Pumping Protocol A Guide to Insulin Pump Therapy Initiation

Transcription

1 Pumping Protocol A Guide to Insulin Pump Therapy Initiation Includes an introduction to continuous glucose monitoring (CGM) and therapy management software Medical Education Academia Innovating for life.

2

3 Table of Contents Purpose... 3 Insulin Pump Therapy Guidelines for Initial Pump Settings... 5 Calculate Starting Doses The Bolus Wizard Calculator Adjusting Pump Settings Basal Rate Adjustments Bolus Adjustments Infusion Site Care DKA Prevention Unexplained High Glucose Prevention of Hypoglycemia Treatment of Hypoglycemia Special Populations Therapy Management Software Continuous Glucose Monitoring (CGM) Forms References and Suggested Reading Table of Contents 1

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. He is active in both the Georgia affiliate of the American Diabetes Association and the Juvenile Diabetes Research Foundation. Dr. Bode is also the editor of the American Diabetes Association s Medical Management of Type 1 Diabetes. Contributors Jennifer Kyllo, MD Jennifer Kyllo, MD is the Medical Director of the McNeely Pediatric Diabetes Center and Endocrine Clinic at Children s Hospitals and Clinics of Minnesota. She attended medical school at the University of Minnesota and completed her residency and fellowship at the University of Iowa. Her principal areas of interest include caring for children with diabetes and improving access to new diabetes technology for children. Francine R. Kaufman, MD Francine Ratner Kaufman, MD is Chief Medical Officer 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 ( ), and serves on the Advisory Council of the Diabetes Branch of the NIH. While every reasonable precaution has been taken in the preparation of this guide, the author, 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. 2

5 Purpose This booklet is designed for clinicians who are just beginning to prescribe pump therapy, as well as those who already have experience and want to review the latest strategies for optimizing glycemic control with insulin pump therapy. It provides information on proper candidate selection and the indications and protocols for initiating insulin pump therapy. Guidelines for fine-tuning insulin doses and strategies for preventing insulin pump problems are also presented. Fundamental Concepts Over the past three decades, insulin pump therapy has proven to be the most effective insulin regimen available for achieving tight glycemic control while minimizing the risk for hypoglycemia. 1 It is readily used for the intensive management of adults, adolescents and children with type 1 diabetes and those with insulin-requiring type 2 diabetes. Effectiveness of insulin pump therapy is attributed to three fundamental principles: 1. Pumps use only rapid-acting insulin for basal and bolus insulin requirements. Eliminating longer acting insulin helps improve glycemic control during fasting states because: The action/peak time of rapid-acting insulin is more predictable and reproducible than long-acting insulin. 2 The tiny basal doses that are continuously delivered over each hour are more consistently absorbed by the body. 2. Pumps deliver insulin in two ways, basal and bolus. Basal Insulin is a continuous infusion of insulin that is delivered automatically 24 hours a day. The purpose of basal insulin is to cover hepatic glucose production and to maintain glucose stability during fasting states (between meals and during sleep). Bolus Insulin is delivered on-demand, by the patient, for food intake and/or to correct glucose levels that are above the patient s target range, delivered separately or together. Food Bolus: Insulin given to cover food or drink that contains carbohydrates. Correction Bolus: Insulin given to correct blood glucose (BG) levels that are abnormal. 3. Medtronic pumps use a Bolus Wizard calculator. The Bolus Wizard calculator helps make diabetes management and bolus dosing easier and more accurate because it: Calculates the bolus amount for the patient, according to their personalized settings. Tracks the amount of active insulin remaining from previous boluses. Subtracts active insulin from correction doses before suggesting the total bolus amount, which helps to prevent lows that result from the stacking of insulin. Records BG readings, carbohydrates consumed, units of insulin delivered and the time each was entered. Data can be downloaded into reports for easier, more accurate evaluation. Purpose 3

6 Insulin Pump Therapy Indications 3-5 Type 1 and insulin-requiring type 2 patients who are unable to achieve acceptable glycemic control, including those with: Elevated A1C. Glycemic variability. Recurrent hypoglycemia, nocturnal hypoglycemia, activity-induced hypoglycemia and hypoglycemia unawareness. Pregnancy/Pre-pregnancy. Recurrent diabetic ketoacidosis (DKA)/recurrent hospitalizations. Dawn phenomenon. Gastroparesis. Patient preference, meal-timing flexibility and normalization of lifestyle. Low insulin requirements (not easily measured via syringe). Inability to self-administer insulin (pre-school/grade school). Inability to predict food or meal intake (infant/toddler). Patient Requirements 5-10 Responsible and psychologically stable Willingness to monitor blood glucose (BG) a minimum of four times a day Willingness to quantify food intake Willingness to comply with medical follow-up Benefits 3,4,7,11 Improved glycemic control and decreased glycemic variability Improved control of dawn phenomenon Decreased severity and frequency of hypoglycemia Increased flexibility, normalization of lifestyle and sense of well-being Precautionary Areas 7 Hyperglycemia and/or DKA if insulin infusion is interrupted Lipohypertrophy (when infusion sites are not rotated properly) Infusion site reactions (rash and skin irritation) or infections 4 Insulin Pump Therapy

7 Guidelines for Initial Pump Settings Insulin pump therapy uses rapid-acting insulin for both basal and bolus insulin requirements. Reduced Dose Based on Daily Injection Dose Injection Dose x 0.75 = Reduced Dose Weight Dose Based on Weight kg x 0.50 or lb x 0.23 = Wt. Dose Pump Total Daily Dose (TDD) Average of Reduced Dose and Weight Dose* (Reduced Dose + Weight Dose) 2 = Pump TDD Total Daily Basal Dose Pump TDD x 40% to 50% = Daily Basal Dose Total Daily Bolus Dose Pump TDD - Daily Basal Dose = Daily Bolus Dose Basal Rate (BR) Daily Basal Dose 24 = Hourly BR Insulin Sensitivity Factor (ISF) 1700 Pump TDD = ISF Insulin-to-Carb Ratio (ICR) Daily Carbs Daily Bolus Dose = ICR * Hypoglycemic unawareness or other concerns, use the lower dose. The percentage split for total daily basal and total daily bolus varies, especially in pediatric populations. Guidelines for Transitioning to Pump Therapy Goal: Eliminate as much intermediate/long-acting insulin as possible before starting pump. Stop intermediate-acting insulin 12 hours before and long-acting insulin 24 hours before initiating pump therapy. Have patient give injections using small amounts of rapid-acting insulin as needed (every 3 to 4 hours) to keep BGs acceptable until pump therapy is initiated. In situations where intermediate or long-acting insulin is not discontinued, program a temporary basal rate to deliver a reduced basal amount (50% to 90% less than calculated starting rate) for the first 12 to 24 hours of therapy. Guidelines for Initial Pump Settings 5

8 Calculate Starting Doses Pump Total Daily Dose (Pump TDD) TOTAL DAILY DOSE The total amount of insulin (basal and bolus) delivered by the pump each day. BASAL INSULIN A continuous infusion of insulin given to cover hepatic glucose production. Intended to mimic pancreatic basal secretion and maintain glucose stability in fasting states (between meals and during sleep). Replaces longacting insulin. Programmed to match patient s individual diurnal variation. BOLUS INSULIN Given on demand by patient, as needed, for carbohydrate intake and correcting abnormal glucose levels. Reduce the current total daily injection dose by 25 percent, calculate the weight dose and then average the two together. REDUCED DOSE Based on daily injection dose Injection Dose x 0.75 = Reduced Dose INITIAL PUMP TDD Take average of Reduced and Weight Dose (Reduced Dose + Weight Dose) 2 = Pump TDD EXAMPLE PATIENT Type 1 Male Weight: 70 kg (154 lb) Current Daily Insulin Regimen Rapid-acting: 11 units pre-meal x 3 33 u/day Reduced Dose 53 u/day x 0.75 = 40 u/day Long-acting: 20 units (Bedtime) Total Daily Injection Dose Initial Pump TDD (40 u/day + 35 u/day) 2 = 37.5 u/day (Reduced Dose) (Weight Dose) (Pump TDD) WEIGHT DOSE Based on weight kg x 0.5 u = Weight Dose or lb x 0.23 u = Weight Dose + 20 u/day = 53 u/day Weight Dose 70 kg x 0.5 u = 35 u/day or 154 lb x 0.23 u = 35 u/day Clinical Considerations for Pump TDD Use less than a 25% reduction if daily injection dose is more than 70% rapid-acting insulin. Pediatric patients who have good control on injections may require as little as a 5% reduction. For children & teens, TDD is variable. May require as much as 1.0 u/kg to calculate weight dose. Hypoglycemia or hypoglycemia unawareness, use the lower of the two values. Persistent hyperglycemia, elevated A1C or pregnancy, use the higher value. Erratic glucose control, starting therapy at diagnosis or from oral medications, use weight method. 6 Calculate Starting Doses

9 Total Daily Basal and Total Daily Bolus First, determine the percent of TDD to be delivered as basal insulin and then multiply TDD by that percent. This will give you the Total Daily Basal amount. To calculate Total Daily Bolus subtract the Total Daily Basal amount from the TDD. BASAL Pump TDD x % Basal = Total Daily Basal Total Daily Basal EXAMPLE PATIENT 50% of TDD as Total Daily Basal BOLUS Pump TDD - Total Daily Basal = Total Daily Bolus Total Daily Bolus TOTAL DAILY BASAL Total amount of basal insulin delivered over 24 hours. TOTAL DAILY BOLUS: Total amount of bolus insulin (food and correction) delivered over 24 hours u/day x 0.5 = u/day (Pump TDD) (Total Daily Basal) 37.5 u/day u/day = u/day (Pump TDD) (Daily Basal Amount) (Total Daily Bolus) Clinical Guidelines for Total Daily Basal and Bolus Percentages Total Daily Basal Total Daily Bolus Adults: 40% to 50% 50% to 60% Puberty to Adult: 30% to 40% 60% to 70% Pre-Puberty to Puberty: 20% to 40% 60% to 80% Basal Rate Pump therapy is typically initiated with a single basal rate that is delivered evenly over each hour, 24 hours a day. To calculate the initial basal rate, divide 24 hours into the Total Daily Basal amount. INITIAL BASAL RATE Total Daily Basal 24 hours = Hourly Basal Rate EXAMPLE PATIENT Total Daily Basal: u/day Initial Basal Rate u/day 24 hours = 0.78 u/hour (Total Daily Basal) (Hourly Basal Rate) Start initial basal rate at or units per hour BASAL RATE The amount of basal insulin programmed to deliver evenly over each hour. BASAL RATES <1 UNIT/HOUR Program in unit increments. BASAL RATES >1 UNIT/HOUR Program in unit increments. Calculate Starting Doses 7

10 Calculate Starting Doses INSULIN-TO- CARBOHYDRATE RATIO Number of carbohydrate grams covered by one unit of insulin. ICR is used to calculate food bolus amounts. Insulin-to-Carbohydrate Ratio (ICR) If a patient on multiple daily injections has established an ICR that provides reasonable postprandial control, start pump therapy using that ICR. Or, use one of the methods below to calculate the initial ICR. If a patient is not yet carb counting or does not have an accurate food log, use the 450 Rule. METHOD 1 Estimated Daily Carb Intake OR METHOD Rule Carb Grams Total Daily Bolus = ICR 450 Pump TDD = ICR ESTIMATING DAILY CARBOHYDRATE INTAKE Have patients who are not yet carb counting keep a 24 hour food log for 4 to 7 days. Have diabetes educator review food log and estimate average daily carbohydrate intake. EXAMPLE PATIENT Estimated Daily Carbs: 225 grams Total Daily Bolus: u/day Pump TDD: 37.5 u/day Method grams u/day = 12 grams/unit 1 unit covers ~ 12 grams of carbohydrate ICR = 12 grams OR Method u/day = 12 grams/unit 1 unit covers ~ 12 grams of carbohydrate ICR = 12 grams Fixed Gram or Exchanges per Meal Method For patients who are not yet carbohydrate counting or who have low cognitive ability, use the Fixed Gram or Exchange per Meal method explained below: 1) Calculate patient s ICR using the 450 Rule. 2) Instruct patient on number of carbs or exchanges to enter for: a snack, a small meal, a medium size meal, a large meal. 3) Have patient use the Bolus Wizard calculator to enter current BG and the number of grams or exchanges you told them to use for the size meal they are planning to eat. This allows non-carb counting patients to use the Bolus Wizard and receive similar benefits to a carb counting patient, making diabetes management and record keeping easier. Key Concepts for ICR Patients often require more than one ICR to obtain optimal post-prandial control. Different ICRs can be programmed into the Bolus Wizard for different times during the day. Example: breakfast, lunch, dinner, snack times. 8 Calculate Starting Doses

11 Insulin Sensitivity Factor (ISF) If a patient on multiple daily injections has an established ISF that currently provides reasonable correction doses, you can start pump therapy using that ISF. Or, use one of the methods below to calculate the initial ISF. For patients who have frequent hypoglycemia or hypoglycemia unawareness, use the 2000 Rule. INSULIN SENSITIVITY FACTOR The number of mg/dl one unit of insulin lowers glucose. METHOD Rule OR METHOD Rule Used to calculate correction bolus amounts Pump TDD = ISF 2000 Pump TDD = ISF EXAMPLE PATIENT Pump TDD: 37.5 u/day Method = 45.3 mg/dl One unit decreases BG ~ 45 mg/dl ISF = 45 mg/dl OR Method = 53.3 mg/dl One unit decreases BG ~ 53 mg/dl ISF = 53 mg/dl ISF CORRECTION FORMULA (Current BG BG Target) ISF = Correction Dose EXAMPLE PATIENT BG Target = 100 mg/dl ISF = 45 mg/dl IF BG IS ABOVE TARGET (160 mg/dl): A positive correction dose is calculated. ( ) 45 = 1.3 units IF BG IS AT TARGET: No correction amount is calculated. IF BG IS BELOW TARGET (60 mg/dl): A negative correction dose is calculated and subtracted from the food bolus. (60 100) 45 = 0.9 units BG TARGET BG value used in the correction formula when calculating a correction dose. CORRECTION DOSE Amount of insulin calculated to correct a BG that is above target. Or, the amount of insulin subtracted from a food bolus when the BG is below target. Calculate Starting Doses 9

12 The Bolus Wizard Calculator BOLUS WIZARD CALCULATOR A feature in the pump that calculates meal and correction boluses and tracks active insulin for the patient. ACTIVE INSULIN Insulin remaining from previous boluses that continues to have a pharmacodynamic effect and the potential to lower glucose. Once the Bolus Wizard is programmed with the patient s settings, the patient simply enters their current BG and the grams of carbohydrate they plan to eat. The Bolus Wizard uses this information to calculate the total bolus (called the Estimate Total ) for the patient. Benefits of using Bolus Wizard calculator 12 More accurate bolus dosing Tracks active insulin Helps prevent stacking of insulin doses Reduces risk of lows related to stacking Bolus Wizard Settings Insulin-to-Carbohydrate Ratio (ICR) Insulin Sensitivity Factor (ISF) Keeps comprehensive record of: - BG readings - Carbohydrate grams - Insulin doses - Times of each entry BG Target Range Active Insulin Time Correction Bolus and Bolus Wizard Target Ranges BG TARGET RANGE The range of glucose values the Bolus Wizard uses to determine if a correction dose needs to be calculated. To determine the BG Target Range: Establish the high BG value for the Bolus Wizard to use when correcting elevated BGs. Establish the low BG value for it to use when correcting low BGs. When a BG reading is above the programmed Target Range, the Bolus Wizard uses the higher value in the range to calculate the correction dose. When a BG is below the Target Range, the Bolus Wizard uses the lower value to calculate the negative or reverse correction dose. EXAMPLES OF BOLUS WIZARD CORRECTION CALCULATIONS Target Range Setting = mg/dl ABOVE RANGE: (175 mg/dl) ( ) 45 = 1.4 units (correction bolus) ISF = 45 mg/dl BELOW RANGE: (72 mg/dl) (72-90) 45 = 0.40 units (subtracted from food bolus) Negative correction amounts are subtracted from food boluses before the Estimate Total is given. Multiple target ranges are used to accommodate daytime, nighttime, pre- and post-meal glucose goals. When determining Bolus Wizard target ranges, keep in mind, these are not the same as ADA or AACE BG guidelines; instead they are the values the pump targets when correcting high or low BGs. Clinical Considerations for Setting Initial Bolus Wizard Target Ranges* Daytime Nighttime Adults and Adolescents (13+ yrs) mg/dl mg/dl School Age (6 12 yrs) mg/dl mg/dl Toddler to Pre-school (0 6 yrs) mg/dl mg/dl Hypoglycemia Unawareness mg/dl mg/dl Pregnancy mg/dl mg/dl *Modifications to Bolus Wizard Target Ranges should be based on each patient s clinical history. 10 The Bolus Wizard Calculator

13 Active Insulin Time The length of time rapid-acting insulin lowers glucose varies in each individual. Therefore, Active Insulin Time can be adjusted to track for 2, 3, 4, 5, 6, 7 or 8 hours. The 7 and 8 hour Active Insulin times are only needed if regular insulin is used in place of rapid-acting insulin. The Bolus Wizard tracks and calculates the amount of active insulin based on the patient s individually programmed Active Insulin Time. When a patient s BG is above target, the Bolus Wizard subtracts the active insulin from the correction insulin before calculating the Estimate Total. ACTIVE INSULIN TIME The length of time the Bolus Wizard tracks active insulin after a bolus is given. Clinical Considerations for Setting the Active Insulin Time Adults: 4 to 5 hours Children: 3 to 4 hours Pregnancy: 3 to 4 hours How the Bolus Wizard Calculates the Estimate Total When a patient enters their BG and carbohydrate grams, the Bolus Wizard does the math, using the patient s pre-programmed settings (ICR, ISF, Target Range and Active Insulin Time) to calculate the Estimate Total for the patient. TOTAL BOLUS Food bolus + (Correction bolus - Active Insulin) = Estimate Total EXAMPLE PATIENT ICR: 12 grams ISF: 42 mg/dl BG Target: mg/dl Active Insulin Time: 5 hours Food to be Eaten: 24 grams Current BG: 220 mg/dl Bolus Wizard Settings Estimate Details IMPORTANT POINTS Active insulin is never subtracted from a meal bolus amount. Active insulin is only subtracted from correction bolus amounts. Wizard: On Carb Units: Grams Carb Ratios: 12 Sensitivity: 42 BG Target: Active Ins Time: 5 hours Estimate total: Food Intake: BG: Food: Correction: Active Insulin: 3.0 units 24 grams 220 mg/dl 2.0 units 2.6 units 1.6 units 1. Calculates food bolus: 24 grams 12 grams/unit = 2.0 units (food intake) (carb ratio) (food bolus) 2. Calculates correction bolus: (220 mg/dl 110 mg/dl) 42 mg/dl/unit = 2.6 units (BG) (target BG) (sensitivity factor) (Correction) 3. Subtracts active insulin: 2.6 units 1.6 units = 1.0 unit (correction) (active insulin) (adjusted correction) 4. Adds food + adjusted correction for estimate total: 2.0 units unit = 3.0 units (food bolus) (adjusted correction) (total bolus) The Bolus Wizard Calculator 11

14 Adjusting Pump Settings CARELINK PERSONAL SOFTWARE An online tool that allows patients to upload data from their pump and meter into reports. CARELINK PRO A diabetes therapy management software for personal computers that allows healthcare professionals to upload data from pumps and meters into reports. CARELINK REPORTS Organized graphs and statistical tables that provide a historical review of glucose and pump data. CareLink reports can help make the evaluation and adjustment process more efficient. Evaluating glucose control and adjusting pump settings is a logical, systematic process. It is based on the concept that rapid-acting insulin has a predictable glucose lowering effect, basal insulin covers hepatic glucose production, and bolus insulin covers food intake and the correction of high BGs. Evaluating and adjusting insulin pump settings is accomplished by reviewing pertinent BG data, insulin delivery and carb intake. This data is typically obtained either by having patients manually write the information on a BG log sheet, or by uploading the pump into CareLink Personal or Professional Software and reviewing the CareLink reports. Like all insulin regimens, adjusting insulin is an ongoing process. During the first few weeks of pump therapy, and any time pump settings need to be re-evaluated, have the patient follow these guidelines. Patient Guidelines During adjustment phases check BG as follows: - Upon waking - Bedtime - Pre-meal - Mid-sleep (or every 3 to 4 hours during sleep) - Post-meal (2 hours) Avoid snacking between meals (unless treating a low). Eat low-fat meals in which carb grams can be accurately counted. Use the Bolus Wizard calculator to give all boluses. Upload pump to CareLink Personal every 3 to 7 days. If not using CareLink, record BGs, carbs, boluses on log sheet for review every 3 to 7 days. Call your office if any lows occur (lows must be eliminated to successfully fine-tune). Evaluation Guidelines Evaluate glycemic control by time segments: Bedtime to mid-sleep (or every 3 to 4 hours during sleep) Mid-sleep to wake-up Pre-meal to post-meal (2 hour) Post-meal to next pre-meal Post-meal to bedtime 12 Adjusting Pump Settings

15 Adjustment Guidelines Basal rates, carbohydrate ratios and insulin sensitivity factors are the primary settings that need to be adjusted. While all three are reviewed simultaneously, it is usually best to first focus on getting basal rates (especially overnight) set correctly. The secondary settings, Active Insulin Time and Target Ranges, rarely need to be adjusted, and should not be changed until after primary settings have been verified as correct. To make adjustments: Identify glycemic rise/fall patterns and any other issues in each time segment. Adjust settings based on the glycemic rise/fall pattern and identified issues. Make one (no more than two) changes at a time. - Hyperglycemia Adjustments: Make adjustments after observing pattern for 3 to 7 days. - Hypoglycemia Adjustments: Consider adjusting if any lows occur. Avoiding lows during adjustment phases is key, because lows and the treatment of lows disrupts BG patterns. Re-evaluate BGs 3 to 7 days post adjustment to confirm no other changes are needed. Key Concept Basal insulin delivers in tiny amounts each hour and its affect on glucose takes place over a period of time. Therefore, changes made to basal rates should be programmed to begin 2 to 3 hours prior to the observed BG rise or fall. Goal: Prevent the glycemic excursion from occurring. Typical diabetes management behaviors and therapy checks that should be assessed prior to adjusting insulin settings are listed below. BEHAVIORAL CHECKS Are there 3 or more boluses/day? Are there 4 or more BGs/day? Is the Bolus Wizard calculator being used? Is infusion set changed every 2 to 3 days? Is pump suspended less than 1 hour/day? Troubleshoot decision making Do they use a temp basal for exercise? Are they bolusing before meals? Are they disconnecting appropriately? THERAPY CHECKS Verify pump settings Verify basal percent is < 50% of TDD Evaluate overnight control (basal) Evaluate pre-meal control (basal) Evaluate post-meal control (carb ratio) Are they having significant excursions? Adjusting Pump Settings 13

16 Basal Rate Adjustments BEDTIME BG PATIENT GUIDELINES Instruct patient that bedtime BGs should always be at least 100 mg/dl before going to sleep. When basal rates are set correctly, patients should be able to sleep late, eat late, or even skip a meal without experiencing glycemic excursions. Overnight Basal Rates Evaluation Guidelines Assess overnight control by observing rise/fall patterns across time segments (bedtime to mid-sleep; mid-sleep to wakeup). Adjust basal insulin to match diurnal variations. Adjustment Guidelines Goal: BG remains within target (does not rise or fall >30 mg/dl) through the night. If BG rises or falls >30 mg/dl: Adjust rate by 10 20%, 2 to 3 hours before observed rise or fall. If BG drops below 70 mg/dl: Instruct patient to treat the low and decrease rate 10 20%. Obtaining optimal overnight glycemic control minimizes the risk of nocturnal hypoglycemia, allows patients to sleep through the night and wake within target, making evaluation of daytime basal easier since patients are not treating lows or correcting highs. FASTING METHOD PATIENT GUIDELINES Instruct patient to skip a meal and check BG every hour. Never skip more than one meal per day. NON-FASTING METHOD PATIENT GUIDELINES Instruct patient: Not to eat between meals. Not to correct post-meal highs (unless >250 mg/dl). Used for patients who cannot skip meals (i.e., children, pregnancy). Daytime Basal Rates: Fasting Method Evaluation Guidelines Evaluate BGs across skipped-meal time segment (pre-breakfast to pre-lunch, pre-lunch to predinner, or pre-dinner to bedtime). Adjust/add basal rate(s) based on rise/fall pattern across skipped-meal time. Adjustment Guidelines Goal: BG remains stable (does not rise or fall >30 mg/dl) during skipped-meal time. If BG rises or falls >30 mg/dl: Adjust rate 10 20%, 2 to 3 hours before observed rise or fall. If BG drops below 70 mg/dl: Instruct patient to treat the low and decrease rate 10 20%. Daytime Basal Rates: Non-Fasting Method Evaluation Guidelines Evaluate basal rates by comparing the two-hour post-meal BG to the next pre-meal BG. If a high is corrected, do not include that post- to pre-meal segment in your evaluation. The following principles apply when evaluating basal rates in a non-fasting state: Two-hour post-meal BGs should be 30 to 60 mg/dl higher than pre-meal BGs; Two-hour post-meal BGs should steadily decline and be within pre-meal ranges by next meal. Adjustment Guidelines Goal: Post-meal BGs steadily decline and are back within pre-meal target range by next meal. If BG falls >60 mg/dl, or drops below target: Lower rate 10 20%. If BG rises, stays the same or decreases <30 mg/dl: increase rate 10 20%. 14 Basal Rate Adjustments

17 Bolus Adjustments Insulin-to-Carbohydrate Ratios (ICR) Evaluation Guidelines Evaluate ICRs by comparing each pre-meal BG to its corresponding 2-hour post-meal BG. Adjustment Guidelines Goal: Two-hour post-meal BG is between 30 mg/dl to 60 mg/dl higher than pre-meal BG. If 2-hour post-meal BG has increased more than 60 mg/dl from the pre-meal BG: Decrease ICR 10 20% or 1 to 2 grams/unit. If 2-hour post-meal BG has increased less than 30 mg/dl from the pre-meal BG: Increase ICR 10 20% or 1 to 2 grams/unit. WHEN EVALUATING INSULIN-TO-CARB RATIO Instruct patient: To eat low-fat meals with known carb content. Not to eat between meals. 2-HOUR POST- MEAL TARGET ADA: 180 mg/dl AACE: 140 mg/dl Pregnancy: 120 mg/dl Questions to Ask Prior to Adjusting ICR Were boluses missed or administered late? Boluses should be given before eating. Did the patient count carbohydrates correctly? Did patient adhere to Bolus Wizard calculator recommendations? Insulin Sensitivity Factor (ISF) Evaluation Guidelines Evaluate ISF by comparing pre-correction BG to the 2- and 4-hour post-correction BGs. Adjustment Guidelines Goal: Post-correction, 2-hour BG is about halfway to target and at target by 4 hours. If 2-hour post-correction BG is not halfway to target and 4-hour post-correction is not at target: Adjust ISF 10 20% as needed. Bolus Wizard Target Ranges and Active Insulin Time BG target ranges and active insulin settings are based on patient history, glycemic awareness and clinical judgment. These settings rarely need to be changed and should only be adjusted after primary settings (basal rates, ICRs and ISF) are correctly set. WHEN EVALUATING INSULIN SENSITIVITY FACTOR Instruct patient to: Watch for a time when BG is above target and no insulin has been given or food eaten for ~ 3 hours. Use Bolus Wizard to calculate and give recommended correction dose. Check BG every hour for the next 4 hours. Avoid eating or drinking until the 4 hour BG has been checked. Adjusting ICR and ISF Ratios When working with ICR and ISF ratios: To decrease bolus amounts, increase the ratio. To increase bolus amounts, decrease the ratio. Example: For 60 grams of carbohydrate if ICR is: 1:15 = 4 units; 1:12 = 5 units ; 1:10 = 6 units. Bolus Adjustments 15

18 Infusion Site Care Infusion Sets Medtronic offers many types of infusion sets with varying lengths of cannulas and angles of insertion. Generally, when a patient has minimal subcutaneous fat, a shorter cannula or a set that goes in at an angle is used. Auto-insertion devices designed to ensure proper insertion technique and reduce pain upon insertion are available for most infusion sets. The clinical manager in your area can help you and your patients decide which set is most appropriate. Sites should be changed and rotated every 2 to 3 days. Proper site rotation helps to: - Prevent lipohypertrophy and scar tissue. - Ensure tissue heals before inserting in that area again. - Maintain healthy, viable tissue, which enhances consistent insulin absorption. Patient Guidelines for Insertion and Rotation Instruct patients to: Insert infusion sets into easy-to-access subcutaneous tissue. Insert sets into sites that are at least 2 to 3 inches away from previous site. Use clock, M or W method to help ensure proper rotation. Avoid inserting into scar tissue or areas with lipohypertrophy. Avoid areas subject to excessive movement or constricted by clothing. Commonly Used Infusion Sites Site Rotation Methods PREGNANCY Consider inserting infusion sets in areas of subcutaneous tissue that are not tense from increasing abdominal girth, especially during the third trimester. 16 Infusion Site Care

19 Infection Prevention Infection is rare when proper insertion guidelines are followed. To minimize the risk of infection encourage the use of good clean technique: Wash hands Clean site thoroughly with a skin prep wipe Keep all infusion sets sterile Change set and rotate site every 2 to 3 days If an infection occurs: It is usually staphylococcal in nature and typically requires oral antibiotic treatment. If infections are recurrent, recommend routine: - Use of Hibiclens, followed by alcohol to cleanse the site before inserting the set. - Application of an antibiotic ointment immediately after removing the infusion set. If an abscess occurs, perform an incision, drain the area and culture the fluid. - Rule out methicillin-resistant staphylococcus. - Consider using Bactroban in the nares weekly to minimize recurrent infections. Skin Irritation If skin irritation occurs, different treatment approaches are recommended depending on the source of irritant: Tape: Change type of tape (i.e., Polyskin, IV 3000 or silk tape). Tubing: Place tape under and over tubing (sandwich technique). Soap or Alcohol: Change to antibacterial soap or use Skin Prep wipes. If a patient experiences problems with their infusion set tape, he or she can download a copy of Tape Tips and Site Management at The patient may also call the 24-Hour HelpLine at Key Point: Instruct patients to wait to insert infusion sets until their skin is completely dry. This helps reduce the risk of skin reactions that can occur when adhesive dressing is placed on a wet site that has been cleansed with a skin prep, cleaner or wipe. Infusion Site Care 17

20 DKA Prevention DKA Since signs and symptoms of DKA are similar to flu or stomach virus (nausea, vomiting, stomach pain) patients often mistake nausea and vomiting associated with DKA for the flu. Patients should fully understand that nausea and vomiting can be caused by DKA and they should check their BG and monitor their urine or blood for ketones any time they experience these symptoms. Because insulin pump therapy uses only rapid-acting insulin, the onset of diabetes ketoacidosis (DKA) can occur quickly if insulin delivery is interrupted for a period of time. Therefore, all type 1 patients must be educated on DKA prevention strategies. The most important of which are: 1) adhering to a routine BG monitoring schedule (four to six times per day) and 2) never ignoring an unexplained high blood glucose. Protocol for Treating Hyperglycemia If Ketones are Positive Or nausea and/or vomiting is present Give a correction dose via injection Change infusion set, reservoir and insulin Monitor BG every 1 to 2 hours and give insulin via injection until BGs are within target When BG is 250 mg/dl: Check for KETONES and follow these guidelines: If BG is not decreasing, and you have moderate to high ketones, nausea, vomiting or difficulty breathing, call healthcare provider or go to emergency room The point and time healthcare providers want to be notified varies. Establish a clear protocol for patients to follow. If Ketones are Negative Give a correction dose via insulin pump Recheck BG in one hour If BG has not decreased - Give a manual injection - Change infusion set, reservoir and insulin Continue to monitor BG until glucose levels are within desired range The most common causes of unexplained hyperglycemia that does not respond to a correction bolus include: a kinked or displaced cannula, an infusion set or reservoir issue or a bad (denatured) vial of insulin. Have patients follow the Troubleshooting Guidelines (found on next page) any time they have unexplained high BGs that do not respond to a correction bolus. Best Practice: Provide type 1 patients with a prescription for ketone strips prior to pump initiation. Teach and reinforce the importance of testing for ketones any time BGs are above 250 mg/dl. ILLNESS INCREASES THE RISK FOR DKA Systemic illnesses and localized infections are often forerunners to DKA. It is important for patients to clearly understand that basal insulin is required even when they are not able to eat or when they are nauseated or vomiting. Patients should fully understand the following concepts: Unexplained high BGs should NEVER be ignored. Two unexplained high BGs in a row or a high BG that is not responding to a correction bolus may indicate an infusion set or insulin pump problem. Nausea and vomiting can be caused by DKA. Illness increases the risk for developing DKA. When ill, patients should check BG every one to two hours, check for urine ketones every time they urinate, and drink fluids. Staying hydrated helps prevent DKA. Never exercise when ketones are positive. When DKA does occur, keep in mind that even after DKA has been properly treated and glucose returns to normal ranges, ketones may continue to be present for up to 24 hours. 18 DKA Prevention

21 Unexplained High Glucose TROUBLESHOOTING GUIDELINES What to Check Questions to Ask If Yes Infusion site Infusion set tubing Connection between reservoir and infusion set Reservoir Insulin Is it red, irritated or painful? Is it wet, or does it smell like insulin? Are there bubbles (larger than champagne bubbles) in the tubing? Is there blood in the tubing? Are there leaks/breaks? Is connection loose/easily moved? Is it loaded incorrectly? Is the reservoir empty? Are there excessive bubbles? Has insulin vial expired? Has insulin been exposed to high temperatures or direct sunlight? Change infusion set, reservoir and insulin Change infusion set, reservoir and insulin Change infusion set, reservoir and insulin if unable to correct the problem by tightening Change infusion set, reservoir and insulin if unable to correct the issue Change infusion set and reservoir using a new vial of insulin. (When in doubt, change it out!) Check insulin pump settings - Bolus Delivery - Basal Rates - Time Insulin pump Was last meal bolus missed? Are basal rates set incorrectly? Is time (AM/PM) set correctly? Is insulin pump not working or inoperable? Not sure if insulin pump has a problem? Give correction dose Reset basal rates Set time correctly Call the Medtronic Diabetes 24-Hour HelpLine at (The phone number is located on the back of the insulin pump) Unexplained High Glucose 19

22 Prevention of Hypoglycemia HYPOGLYCEMIA Any glucose level <70 mg/dl. MILD HYPOGLYCEMIA Characterized by symptoms such as sweating, trembling, difficulty concentrating and lightheadedness. SEVERE HYPOGLYCEMIA Characterized by an inability to self-treat due to mental confusion resulting in a loss of judgment, lethargy or unconsciousness. Because the onset and magnitude of symptoms differ greatly in patients from episode to episode, an absolute glucose value cannot be used to measure the severity of a hypoglycemic event. TEMPORARY BASAL RATE Allows basal rate to be immediately increased or decreased for the temporary length of time the patient sets. Can be programmed from 30 minutes up to 24 hours. Insulin pump therapy is associated with a marked reduction in the incidence of severe hypoglycemia. This is due to the predictable glucose lowering effects of rapid-acting insulin and the precise and flexible delivery system of an insulin pump. Patients should be taught the following concepts to help further reduce the risk of hypoglycemia. Check BG a Minimum of 4 to 6 Times a Day Routine monitoring of pre-meal, bedtime, nocturnal and exercise-related blood glucose levels is essential for safe and effective pump use. Therefore consider: Periodic monitoring of post-meal and 3:00 AM BGs regardless of symptoms. Conservative correction doses at bedtime and post-exercise. Periodic CGM use to obtain continuous tracings and confirm trends, patterns and missed hypoglycemia. Use the Bolus Wizard Calculator for all Bolus Doses Using this feature can help prevent hypoglycemia that results from the stacking of insulin and the over-correction of highs when there is active insulin remaining from previous boluses. The Bolus Wizard: Tracks the amount of active insulin remaining from previous boluses. Subtracts active insulin from correction doses before calculating a total bolus amount. BG Target Range Settings can be adjusted to prevent hypoglycemia. Bedtime target ranges can be set higher than daytime target ranges. Patients with a history of hypoglycemia may need a higher target range all day. Exercise Precautions Monitor BG - Pre-exercise (BG must be >100 mg/dl) - Every 30 minutes during exercise - Post-exercise (periodically, until BG lowering effect of exercise has subsided) Use Temporary Basal Rate - Start by decreasing the basal rate 50% one hour before exercise begins, throughout the exercise time, and for at least one hour post-exercise. - Adjust temporary basal rate percentage and duration as needed (varies depending on the intensity and duration of exercise). Use conservative correction doses during the post-exercise period. For intense endurance exercise, patients may need to consume 15 grams of carbohydrate for each 15 to 30 minutes of activity. Titrate according to individual glycemic response. Accurate Carbohydrate Counting Hypoglycemia can result from overestimating carbohydrate intake. Post-meal hypoglycemia is an indication that additional training on carb counting is needed or that the ICR needs to be adjusted. 20 Prevention of Hypoglycemia

23 Treatment of Hypoglycemia A common problem in diabetes is over-treating hypoglycemia, which causes hyperglycemia. To help patients prevent highs that result from over-treating, have patients follow a specific strategy, such as the Rule, for treating low blood sugars. Encourage the use of glucose tablets for treating lows Rule When glucose levels fall below 70 mg/dl: 1) Consume 15 grams of a fast-acting carbohydrate. 2) Recheck BG in 15 minutes. 3) If BG <70 mg/dl, repeat steps one and two until BG returns to normal range (If BG is <50 mg/dl, patient can start treatment with 30 grams). Below 70 mg/dl at Mealtime When BG is below 70 mg/dl at mealtime: Instruct patients to eat and make sure glucose levels are within target before bolusing. Have them give the bolus amount that was calculated using their pre-meal low. GLUCAGON EMERGENCY KIT PATIENT GUIDELINES Instruct patient to be sure family members, co-workers, friends are properly trained on how to administer glucagon. Many find it helpful to write the instructions in their own words on a note card and attach it to the kit. HYPOGLYCEMIA PATIENT GUIDELINES Instruct patients to notify the healthcare team if a hypoglycemic event requiring assistance occurs. Glucagon As with all insulin-requiring patients, provide a prescription for a Glucagon Emergency Kit before starting insulin pump therapy. Refill once a year and immediately upon usage. Reporting Hypoglycemic Events Because some hypoglycemic incidents go unreported, ask about hypoglycemia at every visit Since your last visit, have you had any hypoglycemia that required assistance from a family member? a coworker? others? Is your glucagon kit available? Where do you keep it? Who knows how to use it? Use of Continuous Glucose Monitoring (CGM) Consider the use of CGM in patients who have a history of hypoglycemia and/or those who are unable to alert others when hypoglycemic symptoms occur. Treatment of Hypoglycemia 21

24 Special Populations Type 2 Patients Insulin-requiring, type 2 patients respond favorably to insulin pump therapy. Below are some clinical considerations to assess when placing type 2 patients on pump therapy. Initiation Initiation is the same as in type 1 diabetes. The starting TDD can be based on weight (0.5 x kg = TDD Units). This method has been shown to be effective. Start with 50% as basal and 50% as bolus. Type 2 patients typically require only one or two basal rates. Since many type 2s do not carb-count at initiation, consider using the Fixed Gram or Exchange per Meal method (as explained in the ICR section of this book). Set up the Bolus Wizard using the ICR calculated with the 450 Rule. Evaluate 2-hour, post-prandial control and adjust ICR as needed. Oral Medications 1) Stop sulfonylureas and meglitinides. 2) Continue metformin, incretin mimetics, and insulin sensitizers, if you choose. Once at goal, consider discontinuing any of the above medications, one at a time, to see if they are actually needed. If glucose levels decompensate when discontinued, resume the medication. Insulin Resistance 1) Some type 2s have marked insulin resistance, aggravated by both lipo and glucose toxicity. Once glucose levels normalize, insulin requirements may decrease. When this occurs, adjust pump settings (basal rate, ICR, ISF) to prevent hypoglycemia. 2) In other cases, insulin resistance persists and large insulin requirements continue to be needed. Try to reduce insulin resistance with exercise and by decreasing consumption of calories (specifically high carbohydrate-containing foods). Consider using insulin sensitizers and/or GLP-1 agonists. EASY BOLUS FEATURE An alternate way to program bolus amounts when the patient does not use the Bolus Wizard feature, does not count carbs or check BG before meals. Modified Pump Start For patients who are unable to count carbohydrates and check BGs before meals, consider the fixed unit per meal bolus method using the Easy Bolus feature. 22 Special Populations

25 Pregnancy Patients Maintaining tight glycemic control during pregnancy is key to preventing complications for both mother and neonate. Consider using Continuous Glucose Monitoring (CGM) throughout the perinatal period to help achieve optimal glucose control. BGs should be monitored frequently in pregnancy (pre-and post meal, bedtime and mid-sleep). Adjustments to pump settings need to be made frequently for continued optimal control. Expect insulin requirements to steadily rise as the pregnancy advances. Increased insulin requirements are primarily due to the progressive rise in placental hormones which results in increased insulin resistance and decreased sensitivity to insulin action. 13 Pre-Conception and 1st Trimester Maintaining glucose control during organogenesis greatly reduces the risk of fetal anomalies and spontaneous abortion. The risk of hypoglycemia, especially overnight, increases during the first few weeks of pregnancy and insulin requirements are often less than pre-conception requirements. Monitor fasting glucose and check urine for ketones every morning. Positive ketones with high BG indicate need for additional basal insulin. Positive ketones with normal or low BG is indicative of starvation ketones. Consider increasing bedtime snack or adding a midnight snack. In situations of hyperemesis, consider using a square wave bolus over 30 minutes so bolus can be stopped if vomiting occurs. 2nd Trimester The placenta is fully developed and growth as well as hormones will begin to steadily rise causing insulin requirement to steadily increase as the pregnancy progresses. Usually requires increase in basal, meal, and correction insulin. Pump settings may need to be adjusted every 2 to 3 weeks. SQUARE WAVE BOLUS A feature that allows the patient to deliver a bolus over an extended period of time. Can be programmed to deliver in 30 minute increments from 30 minutes up to 8 hours. 3rd Trimester Maintaining tight glucose control throughout the last trimester helps to enhance fetal lung development, prevent fetal macrosomia and reduce the risk of neonatal hypoglycemia (post-delivery). Insulin requirements typically increase every week (during the last few weeks of gestation). Labor and Delivery Patients can remain on pump throughout labor and delivery. BGs should be monitored every hour and small boluses given (if needed) to keep glucose in desired range. Post-Partum Immediately after delivery and up to 24 hours post-delivery, insulin requirements decrease significantly. Therefore, basal rates, ICR, ISF and Target Ranges should be reduced to preconception settings or to at least half the current settings. Breastfeeding BG levels can drop dramatically during breastfeeding. Instruct mother to: Monitor BGs closely during and for at least an hour after nursing. Always drink and eat while breastfeeding. Consider use of temporary basal rate (reduction up to 50%) for an hour post-nursing. Consider use of CGM. Special Populations 23

26 Special Populations Pediatric Patients Diabetes brings unique challenges in the pediatric, adolescent and young adult age ranges. Depending on cognitive maturity and development skills, the need for increasing independence and the eventual transition to adult care, there is variability in parental/care giver involvement necessary for insulin pump management. PEDIATRIC GUIDELINES Age Knowledge/Skills/Attitudes Diabetes and Pump Management Birth to 3 years of age, infants and toddlers 3 6 years of age, preschool 7 11 years of age, school-aged Inherent trust in parents/care givers Rapid changes in cognitive and motor skills, nutrition requirements, sleep/wake patterns, and acquisition of developmental milestones Unaware and unable to communicate any issues with health and diabetes/glucose levels Temper tantrums may be frequent and associated with diabetes tasks Begins to show some minimal understanding of diabetes procedures and management issues, such as nutrition Might begin to recognize hypoglycemia and tell others Can have negative attitudes Overall still lacks motor skills and cognitive ability to contribute to diabetes management Begins to realize having diabetes is different Increasing awareness of tasks and goals of diabetes management and ability to do them Still reliant on parents/care givers for diabetes decisions Might struggle with being different and begin to be self-conscious about diabetes Might be angry or depressed about diabetes Pumps able to deliver small doses of insulin with accuracy Issues with pump placement, infusion sites, tubing, skin and child acceptance Child cannot understand requirements of diabetes management Erratic food intake, activity, mood, behavior Parents/care givers must do all diabetes management tasks Risk and fear of hypoglycemia Child increasingly aware of presence of devices, early understanding as to need to protect devices More interaction with peers who are interested in devices as well Interacts with decisions as to which finger to check glucose, where pump is worn and infusion set placed Starts to ask about food items and if they can be eaten, and if bolus must be given Emerging ability to carb count, take boluses Increasing ability to manage infusion set, hooks/unhooks More time away from parents/ primary care givers Able to protect devices Able to do blood glucose testing, and knows numbers/goals Some awareness as to role of exercise in glucose control 24 Special Populations

27 PEDIATRIC GUIDELINES Age Knowledge/Skills/Attitudes Diabetes and Pump Management years of age, young adolescents years of age, older adolescents Understands goals of diabetes management Diabetes affected by puberty both physiologically and psychologically Rebellion and risk taking behavior Peer group identification preeminent Issues with body image/weight/ disordered eating More independence, parental conflict Emerging independence Decides education, living location, long term goals/jobs/relationships Risk taking behavior, psychological issues Insulin requirements increase significantly Erratic eating and sleeping behaviors Forgets boluses Beginning of transition of majority of diabetes care to child, although strong parent/care giver presence still required Self-conscious about pump/diabetes, might hide diabetes and devices Can do most diabetes/pump tasks, except might have trouble with changing basal rates and bolus doses Need to follow safe driving principles Begins to fully control and manage diabetes, with parental involvement still present but minimal Begins to be responsible for pump supplies, health care appointments Prepares to transition to adult care By age 12, suggest that your patients/parents hold a weekly diabetes meeting. Rather than parents quizzing the child on what they are doing all day long, they should upload pump and meter data to review reports together. Determine number of BGs, boluses/day, use of Bolus Wizard, infusion site change, carb entries. Use the reports to assess behavior, reward improvement, and identify adherence problems. Resources The National Diabetes Education Program website ( has comprehensive information regarding rights of children with diabetes in school. There are guides for school nurses, teachers, coaches, administrators, parents and students. All diabetes management and safety information is covered, including pump therapy. Special Populations 25

28 Special Populations Hospitalized Patients In general, patients who self-manage on insulin pump therapy prior to hospitalization prefer to stay on the pump when hospitalized. Having patients self-manage their own therapy is practical and easier for staff, as long as the patient remains mentally alert, psychologically sound and physically able. If a hospital does not have a protocol for managing patients on insulin pump therapy, provide orders upon patient admission. Orders should include: Rx for a vial of rapid-acting insulin (supplied by hospital pharmacy). Current settings (Basal Rates, ICR, ISF, Target Range and Active Insulin Time). BG monitoring requirements: - Frequency and if monitoring is to be performed by patient or staff. - Documentation of BG readings. - Glucose levels (upper and lower) at which treatment is required. - Hypoglycemia protocol - Hyperglycemia protocol - Events/glucose levels for which you or your office should be notified. Alternate insulin regimen for procedures: - Lasting longer than 2 hours and require pump removal/discontinuation. - Requiring fasting (basal insulin continues to be needed). - Requiring sedation (intravenous insulin should be started just before discontinuing the pump). Instructions to remove infusion set, sensor, pump and transmitter and leave outside of imaging room for procedures involving MRI, CT scans, X-Ray (reconnect pump upon completion). Procedure to follow if patient status changes and is unable to self-manage. Frequency for infusion site and reservoir change to be completed by patient. Troubleshooting resources such as: - Medtronic HelpLine number (located on back of pump). - Family member who is well versed in pump therapy. - Your office staff contact. Hospitals do not typically stock insulin pump supplies. Instruct patients to bring enough infusion sets and reservoirs to change their infusion site every 2 to 3 days during hospitalization. 26 Special Populations

29 Therapy Management Software Advances in technology have now made it possible to electronically capture glucose data necessary for effective evaluation. CareLink Therapy Management Software organizes captured data (BG values, bolus amounts, basal rates, carb intake) into meaningful reports for a historical, comprehensive review of the cause-and-effect relationship between these parameters. Ask patients to upload their meter and insulin pump regularly. Review reports at each visit. The reports that follow are available through CareLink Pro Software. Example of Daily Detail Report Displays each day s pump and BG meter information and lists the details (time, amount, type) of each bolus that was given. Meter BG Reading Carbohydrate Gram Entries Patient checks BG, enters carbohydrates and boluses simultaneously Basal Rate Change Bolus Delivery Therapy Management Software 27

30 Example of Adherence Report Provides new insights into a patient s self-management behavior and helps confirm optimal device use. Adherence (1 of 1) 6/2/2010-6/15/2010 Data Sources: Paradigm Revel Glucose Measurements Bolus Events Fill Events BG Readings Sensor Duration (h:mm) Manual Boluses Bolus Wizard Events With Food With Correction Overridden Rewind Cannula Fills Cannula Amount (U) Tubing Fills Tubing Amount (U) Suspend Duration (h:mm) Wednesday 6/2/ Thursday 6/3/ Friday 6/4/ Saturday 6/5/ Sunday 6/6/ Monday 6/7/ Tuesday 6/8/ Wednesday 6/9/ Thursday 6/10/ Friday 6/11/ Saturday 6/12/ Sunday 6/13/ Monday 6/14/ Tuesday 6/15/ Summary 4.8/day 0.0/day 8.8/day 63.4% 34.1% 9.8% U /fill 3 8.4U/fill 0m Partial day Note: Partial days will not be included in summary averages. Days on which a time change occurred are considered to be partial days. 1 2 Glucose Measurements This section displays frequency of BG meter tests and duration of glucose sensor tracing information. Bolus Events This section captures the patient s use of the Bolus Wizard calculator including the frequency of manual boluses and overrides. Manual Bolus: A high incidence of manual boluses indicates under-utilization of the Bolus Wizard calculator. 3 4 Fill (Priming) Events This section is used to determine if the patient is rewinding and priming the insulin pump appropriately. Rewinding less than once every three days indicates extended use of infusion sets or insulin Suspend Duration Use this section to evaluate if suspend time is reasonable. Investigate frequent suspends and suspend times greater than one hour. Bolus Wizard Overrides: May be appropriate, but should always be investigated as they may indicate the need for additional patient education, or the need to assess insulin pump settings. 28 Adherence Report

31 Example of Sensor and Meter Overview Report Sensor & Meter Overview (2 of 3) Data Sources: Paradigm Revel /2/2010-6/15/2010 Displays blood glucose meter readings and statistics 24-Hour Meter Glucose Overlay - Readings & Averages (mg/dl) to allow for identification of glycemic excursions and patterns. Sensor & Meter Overview (2 of 3) 1 2 Data Sources: Paradigm Revel /2/2010-6/15/ Hour Meter Glucose Overlay - Readings & Averages (mg/dl) Statistics Statistics Avg B BG 6/2-6/15 Avg BG (mg/dl) 147 ± 56 BG Readings /day Readings Above Target 33 51% Readings Below Target 3 5% Readings Ab Sensor Avg (mg/dl) Readings Be Avg AUC > 140 (mg/dl) Avg AUC < 70 (mg/dl) Sensor & Meter Overview (2 of 3) Avg Daily Carbs (g) 6/2/2010-6/15/2010 Carbs/Bolus Insulin (g/u) Avg Total Daily Insulin (U) 134 ± 23 Data Sources: Paradigm Revel % Avg Daily Bolus (U) % Average BG with standard deviation Meter Glucose Overlay Bedtime to Wake-Up and Meal Periods Readings & Averages (mg/dl) 24-Hour Meter Glucose Overlay - Readings & Averages (mg/dl) 3 Bedtime to Wake-up Bedtime: 8:00 PM - 12:00 AM Wake-up: 5:00 AM - 9:00 AM Breakfast: 6:00 AM - 10:00 AM Meals Analyzed: 9 Lunch: 11:00 AM - 3:00 PM Meals Analyzed: 11 Dinner: 4:00 PM - 10:00 PM Meals Analyzed: 19 Avg Carbs: 28g Avg Insulin: 2.4U Avg Carbs/Insulin: 11.6g/U Avg Carbs: 30g Avg Insulin: 2.5U Avg Carbs/Insulin: 11.8g/U Avg Carbs: 20g Avg Insulin: 1.7U Avg Carbs/Insulin: 12.2g/U 4 BG reading BG reading Off chart Average within target range Average carbs per day when using the Bolus Wizard calculator Average outside target range Average units of insulin per gram of carbohydrate when using the Bolus Meter Glucose Overlay Bedtime to Wake-Up and Meal Periods Readings & Averages (mg/dl) Wizard calculator Breakfast Example Bedtime to Wake-up 9 meals over 14 days Bedtime: 8:00 PM - 12:00 AM Average daily carb Wake-up: 5:00 AM - 9:00 AM intake for breakfast Breakfast: 6:00 AM - 10:00 AM Meals Analyzed: 9 Meal bolus given eading BG reading 2 Readings Above Target 33 Readings Below Target 3 Avg Dail 4.8/day 51% Carbs/Bolus Sensor Avg (mg/dl) Avg Total Daily Avg AUC > 140 (mg/dl) Avg Dail Avg AUC < 70 (mg/dl) Avg Daily Carbs (g) Carbs/Bolus Insulin (g/u) Avg Dail 134 ± ± 1.7 Avg Daily Basal (U) % Avg Daily Bolus (U) % percent of total Average number of units of Lunch: 11:00 AM - 3:00 PM Meals Analyzed: 11 Dinner: 4:00 PM insulin - 10:00 PM bolus per day with Meals Analyzed: percent19of total Avg Carbs: 30g Avg Insulin: 2.5U Avg Carbs/Insulin: 11.8g/U Avg Carbs: 20g Avg Insulin: 1.7U Avg Carbs/Insulin: 12.2g/U Target BG Range* ( mg/dl) Off chart Average within target range 5 hours post-meal Average within target range Average outside target range Average outside target range In 5% Average post-meal glucose in target at 2 and 4 hours BG One reading Off chart hour pre-meal 1 65 Avg Carbs: 30g Avg Carbs: 20g Avg Insulin: 2.5UAverage number of units Avgof Insulin: 1.7U basal insulin per day with Avg Carbs/Insulin: 11.8g/U Avg Carbs/Insulin: 12.2g/U Average pre-meal glucose in target BG reading Avg AUC < 147 ± 56 BG Readings of insulin per day Average daily insulin given for breakfast Meter Glucose Overlay Bedtime to Wake-Up and Meal Periods Readings & Averages (mg/dl) Avg AUC > 1 6/2-6/15 Avg BG (mg/dl) Lunch: 11:00 AM - 3:00 PM Dinner: 4:00 PM - 10:00 PM Avg Total Daily Insulin (U) Meals Analyzed: Average 11 Analyzed: 19 total numbermeals of units Avg Carbs: 28g Avg Insulin: 2.4U Avg Carbs/Insulin: 11.6g/U Bedtime to Wake-up Breakfast: 6:00 AM - 10:00 AM Average carb to insulin ratio for breakfast Meals Analyzed: 9 Bedtime: 8:00 PM - 12:00 AM Wake-up: 5:00 AM - 9:00 AM Avg Carbs: 28g Avg Insulin: 2.4U Avg Carbs/Insulin: 11.6g/U Statistics Number of BGs for the reporting period and average number of BGs/day Number of BGs above and below target* as well as percent of total BGs above and below target Sensor A Statistics 23.0 ± 1.7 Avg Daily Basal (U) Meter Overlay Displays BG meter readings to assist in identifying excursions and/or patterns. 3 edtime to Wake-up Meter Overlay B Displays BG meter readings from bedtime to wake-up to help identify overnight patterns. Statistics Table Displays BG meter, sensor glucose, carbohydrate, and insulin statistics over the reporting period. 4 Meal Meter Overlay Realigns BG meter readings around meals (at the time carbohydrates are entered into the Bolus Wizard) to assess pre- and post-meal control. *Targets determined by provider during report setup Sensor and Meter Overview Report 29

32 2 PM PM 4 PM 5 PM 6 PM Dinner 7 PM 8 PM 9 PM 10 PM 11 PM Example of Logbook Report Daily Totals Average (3): 160mg/dL Carbs: 118g Insulin: 22.9U Bolus: 51% 214 Average (3): 190mg/dL Provides logbook information 24 in an hour-by-hour 25 format to 25 help identify Carbs: repeated 161g patterns and possible causes for glycemic excursions Insulin: 25.6U Bolus: 58% Wednesday 6/2/2010 Thursday 6/3/2010 Friday 6/4/2010 Saturday 6/5/2010 Sunday 6/6/2010 Monday 6/7/ AM AM Tuesday 6/8/2010 Wednesday 6/9/2010 Thursday 6/10/2010 Friday 6/11/2010 Saturday 6/12/2010 Sunday 6/13/2010 Monday 6/14/2010 Tuesday 6/15/2010 < 70mg/dL AM Logbook (1 of 1) 6/2/2010-6/15/ AM 4 AM 5 AM AM AM Breakfast 8 AM 9 AM AM > 140mg/dL Multiple readings (most extreme shown) 141 Manual bolus or bolus with correction AM PM 147 Lunch 1 PM Suspend PM PM 4 PM 5 PM Exercise Other PM Dinner PM Data Sources: Paradigm Revel PM 9 PM PM Partial day 11 PM Pump rewind Daily Totals Average (3): 160mg/dL Carbs: 118g Insulin: 22.9U Bolus: 51% Average (3): 190mg/dL Carbs: 161g Insulin: 25.6U Bolus: 58% Average (4): 133mg/dL Carbs: 108g Insulin: 20.8U Bolus: 48% Average (6): 214mg/dL Carbs: 160g Insulin: 28.1U Bolus: 58% Average (5): 137mg/dL Carbs: 139g Insulin: 23.7U Bolus: 54% Average (3): 140mg/dL Carbs: 141g Insulin: 24.6U Bolus: 56% Average (5): 169mg/dL Carbs: 131g Insulin: 23.9U Bolus: 56% Average (6): 110mg/dL Carbs: 146g Insulin: 21.8U Bolus: 50% Average (6): 123mg/dL Carbs: 109g Insulin: 21.2U Bolus: 49% Average (5): 147mg/dL Carbs: 108g Insulin: 22.1U Bolus: 51% Average (7): 186mg/dL Carbs: 150g Insulin: 26.5U Bolus: 56% Average (4): 103mg/dL Carbs: 146g Insulin: 23.3U Bolus: 51% Average (5): 114mg/dL Carbs: 185g Insulin: 24.7U Bolus: 56% Average (3): 97mg/dL Carbs: 134g Insulin: 22.3U Bolus: 51% Time change Skipped meal Average (4): 133mg/dL Carbs: 108g Insulin: 20.8U Bolus: 48% Average (6): 214mg/dL Carbs: 160g Insulin: 28.1U Bolus: 58% Average (5): 137mg/dL Carbs: 139g Daily Totals Insulin: 23.7U Bolus: 54% Average (3): 140mg/dL Carbs: 141g Insulin: 24.6U Bolus: 56% Average (5): 169mg/dL Carbs: 131g Insulin: 23.9U Bolus: 56% Average (6): 110mg/dL Carbs: 146g Insulin: 21.8U Bolus: 50% Average: Displays the total number of BG meter readings taken and the BG meter average. Carbs: Displays the total amount of carbohydrates entered into the Bolus Wizard calculator. Insulin: Displays the total amount of insulin delivered and the percentage delivered as a bolus. of 1) Average (6): 123mg/dL 30 Top 25Number: BG Meter 8Reading 16 Carbs: 109g Middle Number: Data Carbohydrates Sources: Paradigm Revel - 5 /15/ highlighted 2.05 if above or 0.65 below target.* 1.30 Insulin: 21.2U Bolus: 49% in black background Logbook Cell Section Average (5): 147mg/dL Carbs: 108g Insulin: 22.1U Bolus: 51% Breakfast Lunch Dinner 5 AM AM 7 AM205 Average (7): 186mg/dL 8 AM 9 AM 10 AM 11 AM 12 PM 1 PM 2 PM 3 PM 4 PM 5 PM 6 PM 7 PM 8 PM 9 PM 10 PM 11 PM Carbs: 150g Insulin: 26.5U Bolus: 56% Average 25 (4): 103mg/dL Carbs: 146g Insulin: 23.3U Bolus: 51% Average (5): 114mg/dL Carbs: 185g 2.00 Bottom Number: 2.05Bolus insulin 3.15 delivered Insulin: 24.7U Bolus: 56% Average (3): 97mg/dL Carbs: 134g Insulin: 22.3U Bolus: 51% 1 Logbook Cell Section 2 Daily Totals Each cell contains up to three numbers: 7 45 Summarizes 10 the following values 38from each 25 day Exercise Partial day Time change Top Number: BG meter reading of the 0.83 reporting 1.25 period: Other Pump rewind 108 Middle Number: Carbohydrates 168 Average: Skipped Displays meal 170 the 128 total number of BG meter readings taken and the BG meter 16 average Bottom Number: Bolus Insulin Delivered Carbs: Displays the total 0.23 amount 1.33 of 1.65 carbohydrates 1.25 Meals can be quickly identified by looking for the 63 entered 247 into the Bolus Wizard. carbohydrate amounts (highlighted in black) Insulin: Displays the total 45 amount of insulin delivered 1.60 and the percentage 3.75 delivered 1.15 as a bolus. 223 *Targets determined by provider during report setup Logbook Report

33 Example of Device Settings Report Displays insulin pump and sensor settings. 24-Hour Total TIME 0:00 1:00 3:30 6:00 8:30 16:00 19:00 22: U U/hr Hour Total Device Settings Snapshot Thursday 6/17/2010 7:56 AM Basal Maximum Basal Rate 2.00 U/hr Temp Basal Type Percent of Basal Standard (active) Pattern A TIME 0:00 3:30 5:00 8:00 18: U U/hr Pattern B 24-Hour Total TIME 0:00 1:00 4:30 6:30 15:30 19: U U/hr Bolus TIME 0:00 6:30 11:30 17:30 21:00 Maximum Bolus Dual/Square (Variable) Blood Glucose Reminder Bolus Wizard Units Active Insulin Time (h:mm) Insulin Concentration Ratio On 3: U On Off Easy (Audio) Bolus Off Entry (Step) 0.10 U Carbohydrate Ratio (g/u) g, mg/dl Insulin Sensitivity (mg/dl per U) TIME 0:00 5:00 11:00 Sensitivity Missed Bolus Reminder Start (h:mm) -- Blood Glucose Target (mg/dl) TIME 0:00 5:00 22:00 Off End (h:mm) -- Low High Data Source: Paradigm Revel Sensor Sensor Transmitter ID BG Units Glucose Alerts TIME 0:00 6:00 22:00 Alert Repeat On mg/dl Predictive Alert On Low High (mins) Rate Alert: Fall Rise (mg/dl/min) On Low (mg/dl) : High (mg/dl) : Notes AUC Limit: Low High (mg/dl) Missed Data/Weak Signal (h:mm) 0: Graph Timeout (h:mm) None Auto Calibration Calibration Reminder (h:mm) Calibration (Alert) Repeat (h:mm) -- 0:30 1:00 Utilities Alert Type Beep Medium Low Reservoir Warning Insulin Units 5 4 Amount 20 U Basal Settings Displays the patient s basal rates at the time the patient s device was uploaded. Bolus Settings Displays the patient s bolus settings at the time the patient s device was uploaded. Sensor Settings Displays the patient s sensor settings at the time the patient s device was uploaded. 4 5 Utilities Displays the patient s alert type and low reservoir warning settings at the time the patient s device was uploaded. Notes Section can be used to record notes for patient records, to provide comments and recommendations for patient therapy, and/or to record documentation for health insurance providers. Device Settings Report 31

34 Continuous Glucose Monitoring (CGM) Continuous glucose monitoring measures glucose levels in the interstitial fluid and provides a record of glucose readings 24 hours a day. These glucose tracings detail the patient s daily glycemic control and provide insight into trends and patterns that are often missed with finger-stick monitoring alone. CGM technology can help clinicians and patients make more informed decisions regarding diabetes management. There are two types of CGM systems: Professional and Personal. ROUTINE USE Consider quarterly evaluations, as a compliment to A1C, for type 1 and type 2. PROCESS HCP places patient on CGM. Patient wears CGM 3 days and checks BG 3 to 4 times/day. Patient returns for download of CGM and glucose meter data. Data used for: - Glycemic evaluation. - Therapy modification. - Patient education and consultation. Professional CGM Professional CGM systems are owned and managed by healthcare providers and can be used on multiple patients. Each system consists of a glucose sensor (temporarily inserted into subcutaneous tissue and replaced after each use) and a small recording device that attaches to the sensor. These systems are designed for periodic use and provide detailed continuous glucose data for retrospective evaluation. During the evaluation period, the patient s glycemic levels (blinded to the patient) are recorded continuously. At the end of the evaluation period, the glucose data is uploaded by the healthcare provider to CareLink ipro, where it is compiled into reports. These reports provide comprehensive information about glycemic control. Including: 24-Hour continuous glucose tracings for the entire evaluation period Markers that indicate meal times and medications taken Overlays of post-prandial (breakfast, lunch and dinner) and overnight glucose tracings Hyper- and hypoglycemic area under the curve (AUC) data Pie charts summarizing glycemic control and distribution of hyper- and hypoglycemia These reports provide a historical review of glycemic trends and patterns, allowing clinicians to retrospectively and objectively evaluate a patient s glucose control and make more informed therapy management decisions. DOCKING STATION Charges, downloads and troubleshoots the Recorder. RECORDER Records up to 288 sensor glucose readings every 24 hours. Docking Station Recorder 32 Continuous Glucose Monitoring

35 Personal CGM Personal CGM systems are owned and operated by the patient. These systems consist of the glucose sensors, a transmitter (sends glucose data to a monitor) and a small external monitor. The monitor displays the patient s most recent glucose reading (updated every 5 minutes) and a continuous tracing of the past 24 hours of glucose readings. There are two types of Personal CGM: one is a stand-alone device, and the other is integrated into the insulin pump. Indications for Personal CGM* Patients on MDI or insulin pump therapy who check BG four or more times a day and who have: A1C above goal (non-pregnancy >7%, preconception >6.5%, pregnancy >6%). History of frequent hypoglycemia or hypoglycemia unawareness. Marked glucose variability with multiple glucose readings outside the desired range. Patient Requirements for Starting CGM The same as insulin pump therapy, plus: Willingness to calibrate the glucose sensor a minimum of three to four times a day. Willingness to validate sensor glucose (SG) values with BG test prior to making treatment decisions. Considerations Before Starting CGM Understanding of importance of glucose trends versus point-in-time BG values. Understanding of sensor glucose (SG) versus blood glucose (BG) and the potential differences in the two values. Insurance coverage or ability to pay out-of-pocket. The full benefit of CGM is best realized when current data and historical data are utilized in concert. Target Range Trend Graph Sensor Glucose Value TARGET RANGE The upper and lower glucose values a patient sets for the monitor to alarm when their glucose reaches that level. SENSOR GLUCOSE VALUE The patient s most recent sensor glucose reading. Glucose Sensor Transmitter Trend Arrow TREND GRAPH A tracing of the past 24 hours of glucose readings. TREND ARROW An arrow or arrows that indicate the direction and rate of glucose change. * The insulin pump is indicated for persons of all ages requiring insulin. The REAL-Time Continuous Glucose Monitoring components of the MiniMed Paradigm REAL-Time Insulin Pump and Continuous Glucose Monitoring System are indicated for ages 7 years or older. A version of the product specially designed for children is indicated for patients ages 7 to 17. Continuous Glucose Monitoring 33

36 Blood Glucose Log Sheet Fax to: Patient: DOB: Phone: (Home) (Work) / Basal Rate: Time Rate Meal Bolus: 1 Unit of insulin covers this many grams of carbohydrate. Carb Ratio: (B) (L) (D) A.M. Insulin Sensitivity Factor: 1 Unit of insulin lowers BG mg/dl (Current BG Target) Sensitivity Factor = Correction Dose 4. BG Target Range: Daytime = mg/dl mg/dl 5. BG Target Range: Nighttime = mg/dl mg/dl Date / / 12 A.M. 3 A.M. Pre-Brkfst Post-Brkfst Pre-Lunch Post-Lunch Pre-Dinner Post-Dinner Bedtime Time Blood Glucose Carb Grams Food Dose Correction Dose Total Bolus Date / / 12 A.M. 3 A.M. Pre-Brkfst Post-Brkfst Pre-Lunch Post-Lunch Pre-Dinner Post-Dinner Bedtime Time Blood Glucose Carb Grams Food Dose Correction Dose Total Bolus Date / / 12 A.M. 3 A.M. Pre-Brkfst Post-Brkfst Pre-Lunch Post-Lunch Pre-Dinner Post-Dinner Bedtime Time Blood Glucose Carb Grams Food Dose Correction Dose Total Bolus Date / / 12 A.M. 3 A.M. Pre-Brkfst Post-Brkfst Pre-Lunch Post-Lunch Pre-Dinner Post-Dinner Bedtime Time Blood Glucose Carb Grams Food Dose Correction Dose Total Bolus Date / / 12 A.M. 3 A.M. Pre-Brkfst Post-Brkfst Pre-Lunch Post-Lunch Pre-Dinner Post-Dinner Bedtime Time Blood Glucose Carb Grams Food Dose Correction Dose Total Bolus Notes: Pumping Protocol by Bruce Bode, MD Medtronic MiniMed, Inc. All rights reserved

37 Pump Initiation Settings PRESCRIBER S INSTRUCTIONS TO PATIENT Fax to: Pump Model: Pump Serial Number: Patient Name: Date: DOB: Weight: Current Regimen: = units Total Daily Injection Dose Calculations for Insulin Pump Initiation Settings Formula Calculation Pump TDD Reduced Dose Weight Dose Pump TDD Injection Dose x 0.75 = Reduced Dose Weight (lbs.) x 0.23 = Weight Dose (Reduced Dose + Weight Dose) 2 = Pump TDD units/day x 0.75 = units/day Injection Dose Reduced Dose lbs. x 0.23 units = units/day Weight ( units/day + units/day) 2 = units/day Reduced Dose Weight Dose Weight Dose Pump TDD Basal Rate Total Daily Basal Units Initial Basal Rate Pump TDD x % Basal (40 50%) = Total Daily Basal Total Daily Basal 24 hours = Hourly Basal Rate units/day x = units/day Pump TDD % Basal Total Daily Basal units 24 hours = units/hour Total Daily Basal Initial Basal Rate Total Daily Bolus Units Pump TDD - Total Daily Basal = Total Daily Bolus units/day - units/day = units/day Pump TDD Total Daily Basal Total Daily Bolus ICR ISF Insulin-to-Carb Ratio Insulin Sensitivity Factor Daily Carb Grams Total Daily Bolus = Carb Ratio OR 1700 Pump TDD = Insulin Sensitivity Factor grams units/day = grams/unit Daily Carbs 1700 units = mg/dl/1 unit Pump TDD Total Daily Bolus Insulin-to-Carb Ratio 450 Pump TDD = Carb Ratio 450 units/day = grams/unit Pump TDD Insulin-to-Carb Ratio OR Insulin Sensitivity Factor Basal Rates Time Rate 1) 12 Max Basal Rate: units Comments: (B) (L) (D) Carb Ratio Max Bolus: units Sensitivity Factor ISF = mg/dl/1 unit Active Insulin Time hours Adults: Children: Pregnancy: Pump Settings 4-5 hours 3-4 hours 3-4 hours Instructions for Adjustments If nocturnal, fasting/pre-meal or bedtime BG > target, increase basal 10 20% If nocturnal, fasting/pre-meal or bedtime BG < target, decrease basal 10 20% If post-meal BG > 60 mg/dl above pre-meal BG, decrease carb ratio by 10 20% If post-meal BG < 30 mg/dl above pre-meal BG, increase carb ratio by 10 20% Elevated BG: Verify trends 2 3 days before adjusting Low BG: Consider immediate adjustment Bolus Wizard Calculator Target Ranges Day Night Day Night Adults and Adolescents (13+ yrs): mg/dl mg/dl School Age (6 12 yrs): mg/dl mg/dl Toddler to Pre-school (0 6 yrs): mg/dl mg/dl Hypoglycemia Unawareness: mg/dl mg/dl Pregnancy: mg/dl mg/dl Adjustments should be made when BGs are outside of these ranges Fasting/pre-meal: to mg/dl Post-meal: Bedtime: Nocturnal: These instructions shall be valid for 6 months unless otherwise specified here: months. Prescriber Name: Signature: Date: Call MD for severe low BG or ketones. Call Medtronic for technical issues at Pumping Protocol by Bruce Bode, MD. to mg/dl to mg/dl to mg/dl Medtronic MiniMed, Inc. All rights reserved. 35

38 References 1. Hoogma RP, Hammond PJ, Gomis R, et al. Comparison of the effects of continuous subcutaneous insulin infusion (CSII) and NPH-based multiple daily insulin injections (MDI) on glycaemic control and quality of life: results of the 5-nations trial. Diabet Med. 2006;23: Heinemann L, Weyer C, Rauhaus M, Heinrichs S, Heise T, et al. Variability of the metabolic effect of soluble insulin and the rapid-acting insulin analog insulin aspart. Diabetes Care. 1998;21: Boardman S, Greenwood R, Hammond P, on behalf of the Association of British Clinical Diabetologists (ABCD). ABCD position paper on insulin pumps. Practical Diabetes International. 2007;78: Heller S, Kozlovski P, Kurtzhals P. Insulin s 85th anniversary. 2007;78: Diab Res Clin Pract. doi: /j.diabres Medical management of type 1 diabetes. In: Bode BW, ed. Tools of Therapy Insulin Treatment. 4th ed. American Diabetes Association; 2004; Bode BW, Davidson PC, Tamborlane WV. Insulin pump therapy in the 21st century. Postgraduate Medicine Online. 2002;111(5) Accessed May 10, American Diabetes Association. ADA position statement: continuous subcutaneous insulin infusion. Diabetes Care. 2004;27 (suppl 1): Accessed May 10, Bode BW, Davidson PC, Fredrickson LP, Gross TM, Sabbah HT. Diabetes management in the new millennium using insulin pump therapy. Diabetes Metab Res Rev. Jan Feb 2002;18(suppl 1):S Fernandez MP, Marcus AO. Insulin pump therapy: acceptable alternative to injection therapy. Postgraduate Medicine. 1996, 99: , Keen H, Pickup J. Continuous subcutaneous insulin infusion at 25 years. Diabetes Care. 2002;25: Bode BW, Garg S, Hirsch IB, et al. Continuous subcutaneous insulin infusion (CSII) of insulin aspart versus multiple daily injection of insulin aspart/insulin glargine in type 1 diabetic patients previously treated with CSII. Diabetes Care. 2005;28: Gross TM, Kayne D, King A, Rother C, Juth S. A bolus calculator is an effective means of controlling postprandial glycemia in patients on insulin pump therapy. Diab Technol Ther. 2003;5: Gabbe SG, Graves CR. Management of diabetes mellitus complicating pregnancy. Obstetrics and Gynecology. 2003;102(4): Suggested Reading American College of Endocrinology Consensus Statement on Guidelines for Glycemic Control. Endocrine Practice. 2002;8(suppl 1):5 11. Bailey T, Ellis S, Garg S, Kaplan R, Jovanovic L, Schwartz S, Zisser H. Improvement in glycemic excursions with a transcutaneous, real-time continuous glucose sensor. Diabetes Care. 2006;29: Bartnik M, Betteridge J, Cosentino F, et al. The Task Force of Diabetes and Cardiovascular Diseases of the European Society of Cardiology and of the European Association for the Study of Diabetes. Guidelines on diabetes, pre-diabetes, and cardiovascular diseases: full text. European Heart Journal. 2007;9: Bartocci L, Bolli G, Brunetti P, Cordoni C, Costa E, Di Vincenzo A, Fanelli C, Lepore M, Pampanelli S, Porcellati F. Pharmacokinetics and pharmacodynamics of subcutaneous injection of long-acting human insulin analog glargine, NPH insulin and ultralente human insulin and continuous subcutaneous infusion of insulin Lispro. Diabetes. 2000;49: Battelino T, Bolinder J, Bosi E, et al. Improved glycemic control in poorly controlled patients with type 1 diabetes using real-time continuous glucose monitoring. Diabetes Care. 2006;29: Bode BW, Clark JG, Davidson PC, Fredrickson L, et al. A statistically-based nomogram used as a teaching tool for CSII parameters. [Abstract 2227] Diabetes & Metabolism. 2003;29. Bode BW, Davidson P, Steed R. Reduction in severe hypoglycemia with long-term continuous subcutaneous insulin infusion in type 1 diabetes. Diabetes Care. 1996;19: Bode BW, Strange P. Efficacy, safety, and pump compatibility of insulin aspart used in continuous subcutaneous insulin infusion therapy in patients with type 1 diabetes. Diabetes Care. 2001;24: Boyer BA, Scheiner G. Characteristics of basal insulin requirements by age and gender in type 1 diabetes patients using insulin pump therapy. Diab Res Clin Pract. 2005;69: Brownlee M, Hirsch IB. Should minimal blood glucose variability become the gold standard of glycemic control? J Diabetes Complications. 2004;19: Cersosimo E. Response to Schade: To pump or not to pump? Diabetes Care. 2003;26:967. Cohen O, Basu R, Bock G, Man CD, Campioni M Basu A, Toffolo G, Cobelli C, Rizza RA. Cardiovascular and metabolic risk prediction of postprandial glycemic exposure. Diabetes Care. 2006;29: Diabetes Control and Complications Trial Research Group, The. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993;329(14): Epidemiology of Diabetes Interventions and Complications Research Group. Epidemiology of diabetes interventions and complications (EDIC). Diabetes Care. 1999;22: Franz MJ, Kulkarni K, eds. Hypoglycemia. In: Diabetes Management Therapies: A Core Curriculum for Diabetes Educators. Vol 2. 4th ed. Chicago, IL: American Association of Diabetes Educators; 2003:290. Heise T, et al. Lower within-subject variability of insulin detemir in comparison to NPH insulin and insulin glargine in people with type 1 diabetes. Diabetes. 2004; 53: Hirsch IB. Algorithms for care in adults using continuous glucose monitoring. J Diab Sci Technical. 2007;1: Kovisto VA, Helve E, Karonen SL, Pelkonen R, Yki-Jävinen H. Pathogenesis and prevention of the dawn phenomenon in diabetic patients treated with CSII. Diabetes. 1986;35: Klonoff DC. Continuous glucose monitoring: roadmap for 21st century diabetes therapy. Diabetes Care. 2005;28: Kruger DF, Matheson D, Parkin CG, Ponder S, Skyler JS. Is there a place for insulin pump therapy in your practice? Clinical Diabetes. 2007;25: Kulkarni K, Tomky DM. Intensifying Insulin Therapy: Multiple Daily Injections to Pump Therapy. Mensing C, ed. Chicago, IL: American Association of Diabetes Educators Peters AL, Rosenberg C. Patient Education. In: Davidson MB, ed. Diabetes Mellitus: Diagnosis and Treatment. 4th ed. Philadelphia, PA.: W.B. Saunders Company, A Division of Harcourt Brace & Company: 1998:424. Pickup, J. Are insulin pumps underutilized in type 1 diabetes? Yes. Diabetes Care. 2006;29: Schade DS, Valentine V. To pump or not to pump? Diabetes Care. 2002;25: Wolpert H. Smart Pumping: A Practical Approach to the Insulin Pump. Alexandria, VA: American Diabetes Association; References and Suggested Reading

39

40 Medtronic, Inc. Diabetes Devonshire Street Northridge, CA USA Tel: Hibiclens is registered globally to one or more of the Mölnlycke Health Care Group of Companies. Distributed by Mölnlycke Health Care US, LLC, Norcross, Georgia Mölnlycke Health Care AB. All rights reserved. BACTROBAN OINTMENT is a registered trademark of GlaxoSmithKline. Paradigm, Bolus Wizard, ipro and CareLink are registered trademarks of Medtronic MiniMed, Inc Medtronic, Inc. All Rights Reserved.