PowerPoint slides - AACE/ACE Outpatient Glucose Monitoring

American Association of Clinical Endocrinologists (AACE)

American College of Endocrinology (ACE)

2016 Outpatient Glucose Monitoring Consensus Statement

Task Force Co-ChairsTimothy S. Bailey, MD, FACP, FACE, ECNU

George Grunberger, MD, FACP, FACE

ENDOCRINE PRACTICE Vol. 21 No. 2 February 2016 Pages 231-261.

Copyright © 2016 AACE. May not be reprinted in any form without express written permission from AACE.

2016 Outpatient Glucose Monitoring Consensus Statement Task Force Members

Timothy S. Bailey, MD, FACP, FACE, ECNU (Co-Chair)George Grunberger, MD, FACP, FACE (Co-Chair)Bruce W. Bode, MD, FACEYehuda Handelsman, MD, FACP, FACE, FNLA Irl B. Hirsch, MD Lois Jovanovič, MD, MACEVictor Lawrence Roberts, MD, MBA, FACP, FACEDavid Rodbard, MDWilliam V. Tamborlane, MD John Walsh, PA, CDTC


AACE/ACE Glucose Monitoring Consensus Statement Objectives and Structure

This consensus statement provides recommendations to clinicians regarding the type and frequency of GM technology to be employed in the

management of:

This statement also Provides a primer on GM accuracy Reviews measures of glycemic control (glucometrics) Presents graphical methods to display glycemic data


GDM = gestational diabetes mellitus; GM = glucose monitoring; T1DM = type 1 diabetes mellitus; T2DM = type 2 diabetes mellitus.

Pregnancy complicated by

preexisting diabetes or GDM

T2DM (with and without insulin

therapy)

T1DM(pediatric or adult)

Benefits and Drawbacks of CGMPros Cons

Alerts patients to • Episodes of hypoglycemia

and hyperglycemia • Predicted episodes of

hypoglycemia and hyperglycemia

Issues related to • Accuracy • Comfort• Convenience• Patient acceptance• Expense

Device displays help patients with clinical decision making

Most devices require frequent calibration


CGM = continuous glucose monitoring.

Adult Patients With T1DMFrequent BGM is an essential element in effective T1DM

management because it:

All major clinical practice guidelines recommend individualized, frequent BGM for patients with T1DM1,3-6

CGM is particularly important for patients with a history of severe hypoglycemia or hypoglycemia unawareness1,3,7-8

1. Joslin Diabetes Center, 2014. http://www.joslin.org/docs/Adult_guideline_-update_thru_10-23-14_2.pdf; 2. American Diabetes Association. Diabetes Care. 2015;38(Suppl 1):S1-S94; 3. American Association of Diabetes Educators. 2011. http://www.diabeteseducator.org/export/sites/aade/_resources/pdf/general/PracticeGuidelines2011.pdf; 4. Handelsman Y. Endocr Pract. 2011;17(Suppl 2):S1-S53; 5. International Diabetes Federation. 2009. Available at: http://www.idf.org/guidelines/self-monitoring; 6. Garber AJ. Endocr Pract. 2015;21(4):438-447; 7. Blevins TC. Endocr Pract. 2010;16(5):730-745; 8. Klonoff DC. J Clin Endocrinol Metab. 2011;96(10):2968-2979.

BGM = blood glucose monitoring; CGM = continuous glucose monitoring; T1DM = type 1 diabetes mellitus.


Detects glycemic variability and hypoglycemia

Informs treatment modifications and reflects the impact of food intake and physical activity1-3

Provides important information on

treatment efficacy1,4

http://www.joslin.org/docs/Adult_guideline_-update_thru_10-23-14_2.pdf



http://www.diabeteseducator.org/export/sites/aade/_resources/pdf/general/PracticeGuidelines2011.pdf

http://www.diabeteseducator.org/export/sites/aade/_resources/pdf/general/PracticeGuidelines2011.pdf

http://www.idf.org/guidelines/self-monitoring


Pediatric Patients With T1DMChallenges of glycemic control in pediatric patients:

Changing insulin requirementsUnpredictable food intake and physical activityConcerns about hypoglycemic riskClose monitoring needed to recognize when the patient outgrows their insulin

dose(s)1

1. Niedel S. J Health Services Research Policy. 2013; 2. Phillip M. Pediatr Diabetes. 2012;13(3):215-228.

T1DM = type 1 diabetes mellitus; A1C = glycated hemoglobin; CGM = continuous glucose monitoring.


CGM should be considered for regular daily use in pediatric patients with T1DM who perform frequent blood glucose testing and have:2 • Severe hypoglycemic episodes• Hypoglycemic unawareness (especially in young children)• Nocturnal hypoglycemia • Wide glucose excursions, regardless of A1C • Suboptimal glycemic control, with A1C exceeding target range • A1C levels <7%, to maintain target glycemic control while limiting hypoglycemia risk

Adult Patients With T2DMBGM should be individualized and accessible to all patients

receiving any therapy for T2DM1

Limited data on the use of real-time CGM in patients with T2DM, although available evidence is promising2-3

Trials are ongoing to evaluate the potential use of CGM (masked or unmasked) in patients with T2DM

1. International Diabetes Federation. 2009. Available at: http://www.idf.org/guidelines/self-monitoring; 2. Vigersky RA. Diabetes Care. 2012;35(1):32-38; 3. Tildesley HD. Can J Diabetes. 2013;37(5):305-308.


BGM = blood glucose monitoring; CGM = continuous glucose monitoring; T2DM = type 2 diabetes mellitus.

Patients receiving non-insulin agents associated with hypoglycemia:

• Perform BGM at least once daily (fasting) and periodically at other times

Patients at low risk for increased hypoglycemia risk and not at goal:

• Perform structured testing (eg, before meals and at bedtime) at least weekly



Adult Patients With T2DM

BGM is recommended for patients not taking insulin if1 • Patients and/or caregivers have knowledge, skills, and willingness to

incorporate BGM and therapeutic adjustments into diabetes care plan• Protocols are individualized to meet patient educational/behavioral/clinical

requirements and have been agreed upon by the patient and clinician

1. International Diabetes Federation. 2009. Available at: http://www.idf.org/guidelines/self-monitoring; 2. Polonsky WH. Diabetes Care. 2011;34(2):262-267.

BGM = blood glucose monitoring; T2DM = type 2 diabetes mellitus.


If the patient is on insulin therapy, BGM should be tailored by therapy type• Patients taking prandial and basal insulin should perform BGM when fasting,

premeal, at bedtime, and periodically during the night• Patients taking only basal insulin (with or without other diabetes medications)

should perform BGM at minimum when fasting and at bedtime



Pregnancy Complicated by DiabetesBGM is integral to diabetes management in pregnancy1

Real-time results enable women to make informed daily self-care decisions regarding diet, exercise, and insulin

Retrospective analysis of BGM data helps to: Enable clinicians to develop individualized care plans2

Inform decisions related to insulin initiation and adjustment Recognize the need for interventions to improve self-monitoring3

Potential benefit of CGM in pregnant women with preexisting diabetes is unclear

1. Jovanovic L, Pending publication; 2. Boutati EI. Diabetes Care. 2009;32(Suppl 2):S205-S210; 3. Jovanovic L. Personal communication.

BGM = blood glucose monitoring; CGM = continuous glucose monitoring.


Pregnancy Complicated by Diabetes

1. American Diabetes Association. Diabetes Care. 2004;27(Suppl 1):S88-S90.GDM = gestational diabetes mellitus; MNT = medical nutrition therapy.


•Check blood glucose levels 4 times per day:•Before breakfast (fasting) and after 3 largest meals of the day

GDM managed with MNT

•Before attempting to become pregnant, maintain glycemic control as close to normal as possible for 3 to 6 months1

Preexisting diabetes

•Monitor glucose both before and after each meal (ie, at least 6 times per day)

Diabetes managed with insulin

Glucose Monitoring Accuracy and PrecisionAccuracy is defined as the closeness of agreement between a glucose test

result and an accepted reference value Accuracy improves when it has minimal bias and relative error (%CV,

MARD, and minimal absolute error)Point accuracy refers to blood glucose values and sensor readings at

single points in time


BGM = blood glucose monitoring; CV = coefficient of variation; MARD = mean absolute relative deviation.

Bias: systematic error in meter or sensor measurements

Precision: measurement reproducibility (irrespective of accuracy)

May be due to improper calibration, lack of calibration, or calibration with an inaccurate BGM

May vary depending on the glucose levels being measured

Measurements may cluster around an erroneous value

It is possible to derive a measure of precision without knowing the true value

Measures of Accuracy for BGM and CGM


BGM = blood glucose monitor/monitoring; CGM = continuous glucose monitor.

Arithmetic deviation• The difference between true value and measured

value Absolute deviation

• The absolute value of the arithmetic deviation

Absolute relative deviation (ARD)

• The absolute deviation in relation to true value

Mean absolute relative deviation (MARD):• The mean value of individual absolute relative

deviationsMedian absolute relative deviation (MedARD):• The median value of individual absolute relative

deviations

Measures of Accuracy for BGM and CGM: MARD

This graph shows an example of accuracy results and how MARD values for CGM can vary systematically by day (eg, day 1 vs day 3 vs day 7)1Display shows:Mean (diamonds)Median (horizontal

lines within boxes) 25th and 75th

percentiles (lower and upper box edges)

Minimum and maximum values (antennae)


1. Pleus S. J Diabetes Sci Technol. 2013;7(4):833-841. BGM = blood glucose monitor; CGM = continuous glucose monitor; MARD = mean absolute relative deviation.

Understanding Clinical Standards for Accuracy of Current BGMs and CGMs: Error GridsThe Parkes Error Grid (2000)1 is

one way to measure accuracy Grid regions reflect the potential

risk severity of incorrect treatment triggered by the measurement error

Device performance typically reported as percentage of glucose values in zone A or zones A + B (higher percentages indicate better performance)


1. Parkes JL. Diabetes Care. 2000;23(8):1143-1148.

BGM = blood glucose monitor; CGM = continuous glucose monitor.

Understanding Clinical Standards for Accuracy of Current BGMs and CGMs

ISO Meter Approval StandardsISO 15197 20131 <100 mg/dL

(<5.55 mmol/L) ±15 mg/dL(±0.83 mmol/L)

95%

≥100 mg/dL(≥5.55 mmol/L)

±15%

Both FDA and ISO standards allow 5% of meter values to be outside limits99% of values must be within Consensus Error Grid zones A or B


1. International Organization for Standardization. 2013. Available at: http://www.iso.org/iso/catalogue_detail?csnumber=54976.

BGM = blood glucose monitor; CGM = continuous glucose monitor; FDA = US Food and Drug Administration; ISO = International Organization for Standardization.

http://www.iso.org/iso/catalogue_detail?csnumber=54976

Understanding Clinical Standards for Accuracy of Current BGMs and CGMs

FDA Draft Guidance (2014)1

50-400 mg/dL(2.8-22.2 mmol/L)

±15% 95%

and

50-400 mg/dL(2.8-22.2 mmol/l)

±20% 99%

The draft proposes smaller errors in the hypoglycemic range and fewer outliers

Testing should be performed by non-trained people2 If devices are only tested by

trained technicians, greater accuracy might be seen than when used by untrained people


1. US Food and Drug Administration. 2014. Available at: http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM380327.pdf; 2. Freckmann G, Schmid C. J Diabetes Sci Technol. 2015;9(4):885-894.

BGM = blood glucose monitor; CGM = continuous glucose monitor; FDA = US Food and Drug Administration.

http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM380327.pdf


Clinical Situations Requiring Increased AccuracyPatients Requiring the Highest Possible

Accuracy in Glucose Monitoring History of severe hypoglycemia

Hypoglycemia unawareness

Pregnancy

Infants and children receiving insulin therapy

Patients at risk for hypoglycemia, including: • Patients receiving basal insulin • Patients receiving basal bolus insulin therapy with multiple daily injections • Patients receiving sulfonylureas or glinides (insulin secretagogues)• Patients with irregular schedules, skipped or small meals, vigorous

exercise, travel between time zones, disrupted sleep schedules, shift work

People with occupational risks that enhance possible risks from hypoglycemia (for example, driving or operating hazardous machinery)


What Impacts BGM Accuracy?Manufacturing defects and test-strip lot-to-lot variations

impact BGM accuracy and introduce bias with differences up to 11%1-3

Underfilling the test strip can introduce errors >20%4 Use of alternate sites (sampling from palm, upper arm,

forearm, thigh, or calf) can generate inaccurate resultsParticularly true when glucose levels are changing rapidly

after meals or exercise when the patient is ill or under stress shortly after insulin administration5,6


1. Baumstark A. J Diabetes Sci Technol. 2012;6(5):1076-1086; 2. Kristensen GB. Clin Chem. 2005;51(9):1632-1636; 3. Brazg R. J Diabetes Sci Technol. 2013;7(1):144-152; 4. Pfutzner A. J Diabetes Sci Technol. 2013;7(6):1522-1529; 5. US Food and Drug Administration. 2014. Available at: http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM380327.pdf; 6. Riddle MC. Diabetes Care. 2010;33(5):983-990.

BGM = blood glucose monitor.



Other Factors Affecting Test ResultsFactors that interfere with glucose oxidase or glucose-1-

dehydrogenase enzyme or BGM degrade overall accuracy: Competing blood substrates (eg, maltose, vitamin C)1,2

Environmental issues (eg, cold temperature, high altitude)Contaminants on the skin from food sources and lotions3 Acetaminophen usePhysical compression of the CGM sensor during sleep4,5

Reduced accuracy and precision in tests performed by patients/other lay users compared with trained health professionals6


1. Dungan K. Diabetes Care. 2007;30(2):403-409; 2. Vasudevan S. Diabetes Care. 2014;37(5):e93-e94; 3. Ginsberg BH. J Diabetes Sci Technol. 2009;3(4):903-913; 4. Freckmann G. Diabetes Technol Ther. 2014;16(2):113-122; 5. Helton KL. J Diabetes Sci Technol. 2011;5(3):647-656; 6. Kilo C. Diabetes Technol Ther. 2005;7(2):283-294.


Communicating BGM Device Accuracy DataSample label information for meter and test-strip boxes

Your ABC meter result may vary slightly from your actual blood glucose value. This may be due to slight differences in technique and natural variation in the testing technology.

The chart below shows the results of a study where 350 typical users used the ABC meter to test their blood glucose levels. For example, in this study, the ABC meter gave results within 15% of their true blood glucose level 340 out of 350 times.

Difference in range between the true blood glucose level and the ABC meter result

Within Within Within Within

5% 10% 15% 20%

The percent (and number) of meter results that match true blood glucose level with x%

57% 94% 97% 100%

(200/350) (330/350) (340/350) (350/350)

Accuracy levels Meter results meeting standard

Percentage of meter values compared to laboratory values

Accurate 350 out of 350 ±15%

More Accurate 262 out of 350 ±10%

Most Accurate 175 out of 350 ±5%

Recent FDA proposed guidance document suggests labeling each BGM device and its test strips or sensors with specific performance characteristics2

This allows clinicians and patients to make informed choices


1. US Food and Drug Administration. 2014. Available at: http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM380327.pdf.

BGM = blood glucose monitor; FDA = US Food and Drug Administration.

Improving the Quality of Glycemic Control: More Than Measurement Accuracy Is NeededFeatures that provide additional information and give context to raw

glucose numbers include: Weekly or monthly glucose averages to highlight glycemic variability patterns On-screen analysis capabilities display glucose trend lines over time, and

arrows reflect magnitude of current glucose rate-of-changeBGM clock setting must be accurate, clearly visible, easy to adjust, and

maintained during battery change1 Clocks in meter, CGM, and insulin pump should be synchronized

(automatically if possible), with accommodation for travel across time zones To effectively use these informative features, many users will require

guidance Clinicians should consider ease and speed of BGM data downloading



1. Crowe DJ. Diabetes Technol Ther. 2005;7(5):663-664.

Post-approval Meter AccuracyIndependent laboratories should confirm ongoing routine

quality assurance verification of test-strip lots using a standardized methodology1

Studies confirm:Review of post-approval accuracy of 27 meters under 2003 ISO 15197

standard; >40% of meters failed to meet standard by which they had received approval2

2014 study found only 12 (44.4%) of 27 available BGMs met most recent 2013 ISO 15197 standard3

FDA approval does not mean a BGM will continue to meet FDA accuracy requirements


1. Klonoff DC. J Diabetes Sci Technol. 2013;7(4):1071-1083; 2. Freckmann G. Diabetes Technol Ther. 2010;12(3):221-231; 3. Hasslacher C. J Diabetes Sci Technol. 2014;8(3):466-472.

BGM = blood glucose monitor; FDA = US Food and Drug Administration; ISO = International Organization for Standardization.

Glucometrics: Downloading and Interpreting GM Data Glucometrics is the analysis and display of glucose data1 and can

provide insights into how medications, diet, stress, and activity contribute to diabetes control2,3

Patient-to-health care team communication methods can include:Logbook during office visitComputer outputs Periodic phone calls, faxes, or emails to office Automated transfer from meter or sensor to Internet for review Automated interpretation by glucose monitoring device

Glucose and related data should be integrated with an electronic health record


1. Rodbard D. Diabetes Technol Ther. 2009;11(Suppl 1):S55-S67; 2. Bailey TS. Diabetes Technol & Ther. 2007;9(3):203-210; 3. Rodbard D. J Diabetes Sci Technol. 2007;1(1):62-71.

GM = glucose monitoring.

Representing Glucometric DataMean, median, and %CV metrics describe overall

glycemiaAverage glucose level may represent the mean or median The SD of glucose is highly correlated with mean glucose

%CV is usually the best method to characterize variability1-6

Other methods describe actionable patterns to help clinicians optimize diabetes therapy In graphical presentation, “standard day,” “modal day,”7,8 or AGP

displays individual glucose measurements (pooled over multiple days) by time of day on a single 24-hour scale


1. Kaufman FR. Diabetes Care. 2001;24(12):2030-2034; 2. Potts RO. Diabetes Metab Res Rev. 2002;18(Suppl 1):S49-S53; 3. JDRF. Diabetes Tech & Ther. 2008;10(4):310-321; 4. Rodbard D. Postgrad Med. 2011;123(4):107-118; 5. DeVries JH. Diabetes. 2013;62(5):1405-1408; 6. Rodbard D. J Diabetes Sci Technol. 2015;9(1):56-62; 7. Mazze RS. Diabetes Care. 1987;10(1):111-117; 8. Rodbard D. Diabetes Care. 1988;11(Suppl 1):S54-S61.

AGP = ambulatory glucose profile; CV = coefficient of variation; SD = standard deviation.

Standard or Modal Day

Glucose Profile by Time of Day1 Glucose in Relation to Meals2

The “Standard Day” or “Modal Day” graph indicates both glucose values and times of day when monitoring occursFacilitates detection of consistent patterns in glucose excursions Provides assessment of glucose monitoring adequacyGenerally shows glucose values by time of day but can show them in relation to

meals


1. Rodbard D. J Diab Sci Technol. 2009;3(6):1388-1394; 2. Pernick N. Diabetes Care. 1986;9(1):61-69.

Ambulatory Glucose Profile

Patient With Normal Glucose Tolerance

To generate AGP: Blood glucose levels are measured via BGM or CGM All glucose data pooled and analyzed as if it had been collected during a single

24-hour period Result is a standardized software report that can be displayed graphically

AGP provides an excellent starting point for a standardized computerized display of BGM and/or CGM data by time of day1-3

AGP display for multiple days of CGM data with

estimates of 10th, 25th, 50th, 75th, and

90th percentiles

Patient With T1DM


1. Bergenstal RM. J Diabetes Sci Technol. 2013;7(2):562-578; 2. Rodbard D. J Diabetes Sci Technol. 2015;9(1):56-62; 3. Mazze RS. Diabetes Care. 1987;10(1):111-117.

AGP = ambulatory glucose profile; BGM = blood glucose monitor; CGM = continuous glucose monitor; T1DM = type 1 diabetes mellitus

Graphic AGP Display: T2DMThe solid curve in the

middle represents the smoothed median glucose (50th percentile) values for a 24-hour period

The striped, shaded area shows the presumptive target range (70-180 mg/dL or 3.9-10 mmol/l)

Patient With T2DM


Bergenstal R. J Diab Sci Technol. 2013;7(2):562-578.

AGP = ambulatory glucose profile; CGM = continuous glucose monitor; IQR = interquartile range; T2DM = type 2 diabetes mellitus.

Other Graphical Displays of Glucometric Data

Other ways that graphic data related to glucose changes over time can be displayedPie graphsSimple bar charts Box plotsScattergramsStacked bar chartsHistograms

The purpose of these displays is to help clinicians identify and prioritize clinical problems and educate and motivate the patient to achieve improved glycemic control


RecommendationsPatients should be educated to interpret and use GM data to:

Enhance their ability to self-adjust therapy Decide when to seek medical assistance

To assess glucometrics, physicians should first examine: Overall statistics (mean, SD, %CV)Distribution of glucose valuesGlucose by date, by time of day and in relationship to meals, and by

day of the weekThe most helpful glucometric graphical displays show:

Graphs of glucose by dateAGP by time of dayStacked bar charts and/or box plots by time of day, in relation to

meals, and by day of the week


AGP = ambulatory glucose profile; CV = coefficient of variation; GM = glucose monitoring; SD = standard deviation.

Glucose Monitoring, Looking ForwardImprovements in progress

Data-sharing via the Internet Use of additional displays Improved usability Comprehensive and standardized integration of multiple

data inputs Several mobile health applications have been developed,

enabling patients to monitor and adjust their lifestyle and therapy on a real-time basis

CGM developments may broaden the appeal and applicability of CGM in T1DM and T2DM


CGM = continuous glucose monitoring; T1DM = type 1 diabetes mellitus; T2DM = type 2 diabetes mellitus.