1. A Patient Safety Initiative For Insulin Pumps Manufacturing Standards to improve insulin pump safety and medical outcomes Suggestions for improvements and editorial changes are welcome. Send comments to: John Walsh, PA, CDE at jwalsh@diabetesnet.com and Ruth Roberts, MA rroberts@diabetesnet.com (619) 497-0900jwalsh@diabetesnet.comrroberts@diabetesnet.com Version 2: 09/28/09 Version 1: 12/07/08

2. Definitions TDD – total daily dose of insulin (all basals and boluses) Basal –background insulin pumped slowly through the day to keep BG flat Bolus – a quick surge of insulin as  Carb boluses to cover carbs  Correction boluses to lower high readings that arise from too little basal insulin delivery or insufficient carb boluses Bolus On Board (BOB) – the units of bolus insulin with glucose-lowering activity still working from recent boluses Duration of Insulin Action (DIA) – time that a bolus will lower the BG. This is used to calculate BOB.

3. Background Although insulin pumps * were first designed to improve insulin delivery, new technology has transformed them into data collection centers. Additional data from continuous glucose monitoring devices increases the data’s value. Data necessary for monitoring and clinical decisions is now directly accessible in the pump itself. With regular glucose testing and data analysis, a pump can provide important clinical information to users and clinicians regarding glucose and insulin dosing patterns with recommendations for improvement. * “Pump” collectively refers to the pump body, PDA, cell phone, and other devices that control insulin delivery and store data.

4. Introduction Over 500,000 insulin pumps are in use around the world, yet there are no formal guidelines regarding manufacturing standards and medical practice in the diabetes clinical community and pump manufacturing industry. These suggested standards are intended as imprements for future insulin pumps and in current pumps where software changes allow. They are designed to: Provide safer dosing increments and problem solving to pump users Allow clinicians to make safer and more informed dosing decisions when managing a variety of pumps Facilitate the training of adjunctive medical and accessory personnel (ER, surgical, school nurses, etc.) to improve their familiarity and interactions with insulin pumps

5. Benefits Of Insulin Pump Standards These mechanical standards are designed for: 1.Consistent use of pump settings between pump manufacturers 2.Accuracy and safety of carb and correction factor increments 3.Safety of DIA defaults and consistent use of DIA increments 4.Consistent handling of BOB and insulin stacking 5.Improved monitoring for hypoglycemia & hyperglycemia 6.Direct entry of glucose values into bolus calculations 7.Notification when use of correction boluses is excessive 8.Faster identification of control issues caused by infusion sets

6. Overview #Topic 1Carb Factor Increments 2Correction Factor Increments 3Carb Factor Accuracy 4Correction Factor Accuracy 5DIA Default Times 6DIA Time Increments 7Handling Of BOB #Topic 8.Multi-Linear And Curvilinear DIA 9.Hypoglycemia Alert 10.Hyperglycemia Alert 11.Correction Bolus Alert 12.Insulin Stacking Alert 13.Automatic Entry Of BG Values 14.Infusion Set Monitoring Slides are numbered by topic for easy reference.

7. Safety 1.Increments and Accuracy 1Carb factor 2Correction factor 3DIA 1Defaults 1DIA 2Handling Of BOB 3Hypo Manager #Topic 8.Alerts 1.Hypo frequency 2.Hyper frequency 3.Unusual highs 4.Correction Bolus Excess 5.Insulin Stacking 6.Overview table of alert frequency 13.Infusion Set Monitor

8. Easy Data Access BOB TDD  Correction bolus %  Carb bolus %  Basal % Avg glucose SD Carbs/day with approximate calorie equivalent Accurate carb and correction factors Automatic basal and factor testing How often bolus recommendation is overridden and direction Frequency of occlusions and stops (and length of stops)

9. Review Change in TDD Changes The BG For some later slides, it helps to know how a change in the TDD affects the glucose levels. Using a modified Davidson Rule for the carb factor and a 2000 Rule for the correction factor: 1.25% change in the TDD changes glucose levels about 25 mg/dl when given as a single dose A 5% change in the TDD is equivalent to about a 25 mg/dl rise or fall in the glucose through the day A 5 to 6% change in the carb factor (approx. 2.5% to 3% of the TDD) changes the glucose about 20 mg/dl per meal.

10. Carb Factor Increments 1 Carb Factor (CarbF): the number of grams of carb covered by 1 u of insulin for an individual The smaller the carb factor, the larger a carb bolus

11. Carb factor increments shall be less than or equal to 5% of the next larger whole number so that each single step adjustment causes subsequent carb boluses to change by no more than 5% from previous doses. Recommended minimum carb factor increments: 5 1.0 g/u above 20 g/u 0.5 g/u for 10 to 20 g/u 0.2 g/u for 5 to 9.8 g/u 0.1 g/u for 3 to 4.9 g/u 0.05 g/u for 0.1 to 2.95 g/u Standard For: Carb Factor Increments 1 5 Improved carb factor increments recommended by Gary Scheiner, MS, CDE

12. Issue: Existing carb factor increments are too large. Current carb factors are a safety concern because they lack the precision required to avoid excessive hyperglycemia and hypoglycemia, especially for smaller carb factor numbers. 1 Carb Factor (CarbF) Increments

13. 1 gram per unit is the smallest CarbF increment in most pumps. This increment is relatively large for CarbFs lower than 15 or 20 g/u. For instance, when the carb factor is reduced from 10 to 9 g/u, all subsequent carb boluses are increased by 11.1%. A shift in the carb factor from 1u/5g to 1u/4g causes each subsequent carb bolus to increase by 25%. For most pump users, a change in carb factor of 5 to 6% causes the average glucose to rise or fall by at least 20 mg/dl after all meals. 1 Example Carb Factor Increments

14. Example Impact On BG From CarbF Adjustment Table shows average additional fall in glucose when a carb factor is reduced from 10 gram/u to 9 gram/u. * Calculated as carbs in meal – carbs in meal X 1900 new carb factor old carb factor TDD ** More carbs = greater glucose fall How A Change In The Carb Factor Changes BG When carb factor is changed from 1u/10g to 1u/9g for someone weighing 160 lb with TDD = 40 u and Corr F = 1u/48 mg/dl > 100 Carbs in mealFall in BG per meal* 60 grams*0.67 u x 48 = – 32 mg/dl* 100 grams**1.1 u x 48 = – 53 mg/dl** * Math: 60g / 9 (6.67 u) – 60g/10 (6.0 u) = 0.67u 0.67u x 48 mg/dl per u = 32 mg/dl fall in BG 1

15. Review Median Carb Factor In unpublished data from the Cozmo Data Analysis Study for 135 pump users in good control* (avg BG = 144.0 mg/dl with 4.92 tests/day): The average carb factor was 10.4 g/u Nearly all use a carb factor below 20 g/u Almost 50% of carb factors are 10.0 g/u or less. The smaller the carb factor, the more vulnerable the pumper is to error when an increment is changed 1 * Authors’ unpublished data from subset of over 1,000 complaint-free insulin pumps turned in for software upgrade in 2007.

16. What Current Changes In CarbFs Do Table shows how subsequent carb boluses are affected by a one-step reduction in the CarbF using different CarbF increments. Yellow area shows values for most current pumps. Green areas show safer increments that impact subsequent boluses less than 5%. 1

17. Correction Factor Increments 2 Corr Factor (CorrF): the number of mg/dl (mmol) drop in glucose that is produced by 1 u of insulin for an individual The smaller the corr. factor, the larger a corr. bolus

18. For similar reasons, correction factor increments shall be 5% or less of the next larger whole number so that each single step adjustment causes subsequent correction boluses to change by no more than 5% from previous doses. Recommended minimum correction factor increments: 5.0 mg/dl per uabove 80 mg/dl per u 2.0 mg/dl per ufor 40 to 78 mg/dl per u 1.0 mg/dl per u for 20 to 39 mg/dl per u 0.5 mg/dl per u for 10 to 19.5 mg/dl per u 0.2 mg/dl per u for 5 to 9.8 mg/dl per u 0.1 mg/dl per u for 3 to 4.9 mg/dl per u 0.05 mg/dl per u for 0.1 to 2.95 mg/dl per u Standard For: Correction Factor Increments 2

19. Carb Factor Accuracy 3 Carb Factors are often not physiologically appropriate

20. Standard For: Verification Of Carb Factor Accuracy 3 1.Insulin pump companies shall record and publish each year the carb factors used in insulin pumps returned for upgrade or repair. This report will include sufficient numbers of pumps to ensure statistical significance for commonly used carb factors between 5 and 20 grams per unit. 2.This data is designed to ensure that pump training and clinical followup are assisting in the selection of accurate carb factors. 3.To improve accuracy of carb factors, efforts shall be taken to better train clinicians and users in appropriate selection of physiologic carb factors.

21. Personal Carb Factors Issue: Many carb factor settings in today’s insulin pumps today are physiologically inappropriate. Inappropriate carb factors introduce a significant source for error in carb bolus calculations. 3

22. Review Carb Factors In Use 1 Carb factor settings from 405 Cozmo pumps do NOT have a bell-shaped (physiologic) distribution. “Easy” numbers – 5, 10, 15, and 20 g/unit – are preferred. 7 10 115 20 1 3

23. Correction Factor Accuracy 4

24. Standard For: Verification Of Corr Factor Accuracy 4 1.Insulin pump companies shall record and publish each year the correction factors used in insulin pumps returned for upgrade or repair. This report will include sufficient numbers of pumps to ensure statistical significance for commonly used correction factors between 20 and 80 mg/dl per unit. 2.This data is designed to ensure that pump training and clinical followup are assisting in the selection of accurate correction factors. 3.For more accurate selection of corr. factors, efforts shall be taken to improve corr. factor selection and to automate corr. factor testing.

25. Personal Correction Factors Issue: Many correction factors used in insulin pumps today are poorly tuned to the user’s need. This inaccuracy significantly magnifies other sources of error in correction bolus calculations. 4

26. Review Correction Factors In Use 1 Avg. correction factors in use for 452 consecutive Cozmo insulin pump downloads Like carb factors, correction factors in use are NOT bell-shaped or physiologic. A more accurate choice of correction factors would create a bell-shaped curve. Users or clinicians appear to frequently select “magic” numbers for correction factors. 7 10 115 20 1 4

27. DIA Default Times 5

28. Standard For: DIA Default Times 1.Default duration of insulin action (DIA) times in current pumps vary between 3 and 6 hours. In bolus calculations, a short DIA time shall be set no shorter than 4.5 hours in pumps that determine DIA in a linear fashion and no shorter than 5 hours in pumps that determine DIA in a curvilinear or multi-linear fashion for fast insulins (lispro, aspart, and glulisine) in use at this time. 5

29. DIA Default Time Settings Issue: DIA measures the glucose-lowering activity of a carb or correction bolus over time. Current default times for DIA range from 3 to 6 hours in different pumps. The DIA is often considered another tool to “improve control” rather than being set at an appropriate value and focusing on more appropriate changes in basal rates or carb and correction factors to improve control. A DIA that is too short allows excess unrecognized bolus insulin to accumulate, usually in the afternoon and evening hours. Example: for a DIA of 2.5 hrs, a bolus given at 9 am appears to have no activity after 11:30 am. If a high BG occurs at 11:45 am, more bolus than needed will be given. At lunch, the bolus will be excessive, regardless of the BG at that time, creating stacking and a high likelihood of hypoglycemia. 5

30. Review How Long Do Boluses Lower The BG?  Numerous GIR studies show rapid insulins lower the glucose for 5 hours or more.  With Novolog (aspart) at 0.2 u/kg (0.091 u/lb), 23% of glucose lowering activity remained after 4 hours. 12  Another study found Novolog (0.2 u/kg) lowered the glucose for 5 hours and 43 min. +/- 1 hour. 13  After 0.3 u/kg or 0.136 u/lb of Humalog (lispro), peak glucose- lowering activity was seen at 2.4 hours and 30% of activity remained after 4 hours. 11 These times would be longer if the unmeasured basal suppression in pharmacodynamic studies were accounted for. 11 From Table 1 in Humalog Mix50/50 product information, PA 6872AMP, Eli Lilly and Company, issued January 15, 2007. 12 Mudaliar S, et al: Insulin aspart (B28 Asp-insulin): a fast-acting analog of human insulin. Diabetes Care 1999; 22:1501-1506. 13 L Heinemann, et al: Time-action profile of the insulin analogue B28Asp. Diabetic Med 1996;13:683-684. 5

31. A short DIA time hides true BOB level and its glucose- lowering activity. This can be a safety issue in that it: Leads to “unexplained” lows Leads to incorrect adjustments in basal rates, carb factors, and correction factors Causes users to start ignoring their “smart” pump’s advice An inappropriately long DIA time overestimates bolus insulin activity – this leads to underdosing rather than overdosing on subsequent boluses. DIA should be based on an insulin’s real action time. Do NOT modify the DIA time to fix a control problem Review Short DIAs Hide Bolus Insulin Activity 5

32. Review Duration Of Insulin Action (DIA) 4 hrs 6 hrs 2 hrs 0 Glucose-lowering Activity Accurate bolus estimates require an accurate DIA. DIA times shorter than 4.5 to 7 hrs may hide BOB and its glucose lowering activity 5

33. Review DIA Large doses (0.3 u/kg = 30 u for 220 lb. person) of “rapid” insulin in 18 non- diabetic, obese people Med. doses (0.2 u/kg = 20 u for 220 lb. person) This shows a glucose lowering activity for 7-8 hours Apidra product handout, Rev. April 2004a Regular 5

34. Review Does Dose Size Affect DIA? This graphic suggests that smaller boluses do not lower the BG as long as larger boluses. However, this may not be true – see next 2 slides. Size of the injected Humalog dose for a 154 lb or 70 kg person: 0.05 u/kg= 3.5 u 0.1 u/kg = 7 u 0.2 u/kg = 14 u 0.3 u/kg = 21 u Woodworth et al. Diabetes. 1993;42(Suppl. 1):54A 5

35. Review Pharmacodynamics Is Not DIA The DIA time entered into an insulin pump is based on studies of insulin pharmacodynamics. However, the traditional method used to determine insulin pharmacodynamics may underestimate insulin’s true duration of action, as shown in the next two slides. 5

36. Review Pharmacodynamics Underestimates DIA And Overestimates Impact Of Bolus Size To measure pharmaco- dynamics, glucose clamp studies are done in healthy individuals who receive an injection of fast insulin (0.05 to 0.3 u/kg) Because there is no basal insulin replacement, the injected insulin dose ALSO SUPPRESSES normal basal release from the pancreas (grey area in figure) 5

37. Review Pharmacodynamic Time Does Not Equal DIA After accounting for the lack of basal insulin replacement, True DIA times become longer than the PD times derived in traditional research If basal suppression activity is accounted for, small boluses may be found to have a longer DIA than it currently appears, erasing some of the apparent variation in DIA related to bolus size Some of the apparent inter- individual variation in pharmacodynamics may also disappear 5

38. DIA Time Increments 6

39. For safe and accurate estimates of residual BOB, DIA time increments shall be no greater than 15 minutes. Standard For: DIA Time Increments 6

40. Issue: Current DIA time increments vary from 15 minutes to 1 hour in different pumps When a pump’s DIA time is adjusted, large time increments, such as 1 hr, can introduce large changes in subsequent estimates of BOB. For example, when the DIA is reduced from 5 hours to 4 hours, subsequent BOB estimates are decreased and recommendations for carb boluses are increased by about 25%. 6 DIA Time Increments

41. Most GIR studies suggest that pharmacodynamic action of insulin varies only about 25% to 40% between individuals. For a DIA time of 5 hr and 15 min, a 25% range is equivalent to 1 hr and 20 min, such as from 4 hrs and 30 min to 5hr and 50 min. A pump that has 1 hr DIA increments would enable the user to select only 1 or 2 settings within this physiologic range, while a 30 min increment would allow only 2 or 3 choices that are close to a physiologic range. 6 Review Glucose Infusion Rate (GIR) Studies

42. Handling Of BOB Bolus On Board (BOB) 7 aka: insulin on board, active insulin, unused insulin* * Introduced as Unused Insulin in 1st ed of Pumping Insulin (1989)

43. Standard For: Handling Of BOB For safe and accurate BOB measurement: BOB measurements shall include all carb and correction boluses given within the selected DIA When residual BOB is present at the time of a bolus, the BOB shall be subtracted from both carb and correction bolus recommendations. When BOB exceeds the current correction bolus need or the current carb plus correction need, the user will be alerted to how many grams of carb they need to eat to avert a low. [(BOB – correction & carb bolus need) X carb factor] 7

44. Issue: Current pumps differ significantly in what is counted as BOB and in whether or not BOB is subtracted from subsequent carb boluses. Most insulin pumps assume that excess BOB does not need to be taken into account when determining the next carb bolus. Though commonly determined in this way, the resulting bolus dose recommendations can cause unexplained and unnecessary insulin stacking and hypoglycemia. Handling Of BOB 7

45. Example Insulin Stacking With a bedtime BG of 173 mg/dl, is there an insulin deficit or a carb deficit? 6 pm8 pm10 pm12 am Dinner Dessert Correction Bedtime BG = 173 mg/dl 7

46. Review Frequency Of Insulin Stacking CDA1 Study Results Of 201,538 boluses, 64.8% were given within 4.5 hrs of a previous bolus Although 4.5 hours may underestimate true DIA, use of this minimal DIA time shows that some BOB is present for MOST boluses 4.5 hrs 7

47. Review Bolus On Board (BOB) An accurate measurement of the glucose-lowering activity that remains from recent boluses: Prevents insulin stacking Improves bolus accuracy Allows the current carb or insulin deficit to be determined 7

48. Review How Current Pumps Handle BOB What’s In the BOB & What Is It Applied Against? BOB Includes This Type Of Bolus BOB Is Subtracted From This Type Of Bolus CarbCorrectionCarbCorrection Animas 2020Yes No*Yes Deltec CozmoYes Insulet OmnipodNoYesNoYes Medtronic ParadigmYes No Yes * Except when BG is below target BG *A “Yes” response is generally considered safer 7

49. Example Unsafe BOB 1 Handling If a pump user gets frustrated with a high BG and they overdose to speed its fall, or they exercise longer or more intensely than anticipated, they can acquire a significant excess in BOB. In these situations, most current pumps recommend that a bolus be given for all carb intake regardless of how much BOB is actually present. When the BOB is larger than the correction bolus required at the time, the pump’s bolus recommendation introduces an unnecessary risk of hypoglycemia. 1 Pumping Insulin, 1st ed, 1989, Chap 12, pgs 70-73: The Unused Insulin Rule 7

50. Example Differences In Bolus Recommendations Situation: BOB = 3.0 u and 30 gr. of carb will be eaten at these glucose levels Carb factor = 1u / 10 gr Corr. Factor = 1 u / 40 mg/dl over 100 Target BG = 100 TDD = ~50 u units mg/dl Omnipod bolus cannot be determined - it counts only correction bolus insulin as BOB The graphic shows how widely bolus recommendations vary from one pump to another for the same situation. 7

51. Review Track BOB Or Carb Digestion? For safety after a bolus, it is more important to account for the glucose- lowering action of BOB than the glucose-raising action of digesting meal carbs: When a BG is taken after a meal, the BOB times the correction factor ideally represents the maximum anticipated fall in glucose. Accounting for the impact of the BOB on the current glucose provides the safest approach in the determination of bolus recommendations. Low glycemic index meals, gastroparesis, Symlin, and other issues may counteract a predicted fall in glucose based on BOB, but the user can more easily judge and remedy this situation than dealing with an unknown excess of insulin. 7

52. Exceptions To Usual Handling Of BOB When a second bolus is taken for an unplanned carb intake or a desert that is consumed within 60 minutes* or so of a meal bolus, BOB should not be taken into account for the second bolus because the impact of the first bolus cannot be accurately determined. Given that, it is wise to account for BOB as soon after a meal as possible, such as within 60 to 90 minutes,* to provide early warning if the bolus given was excessive or inadequate. Accounting for all BOB and applying it to subsequent boluses is generally safer, although not always more accurate. 7 * Adjustable setting in pump/controller

53. Multi-Linear And Curvilinear DIA 8

54. Standard For: Multi-Linear And Curvilinear DIA Insulin pumps shall use either a 100% curvilinear or a multi-linear method to improve accuracy and consistency of BOB estimates. 8

55. Review Linear And Curvilinear DIA Issue: Pump manufacturers use at least 3 different methods (100% curvilinear, 95% of curvilinear, and straight linear) to measure DIA and BOB. When a realistic DIA time is selected, a linear determination of residual BOB will not be as accurate as a curvilinear method that incorporates the slow onset of insulin action and its longer tailing off in activity. In most situations, an accurate determination of insulin’s tailing activity will be most important to the pump user. 8

56. Linear And Curvilinear DIA Compared Note how values for the 5 hr linear line in red and the thinner 5 hr curvilinear line diverge in value at several points along the graph. 5 hr Linear 5 hr 95% Curvilinear From Pumping Insulin, 4th ed., adapted fom Mudaliar et al: Diabetes Care, 22: 1501, 1999 8

57. Example A Multi-Linear DIA Use of a multi-linear method to measure DIA improves accuracy. The next page shows a triple-linear example for measurement of BOB. 8

58. Example A Triple-Linear Approximation Of DIA A triple-linear line in red can more closely approximate a curvilinear DIA. For a 5 hr DIA*: 1st 10%** – no change Mid 65%** – fall 75%** Last 25%** – fall 25%** (** adjustable as needed in device) 5 hr Triple Linear 8 * % modification suggested by Gary Scheiner, MS, CDE

59. Hypoglycemia Analysis And Alert 9

60. Standards For: Hypoglycemia Analysis And Alert 1.Insulin pumps that store BG and insulin dosing data can present this BG control data in a readily accessible form on the pump or controller. 2.The pump shall alert the user when the BG data from their glucose meter or continuous monitor suggests they are experiencing frequent* or severe* patterns of hypoglycemia, based on preselected, adjustable criteria. 9 * Adjustable settings in pump/controller

61. Frequent/Severe Hypoglycemia Alert Issue: Although most current insulin pumps contain sufficient data to determine when the user is experiencing patterns of frequent or severe hypoglycemia, pumps give no warning of this to the user. 9

62. Example Pump Screen Hypoglycemia Display 1 9 * Adjustable settings in pump/controller Weekly History – Low BGs # of weeks1248 # BGs/week23252832 % BGs/week < 50 mg/dl* 22%18%11%8% % BGs/week < 70 mg/dl* 35%27%19%16% To improve statistics for a better understanding of the severity and frequency of low glucose events over time (weeks), the pump can provide a screen such as the following: * Modified to % display per Gary Scheiner, MS, CDE

63. Example Pump Screen Hypoglycemia Display 2 9 * Adjustable settings in pump/controller Low BGs By Time Of Day For 1 Week* Avg BGs for 1 week23 (3.3/day) Time Period4a-10a10a-4p4a-10p10p-4a % BGs < 50 mg/dl*57%14%0% % BGs/week < 70 mg/dl*71%28%0%14% * Modified to % display per Gary Scheiner, MS, CDE The daily timing for severity and frequency of hypoglycemia can be shown in a screen such as the following:

64. Solution: Depending on the settings selected by the user and clinician, an alert would sound when a pattern of more than one* hypoglycemia event exceeds their threshold for frequency* or severity* of hypoglycemia. In addition, typical ways to resolve the pattern of hypoglycemia will be presented. Frequent/Severe Hypoglycemia Alert 9 * Adjustable settings in pump/controller

65. Hyperglycemia Analysis And Alert 10

66. Standards For: Hyperglycemia Analysis And Alert 1.Insulin pumps that store BG and insulin dosing data can present this BG control data in a readily accessible form on the pump or controller. 2.The pump shall alert the user when the BG data from their glucose meter or continuous monitor suggests they are experiencing frequent* or severe* patterns of hyperglycemia, based on preselected, adjustable criteria. 10 * Adjustable settings in pump/controller

67. Frequent/Severe Hyperglycemia Issue: Although most current insulin pumps contain sufficient data to determine when the user is experiencing patterns of frequent or severe hyperglycemia, pumps give no warning of this to the user. 10

68. Example Pump Screen Hyperglycemia Display 1 10 * Adjustable settings in pump/controller Weekly History – High BGs # of weeks1248 Avg BGs/week23252832 % BGs/week > 180 mg/dl* 26%30%29%26% % BGs/week >220 mg/dl* 17%18%22%23% To improve statistics for a better understanding of the severity and frequency of high glucose events over time (weeks), the pump can provide a screen such as the following: * Modified to % display per Gary Scheiner, MS, CDE

69. Example Pump Screen Hyperglycemia Display 2 10 * Adjustable settings in pump/controller Low BGs By Time Of Day For 4 Weeks* # BGs for 4 weeks112 (4.0/day) Time Period4a-10a10a-4p4a-10p10p-4a % BGs > 180 mg/dl*1%3%4%21% % BGs/week > 220 mg/dl*0%2%3%18% * Modified to % display per Gary Scheiner, MS, CDE The daily timing for severity and frequency of hyperglycemia can be shown in a screen such as the following:

70. Solution: Depending on the settings selected by the user and clinician, an alert would sound when a pattern of more than one hyperglycemia events exceeds their threshold for frequency* or severity*. In addition, typical ways to resolve the pattern of hyperglycemia will be presented. Frequent/Severe Hyperglycemia Alert 10 * Adjustable settings in pump/controller

71. Correction Bolus Alert 11

72. Standard For: Correction Bolus Alert 1.Insulin pumps shall show in a readily accessible history screen the percentage of the TDD that is used for correction boluses over time, and alarm based on preselected, adjustable criteria. 2.For instance, the insulin pump shall alert the wearer when they use more than 8%* of their TDD for correction bolus doses over the most recent 4 day* period. 11 * Adjustable settings in pump/controller

73. Correction Bolus Alert Issue: Hyperglycemia is more common than hypoglycemia for most people on insulin pumps. When glucose levels consistently run high, many pump users address the problem by giving frequent correction boluses rather than correcting the core problem through an increase in their basal rates or carb boluses. If the correction bolus % becomes excessive relative to the TDD, the pump user is made aware of their excess use of correction boluses. 11

74. Insulin Stacking Alert Accurate accounting of the BOB is important to those who bolus frequently, those who experience frequent or severe hypoglycemia, and those whose average glucose levels are closer to normal values. 12

75. Standard For: Insulin Stacking Alert Insulin pumps shall alert the user when he/she gives a bolus and no glucose value has been entered in the pump, but there is sufficient insulin stacking* to significantly alter the bolus they would otherwise give. The alert is on by default once a DIA time is selected to measure BOB, but may be turned off if the user desires. * Such as when the BOB is greater than 1.25%** of the avg. TDD, sufficient to change the glucose about 25 mg/dl. (** Adjustable setting in pump/controller for a certain fall in glucose selected by the user or clinician) 12

76. Insulin Stacking Alert Issue: Pump users often bolus for carbs without checking their glucose first. With no glucose reading, the pump cannot account for BOB, nor appropriately adjust a recommended bolus for the BOB or the current BG. Even though no BG test is done, data available in the pump when the bolus is given can inform the user when there is sufficient BOB to substantially change their bolus dose. The pump can alert the user to this unseen, substantial insulin stacking. 12

77. When a carb bolus is planned without a recent BG check, but BOB is more than 1.25%* of the average TDD (enough to cause about a 25 mg/dl drop in the glucose), the pump will recommend that the wearer do a BG check due to the substantial presence of BOB. For instance, for someone with: Avg TDD1.25%* of TDD 40 units 0.5 units 50 mg/dl per u (corr factor) X 0.5 u = 25 mg/dl This individual would be alerted when they do not check their glucose and want to give a bolus but have 0.5 u or more of BOB present. Example Insulin Stacking or BOB Alert * Adjustable in pump/controller for a reasonable degree of safety 12

78. Automatic Entry Of BG Values 13

79. Standard For: Automatic Entry Of BG Values For completion of the BG history, improved handling of BOB, and more accurate bolus recommendations, insulin pumps shall be enabled to have wireless or direct entry of BG test results from a glucose meter. Automatic glucose entry from two or more major brands of meters is recommended to increase the likelihood of insurance coverage for test strips. 13

80. Automatic Entry Of BG Values Issue: Pump users do not enter as many BG values into their pump when readings must be entered manually rather than automatically entered from a meter. When a BG is checked but not entered, the lost data cannot be used to account for BOB, warn of insulin stacking (see #12), and are not as accurate when attampting to analyze glucose patterns or the frequency of hypoglycemia and hyperglycemia. Relatively normal and hypoglycemia values are less likely to be entered manually, but are more likely to be influenced by BOB. 13

81. Review Automatic Entry Of BG Values In a study of over 500 insulin pumps where BG values could be entered either manually or automatically, users entered 2.6 BG values per day manually, compared to 4.1 values per day for pumps in which glucose values wre automatically entered. * BOB could typically be taken into account for 1.5 additional boluses per day with automatic entry of BG values. When glucose values are not automatically entered, BOB cannot be determined and bolus recommendations will not be as accurate. 13 * J. Walsh, D. Wroblewski, T.S. Bailey: unpublished data

82. Review Automatic Entry Of BG Values Automatic entry of glucose values into pumps offers a significant clinical advantage to users and clinicians because more boluses will be adjusted for high and low BGs, and residual BOB is more likely to taken into accout in bolus calculations. Automatic entry of glucose values (along with accurate accounting of BOB, see #7) ensures a greater degree of safety for those who experience frequent or sever hypoglycemia, and those whose glucose values are closer to normal. 13

83. Infusion Set Monitoring 14

84. Standards For: Infusion Sets 1.Insulin pumps shall monitor and record in easily accessible history the duration of infusion set usage recorded as mean, median, and SD of time of use. 2.Insulin pumps shall monitor and report average glucose values over 6 or 12 hour* time intervals between set changes with the ability to change the observation interval, such as the last 1 to 30 set changes*. 3.This monitor allows HCPs and users to identify infusion set problems through loss of glucose control related to length of set use and variations in length of infusion set use. 14 * Adjustable setting in pump/controller

85. Infusion Sets Issue: A significant number of pump wearers encounter partial or complete infusion set failure. Failure may arise from poor infusion set design or poor site preparation. Which users are encountering infusion set problems, how often infusion sets may be responsible for erratic glucose readings, and how significantly infusion set problems impact glucose control are currently difficult for users and clinicians to identify. 14

86. Review Infusion Set Failure Infusion set failure can arise due to occlusions or from a Teflon infusion set coming loose beneath the skin due to movement or tugging. When loosened, some of the infused insulin can leak back to the skin surface and result in unexplained high readings. A complete loss of glucose control can also occur when an infusion set is pulled out entirely. Selecting the right infusion set plus good site technique, especially taping the infusion line to the skin, can significantly minimize unexplained high readings for many pump wearers. 14

87. Why Tubing Needs To Be Taped Many problems with infusion sets come from loosening of the Teflon under the skin, not from a complete pullout. A 1” tape placed on the infusion line: Stops tugging on the Teflon catheter under the skin Prevents loosening of the Teflon catheter under the skin Avoids many “unexplained highs” caused when insulin leaks back to the skin surface Reduces skin irritation And prevents many pull outs 14

88. Tape The Tubing This helps prevent Tugging Irritation Bleeding 14

89. No tape! 14 Examples Lack Of Anchoring Of Sets A review of dozens of pictures of infusion sets online and pump manuals finds that anchoring of the infusion line with tape is rarely recommended or practiced.

90. Review Infusion Set Monitor Many pump wearers experience random erratic readings until they change to a different infusion set or start to anchor their infusion lines with tape to stop line tugging. However, insulin pumps offer no mechanism for clinicians or pump users to detect who may be having problems with their infusion sets. 14

91. Tool Infusion Set Monitor Insulin pumps with direct BG entry can identify those who may be having intermittent loss of glucose control secondary to infusion set failure. The pump: Shows the average time and variation in time of use between reservoir loads or use of the priming function. Shows average BGs for each full or partial 12 or 24* hour time interval following set changes (indicated by the prime function) over a various number of set changes* or as soon as statistical significance is reached. 14 * Adjustable setting in pump/controller