Making The Most of Continuous Glucose Monitoring Gary Scheiner MS, CDE Owner/Director, Integrated Diabetes Services 333 E. Lancaster Ave., Suite 204 Wynnewood, PA 19096 (877) 735-3648 www.integrateddiabetes.com Gary@integrateddiabetes.com 1

Making the Most of Continuous Glucose Monitoring What Information Is Available? How to Use Immediate Data? How to Use Intermediate Data? What Can Be Learned from Retrospective Analysis? Optimizing CGM System Performance

MiniMed Paradigm® & Guardian® REAL-Time CGM Systems On-Screen Reports 3-hr and 24-hr graphs (pump); 3 / 6 / 12 / 24-hr graphs (Guardian) Can scroll back for specific data points  “direction” indicators Updates every 5 minutes Hi/Low Alerts Predictive Alerts (Guardian)

MiniMed Paradigm® & Guardian® REAL-Time CGM Systems CareLink™ Personal: Online Reports Sensor daily overlay Sensor overlay by meal

MiniMed Paradigm® & Guardian® REAL-Time CGM Systems CareLink™ Personal Online Reports Daily summaries & layered reports, including… Sensor tracing Basal & bolus delivery Carbohydrate & logbook entries

DexCom™ Seven Plus® On-Screen Reports 1, 3, 6, 12, 24-hr graphs Updates every 5 minutes Hi/Low alerts Rate of Change alerts

DexCom™ 7 STS® Dexcom DM2 Download Reports Glucose Trend Hourly Stats

DexCom™ 7 STS® Dexcom DM2 Download Reports Trend Analysis BG Distribution

Freestyle Navigator™ On-Screen Reports 2/4/6/12/24-hr line graphs Predictive alerts  “direction” indicators Can scroll back to data points Customizable time range: Highest, Lowest, Avg, SD % Time High, Low, In-Range # Hypo, Hyper events Updates every minute

Freestyle Navigator™ Download to CoPilot Software Modal Day Report Glucose Line Report Statistics Report

Practical Benefits of Real-Time CGM Rumble strips (avoid serious extremes) Peace of mind Basal & bolus fine tuning Postprandial analysis Insulin action curve determination Short-term Forecasting Learning tool & immediate feedback Eliminates some blood glucose checks??? Partially derived from: Hirsch, et al. Clinical Application of Emerging Sensor Technologies in Diabetes Management: Consensus Guidelines for Continuous Glucose Monitoring (CGM). Diabetes Technology & Therapeutics, 10:4, 2008, 232-244.

How to Look at the Information Immediate Intermediate Retrospective                                                 

Immediate Info: Alerts Customizable settings Vibrate and/or beep Alert the user of glucose levels that have crossed specified high or low thresholds (predictive) Alert of anticipated crossing of high or low thresholds

Setting Alerts Hi/Low alarm thresholds are not BG target ranges Balance need for alerts against “nuisance factor”

Alert Settings Recommendation LOW: 80 mg/dl (90+ if hypo unaware) HIGH: 240-300 mg/dL (lower progressively toward 180) It is Medtronic’s recommendation that the starting alert setting on initiation should be a low of 80 mg/dL and a high of 240 mg/dL. It is important that patients do not confuse these alert settings with blood glucose targets. For instance, the low threshold of 70 might mean that the patient would miss hypoglycemia in the 60 or 50 range, or a high setting of 140 would mean that the patient would unnecessarily get alarms when glucose was in the normal range of 120 or multiple alarms when the glucose was in the 160 range. NOT RECOMMENDED: Low 70 mg/dL NOT RECOMMENDED: High 140 mg/dL Derived from: Hirsch, et al. Clinical Application of Emerging Sensor Technologies in Diabetes Management: Consensus Guidelines for Continuous Glucose Monitoring (CGM). Diabetes Technology & Therapeutics, 10:4, 2008, 232-244.

Special Alert Settings Young children (higher, wider range) Hypoglycemia unawareness, high-risk professions (higher hypo setting) Pregnancy (lower, narrower range) HbA1c of 11.0% (higher initially)

Immediate Info: Glucose and Trend Prediction/Forecasting Safety/Performance Driving Sports Tests Third, REAL-Time Trend Arrows. One arrow up or down indicates a change of 1-2 mg/dl/min in the last 20 minutes. Two arrows up or down indicate a change of more than 2 mg/dl/min in the last 20 minutes. Arrows are only displayed if there has been at least a 1 mg/dl/min change in the last 20 minutes. Patients should think about where glucose may be in 20 minutes if it continues at the same rate.

Immediate Glucose Info: Can it Replace Fingersticks? Not during first 1-2 cycles of using the system Wait at least 12 hrs after sensor replacement If BG Stable If Recent calibrations in-line If No recent alarms Third, REAL-Time Trend Arrows. One arrow up or down indicates a change of 1-2 mg/dl/min in the last 20 minutes. Two arrows up or down indicate a change of more than 2 mg/dl/min in the last 20 minutes. Arrows are only displayed if there has been at least a 1 mg/dl/min change in the last 20 minutes. Patients should think about where glucose may be in 20 minutes if it continues at the same rate. 18

Immediate Info: Potential Bolus Adjustment Based on BG Direction BG Stable: Usual Bolus Dose BG Rising Gradually:  bolus 10% BG Rising Sharply:  bolus 20% BG Dropping Gradually:  bolus 10% BG Dropping Sharply:  bolus 20% Third, REAL-Time Trend Arrows. One arrow up or down indicates a change of 1-2 mg/dl/min in the last 20 minutes. Two arrows up or down indicate a change of more than 2 mg/dl/min in the last 20 minutes. Arrows are only displayed if there has been at least a 1 mg/dl/min change in the last 20 minutes. Patients should think about where glucose may be in 20 minutes if it continues at the same rate. 19

Immediate Info: Hypoglycemia Alerts Predictive Hypo Alert or Hypo Alert & recovering: Subtle Treatment 50% of usual carbs Med-High G.I. food Hypo Alert & Dropping: Aggressive Treatment Full or increased carbs High G.I. food Third, REAL-Time Trend Arrows. One arrow up or down indicates a change of 1-2 mg/dl/min in the last 20 minutes. Two arrows up or down indicate a change of more than 2 mg/dl/min in the last 20 minutes. Arrows are only displayed if there has been at least a 1 mg/dl/min change in the last 20 minutes. Patients should think about where glucose may be in 20 minutes if it continues at the same rate. 20

Intermediate Info: Use of 2/3/4 Hr Trend Graphs Effects of different food types Effectiveness of bolus amt. Reveals postprandial spikes Pramlintide/Exenatide Influence Exercise effects Impact of Stress

Intermediate Info: Use of 9 / 12 / 24 Hr Trend Graphs Facilitates decision-making for basal insulin doses Shows delayed effects of exercise, stress, high-fat foods Reveals overnight patterns Lets user know when bolus action is complete

Specific Insights to Derive (a purely retrospective journey)

Before You Analyze, Qualify. Were sufficient calibrations performed? Did the calibrations match the CGM data reasonably well? Was the data mostly continuous? Was the time/date set correctly?

These Are a Few of My Favorite Stats… Mean (avg) glucose % Of Time Above, Below, Within Target Range Standard Deviation # Of High & Low Excursions Per Week

Case Study 1: Effectiveness of Current Program Type 1 diabetes; using insulin glargine & MDI Overnight readings are OK; HbA1c levels are elevated Glucose (mg/dL) 400 300 200 100 3 AM 6 AM 9 AM 12 PM 3 PM 6 PM 9 PM Meal doses insufficient; not covering snacks?

Case Study 2a: Basal Insulin Regulation Glucose (mg/dL) 400 300 200 100 400 300 200 100 3 AM 9 AM 3 PM 9 PM 3 AM 9 AM 3 PM 9 PM Stable 12 AM – 4 AM, then dropping pre-dawn Dropping late afternoon Rising 2 AM – 8 AM

Case Study 2b: Basal Insulin Regulation Type 1 diabetes; using insulin glargine & MDI History of morning lows Now not “covering” highs at night Glucose (mg/dL) 400 300 200 100 3 AM 6 AM 9 AM 12 PM 3 PM 6 PM 9 PM BG dropping overnight; insulin dose too high

Case Study 3: Detection of Silent Hypoglycemia Type1 diabetes; on pump Frequent fasting highs (9 AM) Glucose (mg/dL) 400 300 200 100 3 AM 6 AM 9 AM 12 PM 3 PM 6 PM 9 PM Somogyi effect during the night

Case Study 4: Determination of Insulin Action Curve 3-Hour Duration 4-Hour Duration 5-Hour Duration

Case Study 5: Fine-Tuning Meal Boluses Glucose (mg/dL) 400 300 200 100 3 AM 6 AM 9 AM 12 PM 3 PM 6 PM 9 PM Breakfast and lunch doses may be too low Dinner dose appears OK Night-snack dose clearly insufficient

Case Study 6: Fine-Tuning Correction Boluses Dropping low after correcting for highs at bedtime and wake-up time Glucose (mg/dL) 400 300 200 100 3 AM 6 AM 9 AM 12 PM 3 PM 6 PM 9 PM Need to change correction factor & insulin sensitivity during AM hours

Case Study 7: Postprandial Analysis Pre-meal BG levels are usually in target range HbA1c are higher than expected based on SMBG Tired and lethargic after meals Significant postprandial spikes (300s) Glucose (mg/dL) 400 300 200 100 Meal

Case Study 8: Impact of Physical Activity Type 1 diabetes; pump user Basal rates confirmed overnight Exercises in the evening (9 PM) Glucose (mg/dL) 400 300 200 100 Exercise 3 PM 6 PM 9 PM 12 AM 3 AM 6 AM 9 AM 12 PM Experiencing delayed-onset hypoglycemia

Case Study 9: Impact of Stress Type 1 diabetes; pump user 40 years old; athletic Handsome, excellent speaker Glucose (mg/dL) 400 300 200 100 Late for meeting Gets flat tire; eats 15g carbs to prepare for tire change Spare is flat too!! 9 AM 12 PM 3 PM 6 PM 9 PM STRESS CAN RAISE BLOOD GLUCOSE… A LOT!!!

Case Study 10: Impact of Various Food Types Pasta Meal Stir-Fry Over Rice Cereal Oatmeal Yogurt BG peaks later with pasta than rice Postprandial peak: cereal > oatmeal > yogurt

Case Study 11: Impact of Hi-Fat Meals Saturday Nights, Dinner Out Temp basal increase following hi-fat meals

CGM “Homework” Assignments Verify basal doses See effect of dietary fat Study effects of specific exercises Evaluate impact of different food types Measure insulin sensitivity Determine insulin action curve                                                            

Optimizing CGM System Performance Calibration Site selection/care Signal reception Ingredients for success 39

Optimal Calibration Calibrate at times when blood glucose (BG) is stable (fasting, pre-meals)* Avoid calibrations during times of rapid glucose change* Post meal UP or DOWN arrows are displayed In the period following a correction with food or insulin During exercise * Not required w/Dexcom system The best time to calibrate is when the blood glucose (BG) is stable — before meals or at bedtime—for then it is less likely that rapid changes in BG are going to take place. NOTE: When the BG is rapidly changing and a patient attempts to calibrate with a “single point in time” BG fingerstick reading, there may be enough of a change taking place to cause a calibration error to occur. If 2 calibration errors occur in a row, the glucose sensor can no longer be used and must be replaced. For this reason, patients should try not to calibrate within 2 hours after a meal or when 2 UP or DOWN arrows are displayed beside the current glucose reading on the insulin pump screen. The continuous glucose monitoring system must be calibrated a minimum of every 12 hours. However, 3 to 4 times a day is preferred. If calibration is not done every 12 hours, the insulin pump screen will stop displaying sensor glucose readings until a fingerstick BG value is entered Remind your patient to calibrate before going to sleep to prevent a METER BG NOW alarm from sounding during sleep hours

Optimal Calibration Calibrate before bedtime to avoid alarms during the night Use good technique when performing BG checks for calibration Proper coding Clean hands USE FINGERSTICKS Enter the calibration immediately after the fingerstick (Dexcom, Medtronic systems) The best time to calibrate is when the blood glucose (BG) is stable — before meals or at bedtime—for then it is less likely that rapid changes in BG are going to take place. NOTE: When the BG is rapidly changing and a patient attempts to calibrate with a “single point in time” BG fingerstick reading, there may be enough of a change taking place to cause a calibration error to occur. If 2 calibration errors occur in a row, the glucose sensor can no longer be used and must be replaced. For this reason, patients should try not to calibrate within 2 hours after a meal or when 2 UP or DOWN arrows are displayed beside the current glucose reading on the insulin pump screen. The continuous glucose monitoring system must be calibrated a minimum of every 12 hours. However, 3 to 4 times a day is preferred. If calibration is not done every 12 hours, the insulin pump screen will stop displaying sensor glucose readings until a fingerstick BG value is entered Remind your patient to calibrate before going to sleep to prevent a METER BG NOW alarm from sounding during sleep hours 41

Sensor Sites Site Selection Bleeding/Irritation “Fleshy” areas At least 3” Away from insulin infusion Avoid tight clothing areas, scars, bruises, lipoatrophy Rotate sites Bleeding/Irritation Slight bleeding OK Profuse bleeding: remove Remove introducer needle at proper angle

Sensor Sites Adhesive Site Irritation Completely cover the Transmitter & Sensor (Navigator & Medtronic systems) Check sensor daily for loose tape Apply extra tape over sensor & transmitter if tape patch begins to “curl” around edges Site Irritation Watch for redness, swelling, tenderness Remove sensor with prolonged irritation (>1 hour)

Signal Reception Heed transmitter ranges Medtronic: 6 ft. Dexcom: 5 ft. Navigator: 10 ft. Signals do not travel well through water Wear receiver on same side of body as sensor Keep receiver very close while charging (Dexcom) Charge transmitter fully every 6 days (Medtronic)                     In clinics that have utilized the MiniMed Paradigm REAL-Time System in studies, certain experiences can be gained. An analysis of patients who did well experienced benefits from using it continuously or at least 90 percent of the time. Patients who have experience with insulin pump therapy seemed to benefit more than those who were new to pump therapy and therefore still learning how to optimize their insulin pump usage. Patients who looked at it frequently, almost 10-20 times per day, but did not overreact to the data. Patients who had their CareLink data examined by the healthcare team, and with the help of the healthcare team, looked at trends and patterns and responses of glucose to insulin and made changes in carbohydrate to insulin ratios and basal rates. Patients who used the Bolus Wizard calculator did best and avoided hypoglycemia. It can also be said to the contrary that a lot has been learned from patients who do not benefit as much of the time: patients who did not wear the sensor at least 50 percent of the time; patients who did not trust the readings, and therefore did not look at the sensor; and patients who became extremely frustrated with nuisance alarms, causing them to stop using the sensor. So patient behavior during wearing CGM is also a key factor to achieve a better outcome.

Ingredients For Success Wear the CGM at least 90% of the time Look at the monitor 10-20 times per day Do not over-react to the data; take IOB into account Adjust your therapy based on trends/patterns Calibrate appropriately Minimize “nuisance” alarms In clinics that have utilized the MiniMed Paradigm REAL-Time System in studies, certain experiences can be gained. An analysis of patients who did well experienced benefits from using it continuously or at least 90 percent of the time. Patients who have experience with insulin pump therapy seemed to benefit more than those who were new to pump therapy and therefore still learning how to optimize their insulin pump usage. Patients who looked at it frequently, almost 10-20 times per day, but did not overreact to the data. Patients who had their CareLink data examined by the healthcare team, and with the help of the healthcare team, looked at trends and patterns and responses of glucose to insulin and made changes in carbohydrate to insulin ratios and basal rates. Patients who used the Bolus Wizard calculator did best and avoided hypoglycemia. It can also be said to the contrary that a lot has been learned from patients who do not benefit as much of the time: patients who did not wear the sensor at least 50 percent of the time; patients who did not trust the readings, and therefore did not look at the sensor; and patients who became extremely frustrated with nuisance alarms, causing them to stop using the sensor. So patient behavior during wearing CGM is also a key factor to achieve a better outcome. Source: Dr. Bruce Bode & Gary Scheiner, personal observation. 45

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