Current And Emerging Technologies In Insulin Pumps

1
Current And Emerging Technologies In Insulin
Pumps Continuous Monitors

• May 8, 2008
• John Walsh, PA, CDE
• jwalsh_at_diabetesnet.com
• [phone]
• Advanced Metabolic Care Research
• 700 West El Norte Pkwy
• Escondido, CA 92126
• [phone]

2
Highlights

• Background
• Smart Pumps and Features
• Pump Control Tips
• DIA and BOB
• Super Bolus
• Continuous Monitors and Tips
• Wrap Up

3
EDIC Study FindingsLower Glucose Prevents Heart
Attacks Early Death

• After the DCCT ended in 1993, the EDIC Study has
  followed these participants.
• Over 11 years, A1c levels in intensive and
  conventional control groups have been identical
  at 7.9 (was 7.4 and 9.1).
• However, heart attacks and strokes have been
  twice as high (98 vs 46) in the original
  conventional versus intensive group, even though
  A1c levels have been identical since the DCCT
  trial ended.

1. EDIC Study Group presentation at 2005 ADA,
K.M. Venkat Narayan Clinical Diabetes 2488-89,
2006
4
EDIC Study FindingsLower Glucose Temporarily
Reduces Nerve Damage

• The tight control group also
  
  experienced half as much neuropathy
• BUT, as shown in figure, improvedcontrol in the
  past delays progression but offers no long-term
  protection
• Also, an A1c of 7.9 does not stopprogression of
  nerve damage (or CVD)
• Take Home Improve control and KEEP it there!

Avg A1c 7.9
Diabetes Care, Vol 29, No. 2, pp. 340-344
5
Goal A Healthy, Saner Life With Less Glucose
Exposure And Variability
The DCCT proved that exposure to high blood
glucose was damaging. New emphasis is on glucose
variability.
Glucose Variability (Swing)
SD from PC or meter
Glucose Exposure
A1c or average BG from meter
6
Current Pump Reality

• Pumps provide only modest improvements in A1c
  levels over MDI
• About 0.6 lower (mid to upper 8 range)
• Avg. A1c of 8.5 is well above goal of less than
  7 or 6.5
• But glucose levels ARE more stable with less
  insulin needed per day

7
Smart Pump Features
8
Smart Pump Features Overview

• Automatic carb and correction calculations based
  on
• Carb and correction factors
• Glucose targets
• DIA avoids insulin stacking
• Carb and correction boluses adjusted for BOB for
  accuracy and safety
• Personal carb database
• Correction bolus shown as of TDD
• Direct glucose entry and detailed glucose history
• Reminders, alerts, weekly schedule, temp basal
  rates, etc.

9
Deltec Cozmo

• Features Pumps
• HypoManager 1
• Weekly Schedule 1
• Missed Meal Bolus 1
• Bolus Not Completed 1
• Disconnect Bolus 1
• Basal Test 1
• Meal Maker with CozFoods 4
• Therapy Effectiveness 2
• BG Variability (SD) 1

10
Meter/CGM Improve BG History

• Pump Meter direct BG entry
• Deltec Cozmo Freestyle CoZmonitor
• Omnipod Freestyle
• Paradigm Lifescan (US)/Bayer (Eur)
• Pump Cont Mon no direct BG entry
• Medtronic x22 Paradigm RT
• Future Pump Meter/Monitor Combos
• Animas pump Lifescan meter
• Cozmo Abbott Navigator
• Animas Omnipod Dexcom
• AccuChek pump meter

11
Disconnect Bolus

• Disconnect up to 2 hrs forsports, sauna, sex,
  etc.
• Useful for Mini-vacations
• User estimates time off andpump gives up to 50
  of missed basal as bolus
• Alarm reminds user to re-connect
• On reconnecting, pump shows missed basal and
  offers to supply the missing amount

12
Weekly Schedule

• Users profile changes automatically for specific
  days of the week
• Allows different basal patterns and missed meal
  bolus alerts for each day of the week
• No need to remember to change basal patterns or
  alerts
• Great for college, shift work, weekends,
  exercise, or other regular variation in schedule

13
Pump As Carb Counter

• Pump or external controller contains
  user-selected food list for accurate carb
  counting for
• Easy carb calculations
• More accurate boluses
• Available in Animas 2020, Deltec Cozmo, Omnipod
  PDM, and Spirit PDA

14
Carb Bolus Varieties

• Regular
• Taken immediately for most meals
• Extended / square wave
• Extended over time gastroparesis
• Combo / dual wave
• Some now, some later bean burrito, some pastas
  and pizzas, Symlin

15
Helpful Aids And Alerts

• Carb or insulin recommendation for each BG
• Bolus-not-completed alert
• Missed meal bolus alert
• Check after high or low BG
• 10 extra units for basal when reservoir reads
  zero
• Easier analysis with TDD and basal/bolus balance
• Overview of basal/bolus balance and correction
  bolus

Not available in all pumps
16
Getting The Big PictureTherapy Effectiveness
A summaryof glucose and insulin history
17
Therapy Effectiveness Scorecard

• Screen 1
• Average BG (over 2 to 30 days)
• BG tests per day
• BG standard deviation (SD)
• Screen 2
• Carbs per day
• TDD
• correction boluses
• carb boluses
• basal rates

Largely available in Paradigm pumps as well
18
Therapy Scorecard Screen 1
Monitor control, testing frequency, glucose
variability
14 Day Average BG 146 mg/dl Tests
3.5/day Std Dev 53 mg/dl
Overall controlAdequacy of testingBG
variability aim forless than 65 mg/dl or less
than half of average BG
19
Therapy Scorecard Screen 2
Monitors carb intake, TDD, basal/carb bolus
balance, correction bolus
14 Day Average Carbs 206 g TDD
48.58 u Meal 38.07 Corr
4.95 Basal 56.98
Boluses taken? Low carb diet?Guides therapy
A1c, lows, etcCarb bolus Correction less than
8 of TDD?Basal at least 40 to 45 of TDD?
20
Check Correction Bolus

• If correction boluses make up more than 8 of the
  TDD (and lows are NOT a problem)
• Move half of the excess units above 8 into basal
  rates or carb boluses
• Raise the basal rates
• Lower the carb factor
• Or stop skipping carb boluses

21
Example Correction Boluses Over 8
10 Day Average Carbs 175 g TDD
54.1 u Meal 36 Corr 21
Basal 43
Over 8

• Move 1/3 to 1/2 of the overage to basals or carb
  boluses
• 21 of 54.1 11.3 units, 8 of 54.1 4.3 units
• 11.3 u - 4.3 u 7 units excess
• 1/3 to 1/2 of 7 u 2.3 to 3.5 u to add to basals
  or carb boluses

22
Therapy Effectiveness Guides

• TDD Raise for frequent highs or high A1c
• Lower for frequent lows or for frequent lows
  and highs
• Basal/Bolus Balance about 50 of TDD
• Correction Factor carb factor X 4.4 (mg/dl),
  carb factor / 4 (mmol)
• Correction Bolus if over 8 of TDD, move
  excess into basals or carb boluses
• Average BG lt 160 when checking before after
  meals, lt 140 when checking mainly before meals
• Standard Deviation
• Keep less than 1/2 of avg BG or below 65 mg/dl

23
Pump Control Tips
24
High BGs? Keep The Usual Suspects In Mind

• I ate too much
• Bad infusion set or site
• Inaccurate carb counts
• Missed or late boluses
• Bad insulin
• Stress hormone rebound
• Empty refrigerator syndrome
• Stress, pain, steroid meds

25
Bad Infusion Set Or Site

• If you have unexplained highs
• How often do they happen?
• Do they correct only when you replace your
  infusion set?
• If you answer yes
• Always use tape to anchor the infusion line
• Consider changing to a different infusion set

The right infusion set and good site technique
prevents headaches and improves your A1c
26
Tape The Tubing!!!

• Put 1 tape on the infusion line to stop Teflon
  tugs
• Tape the tubing down to stop movement of Teflon
  catheter under the skin
• Stops unexplained highs caused when insulin
  leaks back to surface
• Less skin irritation
• Prevents pull outs
• Lose tape not insulin!

No anchor!
27
Tape The Tubing!!!

• Lose tape not insulin!

Photo courtesy of kerri_at_sixuntilme.com
28
Use Sterile Technique For Site Prep

• 30 of people are constant staph carriers and 25
  are intermittent. MRSA is now common. Prevent
  infections
• Wash hands
• Sterilize skin with IV Prep
• Place bio-occlusive IV3000 over site
• Insert infusion set through IV 3000
• Steps for staph carriers
• Use antiseptic soap all over body once every 1-2
  weeks
• Occasionally, apply bacitracin ointment to inside
  of nose

29

• Pump Settings That Affect Control

30
Important Pump Settings

• TDD adjust when having frequent lows or highs
• Basal basal/bolus balance, secure sleep
• Basal rate variation large variation not
  physiologic
• Carb factor postmeal control
• Carb factor variation may indicate basal
  problem
• Correction factor lower high BGs safely
• DIA bolus accuracy, HypoManager

31
CDA1 StudyCarb Factors From Cozmo CDA Study

• Note how actual carb factors are distributed in
  blue
• They are NOT bell-shaped!!!
• People prefer magic numbers 7, 10, 15, and 20
  (grs/unit) for their carb factors
• A normal, bell-shaped, physiologic distribution
  is shown in green
• MANY magic carb factors are inaccurate

10
7
115
20
32
Carb Factors From CDA1 Sudy

• Graph shows carb factor versus TDD for 200 pumps
  with better control (avg BG lt 209 mg/dl)
• Note a break in relationship (red line) near a
  TDD of 40 u/day or carb factor of 10
• Suggests that people are hesitant to lower carb
  factors below 10

33
CDA1 Carb Rule s Compared To PI
Carb Rule s
450-475
475-625

• The average carb factors in the blue boxes are
  those used in pumps with better control where the
  avg BG was 209 mg/dl or less. TDDs are shown in
  the tan box on the left.

34
CDA1 Basal/Bolus Balance

• As TDD rises, basal percentage falls slightly
  from 51.7 at a TDD of 20 u to 49.4 at 40 u and
  48.3 at 80 u
• Basals vary widely 27 to 83 of TDD
• Many basal rates do not appear to be accurate
• If correction bolus excess is distributed evenly
  into basals and carb boluses, real basal rates
  would average over 50 of TDD

35
Walsh-Roberts Rules For Optimum Readings

• Starting TDD (TDD X 0.9) (wt lbs/4 X 0.9)
  2
• Keep Basal/Bolus Balance near 50/50
• Basal test rise/fall less than 30 mg/dl (1.7
  mmol) over 8 hrs
• 500 Rule for Carb Factor
• 2000 Rule for Correction Factor (110 Rule for
  mmol)
• Set DIA at 4 to 6 hrs
• Keep correction boluses less than 8 of TDD
• or kg/1.8 If current TDD less than wt/4
  with good control, TDD current TDD X 0.90

J Walsh and R Roberts Pumping Insulin, 2006
36
Delay Eating When BG Is High
Glucose exposure is reduced when high readings
are allowed to fall before eating. Remember
Test early Dont forget to eat on time Dont
forget you bolused
37
Duration Of Insulin Action (DIA)How long a bolus
lowers your glucoseBolus On Board (BOB)Bolus
insulin still active from previous boluses
38
ProblemMost Carbs Are Faster Than Rapid Insulin
An hour later, half of most meals glucose rise
has occurred, but 80 of rapid insulin activity
remains
Time over which most meals affect the BG
bolus activity remaining
Take Home Bolus 15 to 30 minutes before meals
Use extended and combo boluses sparingly
From Pumping Insulin
39
Typical Carb Digestion Times

• Food Digestion Time
• water 0 m
• fruit/veg juice 5-20 m
• fruit/veg salad 20-40 m
• melons/oranges 30 m
• apples/pears 40 m
• broccoli/caulif 45 m
• raw carots/beets 50 m
• potatoes/yams 60 m
• cornmeal/oats 90 m

Food Digestion Time fish 30-60
m milk/cot cheese 90 m legumes/beans 120
m egg 45 m chicken 1.5-2 hr seeds/nuts
2.5-3 hr beef/lamb 3-4 hr cheese 4-5 hr
Take Home Choose combo foods to lengthen carb
digestion time
40
Best Bolus Timing For Carbs

• Figure shows rapid insulin injected 0, 30, or 60
  min before a meal
• Normal glucose and insulin profiles shown in the
  shaded areas
• DO NOT bolus an hour ahead of your meals!!!

41
Accurate DIA Prevents Lows

• Accurate DIA Time
• Accurate BOB
• Accurate Boluses Accurate HypoManager
• Prevents Lows

42
Short DIAs Hide Bolus Insulin Activity

• A short DIA hides true BOB level and its
  glucose-lowering activity
• Causes unexplained lows
• Leads to incorrect adjustments in basal rates,
  carb factors, and correction factors
• Or user starts to ignore smart pumps advice
• Set DIA based on real insulin action time.
• Do not modify DIA time to fix a control problem.

43
Duration Of Insulin Action (DIA)
Accurate boluses require an accurate DIA
DIA times shorter than 4 to 7 hrs will hide BOB
and its glucose lowering activity
Glucose-lowering Activity
6 hrs
2 hrs
0
4 hrs
44
Large Doses, Longer Duration

• Large doses (0.3 u/kg or 30 u for 220 lb. person)
  of rapid insulin in 18 non-diabetic, obese
  people show significant activity beyond 4 hours.
• Medium doses (0.2 u/kg or 10 u for 110 lb.
  person) show similar results.
• Large doses may lengthen DIA

Apidra product handout, Rev. April 2004a
45
Dose Size May Affect Duration Of Action

• For a 154 lb or 70 kg person
• 0.05 u/kg 3.5 u
• 0.1 u/kg 7 u
• 0.2 u/kg 14 u
• 0.3 u/kg 21 u

Woodworth et al. Diabetes. 199342(Suppl. 1)54A
46
But Studies Routinely Underestimate DIA

• To measure pharmacodynamics, glucose clamp
  studies are done in healthy individuals
• SQ doses from 0.05 to 0.3 u/kg
• But injected insulin ALSO SUPPRESSES normal basal
  release from the pancreas (grey area in figure)
• Unmeasured basal suppression makes smaller
  boluses appear to have a shorter DIA
• When basal suppression is accounted for, true DIA
  times become longer

47
Recommended DIA Times

• A DIA of 4 to 6 hrs gives best estimate for
  residual bolus activity
• A longer DIA is a safer DIA

4 hr Linear
4 hr Curvilinear
From Pumping Insulin, 4th ed., adapted fom
Mudaliar et al Diabetes Care, 22 1501, 1999
48
DIA Time Selection

• Current limited research suggests that DIA times
  are NOT different between children and adults
• Immediate factors can change insulin action time
• Shorter with activity and exercise
• Shorter in hot weather
• Longer with fat in diet
• Do not change DIA time for temporary factors

49
DIA Tips

• If pump often suggests boluses that are too
  small, do not shorten the DIA it is rarely NOT
  problem
• Instead, ask what is causing the highs and where
  more insulin is needed in basal rates, in carb
  boluses, or both
• DO NOT shorten the DIA for occasional activity.
  Instead
• lower boluses or basals ahead of time for planned
  activities
• or eat more carbs or lower basals for unplanned
  activities
• Basal rates that are too low make the DIA appear
  SHORT!

50
How Different Pumps Handle DIA
Differences In DIA Calculations Differences In DIA Calculations Differences In DIA Calculations Differences In DIA Calculations Differences In DIA Calculations Differences In DIA Calculations
DIA Type Of DIA Measured Default DIA My Preferred DIA Time Increment For DIA
Animas 2020 Curvilinear 100 4 hrs 4.5 to 6 hrs 30 min
Deltec Cozmo Linear 100 3 hrs 4 to 5.25 hrs 15 min
Insulet Omnipod Linear 100 4 hrs 4 to 5.5 hrs 30 min
Paradigm 522/722 Curvilinear 95 6 hrs 5 to 6 hrs 60 min
51
Bolus On Board (BOB)Glucose-lowering activity
that remains from recent boluses

• An accurate BOB
• Prevents insulin stacking
• Improves bolus accuracy
• Reveals current carb or insulin deficit
• Basal insulin is NOT measured by BOB!

aka insulin on board, active insulin, unused
insulin Introduced as Unused Insulin in 1st ed
of Pumping Insulin (1989)
52
BOB Prevents Insulin Stacking

• Bedtime BG 173
• Is there an insulin or a carb deficit?

Bedtime BG 173 mg/dl
Correction
Dessert
Dinner
6 pm
8 pm
10 pm
12 am
53
BOB Is Present In 65 Of Boluses

• CDA1 Study Results
• Of 201,538 boluses, 64.8 were given within 4.5
  hrs of a previous bolus
• An accurate DIA shows that BOB is present for
  MOST boluses

4.5 hrs
Take Home insulin stacking is a common threat
54
Blind Boluses Hide BOB

• In 2005, only 28,969 of 117,711 carb boluses
  given by 541 pumps across the US were accompanied
  by a BG value.
• 6 of 7 carb boluses are blind given with no BG
• With no BG, BOB cannot be accounted for by the
  pump in most carb boluses

85.8 blind boluses
55
Before giving a bolus, check your BOB (via
BG).Do not give blind boluses.
56
BOB Is BOB

• If BOB is present, it doesnt matter how it got
  there.
• Safety requires that BOB be subtracted from BOTH
  carb and correction boluses to avoid
  hypoglycemia.
• BOB is measured only when a BG is entered
  into pump!

57
How Different Pumps Handle BOB
Whats In BOB And What Is It Applied Against? Whats In BOB And What Is It Applied Against? Whats In BOB And What Is It Applied Against? Whats In BOB And What Is It Applied Against? Whats In BOB And What Is It Applied Against?
BOB Includes This Type Of Bolus BOB Includes This Type Of Bolus BOB Is Subtracted From This Type Of Bolus BOB Is Subtracted From This Type Of Bolus
Carb Correction Carb Correction
Animas 2020 Yes Yes No Yes
Deltec Cozmo Yes Yes Yes Yes
Insulet Omnipod No Yes No Yes
Medtronic Paradigm Yes Yes No Yes
Except when BG is below target BG
58
Different Pump Bolus Recommendations

• BOB 3.0 u and 30 gr. of carb will be
  eaten at these glucose levels
• Carb factor 1u / 10 gr
• Corr. Factor 1 u / 40 mg/dl over
  100
• Target BG 100
• TDD 50 u

Bolus recommended by each pump when
units
mg/dl
Omnipod cannot be determined here - it counts
only correction bolus insulin as BOB
59
Recommended Bolus Errors Can Be Corrected

• A Paradigm user can scroll down 3 times to see
  active insulin, then adjust dose
• 3
• 1.5
• - 4.5
• 0 u bolus

3.0U 30 gr 160 3U 1.5U 4.5U
30
60
HypoManagerShows current insulin OR carb deficit
61
HypoManager

• Compares BOB to correction bolus need
• When BOB is smaller gt all pumps recommend a
  correction bolus
• When BOB is larger gt Cozmo recommends eating
  carbs
• A very helpful feature
• Shows current carb OR insulin deficit
• Reduces overeating when BG is low
• Warns when carbs may be needed later even though
  current BG is OK or high.

62
HypoManager

• Helps TREAT lows
• Encourage users to test when low
• The BG reading triggers what should be an
  accurate recommendation for carb intake to treat
  that low
• Prevents ETRS Empty The Refrigerator Syndrome
• Dont use with Symlin, ?gastroparesis

63
Continuous Monitors
64
CGM Benefits

• Increased sense of security
• Immediate feedback look and learn
• Control with safety
• Worth out of pocket cost for many
• Reimbursement gradually catching on

65
Continuous Monitor

• A continuous monitor (OR frequent meter checks)
  can assist optimum energy flow

Optimum BG range for energy flow
66
Plus Insulin Pump

• With full BG record, basals and boluses can be
  adjusted to provide optimum fuel flow

Optimum BG range
67
Continuous Monitoring

• Benefits
• Lots more info
• Alarms to prevent lows
  highs
• Security in knowing where the BG
  is and where it is going
• Trends shown by graph, arrows, or predictors

• Limitations
• Accuracy
• Data gaps
• Insurance coverage
• Occ cell phone and other interference

68
Continuous Monitor Tips
69
CGM Look And Learn

• Excess night basal or bedtime bolus
• Breakfast bolus too small or too late
• Lunch bolus too small or afternoon basal too low

70
No Two Points Are Created Equal!
Lower Risk Going Up
Higher Risk Going Down
Level of a BGs risk depends on its trend
71
Turnaround Time A Glucose in Motion Stays in
Motion
72
Dont Stack Insulin
73
Stay Between The Lines
As readings improve, bring the upper glucose
target alert line down
74
Continuous Monitoring Tips

• Be patient, have realistic expectations
• Dont panic when meter and sensor differ
• Expect some lag time
• Dont react too quickly and stack your insulin
• Look at trends, not just individual values
• Rapid rises usually mean more insulin is needed
• Validate your readings with a meter

75
Comparison Of Two Continuous Monitors

• The Dexcom STS 3 Day Paradigm RT continuous
  monitors were worn at the same time by one person
  with Type 1 diabetes. With low alert at 80 mg/dl
  and high alert at 160 mg/dl, 262 readings from
  Ultra meter performed over 33 days. Ultra tests
  done
• As soon as either monitors low or high alert
  sounded
• When values between the monitors disagreed
• And at routine intervals, including calibrations
• Screens show same 3 hr time period (0 to 400
  mg/dl), Ultra reading was 73 mg/dl.

76
GlycensitTM Analysis
B
A

• Simultaneous comparison vs 262 Ultra readings
  over 33 days
• Blue dotted lines ISO meter standard
• Yellow area 95 of all data points
• Red lines min and max deviation by star points
• Ideally, all readings would fall between the blue
  dotted lines

http//tomcatbackup.esat.kuleuven.be/GLYCENSIT/
77
Which Monitor Alerted First?

• This table shows which monitor alerted at least 5
  min earlier for true lows and highs.
• Monitor A was first to alert for readings below
  80 mg/dl 76 of the time, B was first 3 of the
  time, with 21 as ties.
• Monitor A was first to arlert for readings above
  160 mg/dl 68 of the time, B was first 5 of the
  time, with 27 as ties.

78
More On Monitor Accuracy

• Navigator 5 day (shown in graph)1
• Median ARD 9.3
• Clark error grid
• A 81.7
• B 16.7
• C and D 1.7
• Dexcom 7-day (not shown)
• Median ARD 17
• Clark error grid
• A 70
• B 28
• C and D 3

1 R L Weinstein et al Diabetes Care, 30,
1125-1130, 2007
79
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