Medical Education. Personal Continuous Glucose Monitoring Protocol. Innovating for life.

Transcription

1 Personal Continuous Glucose Monitoring Protocol A Guide to Continuous Glucose Monitoring Integrated with Insulin Pump Therapy Includes Alert and Trend Management as well as Threshold Medical Education Innovating for life.

2

3 Table of Contents... Overview and Definitions. Fundamental Concepts Candidate Selection CGM Initial Alert Settings and Adjustments. 6 Low Alarm and Alert Settings. 7 High Alert Settings. 8 Threshold Feature. 9 What to Expect with Threshold 0 Identifying Threshold on the CareLink Daily Detail Report. Graphs and Displays. Using On-Screen Data to Make Therapy Adjustments. Using CareLink Pro Software to Make Therapy Adjustments. CGM Initiation Settings Form. References and Suggested Reading. Table of Contents

4 Bruce W. Bode, MD, FACE An internationally known speaker and author on insulin pump therapy and continuous glucose monitoring, Dr. Bode, a graduate of Emory University School of Medicine, is in private practice with Atlanta Diabetes Associates and is an Associate Professor of Medicine at Emory University. He is active in both Georgia Diabetes Camps and the Juvenile Diabetes Research Foundation. Dr. Bode is also the editor of the American Diabetes Association s Medical Management of Type Diabetes. Francine R. Kaufman, MD Francine Ratner Kaufman, MD is Chief Medical icer and VP of Global Clinical, Medical and Health affairs at Medtronic Diabetes and a Distinguished Professor Emerita of Pediatrics and Communications at the Keck School of Medicine and the Annenberg School of Communications of the University of Southern California. Dr. Kaufman was president of the American Diabetes Association (00-0), and serves on the Advisory Council of the Diabetes Branch of the National Institutes of Health. While every reasonable precaution has been taken in the preparation of this guide, the authors, sponsor and publisher assume no responsibility for errors or omissions, nor for the uses made of the materials contained herein and the decisions based on such use. This document does not contain all of the information necessary for the proper care and treatment of patients with diabetes. As such, no individual may rely on the information presented herein in forming a comprehensive treatment program or in treating any patient with diabetes. No warranties are made, expressed or implied, with regard to the contents of this work or to its applicability to specific patients or circumstances. Neither the author, sponsor, nor the publisher shall be liable for direct, indirect, special, incidental or consequential damages arising out of the use or inability to use the contents of this guide. Authors

5 Overview This guide is for healthcare providers and discusses the personal continuous glucose monitoring (CGM) initiation and adjustment process for patients who are also using insulin pump therapy. In the STAR protocol, patients were started on pump therapy and then began CGM therapy within 7 days using a combination of face-to-face clinic visits, follow-up telephone calls and self-study on-line modules. While timelines and visit schedules may be individualized, the sequential clinical strategy of initiation and fine-tuning glycemic control with Personal CGM is explained. Definitions Professional CGM devices are owned by the healthcare provider, clinic, or hospital. Patients typically wear the device for several days, keeping a record of food and activity, and then return it to the office for download and interpretation. During use, the data can be blinded to the patient, allowing for unbiased assessment of glucose control. Professional CGM in the masked version does not have alerts to indicate hypoglycemia or hyperglycemia, and is recommended for use on an episodic basis. Professional CGM can also be used in real-time on an episodic basis described below. Personal CGM, sometimes referred to as real-time CGM, is owned by the patient. It provides glucose readings up to every five minutes and glucose alerts. CGM systems can be downloaded by the patient and the physician for interpretation. Personal CGM may be a stand-alone device, with the sole function of monitoring glucose, or a device that is integrated into an insulin pump system. * Threshold is available in the MiniMed 0G with Enlite. See the MiniMed 0G System User Guide for complete information and instructions for use. Overview

6 Fundamental Concepts During the past decade, continuous glucose monitoring (CGM) has evolved from being used as a research tool, to being used daily in clinical practice. Today, Personal CGM is successfully used by patients with type diabetes, including children, adolescents, and adults, as well as by patients with type diabetes. Note: MiniMed 0G with Enlite is labeled for use in ages 6 years and older. The Paradigm REAL-Time Revel System, used with Sof-sensor glucose sensor, is indicated for ages 7 years and older. A version of the product specially designed for children is indicated for patients ages 7 to 7. The following fundamental principles guide current CGM practice:. CGM devices measure interstitial glucose, which is related to, but not the same as capillary glucose CGM values will usually lag behind self-monitoring of blood glucose (SM) due to physiologic delay of glucose transfer between interstitial and blood compartments. Depending on the rate of change, CGM values are generally within % 0% of SM values, with greater differences during rapid rates of change.* Patient understanding that blood glucose () does not equal sensor glucose (SG) helps to set realistic expectations and the importance of trends versus discrete values.. CGM systems consist of four components: The glucose sensor is inserted into the subcutaneous tissue, where glucose oxidase measures the interstitial glucose. The transmitter is connected to the glucose sensor, and communicates to the receiver or insulin pump. The receiver or insulin pump displays the glucose values and trends. It also has various alert features and download capabilities. Features of the MiniMed 0G system include: Updated sensor glucose values every minutes Rate of change arrows, 6,, and -hour trend graphs Alert settings for Low and High Glucose Limits, Predictive High and Low, and Rate of Change Threshold (see pages 9 and 0) CareLink Personal and Pro software. CGM devices are indicated for use as adjunctive to SM All treatment changes are to be based on traditional SM tests, not the SG values. The CGM system is calibrated using SM with a glucose meter, usually times a day for optimal results.. The more frequently patients use CGM, the greater improvement in glucose control, Encourage patients to adopt full-time use of CGM. However, patients who use CGM intermittently also benefit. Minimizing excessive alerts upon initiation increases acceptance of the therapy. For those patients who use CGM intermittently, focus on times when glucose management is particularly difficult. Travel Illness Stress Unusual physical activity When glucose targets are not met * The MARD is.6% when calibrating times a day, and.7% when calibrating once every hours during actual use with the MiniMed 0G with the Enlite sensor. Fundamental Concepts

7 Candidate Selection Indications Patients with type diabetes and patients with type managed on insulin with the following characteristics: AC above target Excessive glycemic variability Frequent hypoglycemia or hypoglycemia unawareness Nocturnal hypoglycemia Post-prandial hyperglycemia Pregnancy/Pre-pregnancy* Trouble with glucose control during exercise or periods of stress Patient Requirements Willingness to be attached to a sensor and transmitter Willingness to perform SM to calibrate system and to validate SG values prior to making treatment decisions Willingness to work with healthcare team to analyze data and make appropriate treatment adjustments Precautionary Areas Skin and site irritation and infection Reduces available sites for insulin infusion *Enlite is not approved for pregnant women Candidate Selection

8 CGM Initial Alert Settings and Adjustments Limit Alerts at Initiation It is recommended that patients start with a limited number of alert settings at CGM initiation. This strategy eases patients into their CGM experience by minimizing alerts while they are beginning to learn about their glucose trends and patterns. It balances the benefits of seeing the rate and direction of glucose change, while avoiding information overload and the frustration of excessive alarms. As patients gain an understanding of how food, insulin, and exercise affects their glucose levels, glucose control should begin to improve. Once this occurs, additional alerts may be turned on and limits may be tightened to take full advantage of CGM capabilities. Adding and Adjusting Alerts Using CareLink Pro Software Reports After the patient has become familiar with basic functions of the CGM system and demonstrates the ability to interpret the graphs, additional alert settings can be added. It is important to balance the ability of the patient to tolerate additional alerts with the value of the information obtained from the alerts. In general, most patients want to be alerted only when it is necessary to take action. While it may seem logical for every patient to be alerted of values over 0 mg/dl, patients who have many postprandial glucoses over 0 mg/dl will find the frequency of alerts unacceptable. It is difficult to anticipate how an individual patient will respond to frequent alerts until they are actually utilizing the system. 6 Timely follow-up for alert setting evaluation and adjustment is important for success. Use CareLink software to begin adjusting the settings within the first few days, and no later than 7 days after CGM initiation. The CareLink Therapy Management Dashboard example below demonstrates how to use CareLink reports to individualize settings. For this patient, setting the Threshold at 60 mg/dl, and the Low Glucose Limit at 70 mg/dl at initialization, and later setting the High Glucose Limit at 00 mg/dl may allow the patient to use CGM without receiving excessive alarms. See pages 7 and 8 for recommended initial CGM settings and adjustment considerations. Therapy Management Dashboard Sensor Overlay 6 CGM Initial Alert Settings and Adjustments

9 Low Alarm and Alert Settings Low Alerts are intended to provide warning of actual or impending hypoglycemia so the patient can respond to prevent or reduce the low excursion. Initial settings are intended to balance safety while minimizing nuisance alerts. Settings are individualized in all cases. Alarm and Alerts Initial Settings Considerations and Adjustments Threshold Alarm (MiniMed 0G System only) Alarms with a siren and suspends all insulin delivery when the sensor glucose reaches or falls below the programmed Threshold setting Alarm will continue to siren until patient responds Patient may resume insulin delivery at any time Can be set from mg/dl Low Glucose Limit Alert Alerts when sensor glucose reaches or has fallen below the sensor glucose limit Can be set from 0 90 mg/dl May set up to 8 different time segments per day 60 mg/dl Set higher for hypoglycemia unaware Make sure there is at least 0 mg/dl difference between Low Glucose Limit and Threshold Limit For those patients who need more time to treat before Threshold is activated, consider raising the Low Glucose Limit 70 mg/dl Set higher (90 or 00 mg/dl) for hypoglycemia unaware If patient reports too many alerts, consider setting the limit lower, coupled with therapy adjustments If patient experiences hypoglycemia without alerting, set limit higher Low Predictive Alert Alerts when low glucose is predicted to occur Used to prevent or reduce the severity of the low glucose excursion Can be set at OFF, or from 0 minutes Fall Rate of Change Alert Alerts when sensor glucose has fallen at specified rate of change Fall rate is most important when sensor glucose is near the low limit Can be set from..0 mg/dl/minute OFF OFF Consider using with experienced CGM patients who want more warning before a low occurs Set at 0 minutes Set only if extreme rate of change is valuable, as this setting will increase the frequency of alerts Set at.0 mg/dl/minute If patient reports too many alerts, consider turning this alert OFF Low Repeat Used to select the length of time before the Low Alerts and Threshold alarm repeat after they are cleared, if the condition still exists Is set if one or more of the Low Alert settings or Threshold is turned on Allows time for patient to treat hypoglycemia and for glucose to rise Applies to all Low Alerts and Threshold Can be set from minutes one hour 0 minutes Default is set at 0 minutes Low Alarm and Alert Settings 7

10 High Alert Settings High alerts are intended to detect actual or potential hyperglycemia so the patient can respond and prevent or reduce the high excursion. Initial settings are intended to balance safety while minimizing nuisance alerts. Settings are individualized in all cases. Alerts Initial Settings Considerations and Adjustments High Glucose Limit Alert Alerts when the sensor glucose has reached or risen above the sensor glucose limit Can be set from 0 00 mg/dl May set up to 8 different time segments per day High Predictive Alert Alerts when high glucose is predicted to occur Used to prevent or reduce the severity of the high glucose excursion Can be set from 0 minutes Rise Rate of Change Alert Alerts when sensor glucose has risen at a specified rate of change May be used as indicator for missed boluses Set only if extreme rate of change is valuable Can be set from..0 mg/dl/minute High Repeat Used to select the length of time before the High Alerts repeat after they are cleared, when the condition still exists Can be set if one or more of the High Alert Settings is turned on Allows time for insulin to take effect and high glucose to decrease Applies to all High Alerts Can be set from minutes hours OFF OFF OFF N/A or Two hours Set at 0 mg/dl Alternatively may use CareLink data to determine initial setting If patient reports too many alerts, consider increasing the setting, coupled with therapy adjustment As glucose control improves and hyperglycemia decreases, consider decreasing the setting Set at minutes Consider leaving OFF, to decrease the burden of frequent alerts with limited perceived value If used, consider setting at.0 mg/dl/minute to alert patients only of very rapid changes in glucose levels that may occur when patient misses a bolus If patient reports too many alerts consider turning this alert OFF When patient s missed bolus behavior improves, consider turning feature OFF to prevent excessive alerts Default is set at one hour, so will need to increase setting at initiation to minimize alerts * Bode, BW, Kaufman, FR. Personal Continuous Glucose Monitoring Protocol: A Guide to Continuous Glucose Monitoring Integrated with Insulin Pump Therapy. Northridge, CA: Medtronic, Inc. Diabetes; 0. 8 High Alert Settings

11 Threshold Feature Threshold sirens and shuts off insulin delivery when the sensor glucose value reaches or drops below the programmed Threshold setting. Patient should take a fingerstick and take measures to prevent or treat hypoglycemia. The patient can resume delivery any time. All insulin delivery will be suspended for two hours if the patient is unable to respond to the Threshold alarm. After two hours, the basal rate automatically resumes for four hours. After four hours, if the sensor glucose remains below the Threshold setting, the basal rate suspends again. This cycle continues for a maximum of twelve hours (two cycles), until the calibrations run out, until the pump battery dies, etc. The patient may respond at any time, clear the alarm, and resume insulin delivery. If the patient responds, clears the alarm and chooses to continue the, the pump will stay suspended until the two hour cycle has completed Once basal insulin delivery resumes, if the patient s SG remains or falls below the programmed Threshold setting and his Low Repeat time has passed, then his pump will again suspend insulin delivery for two hours. Threshold Key Points: Makes a siren sound and suspends all insulin delivery when the sensor glucose reaches or falls below the programmed Threshold setting Sirens until the patient clears the alarm Patient can resume delivery at any time Can be set from mg/dl The Threshold Concept Glucose (mg/dl) Insulin infusion stopped Max. duration = h Insulin infusion resumed Glucose (mmol/l) AM AM Time 6 AM. Note: The Threshold feature is available in the MiniMed 0G system only. See the MiniMed 0G System User Guide for complete information and instructions for use. WARNING: The Threshold feature will cause the pump to temporarily suspend insulin delivery for two hours when the sensor glucose reaches a set threshold. Under some conditions of use the pump can suspend again resulting in very limited insulin delivery over a four hour period. Prolonged suspension can increase the risk of serious hyperglycemia, ketosis, and ketoacidosis. Before using the Threshold feature, it is important to read the Threshold information in the MiniMed 0G` System User Guide. Threshold Feature 9

12 What to Expect with Threshold Frequency of Threshold A Threshold event may occur every day or every other day, as some patients commonly experience glucose excursions of mg/dl. The initial setting for Threshold should be at mg/dl, with higher settings (80 90 mg/dl) suggested in those with a history of severe hypoglycemia, renal insufficiency, or other conditions in which avoidance of lower glucose levels is desired. Duration of Threshold The Threshold feature is designed to stop insulin delivery at a user-set threshold when the patient does not respond to a low alarm, such as during sleep. CareLink data from patients using the MiniMed Paradigm Veo system* indicate suspend events that last the full two-hours with no patient response account for 0 % of all threshold suspends, with the majority of these occurring at night. The data from these patients show glucose levels rising on average 0 0 mg/dl per hour for hours after the suspend begins, including after the automatic resumption of basal insulin delivery at the two-hour mark. 7 Threshold and Routine Treatment of Hypoglycemia Threshold should be viewed as a feature for unresponsive patients when there is no one available to help them. When the patient is awake and alert, patients should respond to a Threshold event by cancelling the alarm, checking their by fingerstick and treating their hypoglycemia with oral glucose as directed. They can resume basal insulin delivery upon treatment of the hypoglycemia. Data from CareLink show that during the daytime when Threshold occurs it is most frequently right before lunch or during exercise. 7 Reinforce with families and caregivers that a patient with hypoglycemia who is unresponsive should be treated with glucagon. Recognizing Threshold Events in CareLink Pro Software Threshold events can be easily identified in CareLink reports. A Threshold that lasts two hours and shows no patient response is bounded by an alarm symbol on both ends of the two-hour time period with the basal insulin rate going to zero. A Threshold event that has an alarm symbol only at the start indicates the patient responded and cleared the alarm. *The MiniMed Paradigm Veo insulin pump is not approved for use in the US and uses a slightly different threshold suspend algorithm from the MiniMed 0G insulin pump. 0 What to Expect with Threshold

13 Identifying Threshold on the CareLink Daily Detail Report The Daily Detail reports below each show a Threshold event. Threshold events are indicated by the basal rate drop to 0.0 units/hour as well as a color change from green to red, in the line depicting the basal rate. A patient-initiated suspend is depicted by a basal rate drop to 0.0 units/hour in green. Patient unresponsive. Basal suspended for two hours, then automatically resumed. Patient cleared the alarm, tested, and resumed insulin delivery immediately. Patient cleared Threshold alarm and kept the basal rate suspended. After approximately one hour, the patient resumed basal delivery. Identifying Threshold on the Daily Detail Report

14 Graphs and Displays There are, 6,, and -hour graphs available for display on the MiniMed 0G system. The graphs show High and Low Glucose Limit lines, the sensor glucose (SG) tracing, and the most recent SG value (or the reason why there is no value shown), as well as the time the SG value was updated. Historical data up to hours can be viewed by scrolling back through the graphs. If the SG rises or falls faster than a certain rate, trend arrows automatically appear in the graphs next to the SG measurement. Trend Arrows SG has been falling at a rate of.0 to.0 mg/dl per minute SG has been falling at a rate of.0 mg/dl or more per minute SG has been rising at a rate of.0 to.0 mg/dl per minute SG has been rising at a rate of.0 mg/dl or more per minute Below is an example of a -hour graph. Please see the MiniMed 0G System User Guide for further information about graphs and pump displays. Sensor glucose tracing Time of sensor glucose value update Time of day High alert limit Sensor glucose value Low alert limit Trend arrow Shaded area is the hours from 6 pm to 6 am Graphs and Displays

15 Using On-Screen Data to Make Therapy Adjustments The protocol for the Juvenile Diabetes Research Foundation (JDRF) CGM study provided recommendations for insulin dose adjustments based on trend arrows. 8 The guidelines below are adapted from these recommendations. Trend Arrows After a patient has become comfortable responding to alarms and alerts and interpreting glucose trends, you may want to consider adding trend arrows to the insulin dose adjustments. Patients should use the Wizard calculator using fingerstick values to determine the bolus insulin recommendation, and then can be instructed to consider making dose adjustments to the Wizard estimate based on the on-screen trend arrows. If fingerstick is low before bed, or anytime a low alert occurs Correct the low with glucose tablets Check to see if there are trend arrows on the pump screen Consider taking more glucose if down arrows are present For example, if grams is normally used to treat a low, consider adding grams glucose for one arrow and 0 grams for arrows If fingerstick is low before food intake Do not bolus while glucose is low Treat the hypoglycemia After treating the hypoglycemia and the glucose is within target, calculate the bolus to cover the meal, check for trend arrows on the pump, and adjust based on the arrows using the guidelines below If fingerstick is at or above target before a meal or whenever a high alert occurs Check to see if there are trend arrows on the pump screen Calculate your meal bolus and/or correction dose and adjust based on the trend arrows using the guidelines below Adjustment Guidelines Using Trend Arrows Decrease dose by 0% Decrease dose by 0% No arrows No change in dose Increase dose by 0% Increase dose by 0% Adjustments can also be made for trend arrows when the is within target range. This should be initiated after the patient has experience with adjusting doses for high and low s using trend arrows. When is within target range, use the arrows to give minor correction doses and small amounts of glucose as appropriate. As always, individual patient history should be considered with all recommended dosage adjustments. Using On-Screen Data to Make Therapy Adjustments

16 Using CareLink Pro Software to Make Therapy Adjustments The data provided by CareLink should be reviewed in a systematic format. Start by looking at the Therapy Management Dashboard for a sense of overall control or areas of concern. First, look at the overnight period and make any necessary changes. Next, evaluate the pre-meal time periods and adjust basal rates as needed. Then evaluate the post-meal time periods and adjust carbohydrate ratios or timing of insulin delivery as needed. Identify any behavioral issues that might be impacting the patient s management and counsel or educate as needed. Generally, to therapy changes and to behavioral changes at a time with a follow-up evaluation is appropriate. Therapy Management Dashboard //0 - /7/0 -Hour Analysis Sensor, Insulin, & Settings Statistics Avg Readings Carbs Entered 8 ± mg/dl 6. per day 0 ± 6g per day Hypoglycemic Patterns (6)** : AM-7: AM (9) Time Period :7 PM-:9 PM (7) Insulin (U, active hr) 8:9 PM-0: PM () Basal Rate Insulin Bedtime to Wake-up Bedtime: 8:00 PM - :00 AM Wake-up: :00 AM - 9:00 AM Breakfast: 6:00 AM - 0:00 AM () Pre-meal SG Avg: 09 ± mg/dl Post-meal SG Avg: ± 0mg/dL Avg Carbs: ± 9g Avg Food : 8.9 ±.9U Lunch: :00 AM - :00 PM (6) Pre-meal SG Avg: 9 ± mg/dl Post-meal SG Avg: 0 ± mg/dl Avg Carbs: 0 ± g Avg Food : 6.7 ±.U Hyperglycemic Patterns () :00 PM-: AM Time Period 8:0 AM-0: AM :00 PM-6: PM Pump Use Per Day Insulin TDD.0 ±.U Basal/ Ratio / 8 Manual es 0.0U (0.0 boluses) Wizard.7U (.6 boluses) Food.8U (.9 boluses) Correction.U (.9 boluses) Override (+) 0.U (0. boluses) Override (-) -.U (0. boluses) Dinner: :00 PM - 0:00 PM (9) Pre-meal SG Avg: 7 ± mg/dl Post-meal SG Avg: 6 ± 9mg/dL Avg Carbs: 8 ± g Avg Food :. ±.U Duration h m per day Threshold Events. per day Time Res./Site Change h m per day Every.7 /. days Sensor Use Avg SG Wear Duration 7 ± mg/dl 6d 0h per week Low SG Alarms 0. per day High SG Alarms. per day ** Only highest priority shown. 6 Action Plan Reviewed By Date Sensor Overlay* Evaluate for a sense of overall control or areas of concern. Insulin Profile Graph Evaluate insulin profiles. How many basal rates? Are they appropriate? Is variance appropriate? Evaluate average active bolus insulin. Note active insulin in overnight time period before adjusting overnight basal rate. Sensitivity and Carb Ratio Evaluate insulin sensitivity and carb ratios. Are they appropriate? Consider checking carb ratio against 0 rule (0 divided by TDD) and insulin sensitivity against 700 or 000 rule (700 or 000 divided by TDD). Therapy Management Software Time Bedtime to Wake-up Sensor Overlay* Evaluate sensor glucose from bedtime to wake-up. Is patient within target during this time period? Meal Sensor Overlay* Evaluate glucose values around meal times when patient uses the Wizard. Is pre-meal value within target? Is post-meal rise within 0 60 mg/dl? 6 Action Plan Use this section to record notes for patient records, to provide comments and recommendations for patient therapy, and/or to record documentation for health insurance providers.

17 Example of Therapy Management Dashboard Use this report to review the big picture as well as specific behaviors. Therapy Management Dashboard //0 - /7/0 -Hour Analysis Sensor, Insulin, & Settings Statistics Avg 8 ± mg/dl 7 Statistics Avg 8 ± mg/dl Readings 6. per day Carbs Entered 0 ± 6g per day Readings 6. per day Hypoglycemic Patterns (6)** : AM-7: AM (9) Carbs Entered 0 ± 6g per day Time Period :7 PM-:9 PM (7) Basal Rate Insulin Insulin (U, active hr) 8:9 PM-0: PM () Hyperglycemic Patterns () :00 PM-: AM Time Period 8:0 AM-0: AM :00 PM-6: PM Pump Use Per Day Insulin TDD.0 ±.U 8 Hypoglycemic Patterns (6)** : AM-7: AM (9) Time Period :7 PM-:9 PM (7) 8:9 PM-0: PM () Basal/ Ratio / 8 Bedtime to Wake-up Bedtime: 8:00 PM - :00 AM Wake-up: :00 AM - 9:00 AM Breakfast: 6:00 AM - 0:00 AM () Pre-meal SG Avg: 09 ± mg/dl Post-meal SG Avg: ± 0mg/dL Avg Carbs: ± 9g Avg Food : 8.9 ±.9U Lunch: :00 AM - :00 PM (6) Pre-meal SG Avg: 9 ± mg/dl Post-meal SG Avg: 0 ± mg/dl Avg Carbs: 0 ± g Avg Food : 6.7 ±.U Dinner: :00 PM - 0:00 PM (9) Pre-meal SG Avg: 7 ± mg/dl Post-meal SG Avg: 6 ± 9mg/dL Avg Carbs: 8 ± g Avg Food :. ±.U Manual es 0.0U (0.0 boluses) Wizard.7U (.6 boluses) Food.8U (.9 boluses) Correction.U (.9 boluses) Override (+) 0.U (0. boluses) Override (-) -.U (0. boluses) Hyperglycemic Patterns () :00 PM-: AM Time Period 8:0 AM-0: AM Duration Threshold Events Time h m per day. per day h m per day :00 PM-6: PM Res./Site Change Every.7 /. days Sensor Use Avg SG 7 ± mg/dl Wear Duration 6d 0h per week 9 Pump Use Insulin TDD Per Day.0 ±.U Low SG Alarms 0. per day High SG Alarms. per day ** Only highest priority shown. Basal/ Ratio Manual es / 8 0.0U (0.0 boluses) Action Plan Wizard.7U (.6 boluses) Reviewed By Date Time Food Correction Override (+).8U (.9 boluses).u (.9 boluses) 0.U (0. boluses) Override (-) -.U (0. boluses) 0 Duration Threshold Events h m per day. per day Time h m per day Res./Site Change Every.7 /. days Sensor Use Avg SG 7 ± mg/dl Wear Duration 6d 0h per week Low SG Alarms 0. per day High SG Alarms. per day ** Only highest priority shown. 7 Statistics Table Evaluate average and standard deviation (SD). Mean glucose values between 0 60 mg/dl are generally acceptable to meet AC target. An SD of less than half the mean glucose is generally acceptable. Are there an appropriate number of readings/day? Are the carbs per day appropriate? 8 Hypo- and Hyperglycemic Patterns Tables* Evaluate hypo-and hyperglycemic patterns. Are there areas of concern? Are there extreme excursions of hypo- or hyperglycemia? 9 Pump Use Table Evaluate total daily dose of insulin. Is it appropriate based on weight and age? Evaluate basal to bolus ratio. Is it appropriate for age and type of diabetes? is generally 0%. Evaluate pump features being used, e.g. Wizard, amount of correction, number and type of overrides. Are reservoir and site changes occurring appropriately? 0 Duration*** Evaluate suspend duration. Are there lengthy periods of suspends? Are there frequent Threshold events? Sensor Use Table Evaluate average SG and SD. Evaluate amount of sensor wear. Evaluate number of alarms per day. * Targets determined by provider during report setup. To obtain the Therapy Management Dashboard, a minimum of five days (0 data points) of pump and sensor data are required in the reporting period. *** Threshold Events and Time will be displayed if device supports this feature. Therapy Management Dashboard

18 Example of Episode Summary Use this report to evaluate events that precede hypoglycemic and hyperglycemic episodes. You may also use this as a conversation map to develop questions you may want to discuss with the patient in order to make therapy changes or provide additional education. Episode Summary //0 - /7/0 Hypoglycemic Episodes, by preceding Event Type - Threshold: 70 mg/dl Hyperglycemic Episodes, by preceding Event Type - Threshold: 0 mg/dl Most Common Event Types preceding Hypoglycemia Most Common Event Types preceding Hyperglycemia Event Type Descriptions Event Types % Description Event Type Descriptions Event Types % Description Rapid Falling Sensor Rate Of Change Hyperglycemia Preceding Hypoglycemia Wizard Food 8 8 Consider counseling your patient to take action to avoid hypoglycemia. Consider assessing your patient s insulin sensitivity factors.consider counseling your patient on the management of hyperglycemia. Consider assessing the Wizard settings, counseling your patient on accurate carbohydrate counting, and/or the timing of insulin delivery with respect to carbohydrate intake. Wizard Food Overcorrection of Hypoglycemia Rising Sensor Rate of Change Without 9 Consider assessing the Wizard settings, counseling your patient on accurate carbohydrate counting, and/or the timing of insulin delivery with respect to carbohydrate intake. Consider counseling your patient on the management of hypoglycemia. Consider counseling your patient on bolus use with meals and/or correcting rapid glucose excursions. Other Observations No overall issues observed. Hypoglycemic/Hyperglycemic Episode Charts ( different algorithms)* Use this to assist in identifying and ranking events that precede hypo- and hyperglycemic episodes. There can be more than one event preceding an episode and it is possible that no events precede an episode. You may want to obtain more information from the patient about these events. Most Common Event Types Pie Charts (for top preceding events) Evaluate the hypo- and hyperglycemic episodes in relation to the total number of occurrences for each event during the reporting period. If < 0%, may not require evaluation. Event Type Descriptions Table Consider possible therapy adjustments or education related to hypo- and hyperglycemic episodes. Other Observations Table (6 algorithms) Identify possible behavior changes related to pump, CGM, and/or meter usage. *Targets determined by provider during report setup. To obtain the Episode Summary, a minimum of five days (0 data points) of pump and sensor data are required. 6 Episode Summary

19 Example of Adherence Report Use this report to analyze patient behaviors. Adherence ( of ) //0 - /7/0 Glucose Measurements Events Fill Events Readings Sensor Duration (h:mm) Manual es Wizard Events With Food With Correction Overridden Rewind Cannula Fills Cannula Amount Tubing Fills Tubing Amount Duration (h:mm) Sunday //0 : Monday //0 :00 :00 Tuesday /6/0 7 : : Wednesday /7/0 8 :00 :00 Thursday /8/0 :00 :6 Friday /9/0 Saturday /0/0 Sunday //0 Monday // :0 :00 :00 : :0 :0 : Duration (h:mm) Tuesday //0 6 :0 Wednesday //0 : :7 Thursday //0 Friday /6/0 Saturday /7/0 Summary /day :00 :00 :00 d 6h 00m 0.0/day 7 7.6/day 6 8.9% 6 8.% 7.8% 0.U /fill.u/fill :8 : 0:8 9h m :00 0: :00 Partial day Low s Note: Partial days will not be included in summary averages. Days on which a time change occurred are considered to be partial days. :6 :0 :0 Sensor Duration Evaluate the amount of time per day the sensor is worn. Duration Evaluate the total time the pump is suspended per day (includes Threshold and manual suspend events). Threshold Events Evaluate the number of Threshold events per day. The number of total Threshold events precedes the icon. No number in front of the icon signifies one event. Manual Manual suspends do not have an icon indicator. If there is no Threshold icon, all of the suspend duration is from one or more manual suspends. Adherence Report 7

20 Event Event Events Events Event Event Events Events Time Time : :AM AM Type 66 Type 6: 9:6 AM 0: AM PM 6:AM AM Delivered 9:6 AM 0: AM :06 PM Norm :06.00 Delivered Norm Type 7 6 Type 7 ++ Square Square Portion Portion (U,(U, h:mm) h:mm) 7: PM : 7: PM Statistics : PM PM 6: 6: AM AM Time: : 0: :06 7: : PM Time AM AM 6:6: AM AM 9:69:6 AM AM0: AM AM:06 PM PM 7: PM PM PM Delivered Delivered Norm Norm : Statistics Statistics Event Event Event Time Time : : AM AM 9:6 9:6 AM AM / -/ (mg/dl) Avg Avg (mg/dl) Recommended Recommended /.0.00 / -.00 /7 Example of Sensor & Meter Overview Report: Daily Snapshots Time : AM s Type rm Readings Readings - Difference -Difference ± Readings ReadingsAbove AboveTarget Target 9:6 AM 0: AM :06 7: PM 8.0 : PM Delivered Norm Delivered Norm PM Recommended Recommended Carbs Carbs (g)(g) 89 6./day - - Readings 8 Readings ReadingsBelow BelowTarget Target ++Square (U, Difference Difference Portion Square Portion (U,h:mm) h:mm) - - Setting Carb Ratio -.0 Carb Ratio Setting (g/u) (g/u) Readings Above Target 6% 8% Avg Sensor Sensor Avg(mg/dL) (mg/dl) -6.0 Recommended Recommended Carbs 6.0(g) Carbs - (g) Food Food Readings Below Target -0% Avg % >>0 AUC (mg/dl) Avg AUC 0 (mg/dl) - Ratio Difference -Carb -Difference - Carb Setting -(g/u) Ratio Setting (g/u) (mg/dl) (mg/dl) Sensor Avg (mg/dl) ± 9 7 ± Avg AvgAUC AUC<<70 70(mg/dL) (mg/dl) Carbs (g) Carbs (g) Food Food Sensor & Meter Overview ( of ) Target Target Setting Setting (mg/dl) (mg/dl) //0 - /7/0 Avg AUC > 0 (mg/dl).9 d 0h. d 6h Ratio (g/u).0.0 Carb Carb RatioSetting Setting (g/u) (mg/dl) 8 7 (mg/dl) Insulin Insulin Sensitivity Sensitivity Setting Setting Daily Carbs Daily Carbs(g) (g)6 (mg/dl per per U)U) Avg AUC <- 70.(mg/dL d d 6h -9 7Setting Food 8.0 Setting Food (mg/dl) Target (mg/dl) (mg/dl) h Target Carbs/ Insulin Carbs/ Insulin (g/u) Correction Correction (g/u) (mg/dL) (mg/dl) Insulin 98 Setting Sensitivity Setting Insulin Sensitivity 7 7 Daily Carbs (g) ± 6 (mg/dl (mg/dl per per U) U) Active Active Insulin Insulin (mg/dL).0 Setting Target Target Setting (mg/dl) Total TotalDaily DailyInsulin Insulin 0 Correction Correction Carbs/.0.0 Insulin (g/u) Sensitivity Setting 7 0 Insulin Insulin Sensitivity Setting Daily Basal 6 Daily Basal (mg/dl (mg/dlper peru) U) Active Insulin 0.00 Active Insulin Total Daily Insulin ±. Daily Daily Correction Correction Sensor Sensor trace trace reading reading Linked Linked % 8. % Active Daily Basal Interrupted ActiveInsulin Insulin Interrupted chart chart Calibration Calibration B Fills Fills 6: AM Type Type 6 (U, h:mm) +7Square Portion (U, h:mm) + Square Portion - -Avg (mg/dl) Use this report to analyze glucose levels, carbohydrate intake, and insulin delivery to assist in identifying trends. 8.0 h:mm) us ce bs (g) g (g/u).0.0 us 8.0 mg/dl) 9 08 mg/dl) etting per U) us lin Sensor trace Sensor trace reading reading Basal.0 Linked Linked Daily Basal -Interrupted Interrupted chart chart Calibration Calibration 67%.7 Temp basal Temp basal Fills 8% Pump rewind Pump 7 rewind.0u Threshold Susp Threshold Sensor Sensortrace trace reading reading Linked Linked Basal Basal Time Timechange change Exercise Exercise Interrupted Interrupted chart chart Calibration Calibration Temp Tempbasal basal Pump Pumprewind rewind Threshold Threshold Injected Injectedinsulin insulin Other Other reading Linked Basal Time change Exercise Glucose alert chart Calibration Temp basal Pump rewind Threshold Injected insulin Other Alarm Sensor trace reading Basal Interrupted chart Temp basal Time change Exercise Threshold Injected insulin Other For more details of each day, see the Daily Detail Report reading Glucose Section* chart Evaluate meter and sensor glucose. Basal Temp basal Carbs Section Evaluate carbohydrate intake. Is it appropriate for patient? Is there insulin given for all carbohydrate entries? 8 Daily Snapshots Insulin Section Threshold Evaluate insulin delivery. Are there multiple boluses? Are there frequent Threshold events? Are suspend time periods appropriate? Is the temp basal feature being used? *Targets determined by provider during report setup

21 Event l Time Time : : AM AM 6: 6: AM AM Delivered 9:6 9:6 AM AM 0: 0: AMNorm AM :06 :06 PM PM : 7: PM PM Recommended : : Statistics PM PM / /.0 -/7.0 Carbs 6.0(g) Readings Type Type 6 + Square + 7 Portion (U, (U, h:mm) h:mm) Use this report to look at more specific details (time, amount, type) of each bolus Difference Carb Ratio Setting (g/u).0 Avg given (mg/dl) as well 67as suspend 8 and.0 Readings ± temp basal events. Above Target 6% 6% 6: AM Delivered 9:6 AM 0: Norm AM :06 PM :8.0 PM8.0 Recommended : PM Carbs (g) Food Readings 8 89 Readings 6./day Below Target 0% 0% + + Square Portion (U, (U, h:mm) Difference Carb Ratio Setting (g/u) (mg/dl) Readings Above Target 6% Sensor 8% Avg Avg (mg/dl) ± 9 ± Recommended Daily.00Detail ( of ) Carbs Carbs (g) (g) Food Target 7 Setting 7 (mg/dl) Thursday //0 Readings Below Target 0% Carb Carb Ratio Ratio Setting (g/u) (g/u) (mg/dl) Avg Difference Avg Insulin Sensitivity AUC 7.0 AUC > % 0 > 0 (mg/dl).9.9 d d 0h 0h. Setting 8 7 Sensor Avg (mg/dl) ± 9 7 (mg/dl per U) Carbs (g) (g) Food Food Target 7 7 Setting (mg/dl) Avg 0.0 Avg ± AUC 00 AUC < - 70 < 0 70 (mg/dl) d 0 d 0h 0h Correction.00 C Carb Carb Ratio Ratio Setting (g/u) (g/u) (mg/dl) Insulin 7.0 Avg Sensitivity AUC > 0 Setting (mg/dl) d 7 7 0h. 0 0 d 6h 7 7 (mg/dl per U) Active Daily Insulin Daily Carbs (g) (g) Food Food Target Target 7Setting 6.0 (mg/dl) Avg 0-0 AUC < (mg/dl) d 0-0 0h d 6h Correction.00 Carbs/.0 Insulin (g/u) (g/u) (mg/dl) Insulin Sensitivity Setting (mg/dl per per U) U) Active Insulin Daily Carbs (g) ± Target Setting (mg/dl) Total Total Daily Daily Insulin Correction Carbs/.0.0 Insulin (g/u) Sensor..70 trace.70 reading Linked 08 Insulin 98 Sensitivity Setting (mg/dl per per U) U) Active Active Insulin Interrupted Daily Daily Basal % % 8. chart Calibra Events Total Daily Insulin ±. Statistics / / - /7 Correction Sensor trace reading Linked Daily Daily Basal % 67%.7 Event 6 7 Avg (mg/dl) 67 8 ± Time7: AM 7 9:6 AM 0: AM :06 7PM 7: PM : PM Active Insulin Interrupted Readings Daily Basal /day chart 6.6 % Calibration 8. % Fills Temp Fills basal Pump re 7 Type Delivered Norm + Square Portion (U, h:mm) Recommended Difference Carbs (g) reading Carb Ratio Setting (g/u).0 Food chart chart (mg/dl) 9 Target Setting (mg/dl) 0-0 Basal Insulin Sensitivity Setting (mg/dl per U) Correction : AM Sensor.70 trace Sensor trace Interrupted Linked Calibration Pump rewind Daily Basal 6.6 % 8. %.70 reading chart chart Events Time : AM Event Type Readings Above Target Readings Linked Below Linked Target Sensor Avg (mg/dl) Avg AUC > 0 (mg/dl) Avg AUC < 70 (mg/dl) Daily Carbs (g) Carbs/ Insulin (g/u) Daily.9. d 0h ± 9 6% Calibration d 0h %.7 ±. d 6h ± 6 ±. 8% Basal % Daily 0% Basal.0 d Fills Temp Temp basal basal 6h 8% 6: AM 9:6 6 7 Events Time : AM 6: AM Delivered 9:6 AM 0: Norm AM :06 PM.00 7: PM 8.0 : S Event Event Type Square 7 7 Portion (U, h:mm) No Events Time Time: : AM AM 6: 6: AM AM Delivered 9:6 9:6 AM AM0: Norm 0: AM AM:06 :06 PM.00 PM 7: 7: 8.0 PM PMRecommended : Statistics : /.00 / / Example Event of Daily Detail Report Type Type Square 7 7 Portion (U, h:mm) Difference Avg Avg (mg/dl) Sensor trace trace Interrupted Linked Calibration.60.0 Temp basal.0 Basal Temp basal basal Threshold Pump rewind Total Daily Insulin Time change Injected insulin Threshold Exercise Other 67%.7 8% Time Timc Pump Pump rewind 7 rewind.0u Threshold Injecte Time Time change Exercise Glucose Injected insulin Other Alarm Glucose alert Alarm Active Insulin Fills 7.0U Sensor trace reading Linked Basal Time change Exercise Glucose alert Interrupted chart Calibration Temp basal Pump rewind Threshold Injected insulin Other Alarm Glucose Alert Meter Reading Carbohydrate Gram Entries 6 Basal Rate Change Delivery Patient checked, calibrated, entered carbohydrates and bolused simultaneously Threshold event that was not responded to. Auto resume of basal insulin after hours of suspend shown. Threshold event that was responded to before auto resume of basal. Calibration. Exercise entered via Capture Events feature. User initiated. 6 An example of multiple repeated alerts set at narrow ranges. Daily Detail Report 9

22 Example of Device Settings Report Use this report to evaluate insulin pump and sensor settings. -Hour Total TIME 0:00 :00 :00 6:00 8:00 0:00 :00 7:00 0:00 9. U U/hr Hour Total Device Settings Snapshot Sunday /8/0 0:9 AM Basal Maximum Basal Rate.00 U/hr Temp Basal Type Percent of Basal Standard (active) Pattern A TIME 0:00 :00 :00 6:00 0:00 :00 7: U U/hr Pattern B -Hour Total TIME U/hr TIME 0:00 0:0 7:00 Maximum Dual/Square (Variable) Blood Glucose Reminder Wizard Units Active Insulin Time (h:mm) Insulin Concentration Carbohydrate Ratio (g/u) Ratio On :00.0 U On On Easy (Audio) Entry (Step) 0.0 U g, mg/dl Insulin Sensitivity (mg/dl per U) TIME 0:00 :00 Sensitivity 7 Missed Reminder Start (h:mm) Blood Glucose Target (mg/dl) TIME 0:00 :00 End (h:mm) Low 0 00 High 0 0 Sensor Sensor Transmitter ID Units Glucose Alerts TIME 0:00 Alert Repeat On mg/dl Predictive Alert Low High (mins) On Low (mg/dl) 70 0:0 High (mg/dl) 0 :00 Rate Alert: Fall Rise (mg/dl/min) Notes AUC Limit: Low High (mg/dl) Missed Data/Weak Signal (h:mm) 0: Graph Timeout (h:mm) 0:0 Auto Calibration Calibration Reminder (h:mm) Calibration (Alert) Repeat (h:mm) :00 0:0 Utilities Alert Type Threshold (mg/dl) Low Reservoir Warning Amount Beep Medium 60 Insulin Units 0 U Basal Settings Evaluate basal settings. Is the number of basal rates appropriate? Is variance between rates appropriate? Settings Evaluate bolus settings. Are they appropriate? You may want to check the carb ratio against the 0 rule and the sensitivity against the 700 rule. Are the Wizard glucose targets appropriate? Is the Active Insulin time appropriate? Overall, do the settings make sense? Sensor Settings Evaluate sensor settings. Are they appropriate? Are alerts set appropriately? Utilities Evaluate alert type, Threshold value (if pump is enabled with this feature), and low reservoir warning. Are they appropriate? Notes Use this section to record notes for patient records, to provide comments and recommendations for patient therapy. Provide a copy of this page to the patient for documentation of doses and settings. 0 Device Settings Report

23 Continuous Glucose Monitoring Initiation Settings PRESCRIBER S INSTRUCTIONS TO PATIENT Patient Name: Fax to: Date: DOB: Threshold Alarm (MiniMed 0G system only) On mg/dl (60 90 mg/dl) Low Glucose Alert Start on (date) On OR OR Low Repeat Time Units a.m. mg/dl mg/dl mg/dl mg/dl Base settings on CareLink data Low Predictive Alert On Fall Rate Alert minutes ( 0 min) On mg/dl/minute (..0) minutes ( min hour) Low Repeat is turned on to the default of 0 minutes when any Low Alert setting is programmed. High Glucose Alert Start on (date) On OR OR High Repeat Time Units a.m. mg/dl mg/dl mg/dl mg/dl Base settings on CareLink data High Predictive Alert On Rise Rate Alert minutes ( 0 min) On mg/dl/minute (..0) minutes ( min hours) Default is set at hour. May need to increase to hours to minimize alerts. Yes, patient may adjust settings as necessary after initial use. No, it is preferred that the patient not adjust settings without consulting prescriber. If patient cannot use abdomen*, I authorize use of alternate site(s) as medically necessary. Alternate site(s): Notes (optional): Prescriber Name: Prescriber Signature: Date: 90M Medtronic MiniMed, Inc. All rights reserved. *The clinical trials of sensor accuracy have been based on sensors inserted in the abdominal area. Sensor performance may differ when other insertion sites are used.

24 References and Suggested Readings References. American Association of Clinical Endocrinologists Consensus Panel. AACE Consensus Statement on Continuous Glucose Monitoring. Endocrine Practice. 00;(6):7-7.. Hirsch, IB, Armstrong, D, Bergenstal, RM, et al. Clinical Application of Emerging Sensor Technologies in Diabetes Management: Consensus Guidelines for Continuous Glucose Monitoring (CGM). Diabetes Technol Ther. 008;0()-.. The Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Study Group. Diabetes Care. 009;() Bergenstal, RM, Tamborlane, WV, Ahmann, A. Effectiveness of Sensor-Augmented Insulin-Pump Therapy in Type Diabetes. N Engl J Med 00;6()-0.. Medtronic MiniMed. MiniMed 0G System User Guide. Northridge, CA; Mastrototaro, J, Welsh, JB, Lee, S. Practical Considerations in the Use of Real-Time Continuous Glucose Monitoring Alerts. J of Diabetes Sci and Technol. 00;() Data on file. Medtronic, Inc. Diabetes, 8000 Devonshire Street, Northridge, CA. 8. JDRF Study Group. JDRF Randomized Clinical Trial to Assess the Efficacy of Real-Time Continuous Glucose Monitoring in the Management of Type Diabetes: Research Design and Methods. Diabetes Technol Ther. 008;0()0-0. Suggested Reading American Association of Clinical Endocrinologists Consensus Panel. AACE Consensus Statement on Continuous Glucose Monitoring. Endocrine Practice. 00;(6):7-7. American Diabetes Association Position Statement on Standards of Medical Care in Diabetes 0. Diabetes Care. 0;(suppl )S-S6. Agrawal, P, Welsh, JB, Kannadr, B, Askari, S, Yang, Q, Kaufman, FR. Usage and Effectiveness of the Low Glucose Feature of the Medtronic Paradigm Veo Insulin Pump. J Diabetes Sci Technol. 0;()7-. Bode, BW, Kyllo, J, Kaufman, FR. Pumping Protocol: A Guide to Insulin Pump Therapy Initiation. Northridge, CA: Medtronic, Inc. Diabetes; 0. Buckingham, B, Wilson, DM, Lecher, T, Hanas, R, Kaiserman, K, Cameron, F. Duration of Nocturnal Hypoglycemia Before Seizures. Diabetes Care. 008;()0-. Choudhary, P, Shin, J, Yongyin, W, et al. Insulin Pump Therapy with Automated Insulin Suspension in Response to Hypoglycemia. Diabetes Care. 0;;0-0. Danne, T, Kordonouri, O, Holder, M, et al. Prevention of Hypoglycemia by using Low Glucose Function in Sensor- Augmented Pump Therapy. Diabetes Tech Ther. 0;()9-0. Garg, S, Brazg, RL, Bailey, TS, et al. Reduction in Duration of Hypoglycemia by Automatic Suspension of Insulin Delivery: The In Clinic ASPIRE Study. Diabetes Technol Ther. 0;()0-09. Hirsch, IB. Realistic Expectations and Practical Use of Continuous Glucose Monitoring for the Endocrinologist. J Clin Endocrinol Metab. 009;9(7)-8. The Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Study Group: Tamborlane, WV, Beck, RW, Bode, BW, et al. Continuous Glucose Monitoring and intensive Treatment of Type Diabetes. N Engl J Med. 008;9()6-76. Kaufman, FR. Insulin Pumps and Continuous Glucose Monitoring: A User s Guide to Effective Diabetes Management. Alexandria, VA. American Diabetes Association. 0. Mastrototaro, J, Welsh, JB, Lee, S. Practical Considerations in the Use of Real-Time Continuous Glucose Monitoring Alerts. J of Diabetes Sci Tech. 00;()7-79. Phillip, M, Danne, T, Schlomt S, et al for the Consensus Form Participants. ISPAD Consensus Statement on Use of Continuous Glucose Monitoring in Children and Adolescents. Pediatric Diabetes. 0;:-8. References and Suggested Reading