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An Overview of Continuous Subcutaneous Insulin Infusion Therapy A Continuing Education Monograph for Physicians, Pharmacists, and Nurses CSII This continuing education activity can also be completed online at www.MedEdToday.com. This activity is supported by an educational grant from Novo Nordisk Inc. It has been accredited by Postgraduate Institute for Medicine for physicians, pharmacists, and nurses. An Overview of Continuous Subcutaneous Insulin Infusion Therapy A Continuing Education Monograph for Physicians, Pharmacists, and Nurses CSII This continuing education activity can also be completed online at www.MedEdToday.com. Release date: August 15, 2005 Expiration date: August 30, 2007 Estimated time to complete activity: 1.75 hours Sponsored by Postgraduate Institute for Medicine This activity is supported by an educational grant from Novo Nordisk Inc. i Program Goal This continuing education (CE) monograph is designed to introduce the reader to the concepts of optimal glycemic control in patients with diabetes using continuous subcutaneous insulin infusion (CSII). The principles of CSII therapy and the skills and knowledge needed to fulfill the important role of counseling patients about the benefits and use of CSII are also reviewed. Target Audience This CE monograph is designed for physicians, pharmacists, and registered nurses who treat patients with diabetes and wish to expand their knowledge of insulin therapy and CSII. Purpose Provide clinicians treating diabetic patients with the latest information about Continuous Subcutaneous Insulin Infusion (CSII) including indications, benefits and risks, patient selection and training, types of insulin, basic mechanism of the devices and the signs and symptoms of hypoglycemia and diabetic ketoacidosis. Statement of Need/Program Overview This continuing education (CE) monograph is designed to introduce the reader to the concepts of optimal glycemic control in patients with diabetes using continuous subcutaneous insulin infusion (CSII). The principles of CSII therapy and the skills and knowledge needed to fulfill the important role of counseling patients about the benefits and use of CSII are also reviewed. Educational Objectives After completing this activity, the participant should be better able to: • Describe the basic mechanism of CSII therapy • Review the intent and indications for CSII therapy • Evaluate the benefits and risks associated with CSII therapy • Describe the process for selecting, training, and initiating patients to CSII therapy • Identify the types of insulin used in CSII therapy • Identify the signs and symptoms of hypoglycemia and diabetic ketoacidosis ii Editorial Review Board William V. Tamborlane, MD Professor of Pediatrics and Chief of Pediatric Endocrinology Department of Pediatrics and the General Clinical Research Center Yale University School of Medicine New Haven, CT Thomas S. Sisca, PharmD, FCCP, BCPS Clinical Pharmacist, Antithrombosis Specialist Anticoagulation Clinic/Antithrombosis Services Shore Health System Memorial Hospital Easton, MD Jane Young, RN, BSN, CDE, CPT Diabetes Care Center Genesis Medical Center Davenport, IA Physician Continuing Medical Education Accreditation Statement This activity has been planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of Postgraduate Institute for Medicine (PIM) and Scherer Clinical Communications. PIM is accredited by the ACCME to provide continuing medical education for physicians. Credit Designation Postgraduate Institute for Medicine (PIM) designates this educational activity for a maximum of 1.75 category 1 credits towards the AMA Physician’s Recognition Award. Each physician should claim only those credits that he/she actually spent in the activity. Pharmacist Continuing Education Accreditation Statement Postgraduate Institute for Medicine is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education. Credit Designation Postgraduate Institute for Medicine designates this continuing education activity for 1.8 contact hour(s) (0.18 CEUs) of the Accreditation Council for Pharmacy Education. (Universal Program Number - 809-999-05-048-H01) iii Nursing Continuing Education CNA/ANCC This educational activity for 2.2 contact hours is provided by Postgraduate Institute for Medicine (PIM). PIM is an approved provider of continuing education by the Colorado Nurses Association, an accredited approver by the American Nurses Credentialing Center’s Commission on Accreditation. California Board of Registered Nursing Postgraduate Institute for Medicine is approved by the California Board of Registered Nursing, Provider Number 13485 for 2.2 contact hours. Disclosure of Conflicts of Interest Postgraduate Institute for Medicine (PIM) assesses conflict of interest with its instructors, planners, managers, and other individuals who are in a position to control the content of CME activities. All relevant conflicts of interest that are identified are thoroughly vetted by PIM for fair balance, scientific objectivity of studies utilized in this activity, and patient care recommendations. PIM is committed to providing its learners with high-quality CME activities and related materials that promote improvements or quality in healthcare and not a specific proprietary business interest of a commercial interest. The following faculty reported a real or apparent conflict of interest: Name of Faculty or Presenter Reported Areas of Conflict William V. Tamborlane, MD Consulting Fees: Novo Nordisk Speakers’ Bureau: Novo Nordisk Thomas S. Sisca, Consulting Fees: Aventis PharmD, FCCP, BCPS Pharmaceuticals, Bristol Myers Squibb Co., UPA Jane Young, RN, BSN, CDE, CPT No financial relationships related to this activity The following planners and managers reported a real or apparent conflict of interest: Name of Planner or Manager Reported Areas of Conflict Peter Macholdt No financial relationships related to this activity iv Method of Participation There are no fees for participating and receiving CME credit for this activity. During the period August 2005 through August 31, 2007, participants must 1) read the learning objectives and faculty disclosures; 2) study the educational activity; 3) complete the posttest by recording the best answer to each question in the answer key on the evaluation form; 4) complete the evaluation form; and 5) mail or fax the evaluation form with answer key to the Postgraduate Institute for Medicine. A statement of credit will be issued only upon receipt of a completed activity evaluation form and a completed posttest with a score of 70% or better. Your statement of credit will be mailed to you within three weeks. Media Monograph Disclosure of Unlabeled Use This educational activity may contain discussion of published and/or investigational uses of agents that are not indicated by the FDA. Postgraduate Institute for Medicine (PIM), Scherer Clinical Communications, and Novo Nordisk, Inc do not recommend the use of any agent outside of the labeled indications. The opinions expressed in the educational activity are those of the faculty and do not necessarily represent the views of PIM, Scherer Clinical Communications, and Novo Nordisk, Inc. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications, and warnings. Disclaimer Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patient’s conditions and possible contraindications on dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities. Trademarks Amigo is a trademark of Nipro Diabetes Systems. Animas IR-1000 and Animas IR-1200 are registered trademarks of Animas Corporation. Apidra is a registered trademark of Sanofi-Aventis. Deltec Cozmo is a trademark of Smiths Medical, Inc. ACCU-CHEK, D-TRON, and Dahedi are trademarks of Disetronic Medical Systems. H-TRON plus is a registered trademark of Disetronic Medical Systems. Humulin and Humalog are registered trademarks of Eli Lilly and Company. Novolin and NovoLog are registered trademarks of Novo Nordisk A/S. MiniMed, MiniMed 508, MiniMed Paradigm 512/712, MiniMed Paradigm 515/715, Sof-set, Square Wave, and Dual Wave are registered trademarks of Medtronic MiniMed. DANA Diabecare II is a registered trademark of DanaDiabecare USA. Copyright © 2005, Scherer Clinical Communications. All rights reserved. Published by Scherer Clinical Communications 117 West Prospect Street, Hopewell, NJ 08525 Printed in USA. v Table of Contents Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1 Basics of CSII Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1 The Insulin Infusion Pump . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1 Rationale for CSII . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .4 Potential Advantages of CSII . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .5 Types of Insulin Used in CSII . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .6 Selection of Candidates for CSII . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .6 Clinical Experience with CSII . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .8 Type 1 Diabetes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .8 Type 2 Diabetes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .9 Children and Adolescents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .9 Pregnancy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .10 The Healthcare Team . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .10 Initiating CSII Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .11 Prepump Training . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .11 Starting to Use the Pump . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .12 Establishing and Adjusting Initial Insulin Doses . . . . . . . . . . . . . . . . . .12 Determining the Initial Basal Rate and Bolus Doses . . . . . . . . . . . .12 Individualizing Insulin Dosing . . . . . . . . . . . . . . . . . . . . . . . . . . . . .14 Sick Day Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .14 Record Keeping . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .15 Meal Planning . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .15 Various Activities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .15 Pump Vacations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .16 Risks and Complications Associated with CSII . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .16 Mechanical Problems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .17 Hyperglycemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .18 Hypoglycemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .18 Diabetic Ketoacidosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .19 Skin Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .20 Weight Gain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .20 Long-term Follow-up . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .20 Other Resources for Healthcare Providers and Patients . . . . . . . . . . . .21 Cost/Reimbursement Considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .21 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .21 Case Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .22 Case Study 1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .22 Case Study 2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .23 Case Study 3 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .24 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .25 Post-Test . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .27 Evaluation Form . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .29 vi Introduction This monograph reviews the use of continuous subcutaneous insulin infusion (CSII) therapy for achieving and maintaining glycemic control in patients with diabetes. The basics of insulin pump therapy and patient education, including pump initiation and follow-up care, are covered. The skills and knowledge needed to fulfill the important role of counseling patients about the benefits and use of CSII are also reviewed. Finally, the use of patient and professional support groups and materials as additional resources for counseling patients and helping them to integrate CSII into their daily lives are discussed. Optimal glycemic control is the management of a patient’s blood glucose level toward near-normal glycemia.1 The results of 2 landmark clinical studies, the Diabetes Control and Complications Trial (DCCT)2 in type 1 diabetes and the United Kingdom Prospective Diabetes Study (UKPDS)3 in type 2 diabetes have clearly demonstrated the benefits of optimal glycemic control. Basics of CSII Therapy The Insulin Infusion Pump CSII utilizes a small external mechanical pump into which an insulin syringe or reservoir is placed. A computer chip enables the user to program how much insulin is delivered at any time of the day. Pump components are housed in a small plastic case no larger than a beeper. The pump has a lever that pushes down the plunger of the syringe to administer insulin. Thin 24- or 42-inch long plastic tubing known as an infusion set is used to connect the insulin pump to a cannula which is inserted into subcutaneous tissue, usually the abdomen (Figure 1). Connecting the pump to the cannula creates an open-loop insulin delivery system.1 Figure 1. Example of insulin pump and infusion set. The pump can be worn on the belt or discreetly under clothing. Software is available to download information from pumps to personal computers and other handheld devices such as a wireless personal digital assistant (PDA). Although several newer models can be interfaced with blood glucose monitors, the user must program the pump to deliver the appropriate amount of insulin to cover basal and prandial needs as well as correct high or low blood glucose levels. Since the pump delivers insulin immediately to the user, only rapid-acting insulin formulations are used. 1 Since insulin pumps were first introduced in the 1970s there have been advances in dose adjustment capability, infusion catheters, display screens, programming modes and capabilities, and size.4 Newer models can monitor and record insulin usage and some even interface with blood glucose monitors to receive blood glucose data, thereby alleviating the need to enter it manually. Insulin to carbohydrate ratios and correction factors can also be programmed into the new models of insulin pumps. Patients can then use the pump software to calculate and adjust the meal bolus or deliver a correction bolus. Square Wave® and Dual Wave® options allow the bolus dose to be given over a long time period; these features are useful when eating drawn out meals.4 Implantable insulin pumps are available in Europe and continuous glucose sensors that interface with the pump are currently in development. However, development of a closed-loop system (the artificial pancreas), where an insulin pump can automatically adjust insulin delivery in response to data received from an attached glucose sensor, remains an elusive goal. All changes in insulin delivery via the pump must be programmed by the user. The concepts that are vital for controlling diabetes when using other insulin delivery systems are just as important when using a pump. CSII is simply a different way to deliver insulin. To use a pump, the patient must be willing to check blood glucose frequently and learn how to make adjustments in insulin, food, and physical activity in response to those test results. Five manufacturers marketed or serviced insulin pumps in the United States in 2005. Some examples of currently available pumps and their specifications are listed in Figure 2: Animas (Animas IR-1000®, IR-1200®), Disetronic Medical Systems (D-TRONTM, DahediTM, and H-TRON®plus), Medtronic MiniMed (Paradigm® 512/712 and 515/715 insulin pumps; 508 was discontinued but continues to be serviced), DanaDiabecare USA (DANA Diabecare II), and Deltec (CozmoTM). Due to manufacturing problems identified by the FDA in June 2003, new pumps manufactured by Disetronic are not currently available in the United States but existing pumps, with the exception of the recalled Dahedi, continue to be serviced. Disetronic is currently developing the ACCU-CHEKTM Spirit insulin pump system. In May 2004, Nipro Diabetes Systems issued a voluntary recall of the AmigoTM insulin pump due to deficiencies related to documentation in their quality systems as identified by the FDA; the pump is scheduled to be available again in September 2005. Most insulin pumps are lightweight (2.8 – 4.2 ounces) and small (2.6 –4.2 inches long). Current models vary according to the number of programmable basal rates of infusion (12 – 48 profiles), range of infusion rate (0–99 units/hour), and smallest bolus dose (0.025 –0.1 unit). Today’s pumps all have alarms to alert the user to catheter occlusion or high pressure, and when the insulin reservoir is low. Pump runaway is prevented by built-in safeguard systems. Most hold up to 300 units (3 mL) of a rapid-acting insulin analog or short-acting insulin; enough insulin for several days for most patients. Although insulin pumps can last many years, the infusion set and cannula must be changed every 2 to 3 days. The user can disconnect the tube from the set for sports, showering, or any other short-time activity.5 2 The Medtronic MiniMed Paradigm® 515 contains an insulin-filled 176-unit plastic reservoir, a battery-operated pump, and computer chip that controls insulin delivery. It is 4.62 cubic inches, smaller than the MiniMed 508®, and weighs 3.52 ounces. The Paradigm is programmed to deliver insulin in 0.05-unit increments and programmed bolus delivery from 0.1 to 35.0 units in 0.1-unit increments in normal, Square Wave®, and Dual Wave® modes. These models contain alarms for occlusion, near-empty, and overdelivery of insulin. The Medtronic MiniMed Paradigm® 515 and the Paradigm Link Blood Glucose Meter are available as a set. The pump can receive wireless radio transmissions from the meter which are used in combination with food (carbohydrate) entries to estimate food and correction bolus doses. The Medtronic MiniMed Paradigm® 712 has the same features as the 515 model but holds a larger 300-unit reservoir. New Innovations include the Web-based Medtronic CareLink® Therapy Management System for Diabetes, which charts A1C, blood glucose, carbohydrates, and other trends. Reprinted with permission from Medtronic MiniMed. The DANA Diabecare® II features a 300-unit plastic reservoir, dual microprocessors, and a 24 setting basal profile. The basal delivery interval is 4 minutes with increments adjustable from 0.01 to 16.0 units/hour. Bolus increments are selectable 0.1 unit (up to 10 units) and 1.0 unit (up to 87 units). It is powered by one 3.6 volt DC battery. Its net weight (empty) is 1.8 ounces, and safety settings include maximum bolus, maximum basal, maximum daily total, low reservoir, occlusion, and low battery. Used with permission from DanaDiabecare USA. The features of Deltec CozmoTM insulin pump from Smith’s Medical, Inc., include power by one AAA battery and a large display. The unit features a program lockout that prevents menu entry, a delivery limit alarm to limit insulin delivery within a 60-minute period, a blood glucose test alert, change infusion set reminder, and a missed bolus alarm that alerts users if a meal-bolus dose is not given. The unit utilizes 4 basal patterns with 48 rates in each. The basal range is 0.05 to 35 units/hour whereas the bolus range is 0.05 to 75 units. Insulin doses based on meal carbohydrate as well as correction boluses can be calculated. The CoZmonitor blood glucose module can be attached to the back of the pump. This photo was provided courtesy of Deltec, Inc., St. Paul, Minnesota. The Animas IR-1000® insulin pump from Animas Corporation contains an insulin-filled cartridge and a battery-operated pump motor that delivers insulin every 3 minutes. The pump has four different basal programs and can deliver up to 12 rates per basal program. The basal rates range from 0.05 to 9.9 units/hour in 0.05-unit/hour increments and the bolus ranges from 0.1 to 25 units in increments of 0.1 unit. Safety alarms include low battery, dead battery, occlusion, near-empty cartridge, pump malfunction, and pump delivery error. The IR-1200 pump features a 0.025 to 25 unit/hour basal rate range and an easy to debubble insulin cartridge. The smallest bolus is 0.05 unit. The programming functions of this unit are menu-driven and it is compatible with any infusion set using Luer™ lock connections. Functions to calculate insulin to carbohydrate ratios and a correction bolus dose based on the blood glucose reading are included. The new IR-1250 model includes additional software to count calories and carbohydrate content of various foods and make adjustments in insulin dose. Reprinted with permission from Animas Corporation. Figure 2. Examples of insulin pumps. 3 Rationale for CSII The programming capabilities of the pump and the flexibility CSII provides allows insulin delivery to more closely mimic the activity of the normal pancreas. Plasma concentrations of glucose and insulin in a nondiabetic individual with normal glycemic control are represented in Figure 3.6 In individuals without diabetes, the pancreas secretes sufficient insulin during the fasting state and between meals to maintain blood glucose levels in the range of 60 to 120 mg/dL (3–7 mmol/L), allowing the body’s tissues to have sufficient glucose available for fuel. After a meal, blood glucose levels rise and the pancreas responds by rapidly increasing the release of insulin to maintain blood glucose levels within the normal range. Basal insulin secretion is the amount of insulin secreted by the pancreas independently of meals; it regulates hepatic glucose output. The rate of basal secretion is not constant and has a natural biorhythm in that it is higher in the morning, somewhat lower in the late afternoon, lower at night during sleep, and begins to rise again in the early morning.6 Exercise and stress may also cause metabolic changes that affect the rate of basal insulin secretion. In CSII, the patient can administer a variable basal level of insulin throughout the day and night as well as bolus doses of insulin at mealtimes, in an attempt to simulate the responsiveness of the pancreas in an individual without diabetes to the body’s insulin requirements. CSII therapy is therefore intended to help patients achieve normal or near-normal blood glucose levels. Figure 3. Plasma concentrations of glucose and insulin in the nondiabetic individual. Adapted from: Pickup J, Williams G, eds. Normal metabolism: The physiology of fuel homeostasis. In: Textbook of Diabetes. London: Blackwell Science Ltd; 1998:11.3. Serum insulin profiles for individuals receiving insulin via CSII over a 24-hour period are illustrated in Figure 4. Basal insulin is delivered at a programmable rate set by the patient. The appropriate bolus dose is administered by pressing a button on the pump. The patient can program incremental changes in basal insulin rate at either 30-minute or 1- or 2-hour intervals, depending on the manufacturer, to simulate a natural biorhythm. The preset basal rate can also be adjusted to accommodate exercise, illness (eg, fever), or other changes to the patient’s routine as they occur. At mealtime, the patient is able to deliver a bolus insulin dose to accommodate the increased insulin need after a meal. 4 Figure 4. The insulin delivery under continuous subcutaneous insulin infusion. Reprinted with permission from Disetronic Medical Systems, Inc. Potential Advantages of CSII In comparison with other currently available modes of insulin delivery, CSII therapy provides the closest approximation of normal physiological insulin delivery to the patient with diabetes. Therefore, CSII can be a very effective means to improve diabetes control and attain nearnormal blood glucose levels, which has psychological as well as metabolic, macrovascular, and microvascular benefits.7,8 CSII therapy may improve or stabilize glycemic control for some patients especially if multiple daily injection (MDI) therapy is not effective because of wide glycemic excursions or nocturnal hypoglycemia, or due to the effects of the “dawn phenomenon” (hyperglycemia due to increasing basal insulin requirements during the early morning hours).1,9 Optimal glycemic control is often associated with an increased incidence of hypoglycemia and weight gain; however, the results of some studies suggest that compared with MDI in patients who receive proper training and education, CSII may be associated with a decreased risk of hypoglycemia, dawn phenomenon, glycemic variability, and weight gain.8,10,11 CSII therapy may be able to help certain patients achieve a greater degree of lifestyle flexibility and improved quality of life. Patients undergoing CSII therapy, when properly trained and educated, may experience more freedom and flexibility in eating as well as more freedom to engage in athletic activities.5,12 The lifestyle demands of some patients may result in ineffective MDI therapy and lack of adherence. Some patients may not have privacy at the workplace to inject insulin using a traditional vial and syringe. These patients may view the pump as a more convenient and discreet way to administer insulin. Insulin pumps allow patients to more easily adjust insulin delivery to accommodate physical strain and changes in working conditions. Only short- and rapid-acting insulin preparations (regular human insulin, rapid-acting insulin analogs) (see Types of Insulin Used in CSII) are currently being used in CSII. The abdomen is the preferred site for CSII, although some patients may use the thigh. Abdominal administration allows for relatively rapid and consistent insulin absorption.13 5 Types of Insulin Used in CSII As discussed above, regular human insulin (Humulin®, Novolin®) and rapid-acting insulin analogs are used in CSII therapy.14,15 The analogs are stable, effective, and safe in the management of patients with diabetes using CSII therapy.16–18 Insulin aspart (NovoLog®), insulin lispro (Humalog®), and insulin glulisine (Apidra®) are approved by the US Food and Drug Administration (FDA) for use in external infusion pumps.19–21 Rapid-acting insulin analogs have become the standard formulation to use in insulin pumps.22 The use of rapid-acting analogs in CSII has increased because these agents have less variability in onset, peak, and duration of action compared with regular human insulin. The B chain of the insulin molecule has been modified in the rapid-acting analogs to allow for more rapid absorption of the insulin after subcutaneous injection.19, 21, 23, 24 For example, insulin aspart differs from human insulin at position B28, where proline has been replaced by aspartic acid. The modification allows the analog to dissociate more quickly and be more rapidly absorbed from subcutaneous tissue than regular human insulin.19 With regular human insulin, the onset of glucose-lowering action occurs about 30 minutes after subcutaneous injection, peaks in 3 to 4 hours, and, in high doses, continues to lower blood glucose for 6 to 8 hours after injection. It is important that the patient knows how to administer bolus doses as instructed. Because of the absorption kinetics of regular human insulin, taking the bolus dose too close to a meal may result in postprandial hyperglycemia, followed by hyperinsulinemia and the risk of hypoglycemia. Administering the bolus dose of regular insulin less than 30 minutes before a meal may also result in hypoglycemia. In comparison, the onset of glucose-lowering action for rapid-acting analogs occurs in approximately 10 to 20 minutes, peak activity occurs in 1 to 3 hours, and the duration of action is less than 5 hours.19,21 Because the insulin analogs have a rapid onset of action, bolus doses can be administered immediately before, or in some cases, immediately after, eating a meal. This offers greater convenience and flexibility, which may improve adherence to therapy.25 Because of their rapid action, it is important that the meal is not delayed after a bolus dose of a rapid-acting analog is taken. A recent meta-analysis concluded that compared with regular human insulin, the use of insulin analogs in CSII pumps produces a modest (0.26%) reduction in glycosylated hemoglobin (A1C) and that patients have a greater preference for rapid-acting insulin analogs.26 Furthermore, some studies report that the incidence of hypoglycemia is lower during CSII with rapid-acting insulin analogs.26 Selection of Candidates for CSII Successful CSII therapy includes careful patient selection and training on the use of the pump, continuing care by skilled professionals, and a patient support program. The patient’s commitment to meticulous self-monitoring of blood glucose (SMBG) and record-keeping of SMBG values, hypo- and hyperglycemic experiences, and pump incidents (eg, clogs, blockages, leaks) contribute to better results with CSII.1 The inability to achieve normal or near-normal blood glucose levels on MDI is an important reason to consider a switch to the insulin pump. Patients who experience recurrent episodes of hypoglycemia or hypoglycemic unawareness may also consider switching to CSII. Some patients may be motivated to start CSII from the time of initial diagnosis. Good candidates for CSII therapy include those individuals who can adapt to the use and demands of the insulin pump, those who want a higher level of participation in their diabetes 6 self-care, and those who understand the potential benefits and risks of CSII.27 These individuals are usually highly self-motivated and are ready to take a very active role in the management of their diabetes.28,29 The most common reason patients give in choosing CSII over MDI therapy is the wish to increase flexibility with regard to daily activities.28,30 CSII can make it easier for patients to occasionally skip or delay meals, sleep late on weekends, exercise for prolonged periods, or adjust more easily to time zone changes.12 However, candidates for CSII must understand that any increased flexibility in lifestyle associated with CSII only comes with thorough training, knowledge of how to properly utilize CSII, and a willingness to accept responsibility for day-to-day self-care.27 A supportive home environment is another important consideration. A program of intensive glycemic management requires a commitment by the patient and a sharing of responsibility with the patient’s family and healthcare professional team. Positive characteristics for selection of CSII candidates are listed in Table 1. Table 1. Positive Characteristics of Potential Continuous Subcutaneous Insulin Infusion (CSII) Candidates Motivation and Self-reliance • Strongly self-motivated to improve glycemic control • Ability to adjust insulin doses based on blood glucose levels and carbohydrate content of meals • Technical skills to operate the insulin infusion pump and infusion set and troubleshoot the pump • Willing and able to accept responsibility for daily self-care Acceptance • Can establish realistic goals for pump therapy, understands that CSII is not a cure for diabetes • Feels comfortable relying on the insulin pump and is not self-conscious about wearing the pump • Follows the healthcare provider’s schedule for office visits and phone conversations Family Support • Has support of family members, significant others, and employers (when applicable) Monitoring • Able and willing to self-monitor blood glucose at least 4 times a day • Willing to maintain rigorous and thorough record keeping • Willing to test blood or urine ketones when plasma glucose levels are greater than 250 mg/dL and to follow up in the appropriate manner when ketones are present Adopted from Fredrickson L, ed. The Insulin Pump Therapy Book: Insights from the Experts. Sylmar, Ca: MiniMed Technologies; 1995. Characteristics that may prevent or adversely affect a patient’s ability to adapt successfully to CSII therapy are listed in Table 2. Potential CSII candidates must have access to a well-trained diabetes-care team to make an optimal transition from their previous therapy. 7 Table 2. Undesirable Characteristics of Potential Continuous Subcutaneous Insulin Infusion (CSII) Candidates • Fear of needles, catheters, or pain • Reluctance to tell others about their diabetes history or current therapy • Continually miss healthcare appointments • Cannot or will not follow treatment plans • Psychiatric history, including depression, history of suicidal thoughts or attempts, personality disorders, passive-aggressive behavior, other psychiatric disorders, substance abuse • Severe physical disability affecting the ability to use the pump • Inadequate financial resources • Lack of commitment to strict treatment goals or to frequent self-monitoring of blood glucose Farkas-Hirsch R, Hirsch IB. Continuous subcutaneous insulin infusion: A review of the past and implementation for the future. Diabetes Spectrum. 1994;7:80 –138. Gentili P, Maldonato A, Bloise D, et al. Personality variables and compliance with insulin therapy in type 2 diabetic subjects. Diabetes Nutr Metab. 2000;13:1– 6. Tannenberg RJ. Candidate selection. In: Fredrickson L, ed. The Insulin Pump Therapy Book: Insights from the Experts. Sylmar, Ca: MiniMed Technologies; 1995;32– 47. Clinical Experience with CSII Type 1 Diabetes The earlier trials on CSII involved the use of regular human insulin in patients with type 1 diabetes participating in mostly nonrandomized and poorly controlled studies.31 Studies varied considerably in the outcome variables measured, number of patients, and length of the trial.31–33 In a meta-analysis of 12 randomized controlled trials, most of which were conducted before 1990 with low numbers of patients, CSII therapy provided a small advantage in glycemic control (~0.5% lower A1C) compared with MDI therapy; however, blood glucose levels were less variable in patients receiving CSII and 14% less insulin was used.32,33 These conclusions were supported by an independent meta-analysis of 52 (randomized and nonrandomized) studies31; the risk of developing mild or severe hypoglycemia was also lower with CSII. In general, CSII either improved or did not change the levels of anxiety, quality of life, and compliance.31 A recent meta-analysis comparing the use of rapid-acting insulin analogs in CSII versus MDI showed that insulin pump therapy tended to produce better glycemic control, particularly in patients with high A1C values at baseline.34 The number of patients using CSII has increased exponentially since 1990 in the United States.35 In 2001, 160,000 patients were estimated to be using an insulin pump; the greatest recent increase in use has been noted among children and adolescents. Several recent trials in patients with long-standing uncontrolled hyperglycemia have shown that CSII does produce greater reductions in A1C (0.35% to 0.84% lower) and improvements in general well-being compared with MDI.36,37 The importance of postprandial hyperglycemia in overall glycemic control is now well recognized.38 In 100 patients with type 1 diabetes who previously used an insulin pump, CSII therapy with insulin aspart reduced the number of postprandial glucose excursions and episodes of nocturnal hypoglycemia compared with MDI therapy with insulin glargine and insulin aspart.39 8 Type 2 Diabetes In contrast with type 1 diabetes, there are few published randomized trials of CSII therapy in patients with type 2 diabetes.40 In 20 patients with poorly controlled type 2 diabetes who were randomized to either MDI or CSII therapy with regular human insulin for 4 months, the number of patients achieving satisfactory reductions in A1C (ie, A1C <50 mmol hydroxymethylfurfural/mol hemoglobin) was higher in the CSII group (80% vs 30%).41 In 132 patients with type 2 diabetes, CSII with insulin aspart was equivalent to MDI therapy with insulin aspart and neutral protamine Hagedorn (NPH) insulin for glycemic control after 42 weeks; however, the majority of patients preferred CSII and they had a significantly greater improvement in overall treatment satisfaction.15 The incidence of nocturnal hypoglycemia tended to be lower with CSII (16%) compared with MDI (22%), whereas the overall incidence of hypoglycemia was similar between both groups.15 Children and Adolescents Optimal glycemic control is critical in preventing growth and related disorders in children and adolescents.42 Boland and colleagues7 found that adolescents could achieve optimal glycemic control with the insulin pump and maintain their quality of life. Numerous observational trials and several randomized studies have shown that CSII therapy is safe and effective in pediatric populations including preschoolers and toddlers with uncontrolled type 1 diabetes.43–50 Because newer insulin pumps are smaller, safer, and easier to use, the number of patients aged <20 years using insulin pumps has increased by 20-fold since the late 1990s.4 In general, CSII therapy can reduce A1C and hypoglycemic episodes in children and adolescents with type 1 diabetes without causing abnormal increases in body weight.4 In 75 patients between 12 and 20 years of age who chose either CSII or MDI therapy, reductions in A1C were 0.4% to 0.8% lower and the rates of severe hypoglycemia were 30% to 50% lower with CSII compared with MDI therapy; patients using CSII also found it easier to cope with insulin therapy.7 In 32 patients between 8 and 21 years of age randomized to either MDI therapy with insulin glargine and insulin aspart, or CSII with insulin aspart, A1C decreased by 0.9% with CSII whereas no change occurred with MDI; mean blood glucose levels were also significantly lower at lunch, dinner, and bedtime in the CSII group.45 Reductions in A1C and severe episodes of hypoglycemia during CSII therapy in patients who transitioned from MDI therapy have been found in various observational trials.43,46, 48, 51,52 Parental supervision and involvement in diabetes care are key considerations for determining whether CSII therapy is appropriate for younger patients. Children and adolescents have not always been considered as good candidates for CSII because of the large size and technical limitations of early insulin pump models, psychosocial issues regarding pump use, and potential lack of commitment by patients, families, and clinicians in achieving the goals of intensive glycemic control. Furthermore, many schools do not have trained personnel who can help the child with diabetes management. Therefore, a child using an insulin pump and his or her family must have sufficient knowledge, skills, and attitudes to independently manage the essentials of CSII therapy. This includes managing potential problems including hypoglycemia and pump failure. These skills should be determined by the diabetes-care team along with parents. When glycemic control is suboptimal with CSII, missed boluses are the most likely cause.53 Therefore, healthcare providers and parents need to be vigilant in monitoring children using CSII. The bolus history function of the newer pump models allows parents and clinicians to track compliance with administration of bolus doses by school-age and adolescent patients. Similar methods are not available in children being treated with MDI therapy. 9 Pregnancy In pregnant women with diabetes, fetal abnormalities associated with hyperglycemia and other metabolic anomalies are most likely to occur in the first trimester of pregnancy.54, 55 The attainment of intensive glycemic control is therefore very important for all pregnant women with diabetes. Diabetes care before conception and early in pregnancy has been shown to reduce the risk of congenital abnormalities.55 CSII may be an alternative to MDI for women who intend to become pregnant but have not been able to achieve appropriate blood glucose control with a regimen of 2, 3, or 4 daily insulin injections. CSII may also be appropriate for pregnant women with a history of hypoglycemia or problems with the dawn phenomenon (increased insulin need in the early morning).12 One study compared the level of glycemic control and safety experienced by 3 groups of pregnant women: those initially using MDI therapy who were switched to CSII therapy at 6 to 8 weeks of gestation; those on MDI throughout their pregnancy; and those on CSII prior to and throughout their pregnancy.56 Postpartum A1C levels were ~7% for women in both CSII groups compared with ~9% for those in the MDI group. Overall, congenital malformations (eg, polydactyly, cleft hand, ventricular septal defects) were observed in 10% of the neonates in this study. There were, however, no significant differences in maternal or perinatal outcomes between the groups. Hypoglycemic rates were also similar for all 3 groups. In pregnant patients with type 1 diabetes, CSII was effective and safe for those individuals not achieving acceptable glycemic control with MDI.57 CSII is also effective and safe in pregnant patients with either type 2 diabetes or gestational diabetes needing high doses of insulin.58 The Healthcare Team To achieve optimal glycemic control, the patient with diabetes requires not only the care of a physician but also that of other healthcare professionals. Many diabetes centers routinely include the services of nurse educators, dietitians, pharmacists, psychologists, and podiatrists in the management of diabetes and its related problems.59 Managing diabetes with CSII therapy requires considerable resources, substantial expertise, and a long-term commitment by the patient and their healthcare providers. The patient must have the necessary knowledge, training, support, and resources to be successful with CSII therapy. If the physician, physician assistant, or nurse practitioner does not have the resources for delivering this level of care, the patient should be referred to an endocrinologist or diabetes center that has the required resources. Unfortunately, some patients receive insulin pumps without adequate plans for proper follow-up, resulting in limited effectiveness of the therapy as well as an increased risk for adverse consequences. A qualified pump trainer is the most appropriate person to train and help patients begin CSII therapy. The training is a multifaceted endeavor, and pump trainers include physicians, nurses, pharmacists, dietitians, and lay trainers. Some trainers may only be responsible for technical aspects of pump therapy whereas others troubleshoot elevated plasma glucose, pump alarm systems, and skin infection problems. The trainer should be well educated on the topic and possess a wide range of educational and communication skills to be able to instruct patients on the pump. Trainers should also be able to determine if the patient is capable of using the pump after adequate education and should follow up after the initiation of therapy. Table 3 lists the knowledge and skills required of the insulin pump trainer. 10 The trainer, as well as the other members of the healthcare team, should know when and to whom to refer a patient if the need arises.60 There should be general agreement among the team members about blood glucose goals, initial basal and bolus doses, procedures for adjusting insulin doses, plasma glucose testing schedule, treatment of hyperglycemia and hypoglycemia, and a variety of other issues. Team members should be supportive of each other and provide backup support for the pump trainer. Table 3. Knowledge and Skills Necessary for Pump Trainers • Understanding and knowledge of diabetes and its complications • Knowledge of how to correctly respond to and treat hypoglycemia and hyperglycemia • Understanding the advantages and disadvantages of various diabetes treatment options • Ability to individualize therapy based on patient needs • Knowledge of the use of insulin infusion pumps and infusion sets – Programming – Troubleshooting – Installing batteries, cleaning and maintaining the pump – Filling the reservoir and establishing infusion lines • Calculation of basal rates and bolus doses • Calculation of multiple basal rates • Calculation of insulin to carbohydrate ratios • Ability to understand and explain teaching materials • Effective communication skills • Familiarity with local patient support programs Reprinted from Brackenridge B, D’Almeida B, Fredrickson L, et al. The Pump Trainer Manual. Sylmar, Ca: MiniMed Technologies; 1994. Initiating CSII Therapy Prepump Training The patient should receive comprehensive training on the principles of diabetes selfmanagement and CSII as the first step in beginning CSII therapy.12 The goal of this phase is that the patient understands and is able to explain the following: – The benefits and risks of CSII. – Prevention of diabetic ketoacidosis (DKA) is feasible and dependent upon the following factors: (1) the patient’s ability to recognize an insulin delivery problem; (2) development of medical conditions that trigger adverse metabolic changes (eg, infection, inflammation, emotional stress, myocardial infarction, trauma, surgery, and pregnancy); (3) medications (eg, glucocorticoids, diuretics, and sympathomimetics); and (4) substance abuse. – A potential change in hypoglycemia awareness. Most patients, their family members, or significant others benefit from having 3 separate preparatory visits. It is recommended that the pump trainer, along with the patient, family members, and significant others discuss the following at each visit.12 11 Visit 1: At this visit, the pump trainer should accomplish the following with the patient: (1) collect the patient’s diabetes history; (2) give a detailed overview of pump therapy, including advantages and disadvantages; (3) set realistic goals and expectations of CSII therapy; (4) discuss precautions associated with CSII; (5) identify support groups, dietitians, or counselors; (6) select the insulin pump model to be used; and (7) begin the process of obtaining insurance coverage and discussion of financial issues. Visit 2: This visit is usually scheduled after the patient receives the insulin pump. Before the visit, the patient should read the pump instruction manual, use an accompanying CD-ROM for home computers, watch an educational videotape, experiment with the pump and tubing, and perform minor pump operations. At this visit, the trainer will instruct the patient on all aspects of the pump programming and operation. The patient will learn how to wear the pump, practice using the pump (with saline), prime the tubing, insert the needle using proper hygiene, and how to change the insertion site in the home setting. The patient may also learn that the catheter is not as noticeable or intrusive as initially feared. The patient should also meet with a dietitian (unless the trainer performs this function) prior to the initiation of CSII to obtain a personalized meal plan and to learn carbohydrate counting. Visit 3: Actual CSII therapy may be initiated at this visit or within the next few days.12 The objectives of this visit are to review the patient’s technique, answer questions, and assess the patient’s skills and understanding of pump use and his or her readiness to begin pump therapy. Starting to Use the Pump Except for the pregnant women who need rapid normalization of glucose levels,5 few, if any, patients need to be admitted to the hospital to initiate pump therapy. It is important to commit the necessary time and resources to get the patient off to a good start. Blood glucose levels should be closely monitored during the first week of therapy, and the insulin regimen should be changed as necessary (see Establishing and Adjusting Initial Insulin Doses). Patients should have 24-hour access to information, which can be provided by the pump manufacturer hotline, healthcare team, and the patient’s pump trainer. Patients should be provided with detailed instructions about their treatment plan and how to keep a daily diary that will provide the physician (or other healthcare team member acting under physician supervision) with sufficient data for making precise adjustments in insulin dose and timing.61 Establishing and Adjusting Initial Insulin Doses Determining the Initial Basal Rate and Bolus Doses In general, patients beginning therapy with an insulin pump are started on a lower total daily dose (eg, 10%–25% less) than their total prepump daily insulin dose.62 In adults, basal insulin usually accounts for ~50% of the pump dose and the remaining 50% of the total daily insulin requirement is comprised of the bolus insulin doses administered at mealtimes.62 The basal dose in children is usually >50%. If an adult patient was receiving 42 units/day of insulin prior to initiating CSII, the starting pump total insulin dose would be 32 units/day (0.75 * 42). The initial basal rate would therefore be 0.7 unit/hour (0.50 * 32/24 hours) and the starting bolus doses would be 5.3 12 U/bolus (0.50 * 32/3). Sample guidelines for establishing a patient’s initial basal and bolus insulin doses provided by one of the insulin pump manufacturers are shown in Table 4. Table 4. Sample Guidelines for Calculating Basal and Bolus Insulin Doses for Adults Using Continuous Subcutaneous Insulin Infusion Basal and Bolus Dose Calculation Based on the Total Prepump Insulin Dose: • Identify the total prepump daily insulin amount • Reduce the total prepump dose by 10% to 25% = the starting pump total daily insulin amount • Basal insulin dose (units/hour) = 50% of the starting pump total dose/24 hours • Bolus* insulin dose = 50% of the starting pump total dose/3 Reprinted from Fredrickson L, ed. The Insulin Pump Therapy Book: Insights from the Experts. Sylmar, Ca: MiniMed Technologies; 1995. *Calculate as carbohydrate to insulin ratio with injection therapy or as total daily carbohydrate intake/50% of total daily dose. According to the American Diabetes Association (ADA), blood glucose targets should range between 90 to 130 mg/dL for average preprandial plasma values and be <180 mg/dL for peak postprandial plasma glucose levels in adults with diabetes.63 The American Association of Clinical Endocrinologists recommends that fasting plasma glucose be <110 mg/dL and 2-hour postprandial blood glucose <140 mg/dL.64 Blood glucose target values should be carefully selected to reduce the risk of serious hypoglycemia. Target averages are somewhat lower for pregnant patients, generally not exceeding 105 mg/dL before meals or 130 mg/dL 2 hours after a meal.5,65 These goals are somewhat higher for patients with a history of hypoglycemic unawareness, at least at the start of therapy.9,63 Most adult patients require basal doses ranging from 0.4 to 2.0 units/hour; toddlers and younger children will require less. Patients begin CSII therapy with 1 basal rate but may add 1 or 2 additional rates during the day and/or night as their daily insulin requirements are further established.62 For example, a patient may have a certain basal rate programmed for 9 PM to 3 AM to cover nocturnal insulin needs, a second rate to deliver slightly more insulin from 3 AM to 9 AM to address increased insulin need in the dawn hours, and a third rate to cover the daytime hours from 9 AM to 9 PM. If a patient’s basal rate(s) results in persistent hypoglycemia or hyperglycemia, then a new basal rate should be calculated.62 In adults, once the patient’s individual basal rates are established, they often do not need to be adjusted unless changes in lifestyle, body weight, or health status occur. In children, basal and bolus doses are constantly changing due to growth and pubertal development.66 The basal insulin rate is correctly established if blood glucose levels remain in the target range under fasting conditions. Blood glucose levels should be checked before and after meals (or more frequently if needed) during initiation of CSII. The initial basal rate should also be verified based on overnight blood glucose levels obtained at bedtime, nighttime (midnight and/or 3 AM), and breakfast (7 AM). This is helpful for the early recognition of nocturnal hypoglycemia. The actual test schedules may vary for a specific patient based on varied life schedules and mealtimes. It is important that the patient is instructed in the proper timing of the bolus dose, depending on the type of insulin used. Bolus doses of regular human insulin should be administered 30 minutes prior to eating a meal whereas bolus doses of a rapid-acting insulin analog should be 13 injected within 15 minutes of commencing a meal. Bolus doses are based on premeal blood glucose readings and estimated food intake. With normal bolus dosing, the patient receives an immediate bolus, programmable in 0.025-unit increments of insulin or higher, depending on the pump manufacturer. Some insulin pumps can deliver a normal bolus as well as perform Square Wave and Dual Wave delivery. The Square Wave and Dual Wave boluses are designed to help people better match insulin action to insulin need, such as during periods of extended eating or to compensate for delayed digestion (eg, gastroparesis). Square Wave delivery allows for programming a bolus for delivery over a period of 30 minutes to 8 hours. The Dual Wave bolus combines an immediate bolus with an extended Square Wave bolus in one easy step. The Medtronic pumps offer these insulin bolus delivery options. Other available pumps also offer similar delivery options. Individualizing Insulin Dosing Determining the patient’s individual insulin need is a key step for helping to correct high blood glucose values observed after pump therapy has begun. The amount varies considerably from patient to patient, depending on the degree of insulin resistance, and an estimate should be calculated for each patient. Based on data from the patient’s diary, the physician can estimate how much 1 unit of insulin will lower plasma glucose for that specific patient and then adjust the insulin dose.62, 67 Insulin responsiveness can also be estimated for patients with type 1 diabetes by the “1500 rule” when using regular human insulin or the “1800 rule” when using a rapid-acting insulin analog.67,68 The rule is used to estimate how much 1 unit of regular human insulin or a rapidacting insulin analog lowers plasma glucose when the patient’s total amount of daily regular insulin or analog dose is divided into 1500 or 1800, respectively. For example, if the patient is using 50 units of regular insulin per day, 1500 divided by 50 equals 30, which means that 1 unit of regular insulin lowers plasma glucose 30 mg/dL over a 4- to 6-hour interval. The rule of 1800 is used for a rapid-acting analog because 1 unit tends to lower blood glucose somewhat more over a 2- to 4-hour interval.68 Sick Day Management As with patients using MDI therapy, general principles of sick day management also apply to CSII patients. Plasma glucose as well as blood and urine ketone levels may increase during times of stress or illness. It is important for patients to frequently test for blood or urine ketones during illness (as instructed), or when blood glucose levels are elevated, and adjust their insulin dose accordingly.69 The first step is to make sure that elevated blood glucose levels are not due to an infusion site or other pump problem. This can be accomplished by taking a correction dose and then remeasuring the glucose level in 30 to 60 minutes to make sure that blood glucose values are falling. If not, the infusion set and site should be changed and a correction bolus given by injection. Sites should almost always be changed if the patient is symptomatic and has positive ketones. The patient should contact a diabetes team member if these steps are unable to lower glucose and ketone values or when persistent nausea or vomiting occurs.69 Patients should also plan ahead for sick days. They should have adequate supplies of insulin, infusion sets, extra supplies for glucose and ketone testing, sugar-containing clear fluids, glucagon kit, thermometer, and antiemetic and antidiarrheal medications, which should be used with the guidance of their healthcare team. 14 Record Keeping Rigorous monitoring of blood glucose levels helps to ensure the safety and effectiveness of intensive insulin therapy. The trainer should review the patient’s record-keeping techniques and show the patient how record keeping may differ during pump therapy. The SMBG logs should have notations for diet and activity, bolus dose adjustments, and changes in basal rates to assist the healthcare team in optimizing therapy. Meal Planning Proper nutrition is essential to successful diabetes management.70 Carbohydrate content is used to determine premeal bolus insulin doses in most cases because carbohydrates are the main determinant of meal-related insulin demand. When patients are comfortable with CSII therapy, they should be introduced to the concept of counting carbohydrates and the I:C ratio to allow for more flexible meal planning. Carbohydrate counting allows the patient to determine the premeal bolus of insulin based upon the actual grams of carbohydrate in that meal. This ratio is the number of grams of carbohydrate covered by 1 unit of short- or rapid-acting insulin. This value is calculated by dividing the total grams of carbohydrate consumed in a day by the total bolus insulin administered in a day. A dietitian may assist the pump user in calculating an accurate I:C ratio, which is typically in the range of 10 to 20 grams of carbohydrate per unit of insulin. The labeling of most packaged food contains information on the carbohydrate content in the metric system (ie, grams). Adjustments in dose and the timing of insulin delivery can be made as their diet changes, with guidance from a dietitian or certified diabetes educator working under the supervision of a physician.70 Some patients with diabetes may need to increase their insulin dose when excessive protein is included in a meal. In this situation, enough protein may be converted to glucose to produce a noticeable effect on postprandial hyperglycemia. In addition, excessive dietary fat intake may affect glucose absorption and accentuate and sustain postprandial hyperglycemia.70 For children, the I:C ratio is based on age. Children <5 years start with 0.3 unit/15 g of carbohydrate, 5 to 7 years (0.5 unit/15 g), 8 to 11 (0.7 unit/15 g), 12 to 14 (1.0 unit/15 g), and 15 to 18 years (1.5 units/15 g).4 Various Activities Patients using CSII are encouraged to participate in recreational sports, including contact or water sports. However, it is important for patients to understand that the timing and intensity of a workout can cause hypoglycemia, and patients should be taught how to prevent or treat hypoglycemia during times of mild to intense physical exertion. Patients can compensate for exercise with appropriate adjustments of basal and bolus insulin doses or increased carbohydrate intake. They should also be aware that the risk for nocturnal hypoglycemia is also greater after a day of increased physical activity. Currently or potentially sexually active pump users should be counseled about pump use during sexual activity. They do not have to remove the pump during sexual activity, but if the pump is taken off, it should not be removed for a prolonged period or significant hyperglycemia or DKA may occur. 15 Pump Vacations Patients may need to remove the pump for certain activities such as swimming and showering. If no food is consumed or blood glucose is not elevated, no additional insulin is usually required if the pump is removed for 2 or 3 hours.4 The “quick release” feature of current infusion sets makes such temporary disconnections very easy. The healthcare team and patient should develop strategies for dealing with pump failure or removing the pump for longer periods and for taking pump vacations. These procedures should be reviewed periodically. A randomized crossover trial with 100 individuals showed that patients can temporarily switch from CSII with insulin aspart to basal-bolus therapy with insulin glargine (basal) and insulin aspart.39 The quantity of insulin given in the basal mode should be determined and replaced by a similar amount of NPH or a long-acting insulin analog. Bolus doses can be calculated and given by injection at mealtime.71 The exact requirements should be determined by blood glucose monitoring, expected activity levels, and carbohydrate counting. If the pump vacation is longer than 3 days, a return to a basal-bolus regimen with MDI will be required. Overlap with previous insulin doses via injection should be considered when returning to CSII therapy.71 Risks and Complications Associated with CSII Patient education and the use of specific troubleshooting techniques can prevent, reduce, and help manage complications associated with pump use, thus avoiding a crisis (Table 5). The patient must clearly understand that the insulin pump is not a “closed-loop” system and does not automatically deliver insulin in response to blood glucose levels. It is therefore critical for the patient to understand how to adequately monitor blood glucose levels, correctly program the pump, and perform everyday management techniques to prevent serious metabolic disturbances. The syringe, reservoir, tubing, and injection site should be changed at the same time every 48 to 72 hours. Using good hygiene measures and changing the injection site regularly, as directed, helps to reduce injection-site reactions, infection, and interruptions of insulin delivery.12 16 Table 5. Suggestions for Troubleshooting Continuous Subcutaneous Insulin Infusion Therapy • Review the alarm card • Differentiate between alarm and error messages • Review maximum values for overinfusion alarm • Review possible causes for high blood glucose levels – Loss of insulin potency? – Precipitation or crusting – Bolus dose too small? in tubing or cannula? – Recent illness? – Catheter dislodged? – Leaks or air in tubing? – Pump malfunction? – Crimps in the cannula? – Reservoir out of insulin? – Poor absorption from infusion site? • Change the infusion set if elevated blood glucose values fail to respond to an appropriate correction dose or when a high blood glucose value is accompanied by a positive ketone test • Always be prepared to give insulin by subcutaneous injection with another insulin delivery system and have appropriate supplies available • Check for ketones in the urine or blood • Review possible causes of low blood glucose levels – Basal insulin rate too high? – Bolus insulin dose too large? – Low carbohydrate meal? Miscalculation of meal’s carbohydrate content? – Increased exercise? • Ensure that the patient understands how to prevent low blood glucose levels – Perform self-monitored blood glucose (SMBG) as instructed, especially before a meal or driving – Perform SMBG at bedtime and during the night if necessary – Have a supply of quick-acting carbohydrates available – Review glucagon administration with family members – Always have appropriate supplies available (and not expired) – Contact healthcare team for frequent or asymptomatic hypoglycemia Mechanical Problems Although the new pump models are mechanically very reliable, problems may occur that can result in interrupted or excessive insulin flow. Because only rapid-acting insulin is used in CSII therapy, any disruption in the flow of insulin for whatever reason—from an empty reservoir to a kinked line or loose set to low batteries—can cause blood glucose to quickly become dangerously elevated. Insulin pumps are equipped with sophisticated alarm systems and other safety features, including maximum basal and bolus dose limits. However, patients should be instructed to use SMBG and not to rely solely on alarm systems. Patients should be instructed to monitor blood glucose levels at least before each meal and at bedtime, and once a week at 3 AM.60 Patients should also be instructed to always keep an insulin syringe or insulin pen available (and occasionally practice using it) as a “backup” in the event of mechanical failure of the pump. 17 Hyperglycemia The most common causes of hyperglycemia are the administration of inadequate bolus or basal doses and underestimation of carbohydrate intake. A trend to higher blood glucose levels is the sign that children and adolescents have “outgrown” their current insulin doses. Hyperglycemia can also occur when the insulin is not absorbed properly from the infusion site or because of infusion set crimping, occlusion or leak, empty reservoir, or dislodging of the needle or cannula. CSII patients should be taught to inspect the pump, syringe, and infusion set at least 2 times a day.60 Inspections should also be done whenever a high blood glucose level occurs. Unexplained elevated blood glucose levels should be treated with insulin using appropriate troubleshooting techniques. Patients must adhere to a regular schedule, including changing the infusion set, filling and changing the insulin in the reservoir, and checking for leaks when changing the reservoir and infusion sets. Clogging of the infusion line may also occur. Some infusion sets (eg, Sof-set®) are lined with insulin-compatible material that reduces the incidence of clogging. Hypoglycemia An increased risk of hypoglycemia is associated with intensive glycemic control. Patients and their families should be taught how to recognize, prevent, and treat hypoglycemia. To minimize the risk for hypoglycemia, patients should be educated to perform SMBG and to recognize the symptoms of hypoglycemia (Table 6). Hypoglycemia can be more quickly reversed in patients using CSII because the subcutaneous insulin depot is not as large as with MDI therapy.4 To minimize the risk of severe hypoglycemia, patients must be able to respond to hypoglycemic signs and symptoms by having a fast-acting carbohydrate such as orange or apple juice (1/2 cup), brown sugar (1 tablespoon), or 2 to 3 glucose tablets readily available. A more specific recommendation for children is 8 grams of carbohydrate if blood glucose is <51 to 70 mg/dL, 15 g if it is 41 to 50 mg/dL, and 30 g if it is <40 mg/dL.4 If the patient is unable to orally ingest a carbohydrate, a glucagon injection may be needed. All patients should have a glucagon injection kit available. Glucagon is a counterregulatory hormone that causes the release of glucose from liver glycogen stores. Parenteral administration of glucagon results in prompt mobilization of liver glycogen, thereby raising blood glucose levels. Patients, family members, or significant others should be taught when and how to give a glucagon injection.72 A glucagon injection kit should always be accessible for hypoglycemic emergencies. It should be remembered that a carbohydrate snack may still be needed after the glucagon is administered and that vomiting occurs in some people after the administration of glucagon. Therefore, patients should be positioned on their side or stomach. A glucagon injection will not work if liver glycogen has been depleted by fasting for >24 hours. Therefore, intravenous glucose may need to be administered by emergency personnel. Hypoglycemia can occur when basal insulin rates are calculated incorrectly or because of improperly timed or calculated bolus doses. Carefully programmed insulin delivery can potentially reduce the incidence of hypoglycemic episodes. As discussed earlier, the results of some studies indicate that CSII can be significantly better than MDI in reducing the risks of hypoglycemia in patients who receive proper training and education in the use of the insulin pump.10, 11 Some patients have hypoglycemic unawareness or recurrent episodes of hypoglycemia and require assistance. These patients need to have their target blood glucose ranges carefully established and adjustments made in insulin dosage, food intake, and exercise.72 Bedtime insulin boluses should only be administered with extra caution to minimize the risk of nocturnal hypoglycemia.67 18 Table 6. Common Signs and Symptoms of Hypoglycemia Central Nervous Warning Symptoms System Impairment Miscellaneous Sweating Drowsiness Hunger Tremors Confusion Blurred vision Headache Anxiety Dizziness Nausea Speech impairment Weakness Palpitations Loss of consciousness Shivering Diabetic Ketoacidosis CSII patients use only rapid-acting insulin and therefore do not have the “cushion” of an intermediate-acting insulin to help prevent metabolic decompensation caused by insulin deficiency and associated counterregulatory hormone responses. This results in elevated gluconeogenesis, glycogenolysis, lipolysis, and ketogenesis as well as inhibition of peripheral glucose utilization. During CSII, only relatively small amounts of insulin are continuously infused, resulting in a small subcutaneous depot. Therefore, any interruption in insulin delivery lasting for several hours or more can result in DKA. The risk of DKA can be minimized by frequent SMBG and appropriately responding to elevated blood glucose readings.73 In the presence of severe insulin deficiency, glucose cannot be utilized. Blood glucose levels rise precipitously and a metabolic chain of events is triggered that results in the breakdown of fat for energy and the production of ketones. The signs and symptoms associated with ketone production include the urinary excretion of glucose, dehydration, electrolyte imbalances, and acid-base derangements (Table 7). Severe ketosis may result in vomiting, difficulty breathing, and a fruity breath odor. Patients must be taught the importance of SMBG and of monitoring for blood or urinary ketones. Patients should also be instructed in how to anticipate and recognize the signs and symptoms of DKA.73 Patients should establish a routine of systematically checking the pump, infusion set, and infusion site. Patients with type 1 diabetes, whose blood glucose level is >250 mg/dL by SMBG, should perform a blood ketone check.74 If ketones are positive and the patient cannot find any problem with the insulin pump, they should administer a supplemental bolus dose and recheck plasma glucose, as directed by a healthcare provider. The patient should consider changing the infusion set if blood glucose remains higher than 250 mg/dL because the infusion set may be occluded, and consult with their healthcare provider for further instruction.73 19 Table 7. Signs and Symptoms of Diabetic Ketoacidosis Signs Symptoms Nausea and vomiting Polydipsia and polyuria Tachycardia Hypotension or shock Weakness or anorexia Dehydration Abdominal pain Warm, dry skin Visual disturbances Hyperpnea or Kussmaul respiration Somnolence Impaired consciousness or coma Weight loss Fruity breath Copyright © 2004 American Diabetes Association From: Medical Management of Type 1 Diabetes. Adapted and reprinted with permission from The American Diabetes Association. To order this book, please call 1-800-232-6733 or order online at http://store.diabetes.org. Skin Infections Skin infections are a potential, although preventable, risk of insulin pump therapy. They are associated with prolonged use of a single injection site or poor hygiene. In addition, some patients with a history of Staphylococcus aureus infections or who are nasal carriers of the organism may be at a higher risk of infection. Patient education can help minimize the number of infections a patient may experience.12 Patients can reduce the risk for skin infections by changing the infusion sets every 48 to 72 hours, which can vary depending upon the type of infusion used, adhering to recommendations for skin hygiene, and keeping the infusion site clean and dry.12 If patients develop infections at the needle site, they should clean the skin with an antibacterial soap and consider the use of an infusion set with an antibacterial dressing. They should also visually examine the injection site for signs of inflammation and irritation, change the site if there is a problem with the current site, and seek medical attention if they suspect that infection has occurred. Patients should never reuse an infusion set because this can increase the risk for infection.12 Weight Gain Patients may gain weight when starting CSII therapy as more intensive therapy and improvement in glycemic control makes more calories available from meals because glucose is not excreted in urine. Some clinical data, however, suggest that less weight gain occurs with CSII compared with MDI therapy.8,11 Long-term Follow-up Patient education is an ongoing process. Patients can continue their CSII education by discussing such topics as multiple basal rates, advanced programming, small adjustments of bolus doses, adjusting to exercise and travel, and calculating the I:C ratio. During the first 2 months of CSII therapy, intensive follow-up with the healthcare provider should be conducted to reassure the patient and the healthcare provider. Once the healthcare provider is confident that the patient has mastered the pump and can handle it on his/her own, follow-up visits can be adjusted to adhere to the patient’s needs. It is critically important for the physician and 20 other healthcare professionals to periodically reassess the patient’s knowledge and skills regarding CSII therapy on an ongoing basis. Other Resources for Healthcare Providers and Patients Many health support materials and services are available to the patient and healthcare professional, including instruction manuals, educational brochures, videotapes, newsletters, Websites, and toll-free hotlines. Useful Websites include www.diabetesincontrol.com and www.cdc.gov/diabetes. Many other support materials are produced and available from pump manufacturers, and their Internet sites answer basic questions about diabetic topics and insulin pump therapy, and discuss specific products. Patients, institutions, pump manufacturers, ADA affiliates, and others have formed pump support groups that allow CSII patients to exchange information and provide emotional support. Healthcare professionals should know about CSII support groups in their region and encourage their patients to join. If local groups do not exist, patients and healthcare professionals may consider starting a support group. The American Association of Diabetes Educators (AADE; Website www.aadenet.org) and the American Diabetes Association (Website www.diabetes.org) offer a variety of educational programs for health professionals interested in continuing their education in pump therapy. The insulin pump manufacturers also support educational programs for physicians, diabetes educators, pump trainers and pump users, and provide information and technical support services to patients and diabetes educators on their respective Websites (www.animascorp.com, www.disetronic.com, www.minimed.com, www.danapumps.com, www.delteccozmo.com, www.nipro-diabetes.com). Other online sources that provide direction to patients and healthcare professionals include www.insulin-pumpers.org and www.diabetesnet.com. Cost/Reimbursement Considerations The cost of therapy is an important issue to consider when selecting candidates for CSII therapy. The initial cost for the insulin pump device and the ongoing monthly cost are higher than those for MDI therapy. The approximate cost for a commercially available insulin pump is about $6,000 and infusion sets and dressings can cost $150 to $400 per month; insurance may cover up to 100% of the cost. Many insurers provide coverage for the cost of the pump, medical services associated with training the patient, and the cost of disposable supplies, but the exact coverage usually includes outpatient initiation of pump therapy. Some insurers will not pay for the initial cost or maintenance of the pump whereas others limit coverage on the amount of supplies used within a specified time period. Most insurance plans require documentation of the medical necessity of the pump, according to the insurer’s guidelines, before coverage can begin. Conclusions The findings of landmark trials such as the DCCT and UKPDS provide clear evidence that optimal glycemic control can prevent or delay the development or progression of microvascular complications of diabetes in patients with type 1 or type 2 diabetes. Appropriately selected patients of all ages with type 1 and type 2 diabetes can benefit from intensive glycemic therapy with an insulin pump. As with other modalities, the benefits of treatment with CSII must be weighed against the risks. Intensive glycemic control and the potential for improved quality of life can outweigh the potential complications of CSII for many people. Furthermore, patients with gestational diabetes can also utilize CSII. Insulin pump training is a multifaceted endeavor. Education and intensive pump training by qualified pump trainers and certified diabetes educators working in concert with a healthcare team 21 are critical to the successful implementation and long-term success of pump therapy. It is important that pump trainers and educators have the knowledge and communication skills needed to help the CSII patient achieve the goals of intensive glycemic control. Case Studies The following case studies and questions are presented to challenge and increase your knowledge of insulin pump therapy. Case Study 1 CP is a 56-year-old woman who has had type 1 diabetes for more than 30 years. She indicated that she monitors her blood glucose levels 4 times a day, denies alcohol use, and does not engage in vigorous exercise. Her blood glucose levels can range from 35 to 350 mg/dL, on any given day, and her A1C level was 6.5%. CP has been experiencing 2 to 3 hypoglycemic episodes per week, often requiring paramedic visits several times a year. She does not feel any symptoms of hypoglycemia unless her plasma glucose levels fall well below 50 mg/dL. Her insulin regimen was changed from split NPH and regular insulin to 4 injections per day (3 injections of a rapid-acting insulin analog and 1 basal insulin injection at bedtime), and she received blood glucose awareness training. Her I:C ratio was set at 1 unit of insulin for 15 to 20 grams of carbohydrate. Her plasma glucose levels ranged from 70 to 250 mg/dL within 2 weeks of changing therapy and stabilized at 60 to 210 mg/dL, but she still experienced episodes of hypoglycemia. Questions What is happening to CP? Why would you consider CSII therapy for CP? What should be done immediately? Answers This patient is experiencing hypoglycemic unawareness. Possible causes of hypoglycemia include inappropriate target glucose levels, inappropriate I:C ratio, variable insulin absorption, excessive boluses to correct hyperglycemia, and insufficient or irregular SMBG. Because of the frequency and severity of her hypoglycemic episodes, this patient may benefit from CSII. By frequently monitoring her plasma glucose levels, CP may be able to prevent many hypoglycemic episodes. As an immediate step, CP’s blood glucose target range was raised to 100 to 200 mg/dL. She received specific, individualized guidelines for meal-related bolus doses and was advised to keep fast-acting carbohydrates on hand at all times. Clinical Course CP was concerned about her ability to control her disease without recurring episodes of serious hypoglycemia and elected to discuss pump therapy with her insurer. The insurer was proactive in disease management and willing to pay for the pump. CP received CSII training and began therapy with a rapid-acting insulin analog. Two weeks after initiation, her daily range of plasma glucose excursions improved. At 4 months after the initiation of CSII therapy, her A1C level was 6.7%, and she has not experienced episodes of severe hypoglycemia since beginning CSII. CP is now aware of signs and symptoms of hypoglycemia with plasma glucose readings of ≤70 mg/dL. She is motivated and conscientious in her day-to-day diabetes management. For the first time, she believes that she is in control of her disease and is confident in her ability to manage her diabetes. 22 Case Study 2 PC is a 12-year-old girl who was diagnosed with type 1 diabetes 18 months ago. Two injections per day of a mixture of Lente and insulin lispro were initiated and both PC and her parents received standard diabetes education. PC initially required a total daily dose (TDD) of 1.8 units/kg per day. Although her glucose levels were stable, she experienced hypoglycemia during sports and competitive ice skating. After 1 year, her TDD had been decreased to 1.3 units/kg per day, and she was switched to insulin glargine therapy. She administered insulin glargine once a day (at bedtime), and insulin aspart with 3 meals, using an I:C ratio of 1 unit per 10 g for a TDD of 1.2 units/kg per day. After 1 month, a 3 PM bolus of insulin aspart was added to cover her snack. This regimen worked well, although PC continued to experience hypoglycemia during intense physical activity. Pump Treatment PC and her parents were counseled about the option of CSII therapy. They were informed that CSII offered more convenience and flexibility compared with MDI therapy. The diabetes-care team also described studies in children and discussed how patients with active lifestyles prefer insulin pumps. PC began pump treatment with insulin aspart when she was just over 13 years old. PC did quite well on the pump with programmed basal rates of 1.1 units (12 AM), 0.8 unit (3 AM), 1.0 unit (9 AM), and 1.1 units (9 PM). Her initial I:C ratio was 1 unit per 10 g (TDD of 1.1 units/kg per day). Sports Through trial and error, PC and her parents—with consultation from the diabetes-care team— have learned how to adjust her pump to accommodate the very intense demands of competitive ice skating and avoid either hypo- or hyperglycemia during or after an event or practice. PC learned that she needed to set a temporary lower basal rate for evenings after an intense practice session, as well as during practice sessions to avoid hypoglycemia. She measures her glucose level before, after, and sometimes during practice. For a competition, PC tests before and after the event, but leaves the pump off during the event to prevent hypoglycemia as well as for cosmetic purposes. Metabolic Control PC’s A1C levels rose during the first year of CSII, during which time she reached menarche. Insulin doses were increased (TDD over the next year ranged from 1.3–1.4 units/kg per day), and metabolic control improved shortly thereafter. Because PC seemed to be very sensitive to insulin for the 24-hour period prior to each menses, she learned to reduce her insulin basal doses by more than 50% the day before menses began. If a practice session took place during that day, she decreased the dose even further. PC is now 15 years old and continues to be quite successful with her diabetes care, which she manages with complete independence. She is currently on a TDD of 1 unit/kg per day, with a 1 unit per 7 g carbohydrate bolus dose. She has achieved the ADA’s treatment guideline of an A1C <7%; her last 2 measurements were 5.7% and 6.9%. She has reported many times in her follow-up visits that she is pleased with her decision to begin pump treatment. 23 Case Study 3 JD is a 55-year-old female with a body mass index of 28.2. She was diagnosed as having type 2 diabetes 12 years ago and has been using human insulin formulations for nearly 5 years. JD’s blood pressure is 140/85 mm Hg and she also has signs of neuropathy. Although JD’s A1C level has been reduced to 8.1% with a basal-bolus regimen, she has also experienced wide glucose excursions and nocturnal hypoglycemia. These problems may be related to irregular mealtimes caused by her busy work and travel schedule as a sales rep, and by small peaks of basal insulin or different requirements for basal insulin at different times of the day. Questions Is this patient a candidate for CSII? How should insulin pump therapy be initiated for this patient? Answers Insulin pump therapy is now a viable option for patients with type 2 diabetes. Insulin pumps have increased flexibility and freedom but pump use requires a willingness to monitor blood glucose at least 4 times a day and consistent record keeping. The patient also needs to develop technical skills to operate the pump and adjust insulin doses based on meal carbohydrate intake and blood glucose readings. Because patients generally require less insulin when using CSII, JD’s total insulin administered is reduced by 25% when changing to CSII from MDI. A rapid-acting insulin analog is used with bolus doses administered just before meals. Since the basal dose is usually 50% of the daily CSII dose, the hourly rate is calculated by dividing the daily basal dose by 24. The bolus doses are calculated by dividing by the number of meals with adjustment for carbohydrate content. Discrete adjustments in dosing can be done at any time. Clinical Course After attending some pump pretraining workshops and working with a diabetes educator, JD decides to try the insulin pump. Following early problems adapting to the pump and fine-tuning the dosing by blood glucose monitoring, JD has become very comfortable with CSII therapy after 8 months. Her A1C is down to 7.0% and glucose excursions and nocturnal hypoglycemic episodes have also been reduced. JD attributes the improvements to the convenience and flexibility the CSII regimen offers. The basal infusion rate may be decreased at times when she is physically active and requires less insulin. 24 References 1. Kelley DB. Insulin infusion pump therapy. In: Intensive Diabetes Management. 2nd ed. Alexandria, Va: American Diabetes Association; 1998:102-119. 19. NovoLog [package insert]. Princeton, NJ: Novo Nordisk Inc; 2003. 2. The Diabetes Control and Complications Trial Research Group. 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;329:977-986. 20. Apidra [package insert]. 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Diabetes Care. 2002;25:439-444. 15. 16. 17. Renner R, Pfutzner A, Trautmann M, et al. Use of insulin lispro in continuous subcutaneous insulin infusion treatment. Results of a multicenter trial. German Humalog-CSII Study Group. Diabetes Care. 1999;22:784-788. 18. Zinman B, Tildesley H, Chiasson JL, et al. Insulin lispro in CSII: Results of a double-blind crossover study. Diabetes. 1997;46:440-443. 25 38. Monnier L, Lapinski H, Colette C. Contributions of fasting and postprandial plasma glucose increments to the overall diurnal hyperglycemia of type 2 diabetic patients: Variations with increasing levels of HbA(1c). Diabetes Care. 2003;26:881-885. 56. Gabbe SG, Holing E, Temple P, Brown ZA. Benefits, risks, costs, and patient satisfaction associated with insulin pump therapy for the pregnancy complicated by type 1 diabetes mellitus. Am J Obstet Gynecol. 2000;182:1283-1291. 39. Hirsch IB, Bode BW, Garg S, 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;28:533-538. 57. Lapolla A, Dalfra MG, Masin M, et al. Analysis of outcome of pregnancy in type 1 diabetics treated with insulin pump or conventional insulin therapy. Acta Diabetol. 2003;40:143-149. 58. 40. Kirk SE. Insulin pump therapy for type 2 diabetes. Curr Diab Rep. 2003;3:373-377. Simmons D, Thompson CF, Conroy C, Scott DJ. Use of insulin pumps in pregnancies complicated by type 2 diabetes and gestational diabetes in a multiethnic community. Diabetes Care. 2001;24:2078-2082. 41. Jennings AM, Lewis KS, Murdoch S, et al. Randomized trial comparing continuous subcutaneous insulin infusion and conventional insulin therapy in type II diabetic patients poorly controlled with sulfonylureas. Diabetes Care. 1991;14:738-744. 59. Hirsch IB. The status of the diabetes care team. Clin Diabetes. 1998;16:145-146. 60. Brackenridge B, D’Almeida B, Fredrickson L, et al. The Pump Trainer Manual. Sylmar, Ca: MiniMed Technologies; 1994. 42. Kaufman FR, Halvorson M, Miller D, et al. Insulin pump therapy in type 1 pediatric patients: Now and into the year 2000. Diabetes Metab Res Rev. 1999;15:338-352. 61. Bode BW, Davidson PC. Pattern analysis and record keeping. In: Fredrickson L, ed. The Insulin Pump Therapy Book: Insights from the Experts. Sylmar, Ca: MiniMed Technologies; 1995:84-93. 43. Ahern JA, Boland EA, Doane R, et al. Insulin pump therapy in pediatrics: A therapeutic alternative to safely lower HbA1c levels across all age groups. Pediatr Diabetes. 2002;3:10-15. 62. Bode BW. Establishing & verifying basal rates. In: Fredrickson L, ed. The Insulin Pump Therapy Book: Insights from the Experts. Sylmar, Ca: MiniMed Technologies; 1995:48-56. 44. DiMeglio LA, Pottorff TM, Boyd SR, et al. A randomized, controlled study of insulin pump therapy in diabetic preschoolers. J Pediatr. 2004;145:380-384. 63. American Diabetes Association. Standards of medical care in diabetes. Diabetes Care. 2005;28:S4-S36. 45. Doyle EA, Weinzimer SA, Steffen AT, et al. A randomized, prospective trial comparing the efficacy of continuous subcutaneous insulin infusion with multiple daily injections using insulin glargine. Diabetes Care. 2004;27:1554-1558. 64. American Association of Clinical Endocrinologists. Medical guidelines for the management of diabetes mellitus: The AACE system of intensive diabetes self-management—2002 update. Endocr Pract. 2002;1(Suppl 8):40-82. 46. Litton J, Rice A, Friedman N, et al. Insulin pump therapy in toddlers and preschool children with type 1 diabetes mellitus. J Pediatr. 2002;141:490-495. 65. American Diabetes Association. Gestational diabetes mellitus. Diabetes Care. 2004;27(Suppl 1):S88-S90. 66. 47. Plotnick LP, Clark LM, Brancati FL, Erlinger T. Safety and effectiveness of insulin pump therapy in children and adolescents with type 1 diabetes. Diabetes Care. 2003;26:1142-1146. Amiel SA, Sherwin RS, Simonson DC, et al. Impaired insulin action in puberty. A contributing factor to poor glycemic control in adolescents with diabetes. N Engl J Med. 1986;315:215-219. 67. 48. Sulli N, Shashaj B. Continuous subcutaneous insulin infusion in children and adolescents with diabetes mellitus: Decreased HbA1c with low risk of hypoglycemia. J Pediatr Endocrinol Metab. 2003;16:393-399. Davidson PC. Bolus and supplemental insulin. In: Fredrickson L, ed. The Insulin Pump Therapy Book: Insights from the Experts. Sylmar, Ca: MiniMed Technologies; 1995:58-71. 68. Evert AB, Mauseth RS. The new insulin analogs: Using a team approach to implement basal-bolus insulin therapy. Practical Diabetology. 2004;23:28-37. 69. Dudley WE, Dudley MJ. Everyday management. In: Fredrickson L, ed. The Insulin Pump Therapy Book: Insights from the Experts. Sylmar, Ca: MiniMed Technologies; 2004:94-104. 70. Brackenridge BP, Reed JH. Counting carbohydrates. The key to proper bolusing. In: Fredrickson L, ed. The Insulin Pump Therapy Book: Insights from the Experts. Sylmar, Ca: MiniMed Technologies; 1995:72-83. 71. Beaser RS, Gallego MC. Intensifying insulin treatment program. In: Beaser RS, ed. Joslin’s Diabetes Handbook. Boston, Ma: Joslin Diabetes Center; 2001:273-328. 72. Hirsch IB, Polonsky WH. Hypoglycemia and its prevention. In: Fredrickson L, ed. The Insulin Pump Therapy Book: Insights from the Experts. Sylmar, Ca: MiniMed Technologies; 1995:128-142. 73. Sonnenberg GE, Fredrickson L. DKA prevention. In: Fredrickson L, ed. The Insulin Pump Therapy Book: Insights from the Experts. Sylmar, Ca: MiniMed Technologies; 1995:116-126. 74. Burdick J, Harris S, Chase P. The importance of ketone testing. Pract Diabetol. 2004;23:19-25. 49. Weintrob N, Benzaquen H, Galatzer A, et al. Comparison of continuous subcutaneous insulin infusion and multiple daily injection regimens in children with type 1 diabetes: A randomized open crossover trial. Pediatrics. 2003;112:559-564. 50. Weinzimer SA, Ahern JH, Doyle EA, et al. Persistence of benefits of continuous subcutaneous insulin infusion in very young children with type 1 diabetes: A follow-up report. Pediatrics. 2004;114:1601-1605. 51. Maniatis AK, Klingensmith GJ, Slover RH, et al. Continuous subcutaneous insulin infusion therapy for children and adolescents: An option for routine diabetes care. Pediatrics. 2001;107:351-356. 52. 53. Saha ME, Huuppone T, Mikael K, et al. Continuous subcutaneous insulin infusion in the treatment of children and adolescents with type 1 diabetes mellitus. J Pediatr Endocrinol Metab. 2002;15:1005-1010. Burdick J, Chase HP, Slover RH, et al. Missed insulin meal boluses and elevated hemoglobin A1c levels in children receiving insulin pump therapy. Pediatrics. 2004;113:e221-e224. 54. Greene MF. Prevention and diagnosis of congenital anomalies in diabetic pregnancies. Clin Perinatol. 1993;20:533-547. 55. Mills JL, Baker L, Goldman AS. Malformations in infants of diabetic mothers occur before the seventh gestational week. Implications for treatment. Diabetes. 1979;28:292-293. 26 Post-Test This program can also be completed online at www.MedEdToday.com. Please provide 1 answer for each question (14 correct answers are necessary for successful completion). Place all answers on the exam answer key provided on the evaluation form following this post-test. 1. Which of the following are possible reasons to switch a patient from MDI to CSII therapy? A. B. C. D. 2. Which of the following statements is NOT true about insulin pumps? A. B. C. D. 3. D. Less need to adjust insulin doses Less need for SMBG Greater flexibility to vary mealtimes and activity levels Less need to monitor blood glucose or check ketones during illness Prepump training goals for the patient include all of the following EXCEPT________ . A. B. C. D. 9. True False CSII therapy is associated with which of the following advantages compared with MDI? A. B. C. D. 8. Regular and long-acting insulin preparations are used in CSII therapy Bolus doses of regular human insulin should be administered 30 minutes prior to a meal Some studies suggest that the incidence of nocturnal hypoglycemia is lower when rapid-acting insulin analogs are used for CSII All of the above Because insulin infusion pumps include an alarm system, patients do not need to monitor their blood glucose levels as closely as with MDI. A. B. 7. Self-reliant and motivated Ability to solve problems Willingness to adhere to frequent SMBG All of the above Which of the following is not true? A. B. C. 6. A small external pump connected to an infusion set and cannula A small external pump connected to an infusion set and continuous blood glucose monitor A small implantable pump None of the above Positive characteristics of a good candidate for insulin pump therapy include which of the following characteristics? A. B. C. D. 5. Glucose meters can be interfaced with some insulin pumps The rate of insulin delivery automatically changes in response to readings received from the glucose meter in all pumps Long-acting insulins cannot be used Pump components are housed in a plastic case no larger than a beeper CSII therapy utilizes________ . A. B. C. D. 4. Inability to achieve desired glycemic control with MDI History of hypoglycemic unawareness History of recurrent episodes of serious hypoglycemia Any of the above Understanding of the advantages and risks of CSII therapy Calculating the patient’s insulin sensitivity Procedures for minimizing the risk of DKA Ability to use the pump, prime the tubing, and insert the needle During therapy with CSII, hypoglycemia may occur because of all of the following EXCEPT_______ . A. B. C. D. Basal rates that are set too high Incorrect bolus dose Improperly timed bolus doses Basal rates that are set too low 27 10. CSII is NOT intended for toddlers or adolescents. A. B. True False 11. Which of the following is true for CSII therapy? A. B. C. D. The basal rate is correctly determined if the fasting blood glucose values remain within the target range Patients use an average of 75% less total daily insulin on CSII compared with prepump experience Patients immediately begin CSII with 2 or 3 initial basal insulin rates Both B and C 12. Signs and symptoms of DKA include all of the following EXCEPT________ . A. B. C. D. Fruity breath Hypertension Dehydration Somnolence 13. The risk of DKA can be reduced by________ . A. B. C. D. Consuming a fast-acting carbohydrate Establishing a routine for checking the pump, infusion set, and infusion site Checking blood or urine ketones when plasma glucose levels are above 250 mg/dL Both B and C 14. Which of the following is NOT true for patients on CSII therapy? A. B. C. D. Adjustments in insulin dose should be considered when the patient’s diet changes Basal doses of insulin should be based on the patient’s individualized meal plan Patients should keep a supply of glucagon on hand Both B and C 15. The recommended interval for changing the infusion set in CSII is________ . A. B. C. D. 24 hours 24 to 48 hours 24 to 72 hours 48 to 72 hours 16. Which of the following statements is not true about CSII therapy? A. B. C. D. Patients using CSII therapy can participate in water sports. CSII therapy involves the use of a “closed-loop” system. The patient’s log recordings of SMBG values can be used by the healthcare team to help optimize therapy. None of the above 17. CSII can be used during pregnancy. A. B. True False 18. All of the following EXCEPT ____ are undesirable characteristics of potential CSII candidates? A. B. C. D. Fear of needles and pain Inadequate financial resources Presence of microvascular complications Lack of commitment to strict treatment goals 19. Prepump training is usually conducted over 3 visits. All of the following EXCEPT ____ are covered during visit 2. A. B. C. D. Pump therapy is initiated Trainer instructs patient on all aspects of pump programming and operation Patient practices using the pump with saline Patient learns how to change the insertion site in the home setting 20. Potential risks and complications of CSII therapy include all the following EXCEPT ________ . A. B. C. D. 28 Hypoglycemia DKA Retinopathy Hyperglycemia Evaluation Form An Overview of Continuous Subcutaneous Insulin Infusion Therapy Project ID: 3228 ES 13 Postgraduate Institute for Medicine (PIM) respects and appreciates your opinions. To assist us in evaluating the effectiveness of this activity and to make recommendations for future educational offerings, please take a few minutes to complete this evaluation form. You must complete this evaluation form to receive acknowledgment of participation for this activity. Please answer the following questions by circling the appropriate rating: 5 = Outstanding 4 = Good 3 = Satisfactory 2 = Fair 1 = Poor Extent to Which Program Activities Met the Identified Purpose • Provide clinicians treating diabetic patients with the latest information about 5 Continuous Subcutaneous Insulin Infusion (CSII) including indications, benefits and risks, patient selection and training, types of insulin, basic mechanism of the devices and the signs and symptoms of hypoglycemia and diabetic ketoacidosis. 4 3 2 1 Extent to Which Program Activities Met the Identified Objectives Upon completion of this activity, participants should be better able to: • Describe the basic mechanism of CSII therapy 5 4 3 2 1 • Review the intent and indications for CSII therapy 5 4 3 2 1 • Evaluate the benefits and risks associated with CSII therapy 5 4 3 2 1 • Identify the types of insulin used in CSII therapy 5 4 3 2 1 • Identify the signs and symptoms of hypoglycemia and diabetic ketoacidosis 5 4 3 2 1 Overall Effectiveness of the Activity • Was timely and will influence how I practice 5 4 3 2 1 • Will assist me in improving patient care 5 4 3 2 1 • Fulfilled my educational needs 5 4 3 2 1 • Avoided commercial bias or influence 5 4 3 2 1 Impact of the Activity The information presented (check all that apply): ❏ Reinforced my current practice/treatment habits ❏ Provided new ideas or information I expect to use ❏ Will improve my practice/patient outcomes ❏ Enhanced my current knowledge base ❏ Yes ❏ No Will the information presented cause you to make any changes in your practice? If yes, please describe any change(s) you plan to make in your practice as a result of this activity: How committed are you to making these changes? (Very committed) 5 4 3 2 1 (Not at all committed) Future Activities Do you feel future activities on this subject matter are necessary and/or important to your practice? ❏ Yes ❏ No 29 Please list any other topics that would be of interest to you for future educational activities: Follow-up As part of our ongoing continuous quality-improvement effort, we conduct post-activity follow-up surveys to assess the impact of our educational interventions on professional practice. Please indicate your willingness to participate in such a survey: ❏ Yes, I would be interested in participating in a follow-up survey ❏ No, I’m not interested in participating in a follow-up survey Additional comments about this activity: If you wish to receive acknowledgment of participation for this activity, please complete the post-test by selecting the best answer to each question, complete this evaluation verification of participation and FAX to: 303-790-4876. Post-Test Answer Key 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Request for Credit Name Degree Organization Specialty Address City State Zip Telephone Fax E-Mail For Physicians Only I certify my actual time spent to complete this educational activity to be: ❏ I participated in the entire activity and claim 1.75 credits. ❏ I participated in only part of the activity and claim _____ credits. Signature 30 Date Completed © 2005 Scherer Clinical Communications August 2005 Printed in USA