Insulin and Sensors Where are we now and where are we heading? Bruce W. Bode, MD, FACE Atlanta...
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Transcript of Insulin and Sensors Where are we now and where are we heading? Bruce W. Bode, MD, FACE Atlanta...
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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