1. Healthcare Across Borders - September 2003 Advanced Pumping Concepts John Walsh, P.A., C.D.E. North County Endocrine 700 West El Norte Pkwy Escondido, CA 92126 (760) 743-1431 The Diabetes Mall www diabetesnet.com (619) 497-0900 jwalsh@diabetesnet.com Present/Future Pump & Con Mon Technologies CWD Friends For Life Orlando, Fl, July 21, 2006

2. Healthcare Across Borders - September 2003 Highlights Why we seek better control Where we are today Two Current Concerns Three New Answers Helpful Things To Look At In Your Pump Settings New Technology – Con Mons Future pump features Future devices Wrap up

3. Healthcare Across Borders - September 2003 Why We Seek Better Control

4. Healthcare Across Borders - September 2003 Lessons: DCCT Better Control Reduces Eye And Kidney Damage 55.0 29.8 23.9 5.1 13.4 13.0 7.9 16.4 5.0 2.5 0 10 20 30 40 50 60 Retinopathy Progression 1 Laser Rx 1 Micro- albuminuria 2 Albuminuria 2 Clinical Neuropathy 3 Conventional Intensive 76% Risk Reduction 59% 39% 54% 64% Cumulative Incidence (%) 1.DCCT Research Group, Ophthalmology. 1995;102:647-661 2.DCCT Research Group, Kidney Int. 1995;47:1703-1720 3.DCCT Research Group. Ann Intern Med. 1995;122:561-568.

5. Healthcare Across Borders - September 2003 Lessons: EDIC Better Control Reduces Heart And Nerve Damage Since ending the DCCT in 1993, the EDIC study has followed participants. In this 12 years, A1c levels in the intensive and conventional control groups have been identical at 7.9% (was 7.4% and 9.1%). Since 1993, 98 heart attacks and strokes occurred in conventional control participants, but only 46 in the intensive group. This 53% reduction occurred even though A1c levels were the same since the DCCT ended 11 years earlier. Those who had begun with tight blood sugar control and stuck with it were also 51% less likely to report symptoms of neuropathy, and 43% less likely to show signs of it, compared to those who had started out with conventional control and then went to tight control. Take Home: Start good control ASAP. 1. EDIC Study Group presentation at 2005 ADA, K.M. Venkat Narayan: Clinical Diabetes 24:88-89, 2006 2. Diabetes Care, Vol 29, No. 2, pp. 340-344

6. Healthcare Across Borders - September 2003 Where We Are Today

7. Healthcare Across Borders - September 2003 Little Change In A1c Since The DCCT 8.6% in 396 Canadian Type 1s in 1992 1 9.7% in 1,120 German children in 1996 2 9.7% in in U.S. in NHANES III, 1988 to 1994 8.6% in 2,873 European kids & adolescents, 1997 3 9.2% in 62 Canadian Type 1s in 2004 7.9% in EDIC trial (followup to DCCT) 1. Diabetes Care. 1997 May;20(5):714-20 2. Horm Res 1998;50:107–140 3. HB Mortensen et al: Diabetes Care. 1997 May;20(5):714-20 A1c GOAL < 6.5% to 7%

8. Healthcare Across Borders - September 2003 Today’s Control – A1c Level HbA 1c 10% 9% 8% 7% 6% ADA EASD/AACE ADA = American Diabetes Assoc., IDF = Inter. Diabetes Federation, EASD is European Assoc. for the Study of Diabetes, AACE is American Association of Clinical Endocrinologists From Novo Nordisk Type 2 diabetes market research, Roper Starch, ADA, EASD, IDF, AACE, Wright A., Burden et al, Diabetes Care 2002; 25:330–336, Turner RC, Cull et al, JAMA 1999; 281:2005–2012 2/3 with diabetes are out of control A1c in TYPE 1 A1c on Pumps Goal A1c 5%

9. Healthcare Across Borders - September 2003 Targets Keep Getting Lower The European Diabetes Policy Group recommends that after meal glucoses not exceed: 135 mg/dl (7.5 mmol) to reduce arterial risk 165 mg/dl (8.9 mmol) to reduce microvascular risk 1 High blood sugars damage arterial walls through: Oxidative stress Harmful changes to endothelial cells that line blood vessels Increased clotting Structural changes to cholesterol from glycosylation E Bonora: Int J Clin Pract Suppl 129: 5-11, 2002

10. Healthcare Across Borders - September 2003 Two Current Concerns – Glucose Exposure or high blood sugars Measured by A1c or average glucose on meter Glucose Variability or up and down blood sugars Measured by standard deviation

11. Healthcare Across Borders - September 2003 Exposure And Variability The DCCT proved that exposure to high blood glucose was damaging. New emphasis is on glucose variability. Exposure or Average = Variability or Swing = A1c or avg. BG from meter SD from PC or meter 24 hrs

12. Healthcare Across Borders - September 2003 Exposure And Variability Are Different Glucose variability (SD) and A1c in two individuals: Top: A1c = 6.6% SD = 20 mg/dl (1.1 mmol) Bottom:A1c = 6.7% SD = 61 mg/dl (3.4 mmol) R. Derr et al: Diabetes Care, 26: 2728-33, 2003

13. Healthcare Across Borders - September 2003 Classic Pumps & MDI Better At Same A1c The DCCT conventional group (top) was 22 times more likely to have retinopathy worsen at A1c of 9%. The intensive group at the same A1c was only 8 times as likely to have retinopathy worsen. This reduced risk may result from less glucose variability with pumps and MDI. Irl Hirsch: Amer J Med 118 (5A): 21S-26S, 2005 1-2 Injections/Day Classic Pumps and MDI

14. Healthcare Across Borders - September 2003 Less Exposure & Variability On Classic Pumps Pumps and MDI compared: Significantly less time was spent in hypo and hyperglycemia by 23 children on pumps in random crossover study. 1 Lower A1c and less nocturnal hypoglycemia in 53 children (10.7 =/-3.7 yrs) in pre-post study. 2 Lower A1c (7.7 to 7.2) and less serious hypoglycemia (1.23 to 0.29 cases/patient/year) in 103 Type 1s (33 =/-11 yrs) in pre-post study. 3 Lower BGs (175 to 165 mg/dl), lower BG SD (82 to 73 mg/dl), and less insulin (47.3 to 38.5 u/day) in 41 Type 1s (43.5 =/-10.3 yrs) in 4 month random crossover study. 4 Lower A1c (9.5 to 8.8%), less hypoglycemia (< 3.3 mmol, 6.5 to 3.3 events/patient/30 days), and less insulin (1.03 to 0.74 u/kd/day). 5 Fewer lows, lower A1cs, less glucose variability, less insulin 1.N. Weintraub et al: Arch Pediatr Adolesc Med. 158: 677-684, 2004 2.SM Willi et al: J Pediatr 143: 796-801, 2003 3.R Linkeschova et al: Diabet Med 19: 746-751, 2002 4.H Hanaire-Broutin et al: Diabetes Care 23: 1232-1235, 2000 5.N Sulli and B Shashaj: J Ped Endocrinol Metab 16: 393-399, 2003

15. Healthcare Across Borders - September 2003 Three New Answers – Symlin Less glucose variability Smart Pumps More accurate doses Con Mons Less glucose exposure

16. Healthcare Across Borders - September 2003 Symlin Amylin – a hormone that is secreted with insulin by beta cells is also lost in Type 1 diabetes Helps slow food digestion Reduces release of glucagon after meals Reduces spiking of glucose after meals May lessen appetite at higher doses and help weight loss May cause severe hypoglycemia when restarted – lower insulin doses are required at this time Like insulin, dose requirements differ between people! Slows all carbs – be patient when treating lows! Not yet approved for those less than 18 yo

17. Healthcare Across Borders - September 2003 Toward The Closed Loop InsulinInsulin MonitoringMonitoring HCPSelf ManagementAutomation 1922 Insulin & syringes 1979 Pumps 1983 Pens Connectivity 1926 Clinic Monitoring 1971 Home Monitors Data Management Advice/Feedback DeliveryDelivery Closed Loop We are here Adapted courtesy Roche/Disetronic 2006 Continuous Monitors Most work in this phase 2002 Smart Pumps

18. Healthcare Across Borders - September 2003 Smart Pumps Reduce Exposure & Variability Even More Frequent testing Frequent boluses Most dependable insulin action Accurate carb counting Easy bolus calculations Accessible history Basal adjusted to precise need Boluses adjusted to carbs & BG Less insulin stacking Reminders prevent skipped doses Bolus tipping avoids overcorrection of lows When SET UP and USED CORRECTLY!

19. Healthcare Across Borders - September 2003 How Smart Pumps And Con Mons Help H igh A1c levels demonstrate that BG control is complicated Important decisions that affect control need to be made several times a day. Intelligent devices can help make decisions and ease the care burden faced by consumers and health care providers. Glucose trends from a con mon plus a pump’s history of actual insulin use helps decisions in situations that are often complex Quicker corrections can be made by identifying trends & patterns Glucose results from a con mon every 1-5 mins. Automatic basal and bolus testing is possible Rapid communication improves problem solving

20. Healthcare Across Borders - September 2003 Continuous Monitors Reduce Glucose Variability 15 users with implanted Dexcom continuous monitors blind to glucose readout for the first 50 days, then open readout for the next 44 days. hrs/day blood sugar - 65 min + 32 min + 250 min -13 min -160 min

21. Healthcare Across Borders - September 2003 Helpful Things To Look At In Your Pump Settings The right basal and bolus settings for you will greatly improve control!

22. Healthcare Across Borders - September 2003 Stop Lows First Many lows may be treated with no meter test (NO RECORD!) Release of stress hormones worsens control Often results in over treatment or skipping of boluses Prevention improves the accuracy of other dose decisions * When a low is overtreated, “count the wrappers” and bolus right away for any excess carbs

23. Healthcare Across Borders - September 2003 Important Pump Settings Time and date Basal rates Carb factor Correction factor Blood sugar target or range Duration of insulin action

24. Healthcare Across Borders - September 2003 Smart Pumps Features Basal Options Carb Factor Correction Factor Target(s) Duration of Insulin Action Bolus on Board Direct Meter Entry Reminders and Alerts History of insulin use: TDD Basal/Bolus Balance Correction Bolus %

25. Healthcare Across Borders - September 2003 The Target Blood Glucose What blood glucose to aim for – NOT the same as a control range Single target = 120 Suggested bolus adds insulin for glucoses above target (120) and subtracts for glucoses below Target range = 100 - 140 Suggested bolus adds insulin for glucoses above upper number and subtracts for glucoses below lower number Less is added for highs, but LESS IS SUBTRACTED for lows If using a target range, make the lower value no lower than the number you would select for a single target!

26. Healthcare Across Borders - September 2003 Pump Info That Helps Improve Control Check These Regularly On Pump’s Analysis Screens Avg # of carbs per day (adequate carbs being covered?) Avg. total daily dose (TDD) Avg % of TDD for correction boluses Avg % of TDD for carb boluses Avg % of TDD for basal Avg # of BG tests Avg BG value BG standard deviation Avg. of 7 to 30 days’ results are needed for accuracy

27. Healthcare Across Borders - September 2003 TDD – The Kingpin For Control An accurate TDD is the most important thing for good control. When a major control problem exists, check the TDD (also your infusion site) first: 1.What is the average TDD? 2.How steady is it? 3.Change the TDD when A recent A1c is high There are frequent highs (or a high avg. BG on meter) There are frequent lows Or there are both highs and lows (which comes first?) 4.Adjust by 5% to 10% (usually) Too much? Too little?

28. Healthcare Across Borders - September 2003 Use A Recent A1c To Adjust TDD Sample: someone with a TDD of 35 units and an A1c of 9% with few lows can add about 3.2 units to their TDD © Pumping Insulin, 2006

29. Healthcare Across Borders - September 2003 Basal Rate(s) The First Half of Control About half of your control and half of your TDD (even MORE in kids who need to eat a lot!) Use temporary basals For sports, illness, etc For basal testing For basal-bolus shifting Use alternate basal profiles For weekends, menses, etc. For basal testing to preserve original profile

30. Healthcare Across Borders - September 2003 Basal Tips 1.50% Rule: basals make up 40-65% of TDD 2.Start with 50% of an accurate TDD as basal 3.Basal rates will be similar through the day, such as between 0.45 and 0.7, or between 1.0 and 1.4 4.Adjust basal rate in small steps – 0.05 to 0.1 u/hr, unless a major change is required for illness, etc 5.Make change 4 to 8 hours before need arises

31. Healthcare Across Borders - September 2003 Basal/Bolus Balance Usual balance = ~50% basal and ~50% bolus Periodically check basal/bolus balance to see how insulin is being used! < 50% Basal~ 50% Basal> 50% Basal Duration < 5 yrs Thin Physically active High carb/low fat diet Most peopleDuration > 5 yrs Puberty Less active Insulin resistant Low carb diet Teens with hormones

32. Healthcare Across Borders - September 2003 Carb Factor The Second Half of Control # of grams of carb covered by one unit of insulin Success carb boluses requires Accurate carb counting (or a built-in carb database) Accurate carb factor Accounting for BOB from previous boluses Accurate duration of insulin action

33. Healthcare Across Borders - September 2003 Pump As Carb Counter Pump has user-selected food list for accurate carb counting Easy carb calculation improves bolus accuracy Available now in Animas 1250 (#500) and Deltec Cozmo (#150 to 200) pumps

34. Healthcare Across Borders - September 2003 Bolus Timing – Carbs Are Faster Than Insulin Take Home: Bolus 15 to 30 minutes before meals when possible and use extended and square wave boluses sparingly Insulin action Blood sugar after typical meal 4 hrs At 1 hr, 85% of rapid insulin activity remains while over half of the glucose rise from a typical meal has already occurred 6 hrs 2 hrs 0

35. Healthcare Across Borders - September 2003 Bolus Timing Research An infusion of rapid insulin starting just before a meal, or 30 or 60 minutes before a meal Note how different glucose and insulin levels (shown by the shading) are in people without diabetes.

36. Healthcare Across Borders - September 2003 Bolus Timing Premeal Blood Sugar Bolus Timing Low Use fast carbs, check BOB, and give carb bolus at start of meal with current BG NormalIf possible, bolus 15 to 20 minutes before meal High Give carb plus correction boluses earlier Check your blood sugar 2 hours later to verify the dose

37. Healthcare Across Borders - September 2003 Correction Factor How many mg/dl (mmol) the blood glucose falls per unit of insulin Success requires Accurate blood glucose Accurate correction factor Accounting for BOB from previous boluses Accurate target Accurate duration of insulin action Check periodically – keep correction boluses less than 8% of TDD

38. Healthcare Across Borders - September 2003 The Correction Bolus % Gives Insight When Doses Need To Increase  Check the correction bolus % at least once a month  Move any excess over 8% to basal rates or carb boluses  When an average of the correction boluses makes up more than 8% of the TDD, move the excess into basals or carb boluses whichever is smaller or into both if basals and carb boluses are balanced  Easy to do on pumps or software that separate carb and correction boluses

39. Healthcare Across Borders - September 2003 Check TDD And Correction Bolus % Goal: 8% or less of TDD or ~16% of bolus insulin in Paradigm This pumper’s correction boluses are 21% or well above 8% of TDD. Move 1/3 to 1/2 of the overage to basals or carb boluses 8% of 54.09 = 4.33 11.34 - 4.33 = 7 units 1/3 to 1/2 of 7 units = add 2.3 to 3.5 units to basals or carb Insulin Summary 36% of TDD 21% of TDD 43% of TDD TDD 10 day average: Meal 19.41 u Corr 11.34 u Basal 23.34 u Total 54.09 u Carb 175 g

40. Healthcare Across Borders - September 2003 Duration Of Insulin Action How long a bolus will lower the blood sugar & Bolus On Board (BOB) How much glucose-lowering potential remains from recent boluses aka: insulin on board, active insulin, unused insulin

41. Healthcare Across Borders - September 2003 Duration Of Insulin Action

42. Healthcare Across Borders - September 2003 DIAs Are Calculated Differently In Different Pumps General recommendations: For a curvilinear DIA (Animas 1250 & Paradigm 5/715 & 5/722) use 4 to 6 hours For a linear DIA (Deltec Cozmo & Insulet Omnipod) use 3.5 to 5:15 hrs If you use large boluses (>12-20 u at a time) use a longer DIA

43. Healthcare Across Borders - September 2003 How Long Will A Bolus Lower The Blood Sugar? Adapted fom Mudaliar et al: Diabetes Care, 22: 1501, 1999 4 hrs The duration of insulin action (DIA) in current pumps can be set from 2 to 8 hours. This time range is far wider than actual insulin action. An accurate DIA can significantly affect control.

44. Healthcare Across Borders - September 2003 Test The Duration Of Insulin Action 0 hrs 100 (5.6) 200 (11) 400 (22) 300 (17) Bolus too large DIA & bolus just right DIA too short 2 hrs1 hr3 hrs4 hrs When DIA is correct, a correction bolus returns high BG to normal  by the end of the selected DIA  without a low BG in next 2 hours! Correction bolus given Selected duration of insulin action © Pumping Insulin, 2006 Automatic in Future Pumps

45. Healthcare Across Borders - September 2003 Bolus On Board Prevents lows caused by stacking of bolus insulin Greatly improves bolus accuracy Acts as guide to whether there is a current carb or insulin deficit (such as a carb deficit when a BG is 130 mg/dl but there are 5 u of BOB left Requires a blood sugar test to evaluate the effect of any recent bolus and an accurate duration of insulin action. No BG test, no BOB determination!

46. Healthcare Across Borders - September 2003 Use BOB To Prevent Insulin Stacking Insulin stacking occurs when several boluses are given, such as during the evening below. How much BOB remains when the bedtime BG is 163? Is there an insulin deficit or a carb deficit at this time? 6 pm8 pm10 pm12 am Dinner Dessert Correction Bedtime BG = 163 mg/dl Insulin stacking is common in adults and especially in children who need frequent boluses!

47. Healthcare Across Borders - September 2003 All Pumps Subtract BOB From Correction Boluses Excess BOB is subtracted from correction boluses 4.0U 45 gr 160 3.0U 2.0U 1.0U (3+2) - 1 = 4 u

48. Healthcare Across Borders - September 2003 Paradigm & Omnipod Do Not Subtract BOB From Carb Boluses 3.0U 45 gr 160 3.0U 2.0U 5.0U 5 - (3+2) = 0 u This may make a bolus estimate too large

49. Healthcare Across Borders - September 2003 Reminders And Alerts Test after a bolus Test after a low reading Test after a high reading Give a bolus at certain time Warn if bolus was not given at a certain time of the day Warn when bolus delivery was not completed, etc. Change infusion site Warn of low reservoir (20, 10, 5 and 0 units and in one pump an extra 10 “hidden” units to use in basal delivery)

50. Healthcare Across Borders - September 2003 Many Features Go Unused In Today’s Smart Pumps Underused features that can help control: Entry of blood sugars Carb counting or use of a carb database Alternate and temporary basals Tracking of BOB Use of DIA Review of history and pump use Reminders and alerts Poor design or poor training ?

51. Healthcare Across Borders - September 2003 Wearable Pumps Lower startup cost No infusion line Cannot detach Helpful for those who desire a hidden pump or no infusion line Comparison: Omnipod200 u2.4 x 1.6 x 0.71.1 oz Animas 200 u2.9 x 2.0 x 0.753.1 oz

52. Healthcare Across Borders - September 2003 New Technology – Con Mons Going from fingersticks to a Con Mon is like going from urine to blood testing (SMBG) in the early 80's.

53. Healthcare Across Borders - September 2003 Pumps With Meters Or Con Mons Enters glucose values directly into pump to eliminate transfer errors and assist data collection Deltec Cozmo + Abbott CoZmonitor Omnipod + Abbott Freestyle Medtronic Paradigm RT 522/722 Soon: Abbott Navigator + Abbott Aviator or Deltec Cozmo or Omnipod, Animas + Lifescan, AccuChek Spirit & meter and Sooil pump and meter

54. Healthcare Across Borders - September 2003 The Value of Frequent Testing Breakfast 100 (5.6) 200 (11) 400 (22) 300 (17) DinnerLunchBed 7 opportunities to intervene versus 1!

55. Healthcare Across Borders - September 2003 Continuous Monitoring Features Alarms to prevent lows & highs Great security in knowing where you are Trends shown by graph, arrows, or predictors Trends more important than readings Limitations Cost, little ins. coverage Inaccuracy: +/- 40 or more mg/dl – confirm with a fingerstick Data gaps Needs calibration “3-day” Takes more power – recharging or a shorter battery life

56. Healthcare Across Borders - September 2003 Basal/Bolus Testing With Con Mon 10 pm 2 am 8 am 120 6 pm 8 pm 10 pm 300 200 100 60 6 pm 8 pm 10 pm 300 200 100 60 Basal test Carb bolus test Correction bolus test Basal and bolus testing is much easier with a continuous monitor. © Pumping Insulin, 2006

57. Healthcare Across Borders - September 2003 Sample CGMS Reports Daily Blood Glucose Reports Above: overtreatment of lows, postmeal spikes, excess correction boluses and excess TDD Commonly uncovered problems: spiking after meals and frequent night lows

58. Healthcare Across Borders - September 2003 Dexcom STS Monitor FDA release with availability 3/27/06 Approved for 18 and older One high and two low alerts Readings every 5 min. over 3-7 days $500 introductory cost (retail $800) + $35 per “3” day sensor Sensor & Transmitter Receiver 0.8 x 1.5 inches

59. Healthcare Across Borders - September 2003 Continuous Monitors Reduce Exposure & Variability 15 users with implanted Dexcom continuous monitors blind to glucose readout for the first 50 days, then open readout for the next 44 days. hrs/day blood sugar - 65 min + 32 min + 250 min -13 min -160 min

60. Healthcare Across Borders - September 2003 Paradigm RT 522/722 A = reading B = high/low alarm C = trend arrow D = BG graph A = pump B = infusion set C = sensor D = radio transmitter Con Mon readout on pump screen

61. Healthcare Across Borders - September 2003 Medtronic Paradigm RT Released 4/13/06 Paradigm 522/722 pump available now Sensors available “this summer” Approved for 18 and older One high and one low alert plus trend arrows Readings every 5 min. over 3 days $999 + $35 per “3” day sensor

62. Healthcare Across Borders - September 2003 FreeStyle Navigator TheraSense Continuous Glucose Monitor Meter replacement Investigational Device.Limited by U.S. Law to Investigational Use

63. Healthcare Across Borders - September 2003 Therasense Navigator System Best current accuracy Calibrated 1-2 times per day Readings every 1-2 minutes 5 day use High and low glucose alarms Good accuracy below 100 mg/dl Trend arrow Discussions underway for use in Deltec Cozmo and Omnipod pumps Investigational Device.Limited by U.S. Law to Investigational Use

64. Healthcare Across Borders - September 2003 Future Pump Features

65. Healthcare Across Borders - September 2003 Future Intelligent Pump Features Automatic Basal/Bolus Testing Pattern Analysis Alternate Insulin Profiles (basals and bolus factors) Insulin deficit versus carb deficit (not just BOB) Insulin Action Mirror Time To Eat Alert Delayed Eating Alert Super Bolus Dual bolus reductions Micro MEMS Pumps Peritoneal Delivery

66. Healthcare Across Borders - September 2003 Automatic Basal/Bolus Testing Auto testing could be done with current pump and 6-9 tests/day on current meter. NO continuous monitor required! Test TDD Average blood sugar, standard deviation, frequency of lows % TDD used for corrections Basal/bolus balance Test Basal rates Overnight with automatic accounting of BOB at bedtime Daytime when a meal is skipped Test Carb factor Premeal, 2 hr postmeal peak, normal in 4-5 hrs? Test Correction factor High-to-normal in 4-5 hours? A Current And Future Feature

67. Healthcare Across Borders - September 2003 Some Patterns Can Be Spotted In Modal Day Pattern to left shows inadequate carb boluses or basal (or missed boluses) at breakfast with possible excess correction boluses for highs at lunch (or testing only when low)

68. Healthcare Across Borders - September 2003 Time To Eat Alert A timer would alert pumper 15 to 30 minutes after a bolus that it is now OK to eat a high GI food or a meal with a large amount of carb. A Future Feature* * Not for children or anyone acting like a child! Eating can be delayed to allow insulin to start working before carbs begin raising the glucose. Helps reduce glucose exposure Can be dangerous

69. Healthcare Across Borders - September 2003 Delay Eating Alert Reduces Glucose Exposure A lower glucose at the start of a meal reduces glucose exposure. Rules: Test early Bolus early Don’t forget to eat on time Don’t forget you’ve already bolused A Future Feature*

70. Healthcare Across Borders - September 2003 Basal/Bolus Shifting Basal Reduction For Excess BOB A temporary basal reduction offsets excess BOB so it is not necessary to eat at bedtime. A Future Feature

71. Healthcare Across Borders - September 2003 A Super Bolus For A High GI Meal A Super Bolus shifts future basal insulin into an immediate bolus. Part of the next 2-4 hours of basal insulin is shifted into a bolus to give a faster insulin effect for high GI and large carb meals without causing lows. Could be activated when user wants to eat more than a pre-selected quantity of carbs, such as 30 or 40 grams A Future Feature*

72. Healthcare Across Borders - September 2003 Using A Super Bolus For A Postmeal High When the carb content of a meal has been underestimated, a super bolus enables a faster, safe correction. A Future Feature*

73. Healthcare Across Borders - September 2003 The Insulin Lookback When a low or high reading occurs, a pump should tell the user: how much basal and how much bolus (plus BOB) was active in the previous 5 hours or so. For lows, usually lower the higher number For highs, give consideration to uncovered carbs or consider raising the lower number

74. Healthcare Across Borders - September 2003 Future Devices

75. Healthcare Across Borders - September 2003 Intelligence (Improved Control) Can Be Added To Pumps Pens Meters PDAs Smart phones Or any combination Goal: Better management of complex situations Requires a central reporting station to identify problems and notify user, guardian, or MD/RN

76. Healthcare Across Borders - September 2003 Smart Phones And PDAs Convenient bolusing from a remote device Easy messaging Better graphics Large carb database and memory Better analysis Direct fax to physician Two-way communication Can combine multiple data sources (pen, pump, meter, carb database, exercise component, communication)

77. Healthcare Across Borders - September 2003 DexCom Implanted Sensor Investigational Device.Limited by U.S. Law to Investigational Use Implanted sensor is designed to to be surgically placed under the skin for 6-12 mos as an outpatient procedure.

78. Healthcare Across Borders - September 2003 Animas-Debiotech Micropump Debiotech develops small pumps from Micro-Electro-Mechanical Systems or MEMS technology. These devices are made from silicon (not silicone!) that can be mass-produced at low cost. Silicon is harmless, but it is not clear how insulin interacts with silicon surfaces.

79. Healthcare Across Borders - September 2003 Other Con Mon Approaches Flourescent Measure glucose through non- binding interaction in porous, dermal implant Ocular NIR Measures glucose in vessels in the white of the eye using near infrared light waves Electrical Inpedance Measures glucose indirectly by how it affects electrical impedance in the skin Etc.

80. Healthcare Across Borders - September 2003 Ocular Near-Infrared Sensors Intermittent use at first Possible continuous use in eyeglass frame Accuracy yet to be proven

81. Healthcare Across Borders - September 2003 Flourescent Glucose Sensors Advantages: Stable, reversible action Fast response and recovery High sensitivity and specificity to glucose Does not require oxygen Does not consume or produce anything Does not require frequent calibration Low power requirement for LED Can be miniaturized and manufactured in volume Implanted under skin or as an ocular lens

82. Healthcare Across Borders - September 2003 GlucoWatch ® Biographer First FDA Approval – Now owned by Animas

83. Healthcare Across Borders - September 2003 Animas-Debiotech Microneedles Silicon microneedles can be used to infuse insulin or allow glucose measurements in interstitial fluid.

84. Healthcare Across Borders - September 2003 Pressure Pumps Use of pressure eliminates need for motor and standard reservoir Precise insulin delivery Capable of dual pumping action Insulin plus symlin Insulin plus glucagon Pull/push interstitial glucose monitoring

85. Healthcare Across Borders - September 2003 Wrap Up Pumps and devices offer the latest technology for improved control Benefits: more flexibility, less hypoglycemia, less glucose exposure and variability, and a healthier life Change doses for seasons & schedules Involve child/teen in how to improve control A pump does require commitment, responsibility, and training The best in pumps and monitors is yet to come

86. Healthcare Across Borders - September 2003 Questions And Discussion