Current And Emerging Technologies In Current And Emerging Technologies In Insulin Pumps & Continuous MonitorsInsulin Pumps & Continuous Monitors

Phoenix, AZPhoenix, AZJune 18, 2008June 18, 2008

John Walsh, PA, CDEjwalsh@diabetesnet.com

(619) 497-0900

Advanced Metabolic Care + Advanced Metabolic Care + ResearchResearch

700 West El Norte Pkwy700 West El Norte Pkwy

Escondido, CA 92126Escondido, CA 92126

(760) 743-1431(760) 743-1431

Highlights

Background

Smart Pump Features

Control Tips For Pumps

DIA and BOB

Super Bolus

Continuous Monitors and Tips

Wrap Up

Talk The Talk

TDD – total daily dose of insulin (all basals and boluses)

Basal –background insulin released slowly through the day

Bolus – a quick release of insulin Carb bolus – covers carbs Correction bolus – lowers high readings

Bolus On Board (BOB) – bolus insulin still active from recent boluses

Duration of Insulin Action (DIA) – time that a bolus will lower the BG – used to measure BOB

Pump Features

Pump Features

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.

Special FeaturesFeature: Pumps:

Cont Monitor readout Paradigm

No tether Omnipod

Lowest basal rate Animas

HypoManager Cozmo

Weekly Schedule Cozmo

Missed Meal Bolus Cozmo

Bolus Not Completed Cozmo

Disconnect Bolus Cozmo

Food/Carb List Animas, CozmoOmnipod,

Spirit

Therapy Effectiveness Cozmo, Paradigm

Glucose SD (Variability) Cozmo

HypoManager

Shows current insulin OR carb deficit

Compares BOB to correction bolus need: When BOB is smaller –> Cozmo recommends a correction

bolus When BOB is larger –> Cozmo recommends eating carbs

A very helpful feature:• Reduces overeating when BG is low

• Warns when carbs may be needed later even though current BG is OK or high

HypoManager

Always 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”

Do not use with Symlin, gastroparesis

One Touch Ping

Dexcom

Ping meter sends BG result directly to new Animas pump

Give carb and correction boluses directly from meter – remote bolusing

Like other meter–pump combos, provides more accurate history

Weekly Schedule

User’s 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 variations in schedule

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

Carb Boluses

Regular Taken immediately – MOST meals

Combo / dual wave Some now, some later – bean burrito,

some pastas and pizzas, Symlin, precose

Extended / square wave Extended over time – gastroparesis

CDA1: Temporary Basal Rate

Used by 33.8% of pumpers

Great for: Exercise Illness Testing new basal rates

Should it be used by more?

Temp Basal Tips

Never suspend pump

May forget to restart

May restart too late

Does not work for treatment of lows

Need multistep temp basal reductions

Need “temp insulin adjustments” – basal insulin does not live alone

Sample Temp Basal Reduction

•

• Max temp basal reduction: 0% for 60 min

• Start temp basal reduction before exercise if possible

Disconnect Bolus To Cover Basal

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

Getting The Big PictureTherapy Effectiveness – Glucose and insulin

history

Your Goal

Stable and relatively normal glucoses

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

Available in Cozmo and Paradigm pumps

Therapy Scorecard Screen 1

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

Monitor control, testing frequency, glucose variability

Therapy Scorecard Screen 2

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?

Monitors carb intake, TDD, basal/carb bolus balance, correction bolus%

Check Your Correction Bolus %

If correction boluses make up more than 8% of the TDD (and lows are NOT a problem):

Move at least half of any excess units above 8% into basal rates or carb boluses

Raise the basal rates

Lower the carb factor

Or stop skipping carb boluses

Example: Correction Boluses Over 8%

10 Day Average:

Carbs 175 g TDD 54.1 u Meal 36% Corr 21% Basal 43%

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

Over 8%

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 4.5 (mg/dl) (carb factor / 4 in mmol)

Correction Bolus % – if over 8% of TDD, move excess into basals or carb boluses

Average BG – < 160 when checking before & after meals, < 140 when checking mainly before meals

Standard Deviation –

Keep less than 1/2 of avg BG or below 65 mg/dl

Look At The Long And The Short – BG And Insulin Doses

Long: trends and history over 14 to 90 days

Short: instant analysis via 5 Hr TrackBack

The Long – Glucose Trends And History

Is your A1c between 6% and 7%?

Is your meter average below 150 mg/dl (8.2 mmol)?

Do you have frequent lows?

Does BG go below 50 (2.7 mmol)?

Do basal doses = ~half your TDD?

Does correction factor = 4.5 X carb factor

The Short – Instant Analysis Of Insulin

Starting BG In Target

Too Low

Too High

If yourcurrent BG is:

Optimal

Too High

Too Low

Your insulin level over the last

5 hrs was:

high, low, or normal

Instant Analysis – 5 Hr TrackBack

Whenever you have a low or high reading, compare:

how much basal and how much bolus was active over the previous 5 hours

Lows – usually caused by the larger insulin amount

Highs – usually caused by the smaller insulin amount

Assume that your boluses work for 5 hours!

Future Pump Feature

Examples – 5 Hour TrackBack # 1

BG = 54 mg/dl (3 mmol) at 1:00 am

In previous 5 hours:

Boluses = 9.2 u

Basal = 4.6 u

# 2

BG = 252 mg/dl (14 mmol) at 4:30 pm

In previous 5 hours :

Boluses = 6.5 u

Basal = 2.4 u

basal

bolus

After The Instant Analysis

Decide on a better plan for the next time

Always aim for a normal reading 4 to 5 hours from now.

Continuous Monitors

Trends Or Static Readings?

CGM shows the wearer only a few carbs may be needed. Meter reading gives no clue.

Meter or CGM Improves Tracking & Insight

• Pump + Meter for direct BG entry• Deltec Cozmo + Freestyle CoZmonitor• Omnipod + Freestyle• Paradigm + Lifescan (US)/Bayer (Eur)• Animas + One Touch Ping

• Pump + Cont Mon• Medtronic x22 + Paradigm RT

• Future Pump + Meter/Monitor Combos• Animas pump + Dexcom• Cozmo + Abbott Navigator• Omnipod + Dexcom and Navigator

CGM–Pump Combos

Animas

Cosmo

Omnipod

Medtronic

Dexcom

Navigator

Paradigm RT

CGM Benefits

Increased sense of security

Immediate feedback – look and learn

Control with safety

Worth out of pocket cost for many

Insurance reimbursement gradually catching on

Continuous Monitor

A continuous monitor OR frequent meter checks lets the user see where they stand in relation to optimal energy flow

Optimal BG range for energy

Plus Insulin Pump

With full BG record, basals and boluses can be adjusted to provide optimal energy flow

Optimal BG rangefor energy flow

Better growth, better performance, better grades

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

No Two Points Created Equal!

20

30

40

50

60

70

80

90

100

0 50 100 150 200Minutes

Glucose (mg/dl)

Lower Risk Going Up

Higher Risk Going Down

Level of a BG’s risk depends on its trend

Turnaround Time A Glucose in Motion Stays in Motion

Don’t Stack Insulin

Stay Between The Lines

As readings improve, bring the upper glucose target alert line down

Be Careful In CGM Interpretation

CGM wearer said “This showed me where my “problem phases” lie. My post-meal results after breakfast and lunch consistently sucked. So I’m taking action: tofu and scrambled eggs for breakfast; earlier, more aggressive injections….and I’ve tightened my insulin-to-carb ratio a bit.”

But the bigger problem starts near midnight when the overnight basal is unable to keep the BG from rising before breakfast.

When adjusting insulin, don’t focus on only carb boluses or only basal rates!

Detection Of Hypoglycemia

HA Wolert: Use of Continuous Glucose Monitoring in the Detection and Prevention of Hypoglycemia Journal of Diabetes Science and Technology V1, #1, Jan 2007

Continuous Monitor Accuracy

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

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%

CGM Tips

Be patient, have realistic expectations

Don’t panic when meter and sensor differ

Expect some lag time

Don’t 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

Check For Patterns

Frequent highs

Frequent lows

High at B/L/D/Bed

Low at B/L/D/Bed

Low to high

High to low

Keep:

• TDDs similar from day to day

• Basals and boluses balanced

• Correction bolus below 8% of TDD

Sample Pattern

Paradigm RT Meal Breakout

CGMS Data Disaster

Correlation coefficient, MAD%, avg. BG, pie charts, %Hi, %Low, 1-Hr and 3 Hr postprandial averages…

What you or your physician have to deal with!

Why not bottom line it?

Case Study – Type 1 on Pump

Overeating forbedtime lowsor low basal

Too little carb coverage

Excess correction

A1c = 8.6%

Case Study – Bottom Line

A1c = 8.6%

Raise the correction factor for smaller correction boluses Check night basal after stopping bedtime lows Consider raising the TDD to lower A1c once lows are stopped

Bottom Line

If your smart pump is not giving you great control, check your pump

settings and infusion sets.

And demand that all you device companies “bottom line” your data.

Control TipsCommon control problems and what to do about them

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

Always Tape The Tubing!!!

Put 1” tape on the infusion line to stop Teflon tugs

• Stops movement of Teflon catheter under the skin

• Stops “unexplained highs” caused when insulin leaks back to surface

• Less skin irritation

• Prevents many pull outs

Lose tape not insulin!

No anchor!

Lose Tape Not Insulin!!!

Most insulin is lost when the Teflon comes loose, not from a complete pullout

Photo courtesy of kerri@sixuntilme.com

No tape on infusion line!

High BGs? Keep Usual Suspects In Mind

Bad infusion set or site

Inaccurate carb counts

Missed boluses

Bad insulin

Stress hormone rebound

Empty refrigerator syndrome

Stress, pain, steroid meds

I ate

too much

Pump Settings That Affect Control

TDD – adjust when having frequent lows or highs

Basal % – basal/bolus balance, secure sleep Basal rate variation – large variations are NOT physiologic

Carb factor – postmeal control Carb factor variation – may indicate basal problem

Correction factor – lower high BGs safely

DIA – bolus accuracy, HypoManager

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

7

10

115

20

J. Walsh, D. Wroblewski, and TS Bailey: Insulin Pump Settings – A Major Source For Insulin Dose Errors, Diabetes Technology Meeting 2007

Carb Factors From CDA1 Sudy

Graph shows carb factor versus TDD for 200 pumps with better control (avg BG < 209 mg/dl)

Note break in relation (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

CDA1 Carb Rule #s

Avg. carb factors in blue boxes for pumps with better control (Avg BG 209 mg/dl or less). TDDs in the tan box to the left. Rule #s of 500-625 for higher TDDs may reflect hesitance to lower CF below 10.

TDD

450 Rule (40% basl)

500 Rule (50% basl)

550 Rule (60% basl)

CrbF <40 BG <209

Rule# CrbF <40 BG<209

CrbF >40, BG <209

Rule# CrbF >40 BG<209

20.0 22.5 25.0 27.5 20.6 412.0

25.0 18.0 20.0 22.0 18.3 456.3

30.0 15.0 16.7 18.3 15.9 477.0

35.0 12.9 14.3 15.7 13.6 474.3

40.0 11.3 12.5 13.8 11.2 448.0 10.9 437

45.0 10.0 11.1 12.2 10.5 474

50.0 9.0 10.0 11.0 10.2 508

60.0 7.5 8.3 9.2 9.4 563

70.0 6.4 7.1 7.9 8.6 603

80.0 5.6 6.3 6.9 7.8 627

90.0 5.0 5.6 6.1 7.1 636

100.0 4.5 5.0 5.5 6.3 630

450-475

475-630

Carb Rule #s

Your carb factor X your TDD = your carb factor rule #

CDA1 Basal/Bolus Balance

QuickTime™ and aTIFF (Uncompressed) decompressor

are needed to see this picture.

As TDD rises, avg. 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 may not be accurate

J. Walsh, D. Wroblewski, and TS Bailey: Insulin Pump Settings – A Major Source For Insulin Dose Errors, Diabetes Technology Meeting 2007

Walsh-Roberts Rules For Optimal BGs

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

Use 450 Rule for Carb Factor

Use 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

Adapted from J Walsh and R Roberts: Pumping Insulin, 2006

Delay Eating When BG Is High

Glucose exposure is reduced if eating is delayed when a reading is high.

Remember:

Test early

Don’t forget to eat on time

Don’t forget you bolused

Duration Of Insulin Action (DIA)How long a bolus lowers your glucose

Bolus On Board (BOB)Bolus insulin still active from previous boluses

Most Carbs Are Faster Than Insulin

Time over which a bolus lowers the BG

From From Pumping InsulinPumping Insulin

Take Home: Bolus 15 to 30 minutes before meals Use extended boluses sparingly.

Meal’s impact on BG

One hour after a meal, half a meal’s glucose rise is gone, but 80% of the “rapid” insulin’s activity remains

DCA – Duration Of Carb Action

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

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

Best glucose profile when bolus given 60 min ahead

But DO NOT bolus an hour ahead of your meals!!!

Accurate DIA Prevents Lows

Accurate DIA Time

Accurate BOB

Accurate Boluses Accurate HypoManager

Prevents Lows

A short DIA hides true BOB level and its glucose-lowering activity

Leads to “unexplained” lows

Leads to incorrect adjustments in basal rates, carb factors, and correction factors

Or user starts to ignore “smart” pump’s advice

Set DIA based on real insulin action time.

Do NOT modify DIA time to fix control problems

Short DIAs Hide Bolus Insulin Activity

Duration Of Insulin Action (DIA)

4 hrs 6 hrs2 hrs0

Accurate boluses require an accurate DIA

Glu

cose

-lowe

ring

Activ

ity

DIA times shorter than 4 to 7 hrs will hide BOB and its glucose lowering activity

More DIA

Large doses (0.3 u/kg = 15 u for 110 lb. person) of “rapid” insulin in 18 non-diabetic, obese people

Med. doses (0.2 u/kg = 10 u for 110 lb. person)

Apidra product handout, Rev. April 2004a

Regular

Does Dose Size 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. 1993;42(Suppl. 1):54A

DIA May Be Underestimated In Studies

To measure pharmacodynamics, glucose clamp studies are done in healthy individuals

SQ doses = 0.05 to 0.3 u/kg Injected insulin dose 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

How Long Do Boluses Lower Your BG?

Novolog claims 3 to 5 hours 10, but numerous studies show rapid insulin lowers the glucose for 5 hours or more.

With Novolog (aspart) at 0.2 u/kg (0.091 u/lb), 23% of glucose lowering activity remained after 4 hours.12

Another study found Novolog (0.2 u/kg) lowered the glucose for 5 hours and 43 min. +/- 1 hour.13

After 0.3 u/kg or 0.136 u/lb of Humalog (lispro), peak glucose-lowering activity was seen at 2.4 hours and 30% of activity remained after 4 hours. 11

10 Novolog product labeling information, October 21, 2005. 11 From Table 1 in Humalog Mix50/50 product information, PA 6872AMP, Eli Lilly and Company, issued January 15, 2007.12 Mudaliar S, et al: Insulin aspart (B28 Asp-insulin): a fast-acting analog of human insulin. Diabetes Care 1999; 22:1501-1506.13 L Heinemann, et al: Time-action profile of the insulin analogue B28Asp. Diabetic Med 1996;13:683-684.

My Recommended DIA Times

Set DIA to 4 hrs to 6 hrs to calculate BOB and bolus doses accurately

4 hr Linear

4 hr Curvilinear

From Pumping Insulin, 4th ed., adapted fom Mudaliar et al: Diabetes Care, 22: 1501, 1999

DIA Time Selection

Current research suggests that DIA times are NOT different between children and adults

Temporary factors can shorten insulin action time:

Activity and exercise

Hot weather

Don’t shorten DIA for temporary factors

DIA Tips

DIA times NOT different between children and adults

If your pump does not “give enough bolus insulin”, do NOT shorten the DIA to get larger boluses

Look for the real reason:

a basal rate too low

or carb factor too high

Low basal rates and insufficient carb boluses make the DIA appear SHORT!

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)

BOB Prevents Insulin Stacking

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

6 pm 8 pm 10 pm 12 am

DinnerDinner

DessertDessertCorrectionCorrection Bedtime BG

= 173 mg/dl

BOB Is Present In 65% Of Boluses

CDA1 Study ResultsOf 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

Take Home: insulin stacking is a common threat

4.5 hrs

J. Walsh, D. Wroblewski, and TS Bailey: Disparate Bolus Recommendations In Insulin Pump Therapy. AACE Meeting 2007

BOB Is BOB

If BOB is present, it doesn’t 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!

How Different Pumps Handle BOB

What’s In the BOB & What Is It Applied Against?

BOB Includes 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

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

0

1

2

3

4

60 90 120 150 180 210 240

Deltec Cozmo Animas 1250 Medtronic 522

units

mg/dl

Omnipod cannot be determined here - it counts only correction bolus insulin as BOB

Bolus recommended by each pump when:

The Super Bolus

A way to safely speed up insulin’s action.

Rob Peter to pay Paul

Temp Basal Reduction For Excess BOB

Here a temporary basal reduction is used to compensate for excess BOB at bedtime.

This allows the person to go to bed without needing to eat.

Super Bolus For A High GI Meal

A Super Bolus shifts part of the next 2 to 4 hrs of basal insulin into an immediate bolus. This speeds up the action of the insulin for a high GI or a large carb meal with less risk of a low later.

Super Boluses are useful when eating more than 30 or 40 grams of carb, especially for high GI meals like cereal.

Future Pump Feature

Super Bolus For A Postmeal HighShift Basal To Bolus

Enables a faster correction of highs with less risk of a low.

Future Pump Feature

Answers To Your Questions

Available at www.diabetesnet.com or 800-988-4772