3/7/2015

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Continuous Glucose Monitoring & Diabetes Management

Tomas C. Walker, DNP, APRN, CDEDirector, Clinical Projects

Dexcom, Inc.San Diego, CA

This talk is for discussion ONLY – It does not represent clinical advice! *All care decision should be reviewed with your health care provider!*

Objectives

1. Review current limitations of SMBG2. Understand Current SMBG Accuracy

Standards 3. Discuss the Impact of CGM in Personal &

Professional Care 4. Review the impact of hypoglycemia on

Diabetes

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Tracking Glucose 1970• The Ames Reflective Meter (ARM)

was first Marketed in 1969.• Designed for Medical office use-

was not sold to patients in any quantity

• The ARM Glucometer– Use whole blood– Weighed 3 pounds– Took 3 minutes to read and

SEVERAL steps-including rinsing and drying.

– Used a meter arm as a display– Cost $495 (1969 Dollars!!)– Had a re-chargable lead acid

battery

Glucose Monitoring Today

• Measure glucose in seconds

• Use Serum

• Cost $30 (Free?)

• Are EXTREMELY reliable

• Designed for use by all persons with diabetes!

ISO Standards

International standards for BGM Accuracy

• ISO 15197:2003– 95% of the readings

• ±15 mg/dL for glucose < 75 mg/dL

• ± 20% for glucose concentrations ≥ 75 mg/dL

• ISO 15197:2013– 95% of the readings

• ±15 mg/dL for glucose < 100 mg/dL

• ± 15% for glucose concentrations ≥ 100 mg/dL

This Looks Just Like a Number… Doesn’t It?

This is not a number – this is a range – the Blood Sugar could be ± 15 mg/dL – So are you 90 or 120? Does that impact your insulin decision?

If the glucose was rising or falling,would the decision change?

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SMBG is the Standard of Care

BUT….– Misses highs & lows– Accuracy can be problematic1

• Many BGMs fail ISO standards

• Inaccuracies increase Co$t$

– No information on rate/direction of change/or recent past

– Its Really NOT answering the questions

Klonoff & Reyes, 2014

Potential BG Measurement Errors

Failure to testWrong siteFailure to wash and dry handsSample application errors Inaccurate record keeping Strip exposure to cold, heat or humidity (failing to re-cap vial)Outdated strips

Use

err

ors

Inte

rfe

ren

ces

Oth

er

Fac

tors

AcetaminophenAscorbic acidMaltose, galactose, and xyloseHematocrit extremes Oxygen extremes Hyperuricemia, HyperbilirubinemiaHypertriglyceridemia

Marked dehydration, Vasoconstriction,Rapidly changing glucose

Studies on SMBG Accuracy

• How many published papers have looked at this since January 2014? – 20?

– 50?

– 100?

→    > 100 ! !

And the Accuracy is… ? • In a word

“Problematic” • Several papers found less than half of the

meters passed the old standard – NONE of the “generic” Meters past the old or the

new standards

• SMBG inaccuracy leads authors to conclude that patients are experiencing elevated HbA1c levels and increased rates of hypoglycemia directly as a result of this

(Boettcher, 2015; Klaff et al., 2014)

Everyday Life • Life with diabetes is easy

• Everyday is exactly the same as the next

• Every dose of insulin responds the same

• Your BGM always gives you accurate data

• What?????

Patient ConsiderationsSimple

Carbs

Blood Glucose

Levels

Fast constipation

insomnia

exposure to cold

menstruation

illness

medication

emotion

stress

time change

caffeine

smoking

French Meal

Fatty MealComplex Carbs

SlowVery

Slow Still there the next day

See French Meal

Exercise

Rapid

DigestionBrain function

2% of body mass,

25% of glucose consumption

Variable Sustained

Gastroparesis

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The Underlying Management Problems

Delivering Insulin• Variable response

– First Discussed 19221

• Dosing Errors• Poor Compliance• Managing complex

issues2

– Activity– Meals – Stress

Monitoring Glucose

• Measure glucose in seconds

• Use Serum

• Cost: “Free” + Strips

• SMBG Accuracy

• Only providing a point snapshot

1. Joslin, Grey & Root, 19222. Wild et al.,  2007

Life with CGM

CGM: Indications for use *Aid in the detection of hyper- and hypo- glycemia*

• Facilitate acute and long-term therapy changes• Assist in minimizing glucose excursions• Can be safely used for T1 & T2DM –with/without insulin pumps

– Age 2 yo and Older Dexcom G4P– Age 7yo and Older Medtronic Sof-Sensor– Age 16yo and older for Medtronic 530G Enlite

• Are adjunctive therapy – NOT a FS replacement• ALL Electro-chemical Sensors have an

ACETAMINOPHEN Contraindication

This is the SMBG Difference

CGM Values for 24 Hour PeriodImproved Glycemic Control with

STSTM System

Source: Improvement in Glycemic Excursions with a Transcutaneous, Real-Time Continuous Glucose Sensor. Diabetes Care, January 2006

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Professional Use of CGM

Are the insulin’s doing what we ask of them?

16 yo Female‐‐Onset T1DM x 18 mos‐Poor Control115#On Insulin Glargine 14 u once a day q AMInsulin Aspart TID w/ meals

• C.U., 49yo F, Type I DM x 33 years, A1C 9%

• Poor control, significant postprandial • Avg. Gluc 176 mg/dl / SD 66 mg/dl

After Pramlintide:

• Avg Glucose 122 mg/dl / SD 30 mg/dl• Can we see improvement?• A1C 7.4%—and she has lost 12#

How are Patients Using CGM Information?

These examples are for illustrative purposes ONLY they do not represent clinical advice! *All therapy changes should be reviewed with your health care provider!*

Going out to Lunch

Going to have a nice lunch

You are going to eat 80 gm CHO

You take 1u Insulin for every 20 GM CHO

Your target is 80 – 140 mg/dL

Your glucose is 104 mg/dL

So you should take 4 units – Right??

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Going to Lunch with CGM

Blood Sugar is dropping 2‐3 mg/min 

Down 10‐15mg in the next 5 minutes 

Still want 4 units?

Heading off to work in the AM

30 minute drive to work

5 minutes extra to drop off a child at school

Glucose is 116 mg/dl

Am I safe to drive?

Should I eat carbs?

?Do most patients even check their glucose before driving?

THEY SHOULD!

Heading off to work in the AM 30 minute drive to work

5 minutes extra to drop off a child at school

Glucose is 116 mg/dl

Am I safe to drive to work?

Should I eat carbs?

With push of a button, you see

• Glucose value

• Trend arrow

• Rate of change

• Trend Graph – Know where you are

by how you got there AND where its going

Lets Talk about Arrows Patient Survey Data • 222 subjects with T1DM

– HbA1c 6.9±0.8 (self reported) – 75% CSII

– CGM users for > 1 year

• Asked 70 scenario based questions– Focused on how patients are using CGM data

– Looked at impact of ROC arrows and patient decision making.

ADA, 2014 – Real‐time CGM users make significant adjustments to insulin doses based on CGM ROC arrows  ‐Edelman,S.  P‐836 

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Current Recommendations For Adjusting Insulin Based On Real-time CGM Data

10% lower

10% higher

20% higher

20% lower

20% lower

20% higher

No change

Buckingham B for the Diabetes Research In Children Network (DirecNet) Study Group. Pediatric Diabetes 2008;9:142–147.2) The Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Study Group. Diabetes Technol.Ther.2008;10(4):310‐321.

Recommended Action• It has been 4 hours since your last dose of insulin & meal

If you were NOTplanning on eating or exercising, what dose of insulin would you give yourself to bring your glucose down to around 120mg/dl (6.7mmol/dl)? 

Correcting for a high BG with stable

• Your CGM receiver shows a value of 220 mg/dl (matching your fingerstick BG of 220 mg/dl) with arrow and trend graph flat (straight across). 

ADA, 2014 – Real‐time CGM users make significant adjustments to insulin doses based on CGM ROC arrows  ‐Edelman,S.  P‐836 

How much insulin would you give yourself to bring your glucose down to around 120mg/dl

AVERAGE ANSWER

2.8 units

AVERAGE CORRECTION FACTOR

35.7 mg/dL/unit 

What if we ask the same question – with a different trend?

ADA, 2014 – Real‐time CGM users make significant adjustments to insulin doses based on CGM ROC arrows  ‐Edelman,S.  P‐836 

How much EXTRA insulin would you give yourself to bring your glucose down to around 120mg/dl

AVERAGE ANSWER

3.1 EXTRA units(111% increase)To A Total of 

5.9 units 

ADA, 2014 – Real‐time CGM users make significant adjustments to insulin doses based on CGM ROC arrows  ‐Edelman,S.  P‐836 

If you are not planning on eating or exercising, how much insulin would patients give to bring their

glucose down to 120mg/dL?

AVERAGE ANSWER

4 EXTRA units(140% increase)

ADA, 2014 – Real‐time CGM users make significant adjustments to insulin doses based on CGM ROC arrows  ‐Edelman,S.  P‐836 

If you are not planning on eating or exercising, how much insulin would patients give to bring their glucose down to

120mg/dL?

40%mean decrease

Correcting for a high BG with falling

2.8 Units ‐> 1.7 units 

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If you are not planning on eating or exercising, how much insulin would patients give to bring their glucose down to 120mg/dL?

42% mean decrease

Correcting for a high BG with falling

2.8 units ‐> 1.6 units

BUT….

25% would take NO insulin 

Arrow Indication Recommended Insulin DoseAdjustment

Participants ReportedInsulin Dose Adjustment

Constant – not increasing/ decreasing more than 1mg/dL/min

No Change NA

Slowly Rising – Rising 1‐2 mg/dL/min

10% Higher

Rising – 2‐3 mg/dL/min 20% Higher 111% Higher

Rapidly Rising – >3 mg/dL/min

20% Higher 140% Higher

Slowly Falling – Falling 1‐2 mg/dL/min

10% Lower

Falling – 2‐3 mg/dL/min 20% Lower 40% Lower

Rapidly Falling ‐ > 3 mg/dL/min

20% Lower 42% Lower

What is the biggest barrier to good glucose control?

Hypoglycemia• Fear of Hypoglycemia is recognized as the

number one barrier to achieving good glycemic control4

– Hypoglycemic Unawareness– Happens quickly within 5 years of dx1

– Affects more than 20% of people with T1DM4

– Patients have a negative response to hypoglycemia2

– Worry leads to avoidance & Suboptimal Control3

• Nocturnal Hypoglycemia is a significant cause of death among persons < 40 yr with Type-1 DM5

• What is the Co$t of Hypoglycemia?

1. Carroll, Burge, Schade, 2003      2.  Graveling & Frier, 2010     3. Irvine, Cox & Gonder‐Frederick, 19924. Graveling & Frier, 2010      5. Cryer, 2012 Diabetes Care 34, 1814 ‐1816

• 78% reported a DECREASE in the frequency and severity of hypoglycemic episodes

• 70% of subjects stated they were alerted at night to hypoglycemia at lease ONCE PER WEEK by their CGM

• 33% stated their CGM would alert them to a low PRIOR to any symptoms being present

• 42% of subjects stated that at least once in the last 6 months the device alerted SOMEBODY ELSE around them when they could not respond

Did their CGM Impact Hypoglycemia?

ADA, 2014 – Real‐time CGM users make significant adjustments to insulin doses based on CGM ROC arrows  ‐Edelman,S.  P‐836 

Why don’t Patients use CGM?

1.Training

2.Cost

3.Extra device to carry

4.Accuracy

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Accuracy is COMMONLY cited as a barrier to use

*Schmidt S, Duun‐Henriksen AK and Nørgaard K “Psychosocial Factors and Adherence to Continuous Glucose Monitoring in Type 1 Diabetes” J Diabetes Sci Technol 2012 Jul 1;6(4):986‐7. 

A survey of pregnant women with diabetes using CGM (2012)**

“Main causes behind early removal of continuous glucose monitoring were … technical problems and continuous glucose monitoring inaccuracy…”

A survey of sensor‐augmented pump users (2012)*

“… a major complaint coming from both current and former SAP users was CGM inaccuracy…”

**Secher AL et al. “Patient satisfaction and barriers to initiating real‐time continuous glucose monitoring in early pregnancy in women with diabetes” Diabet Med. 2012 Feb;29(2):272‐7.

Major reasons

Numbers couldn’t be trusted* 34%

Too many false alarms* 26%

Too often the device stopped working 22%

Cost 28%

Too many things to carry around * 27%

A Survey of 102 Ex-CGM Users

Polonsky and Hessler, 2013

How Should we Measure Accuracy?• Mean Absolute Relative Difference– Average disparity between the sensor and the reference measurement (YSI).

• Clarke Error Grid

• Number of outliers?

15%     ?   20%   ?

• Alarm Accuracy?

1. Chamberlain et al 2013 Persistence of CGM use, Clinical Diabetes 31(3)2. Pickup et al. 2011 Glycaemic control in type 1 DM, BMJ, 343

Dexcom Demonstrates Continuous Advances in Accuracy

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STS 3-day Seven Seven Plus Gen 4 Pt Gen 4 Pt 505

Mea

n A

RD

(%

)

Accuracy (Mean ARD) for Dexcom Product Generations

15.9%

Home Use SMBG Meters

26%

G4 Platinum G4 PlatinumWith SW 505

9%

13.2%

A New Algorithm to Improve Accuracy…. The 505 Software

Dexcom G4P w/ 505 Performance

Performance Parameters CGM vs. YSI CGM vs. SMBG

Subjects N 51 51

Temporally matched pairs (N) 2263 2992

Pearson Correlation Coefficient 0.97 0.98

Mean Absolute Relative Difference (ARD) % 9.0% 11.3%

% 20/20|%30/30 93.0%|98.0% 86.6%|95.8%

Mean ARD within Day 1|Day 4|Day 7 10.7%|8.0%|8.5% 12.2%|10.1%|9.7%

Mean Absolute Difference (MAD), at Hypoglycemia BG <= 70 mg/dl | (N) 

6.4 mg/dL|(252) 7.9 mg/dL|(337)

Mean ARD at Euglycemia 70  > BG <= 180|(N)  9.7%|(851) 11.6%|(1494)

Mean ARD at Hyperglycemia BG > 180 mg/dl|(N) 8.0%|(1160) 10.1%|(1161)

Overall CEG A+B Zones|A Zone 99.5%|92.4% 98.9%|85.4%

Bailey, Chang & Christiansen (2014) JDST Published ahead of print – Nov 6 2014Clinical accuracy of a CGM system with advanced algorithm 

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SW 505 Results from Pediatric Study

• During clinic session, G4 PLATINUM with Software 505 detected:

91% (225/247) of low (≤80 mg/dL) YSI readings within 15 mins

97% (1038/1070) of high (≥200 mg/dL) YSI readings within15 mins

G4 PLATINUMwith SW 505 Accuracy versus YSI over the Glucose Range 40‐400 mg/dl (2.2  – 22.2 mmol/L)

StudyDays 1‐7

N MARD %20/20

G4 PLATINUM with SW 505 Adults 2263 9 93

G4 PLATINUM with SW 505 Pediatrics 2262 10 91

Laffel et al. “Performance of a New Continuous Glucose Monitoring System (CGM)  in Youth” ATTD 2015

Annual rates of SH, requiring third-party help at baseline & 12 months after starting CGM

Choudhary et al. Diabetes Care 2013;36:4160-4162

Type 1 DM (n=35) with severe hypo and hypo unawarenesson CSII, switched to CGM

Baseline 3 months Last value

Choudhary et al. Diabetes Care 2013;36:4160-4162

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7.5A1c, %

Reduction of SH with CGMOccurred with Improvement of A1c When Things Go VERY Wrong

True Alerts in Hypoglycemia

Enlite1 G4P w/ 5052

Detection of Hypo < 70 mg/dl

73%1 91(94)%2

1. Bailey 2014 DTT .2. Bailey et al. 2014, JDST 

*Assuming calibration every 12 hours via SMBG1.MDT ENLITE within 30 minutes of Hypoglycemic Event 2.Dexcom G4P w/ 505 within 15 (30) minutes At 95% CI 2.

A Survey of 102 Ex-CGM Users1. Numbers couldn’t be trusted

– MARD down to 9% 2. Cost

– 98% of health plans offer CGM benefits 3. Too many things to carry around

– Integrating into consumer electronics4. Too many false alarms

– Hypoglycemic accuracy = less false alarms 5. Device stopped working

– Receiver warrantied for 1 year, transmitter for 6 months.

Polonsky and Hessler, 2013

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CGM Is about PATIENTS having access to more information…

Famous Words• “In diabetes the

careful instruction of the patient is the keystone of treatment.”Dr. Elliot P. Joslin(1869-1962)

1916 1st Edition