004:00

BreakfastBreakfast LunchLunch DinnerDinner

8:008:0012:0012:008:008:00

TimeTime

Basal infusion

Bolus Bolus Bolus

Pla

sma

insu

lin

Pla

sma

insu

lin

Variable Basal Rate: CSII Program

History of Pumps

Pump Infusion Sets

Metabolic Advantages with CSII

Improved glycemic control

Better pharmacokinetic delivery of insulin

– Less hypoglycemia

– Less insulin required

Improved quality of life

CSII Reduces HbA1c

5.05.56.06.57.07.58.08.5.099.5

10.0

n = 58 n = 107 n = 116 n = 50 n = 25 n = 56Mean dur. = 36

Adolescents Adults

Mean dur. = 36 Mean dur. = 54 Mean dur. = 42 Mean dur. = 12 Mean dur. = 12

Chantelau E, et al. Diabetologia. 1989;32:421–426; Bode BW, et al. Diabetes Care. 1996;19:324–327;Boland EA, et al. Diabetes Care. 1999;22:1779–1784; Bell DSH, et al. Endocrine Practice. 2000;6:357–360;Chase HP, et al. Pediatrics. 2001;107:351–356.

Bell Rudolph Chanteleau Bode Boland Chase

Pre-pump Post-pump

Hb

A1

c

CSII Reduces Hypoglycemia

0

20

40

60

80

100

120

140

160

n = 55Mean age 42

n = 107Mean age 36

n = 116Mean age 29

n = 25Mean age 14

n = 56Mean age 17

Eve

nts

per

hu

nd

red

p

atie

nt

y ea r

s

Chantelau E, et al. Diabetologia. 1989;32:421–426; Bode BW, et al. Diabetes Care. 1996;19:324–327;Boland EA, et al. Diabetes Care. 1999;22:1779–1784; Chase HP, et al. Pediatrics. 2001;107:351–356.

Bode Rudolph Chanteleau Boland Chase

Pre-pump Post-pump

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)

CSIIFactors Affecting A1C

Bode et al. Diabetes 1999;48 Suppl 1:264

Bode et al. Diabetes Care 2002;25 439

Insulin aspart versus buffered R versus insulin lispro in CSII study:

Bode et al: Diabetes Care, March 2002

Insulin aspart

Buffered regular human insulin (Velosulin®)Screening

Insulin lispro–2 0 16

weeks weeksweeks

146 patients in the USA; 2–25 years with Type 1 diabetes;

7% HbA1c 9%; previously treated with CSII for 3 months

Glycemic Control with CSII

NovoLog®Human insulin

Humalog®

7.0

7.2

7.8

8.0

Hb

A1

c (

%) 7.6

7.4

Baseline Week 8 Week 12 Week 160

Bode, Diabetes 2001 ; 50(S2):A106

Type 1 Diabetes

Self-Monitored Blood Glucose in CSII

NovoLog® Buffered Regular Humalog®

80

100

120

140

160

180

200

220

Blo

od

Glu

cose

(m

g/d

l)

* *

*

Bedtime 2 AMBefore and90 min. after

breakfast

Before and90 min. after

lunch

Before and90 min. after

dinner

Type 1 Diabetes

Bode, Diabetes 2001 ; 50(S2):A106

Pharmacokinetic Comparison Aspart vs Lispro

300

350

250

200

150

100

50

0

7 8 9 10 11 12 13

Aspart

Lispro

Fre

e In

sulin

(p

mo

l/L)

Time (hours)Hedman, Diabetes Care 2001; 24(6):1120-21

Ep

iso

des

/mo

nth

/pat

ien

t

0

2

4

6

8

10

12

insulin aspart human insulin insulin lispro

pp < 0.05 < 0.05

pp < 0.05 < 0.05

Symptomatic or Confirmed Hypoglycaemia

30% relative reduction

Bode et al: Diabetes Care, March 2002

0

10

20

30

40

50

Insulin aspartBuffered human insulin

Insulin lispro

Pat

ien

ts w

ith

tro

ub

le-f

ree

use

(%

)

Insulin aspart versus buffered R versus insulin lispro in CSII study: pump compatibility

Data on file (study ANA 2024)

0

100

200

300

400

500

600

700

5/9/2001 5/29/2001 6/18/2001 7/8/2001 7/28/2001 8/17/2001 9/6/2001 9/26/2001 10/16/2001 11/5/2001

LisproAverage = 7.8SD = 6.6

AspartAverage = 6.6SD = 4.0

DM 1 CSII Patient: Lispro to Aspart

Long-term Heat Stability of Insulin Aspart in Infusion Pumps

Co

nc

entr

ati

on

(n

M)

100

600

500

400

300

200

0

700

Day 05°C

Day 2 Day 6

MiniMed (506) pumps

Disetronic H-Tron plus V100• Antimicrobial Effectiveness and

Particulate Matter were within USP requirements after 6 days.

• Stable pH during the 6 days

• Physico-chemical integrity of insulin aspart was retained.

In-vitro 6-day stability study under conditions of simulated CSII pump use (37°C with constant shaking)

Glycemic Control in Type 2 DM: CSII vs MDI in 127 patients

A1C

7.0

7.2

7.4

7.6

7.8

8.0

8.2

8.4

CSII MDI

Baseline

End of Study (24 wks)

Raskin et al. Diabetes 2001;50 Suppl 2:A128

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

Less Social Limitations

MDICSII

CSII vs MDI in DM 2 Patients

Raskin et al. Diabetes 2001;50 Suppl 2:A128

DM 2 Study: CSII vs MDI

93% in the CSII group preferred the pump to their prior regiment (insulin +/- OHA)

Overall treatment satisfaction improved in the CSII group: 59% pre to 79% at 24 weeks

CSII group had less hyperglycemic episodes (3 subjects, 6 episodes in CSII group vs. 11 subjects, 26 episodes in the MDI group)

Raskin et al. Diabetes 2001;50 Suppl 2:A128

Normalization of Lifestyle

Liberalization of diet — timing & amount

Increased control with exercise

Able to work shifts & through lunch

Less hassle with travel — time zones

Weight control

Less anxiety in trying to keep on schedule

N = 165Average Duration = 3.6 yearsAverage Discontinuation <1%/yr

Continued 97%

Discontinued 3%

Current Continuation RateContinuous Subcutaneous Insulin Infusion (CSII)

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

6,600 8,700 11,40015,000

20,00026,500

35,00043,000

60,000

81,000

120,000

157,000

200,000

0

50,000

100,000

150,000

'90 '91 '92 '93 '94 '95 '96 '97 '98 '99 2000 2001 2002

U.S. Pump UsageTotal Patients Using Insulin Pumps

Current Pump Therapy Indications

Diagnosed with diabetes (even new onset DM 1)

Need to normalize blood glucose (BG)

–A1C 7.0%

–Glycemic excursions

Hypoglycemia

Poor Candidates for CSII

Unwilling to comply with medical

follow-up

Unwilling to perform self blood glucose monitoring 4 times daily

Unwilling to quantitate food intake

Meal bolus

1

2

3

4

5

6

12 am 12 pm 12 am

Time of day

Basal rate

Pump Therapy

Units

Meal boluses Insulin needed pre-meal

– Pre-meal BG– Carbohydrates in meal– Activity level

Correction bolus for high BG

Basal rate Continuous flow of

insulin Takes the place of NPH

or glargine insulin

“Average Joe” adult target ranges:

– Preprandial:4 – 8 mmol/l

– 2 hr postprandial: < 9 mmol/l

– Bedtime 5 – 8 mmol/l

– 3 am: > 4.5 mmol/l

Individually set for each patient

Target BG Ranges for MDI or CSII

DCCT, N Engl J Med 1993, 329:977-986.ADA: Clinical Practice Recommendations, 2001.

Hypoglycemic unawareness

– Preprandial: 4.5 – 9.0 mmol/l

Pregnant

– Preprandial: 3.3 – 5.0 mmol/l

– 1 hr postprandial: < 6.7 mmol/l

– 2 hr postprandial: < 6.7 mmol/l

Individually set for each patient

Target BG Ranges for MDI or CSII

Fanelli CG et al., Diabetologia 1994, 37:1265-76.Jovanovich L, AMJObGynec 1991, 164:103-11.

Initial Adult Dosage Calculations

Starting Doses

–Based on pre-pump Total Daily Dose (TDD) Reduce TDD by 25-30% for Pump TDD

–Calculated based on weight

0.53 x weight in kg

Bode BW, et al., Diabetes 1999,(Suppl 1):84.Bell D and Ovalle F, Endocrine Practice 2000, 6:357-360.Crawford, LM, Endocrine Practice 2000, 6:239-43.

Initial Adult Dosage Calculations

Basal Rate

–50% of pump Total Daily Dose

–Divide total basal by 24 hours to decide on hourly basal

–Start with only one basal rate

–See how it goes before adding additional basals

Initial Dosage Calculations

Meal (food) Bolus Method

- Divide total bolus dose by 3

- Test BG before meal

- Give correction bolus

- Give pre-determined insulin dose for pre-determined CHO content

- Test BG after meal

Individually determined

1st option:

CIR = (1.3 x Wgt in kg) / TDD

2nd option:

500 divided by TDD

Anywhere from 5 to 25 g CHO is covered by 1 unit of insulin

Estimating the Carbohydrate to Insulin Ratio (CIR)

What Type of Bolus Should You Give?Immediate vs Square vs Dual Wave

9 DM 1 patients on CSII ate pizza and coke on four consecutive Saturdays

Dual wave bolus (70% at meal, 30% as 2-h square):

0.5 mmol/l glucose rise

Single bolus: 1.8 mmol/l rise

Double bolus at -10 and 90 min: 3.7 mmol/l rise

Square wave bolus over 2 hours: 4.4 mmol/l rise

Chase et al, Diabetes June 2001 #365

Basal Dose Adjustment

Rule of 1.7:

Basal Rate(s) Adjustments Overnight

– Check BG

Bedtime

12 AM

3 AM

7AM

– Adjust overnight basal if readings vary > 1.7 mmol/l

Insulin Dose Adjustment

Rule of 1.7:

Basal Rate(s) Adjustments Daytime

–Check BG

Before usual meal time

Skip meal

Every 2 hrs (for 6 hrs)

–Adjust daytime basal if readings vary > 1.7 mmol/l

Prevention of Hypoglycemia

Monitor BG

–4-6 times a day

–Set appropriate BG target range

Set minimum BG level before sleep

–Never < 4.5 mmol/l, unless pregnant

Treatment of Hyperglycemia

If blood glucose is above 15 mmol/l

– Take a correction bolus by pump– Check BG again in 1 hr

If still above 15 mmol/ll

– Take correction bolus by syringe– Change infusion set and reservoir– Check BG again in 1 hr

If BG has not decreased

– Increase correction bolus by syringe– CALL PHYSICIAN

If A1C is Not to 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 A1C Not to Goal and No Reason Identified

Place on a continuous glucose monitoring system (CGMS by Medtronic Minimed, Glucowatch by Cygnus) to determine the cause

Medtronic MiniMed Continuous Glucose Monitoring System (CGMS)

Physician downloads data for retrospective analysis

Com-Station and software packages combine data from:

– Sensor

– Models Paradigm, 508 and 507C insulin pumps

– Traditional glucose meters

Physician Product

CGMS

CGMS Sensor

GLUCOSE MONITORING SYSTEMS - Telemetry

“Real time” glucose readings

Wireless communication from sensor to monitor

High and low glucose alarms

FDA panel pending

Consumer Product

GlucoWatch® Biographer

Therasense Continuous Glucose Monitoring System

Features– Easy to use, 3 day, disposable sensor

– Hyperglycemia/hypoglycemia alarms

– Interstitial fluid glucose values & trends

– Memory

– FreeStyle calibration built in

The DexCom Continuous Glucose Sensor System Technology Description

Sensor

– Multi-layer membrane

• Modifies foreign body response

• Promotes local vascularization

• Glucose oxidase

– Measures glucose every 30 seconds

– Wireless transmission to receiver •Receiver

– Receives and processes data from sensor– Updates value every 5 minutes– Displays glucose value– Displays 1, 3, and 9 hour graphic trends– High and low Alerts

Implantable Insulin Pump

Average HbA1c 7.1%

Hypoglycemic events reduce to 4 episodes per 100 pt-years

The Long-Term Sensor System: a prototype of implantable artificial pancreas

Sensor Tip

Abdominal Lead Assembly (ALA)

Catheter Tip for Insulin Delivery

Catheter Header with Inlet Port

Sensor Connection to the Pump

Inlet to Pump

Results to date:

– 18 patients

– Sensor life >14 months

– Calibration check once per week

– Learning about insertion / positioning

– Four closed-loop experiments

Medtronic-Minimed Medtronic-Minimed Long-term IV Glucose Sensor (LTSS)Long-term IV Glucose Sensor (LTSS)

Re-Calibrated

0

50

100

150

200

250

300

350

26 Thu

Oct 2000

27 Fri 28 Sat 29 Sun 30 Mon 31 Tue 1 Nov 2 Thu 3 Fri 4 Sat 5 Sun 6 Mon 7 Tue

Sensor Vs. HemoCue (Finger) Glucose --- Sensor # 6989Long-Term Implanted Glucose Sensor System (12 Days)

Glu

cose

(m

g/d

L)

Medtronic Minimed Long-Term Sensor System Medtronic Minimed Long-Term Sensor System (LTSS)(LTSS)

Source: Medical Research Group, Inc.

Human Clinical Trial

IV Sensor Performance IV Sensor Performance in a Diabetic Patient over 11 Monthsin a Diabetic Patient over 11 Months

0

50

100

150

200

250

300

350

400

24 TueApr 2001

25 Wed 26 Thu 27 Fri 28 Sat 29 Sun 30 Mon 1 May

Glu

cose

(m

g/dL

)

0

50

100

150

200

250

300

350

400

24 SunJun 2001

25 Mon 26 Tue 27 Wed 28 Thu 29 Fri 30 Sat 1 Jul

Glu

cose

(m

g/dL

)

0

50

100

150

200

250

300

350

400

25 ThuOct 2001

26 Fri 27 Sat 28 Sun 29 Mon 30 Tue 31 Wed 1 Nov

Glu

cose

(m

g/dL

)

50

100

150

200

250

300

350

400

1 JanJan 2002

2 Wed 3 Thu 4 Fri 5 Sat 6 Sun 7 Mon 8 Tue

Glu

cose

(m

g/dL

)

Month 2Month 2 Month 4Month 4

Month 8Month 8 Month 11Month 11

E. Renard et al, Lapeyronie Hospital, Montpellier, FranceE. Renard et al, Lapeyronie Hospital, Montpellier, France

Medtronic Minimed Artificial Pancreas

Blood Glucose Profile, Before, During and After Blood Glucose Profile, Before, During and After Closed Loop using LTSSClosed Loop using LTSS

0

50

100

150

200

250

300

350

400450

26 SunAug 2001

27 Mon 28 Tue 29 Wed 30 Thu 31 Fri 1 Sep 2 Sun

Glu

cose

(m

g/d

L)

closed loop

Distribution of Blood Glucose One Week Before and During 48H-‘Closed-Loop

0 %0 %5 %5 %>13 mmol/l>13 mmol/l

26 %26 %45 %45 %6.7 – 13 mmol/l6.7 – 13 mmol/l

60 %60 %25 %25 %3.8-6.7 mmol/l3.8-6.7 mmol/l

1414 %%25 %25 %< 3.8 mmol/l< 3.8 mmol/l

During ‘Closed-During ‘Closed-Loop ’Loop ’

Before Closed-LoopBefore Closed-LoopReference Point Reference Point RangeRange

Average Glucose (mmol/l)Average Glucose (mmol/l) 6.4 6.4 5.8 5.8

Daily Insulin Use (IU)Daily Insulin Use (IU) 35 35 45 45

E. Renard et al, Lapeyronie Hospital, Montpellier, FranceE. Renard et al, Lapeyronie Hospital, Montpellier, France

Closed-loop control using an external insulin pump and a subcutaneous glucose sensor

subcutaneous glucose sensor

Insulin infusion pump(currently MiniMed 511)

+

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

Conclusion

Intensive therapy is

the best way to treat

patients with diabetes

Questions

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