Objectives Continuous Glucose Monitoring & Diabetes Management Tomas C. Walker, DNP, APRN, CDE Director, Clinical Projects Dexcom, Inc. San Diego, CA 1. Review current limitations of SMBG 2. Understand Current SMBG Accuracy Standards 3. Discuss the Impact of CGM in Personal & Professional Care 4. Review the impact of hypoglycemia on Diabetes. This talk is for discussion ONLY It does not represent clinical advice! *All care decision should be reviewed with your health care provider!* Tracking Glucose 1970 The Ames Reflective Meter (ARM) was first Marketed in 1969. Designed for Medical office usewas 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 $30 (Free?) Are EXTREMELY reliable Designed for use by all persons with diabetes! ISO Standards International standards for BGM Accuracy ISO 15197:2003 95% of the readings ±15 mg/dl for glucose < 75 mg/dl ± 20% for glucose concentrations 75 mg/dl ISO 15197:2013 95% of the readings ±15 mg/dl for glucose < 100 mg/dl ± 15% for glucose concentrations 100 mg/dl This Looks Just Like a Number Doesn t It? This is not a number this is a range the Blood Sugar could be ± 15 mg/dl So are you 90 or 120? Does that impact your insulin decision? If the glucose was rising or falling,would the decision change?. 1
SMBG is the Standard of Care BUT. Misses highs & lows Accuracy can be problematic 1 Many BGMs fail ISO standards Inaccuracies increase Co$t$ No information on rate/direction of change/or recent past Its Really NOT answering the questions Potential BG Measurement Errors Use errors Failure to test Wrong site Failure to wash and dry hands Sample application errors Inaccurate record keeping Strip exposure to cold, heat or humidity (failing to re-cap vial) Outdated strips Other Factors Interferences Marked dehydration, Vasoconstriction, Rapidly changing glucose Acetaminophen Ascorbic acid Maltose, galactose, and xylose Hematocrit extremes Oxygen extremes Hyperuricemia, Hyperbilirubinemia Hypertriglyceridemia Klonoff & Reyes, 2014 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 constipation insomnia exposure to cold menstruation illness medication emotion stress Patient Considerations Simple Carbs Fast Complex Carbs Slow Blood Glucose Levels Fatty Meal Very Slow French Meal Still there the next day Gastroparesis See French Meal What????? time change caffeine smoking Variable Sustained Brain function Digestion 2% of body mass, Rapid Exercise 25% of glucose consumption 2
The Underlying Management Problems Monitoring Glucose Measure glucose in seconds Use Serum Cost: Free + Strips SMBG Accuracy Only providing a point snapshot 1. Joslin, Grey & Root, 1922 2. Wild et al., 2007 Delivering Insulin Variable response First Discussed 1922 1 Dosing Errors Poor Compliance Managing complex issues 2 Activity Meals Stress 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 Period Improved Glycemic Control with STS TM System Source: Improvement in Glycemic Excursions with a Transcutaneous, Real-Time Continuous Glucose Sensor. Diabetes Care, January 2006 3
Are the insulin s doing what we ask of them? Professional Use of CGM 16 yo Female Onset T1DM x 18 mos Poor Control 115#On Insulin Glargine 14 u once a day q AM Insulin 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?? 4
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. 5
Current Recommendations For Adjusting Insulin Based On Real-time CGM Data 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 No change 10% higher 20% higher 20% higher 10% lower 20% lower 20% lower Correcting for a high BG with stable It has been 4 hours since your last dose of insulin & meal 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). If you were NOT planning on eating or exercising, what dose of insulin would you give yourself to bring your glucose down to around 120mg/dl (6.7mmol/dl)? 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 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 What if we ask the same question with a different trend? 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) Correcting for a high BG with falling 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 2.8 Units > 1.7 units 6
Correcting for a high BG with falling 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 2.8 units > 1.6 units BUT. 25% would take NO insulin Arrow Indication Recommende d Insulin Dose Adjustment Constant not increasing/ decreasing more than 1mg/dL/min Slowly Rising Rising 1 2 mg/dl/min No Change 10% Higher Participants Reported Insulin Dose Adjustment NA Rising 2 3 mg/dl/min 20% Higher 111% Higher Rapidly Rising >3 mg/dl/min Slowly Falling Falling 1 2 mg/dl/min 20% Higher 140% Higher 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 control 4 Hypoglycemic Unawareness Happens quickly within 5 years of dx 1 Affects more than 20% of people with T1DM 4 Patients have a negative response to hypoglycemia 2 Worry leads to avoidance & Suboptimal Control 3 Nocturnal Hypoglycemia is a significant cause of death among persons < 40 yr with Type-1 DM 5 What is the Co$t of Hypoglycemia? 1. Carroll, Burge, Schade, 2003 2. Graveling & Frier, 2010 3. Irvine, Cox & Gonder Frederick, 1992 4. Graveling & Frier, 2010 5. Cryer, 2012 Diabetes Care 34, 1814 1816 Did their CGM Impact Hypoglycemia? 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 Why don t Patients use CGM? 1.Training 2.Cost 3.Extra device to carry 4.Accuracy 7
Accuracy is COMMONLY cited as a barrier to use A survey of sensoraugmented pump users (2012)* a major complaint coming from both current and former SAP users was CGM inaccuracy 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 *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. **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. A Survey of 102 Ex-CGM Users 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% 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? Dexcom Demonstrates Continuous Advances in Accuracy Mean ARD (%) 20 18 16 14 12 10 8 6 4 Accuracy (Mean ARD) for Dexcom Product Generations 26% Home Use SMBG Meters 15.9% 13.2% 9% STS 3-day Seven Seven Plus Gen G4 Platinum 4 Pt Gen G4 Platinum 4 Pt 505 With SW 505 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 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 2014 Clinical accuracy of a CGM system with advanced algorithm 8
SW 505 Results from Pediatric Study Annual rates of SH, requiring third-party help at baseline & 12 months after starting CGM G4 PLATINUM with SW 505 Accuracy versus YSI over the Glucose Range 40 400 mg/dl (2.2 22.2 mmol/l) Study Days 1 7 N MARD %20/20 G4 PLATINUM with SW 505 Adults 2263 9 93 G4 PLATINUM with SW 505 Pediatrics 2262 10 91 Type 1 DM (n=35) with severe hypo and hypo unawareness on CSII, switched to CGM 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 Laffel et al. Performance of anew Continuous Glucose Monitoring System (CGM) in Youth ATTD 2015 Choudhary et al. Diabetes Care 2013;36:4160-4162 Reduction of SH with CGM Occurred with Improvement of A1c When Things Go VERY Wrong 8 A1c, % 7.5 7 Baseline 3 months Last value Choudhary et al. Diabetes Care 2013;36:4160-4162 True Alerts in Hypoglycemia Detection of Hypo < 70 mg/dl Enlite 1 G4P w/ 505 2 73% 1 91(94)% 2 *Assuming calibration every 12 hours via SMBG 1.MDT ENLITE within 30 minutes of Hypoglycemic Event 2.Dexcom G4P w/ 505 within 15 (30) minutes At 95% CI 2. 1. Bailey 2014 DTT. 2. Bailey et al. 2014, JDST A Survey of 102 Ex-CGM Users 1. 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 electronics 4. 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 9
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 1 st Edition 10