Pump Therapy Indications:

Insulin Pumping Getting Started March 7, 2008 Clinical Pearls To understand the rational behind pump therapy To explore patient preferences for and against insulin pump therapy Realistic expectations for pump therapy Discuss special circumstances where pump therapy would be advantageous Discuss basic starting calculations for pump therapy Insulin Pumps 1

90 o Insertion Angled Insertion QuickSerter TM SofSerter TM SilSerter TM Pump Therapy Indications: Frequent hypoglycemia Dawn phenomenon Pediatrics Preconception and pregnancy?? anyone with type 1 DM Gastroparesis Unpredictable schedule Increased A 1C Exercise Lifestyle/Improved quality of life Metabolic Advantages with pump therapy Improved glycemic control Better delivery of insulin Less hypoglycemia Less insulin required Improved quality of life 2

Normalization of Lifestyle Liberalization of diet timing and amount Increased control with exercise Able to work shifts and through lunch Less hassle with travel time zones Disadvantages and areas of concern Cost improving with ADP assistance and third party insurance coverage Development of diabetic ketoacidosis ** Insertion site infections Psychological barriers Uncertainty about specific circumstances exercise, sleep, showering, sex Unrealistic expectations With normalization of diet there can be a Potential for weight gain Diabetic Ketoacidosis No pool or depot insulin as in injections Accelerated risk of DKA Interruption of the flow of insulin, can result in DKA symptoms in only 4 hours DKA is preventable! 3

Why Pump Therapy Is More Effective Because it works more like a healthy pancreas More predictable insulin absorption More flexible basal rates More accurate bolus dosing Bode B, Sabbah H, Gross T, Fredrickson L, Davidson P. Diabetes management in the new millennium using insulin pump therapy. Diabetes Metabolism Research and Reviews. 2002; 18 (Suppl. 1): S14-S20. The Insulin Pump: More Like A Healthy Pancreas Delivery that's customizable, flexible, adjustable Can more closely match the natural delivery patterns of the pancreas Normal Insulin Secretion Pump Delivery Insulin 0 hr 12 hrs 24 hrs Schematic representation only Conventional Therapy: NPH and Short-Acting Insulin Injection Injection Normal Insulin Secretion Short-acting Insulin NPH Insulin 0 hr Schematic representation only 12 hrs 24 hrs 4

Intensive Therapy: MDI With Lantus and Rapid-Acting Insulin Long-acting basal insulin plus rapid-acting insulin before meals Requires 4 5 injections / day Injection Injection Injection Injection Insulin Normal Insulin Secretion Rapid-acting Insulin Lantus 0 hr 12 hrs Schematic representation only. Lantus is a registered trademark of Aventis Pharmaceuticals. 24 hrs Injections With Long-acting Insulin Deposit up to a full day s dose of insulin under the skin Expectation is that it will be used at the same rate, day-in and day-out. Absorption of long-acting insulin can vary up to 52%, which explains as much as 80% of the day-to-day BG variations. 1 Lauritzen T, Pramming S, Deckert T, Binder C. Pharmacokinetics of Continuous Subcutaneous Insulin Infustion. Diabetologia 1983; 24: 326-9. Long-acting Insulin Absorption Doesn t always work the same, even with a strict routine Day 1: Expected peak 1 Insulin Action (peak) Day 2: Example of premature peak 2 Day 3: Example of delayed peak, the result of insulin depot 2 0 6 12 18 24 Hours of Action 1. Lauritzen T, Pramming S, Deckert T, Binder C. Pharmacokinetics of Continuous Subcutaneous Insulin Infusion. Diabetologia 1983; 24: 326-9. Scholtz HE, et al. An assessment of the variability in the pharmacodynamics (glucose lowering effect) of HOE901 (glargine-lantus) compared to NPH and ultralente human insulins using the euglycaemic clamp technique. Abstract 0882. Poster Event D: 1999, Brussels, Belgium. 2. Time Activity Profiles of Lilly Insulins. www.lillydiabetes.com/using_insulin/what_types_of_insulin.jsp Note: Schematic representation only. 5

Normal Insulin Production: The Pancreas A healthy pancreas releases insulin automatically, on average, every 10-to 14-minutes 1, in amounts appropriate for your varying blood glucose levels. Bolus dose Normal Insulin Secretion Insulin Basal dose 0 hr 12 hrs 24 hrs Adapted from 1. Marchetti, P, et al. Diabetes, Vol 43, p. 827-839, June 1994. Schematic representation only Insulin Pump Therapy The insulin pump is customized to deliver basal and bolus insulin precisely to meet individual requirements. 6.0 Programmable Insulin Delivery with Medtronic MiniMed Pump Therapy Bolus insulin delivery Units of insulin 5.0 4.0 3.0 2.0 Basal insulin delivery Basal programmed to help prevent dawn phenomenon Dual Wave Bolus for brunch Temporary basal during walking to help prevent hypoglycemia Basal reduced to help prevent nocturnal hypoglycemia Dinner bolus 1.0 0 12am 4am 8am 12pm 4pm 8pm 12am Schematic representation only Attitudes and Attributes for Successful Insulin Pump Therapy Maturity Acceptance of diabetes Ability to problem solve Self-motivation Willing to monitor and record BG Motivated to take insulin Willing to quantify food intake Willing to act on results of blood glucose measurements Willingness to have continued contact with HCP 6

Starting on an Insulin Pump You must remember to safely cut back hs insulin the night before pump therapy is initiated NPH and others cut back 50% of the hs dose Lantus/Levemir cut back 25-50% of the hs dose No long acting insulin the morning of pump initiation Initial Adult Dosage Calculations Starting doses Based on pre-pump total daily dose (TDD) reduce TDD by 25% to 30% for pump TDD Calculated based on weight 0.24 x weight in lb (0.53 x weight in kg) Adapted from Bode BW, et al. Diabetes. 1999;48(suppl 1): 264. Bell D, Ovalle F. Endocr Pract. 2000;6:357-360. Crawford LM. Endocr Pract. 2000;6:239-243. Initial Adult Dosage Calculations Basal rate 45% to 50% of pump TDD Divide total basal by 24 hours to decide on hourly basal Start with only 1 basal rate See how it goes before adding variable basal rates 7

Principles of Early pump adjustments Do not start anyone on a basal rate higher than 1.0u/hr Raise or lower basal by only.05-0.1u/hr at a time Set alternate basal rates in 3-6 hour time blocks Understand that basal rate has a 2 hour lag time. If BG high at midnight, need to set the increased profile start time at 10pm. A well-set basal will: Let you sleep-in Allow you to delay or skip meals Make it easier to adjust for changes in plans Just make life easier BUT It takes work to get them set AND you may need more that one pattern Variable Basal Rate Insulin Pump Therapy Breakfast Lunch Dinner Plasma insulin Bolus Bolus Bolus Basal infusion 4:00 8:00 12:00 16:00 20:00 24:00 4:00 Time 8:00 8

Different Basal Patterns: Workdays vs. weekends Exercise days Premenstrual Stress days Bolus Doses 40 to 50% of the TDD is given by the patient via premeal bolusing Patient activates pump to give insulin before meals (bolus insulin) The bolus dose is based on Pre-meal blood glucose Carbohydrates in meal Activity level Carbohydrate-to-insulin ratios help determine meal bolus dose Correction bolus for high blood glucose levels Different Types of Boluses: Standard bolus-given up front to cover carbohydrate intake Extended bolus-given over a period of time to accommodate gastroparesis or prolonged meals Combination bolus-some insulin up front and rest given over a period of time to allow for delayed absorption of foods such as fatty foods Correction bolus-given up front to correct hyperglycemia 9

Estimating the Insulin to Carbohydrate Ratio (ICR) Individually determined ICR = (2.8 x weight in lbs) / TDD Anywhere from 5 to 25 g CHO is covered by 1 unit of insulin Davidson, et al. Diabetes Tech & Therap. 2003 Estimating an Insulin-to-Carbohydrate Ratio Use the 500 Rule: 500 divided by total daily insulin dose Example: 500 / 50 = 10 Insulin to carb ratio = 1u for 10g Adapted from Warshaw, H. 2001, ADA Insulin-to-Carbohydrate Ratio Individually determined, for example: Kate: 1.0 unit of insulin for 15g carbs Luis: 1.0 unit of insulin for 7g carbs Tim: 1.0 unit of insulin for 75g carbs 10

Correction Bolus Must determine how much glucose is lowered by 1U of rapid-acting insulin This number is known as the insulin sensitivity factor (ISF) Use the 100 rule to estimate the ISF 100 divided by the TDD gives you your ISF Correction Bolus Formula Current BG - Ideal BG Insulin Sensitivity Factor Example: Current BG: 12.2 mmol Ideal BG: 5.6 mmol Glucose ISF: 2.8mmol 12.2-5.6 2.8 = 2.4 U Bolus Possible Source of Errors Inability to count carbs correctly Lack of knowledge, skill Lack of time Too much work Incorrect use of SMBG number Incorrect math in calculation WAG estimations 11

Bolus Possible Source of Errors Under-estimation of carbohydrates consumed (CHO bolus) Over-correction of post-prandial elevations (CF bolus) Remaining unused, active insulin Stacking of boluses PK vs. PD Pharmacokinetic (PK) The rate of appearance into the blood Pharmacodynamic (PD) The time for the biological effect to occur This is the most important concept for the patient to understand because PK PD Adapted from Mudaliar SR et al: Diabetes Care 22:1501, 1999 PK vs. PD For Insulin Aspart 120 100 PD % peak value 80 60 40 PK 20 Adapted from Mudaliar SR et al: Diabetes Care 22:1501, 1999 0 0 60 120 180 240 300 360 Time (minutes) 12

The Bolus Wizard Calculator Can be customized with up to eight different settings per day for: Blood glucose targets Carbohydrate ratios Insulin-sensitivity factors Simplifies diabetes management May reduce math errors Decreases the number of correction boluses required Lowers the entry error rate when using the Paradigm Link Blood Glucose Monitor, powered by BD Logic Technology Paradigm is a registered trademark and Bolus Wizard and Paradigm Link are trademarks of Medtronic Diabetes. BD and BD Logic are trademarks of Becton Dickinson and Company Bolus Automatically Calculated 9-20 8:00 AM The Gold Standard in Insulin Pump Therapy The Bolus Wizard Calculator Paradigm Link Glucose Monitor MiniMed MiniMed Estimate Details 12.2 Paradigm mmol Insulin Pump Est total: 8.0 U Food intake: 60 gr ICR 1:10 gr BG: Food: Correction: 12.2 6.0 U 2.0 U WIRELESS Diabetes Management System Active ins: ACT to proceed, ESC to back up 0.0 U 12.2-5.6 = 2.0 u 2.8(SF) MiniMed Meter BG 12.2 Automatically calculates insulin bolus for the patient Clinical Pearls Pump Success requires: Accurate calculation of basal and bolus insulin Accurate carbohydrate counting and insulin to carbohydrate ratio Correction factor Knowledge of circumstances which may change basal and bolus patterns Flexibility and ongoing learning by the user 13

Current Continuation Rate of CSII Continued 98% Discontinued 2% Bode BW, Tamborlane WV, Davidson PC. Insulin pump therapy in the 21st century: Strategies for successful use in adults, adolescents, and children with diabetes. Postgraduate Medicine, 2002;111: 5; 69-77. Satisfaction QOL Health-Related Quality of Life Assessment CSII vs MDI MDI CSII 90 80 70 60 50 40 30 20 10 0 Treatment Satisfaction Clinical Efficacy Diabetes Worries Social Burden Overall Overall Preference Preference (4 items) (3 items) Peyrot M, Rubin R. Validity and Reliability of an Instrument for Assessing Health-Related Quality of Life and Treatment Preferences: The Insulin Delivery System Rating Questionnaire. Diabetes Care 2005; 28:53 58. Clinical Pearls Insulin pump therapy is safe and effective treatment modality for type 1 diabetes After an initial training period most people experience better quality of life on a pump as compared to multiple daily injections Continuing education on the part of the patient and health care team essential for ongoing success 14