1. Advanced Pump Features And Their Use Children With Diabetes La Jolla, CA John Walsh, PA, CDE jwalsh@diabetesnet.com (619) 497-0900 Advanced Metabolic Care + Research 700 West El Norte Pkwy Escondido, CA 92126 (760) 743-1431

2. Disclosure Book sales – all pump companies Advisory Boards – Agamatrix, Tandem Diabetes, Unomedical Consultant – Bayer, Accu-Chek, Medingo Speakers Bureau – Tandem Diabetes Instructor – J&J Diabetes Institute Sub-Investigator – Glaxo Smith Kline, Animus, Sanofi- Aventis, Bayer, Biodel, Dexcom, Novo Nordisk Pump Trainer – Accu-Chek, Animas, Medtronic Web Advertising –Sanofi-Aventis, Sooil, Medtronic, Animas, Accu-Chek, Abbott, etc.

3. Outline Goals Special Pump Features Future Pump Features CGMS Pump Settings Pumps For Type 2s DIA and BOB

4. Goal One Near normal Least hypoglycemia possible Day’s glucose without diabetes

5. Special Pump Features Feature: Pumps: Cont monitor readoutParadigm No tetherOmnipod Remote bolusAnimas, Omnipod, (Combo) Lowest basal rateAnimas Color screenAnimas Food/Carb ListAnimas, Omnipod, Spirit

6. Combo Boluses – Part Now & Part Later Great for Symlin, low GI carbs, hi-protein meals, gastroparesis Helps when carb counts or meal timing are uncertain  Give part of bolus early to get insulin working  Give rest over time – discontinue if meal has fewer carbs than expected. Give 2nd bolus if meal contains more carbs. Picky-eater parents love combo boluses

7. Temp Basal Rates Great for: Exercise Illness Testing new basal rates Offsetting excess BOB Safely “stopping” a pump

8. Patch Pumps – Lose The Tether Omnipod – 1st patch pump Pending patch pumps: Medingo Solo Debiotech & STMicro- electronics nano-pump Medtronic Valeritas V-Go NiliMEDIX Calibra, Medsolve, CellNOVO, Altea

9. Remote Boluses Bolusing from a meter or a PDA allows the pump to stay hidden: Bolus and basal adjustments in Accu-Chek Combo (not yet FDA approved)

10. Cozmo – Best Management Tools Feature: Pumps: HypoManagerCozmo Safe BOB HandlingCozmo Bolus Not CompletedCozmo Weekly ScheduleCozmo Missed Meal Bolus AlertCozmo Disconnect BolusCozmo Glucose Variability (SD)Cozmo Basal TestingCozmo Data summarized in pumpCozmo, Paradigm

11. HypoManager TM Shows insulin OR carb deficit when BG is checked. BOB is compared to correction bolus need: If BOB is smaller –> pump recommends correction bolus If BOB is larger –> pump recommends carbs be eaten Benefits: Less overeating when low (Test when low to get accurate carb recommendation) Prevents ETRS or “Empty The Refrigerator Syndrome” Warns when carbs are needed later even though current BG is OK or high (the poor man’s continuous monitor) Not accurate with low GI meals, Symlin, or gastroparesis

12. HypoManager TM BG reveals whether there’s an insulin or a carb deficit 1 BG = 173 mg/dl (9.6 mmol) Bolus on board = 0.4 u Correction bolus: 1.2 u Insulin deficit = - 0.8 u Give 0.8 u now 2 BG = 173 mg/dl (9.6 mmol) Bolus on board = 4.6 u Correction bolus: 1.2 u Insulin excess = 3.4 u 37 grams of carb may be needed later to prevent a low (hypo predictor) Helps prevent & treat hypoglycemia and avoid over-treatment

13. Easy Data Access 14 Day Average: BG 146 mg/dl Tests 3.5/day Std Dev 53 mg/dl Overall control Adequacy of testing BG variability – aim for less than 65 mg/dl Screen 1: BG control, test frequency, glucose variability

14. Easy Data Access 14 Day Average: Carbs 206 g TDD 48.58 u Meal 38.07% Corr 4.95% Basal 56.98% Boluses taken? Low carb diet? Adjust for A1c, BGs, etc Carb bolus % OK? Correction less than 8% of TDD? Basal at least 40 to 45% of TDD? Screen 2: carb intake, TDD, basal/carb bolus balance, correction bolus%

15. Check Your Correction Bolus % When correction boluses make up more than 8% of the TDD, and lows are NOT a primary problem: Move at least half of any excess units above 8% into basal rates or carb boluses  Raise basal rates  Lower carb factor (or stop skipping carb boluses)

16. Example: High Correction Bolus % 10 Day Average: Carbs 175 g TDD 54.1 u Meal 36% Corr 21% Basal 43% Move 1/3 to 1/2 of the overage to basals or carb boluses: 21% of 54.1 = 11.3 units, 8% of 54.1 = 4.3 units 11.3 u - 4.3 u = 7 units excess 1/3 to 1/2 of 7 u = 2.3 to 3.5 u to add to basals or carb boluses Over 8% of TDD

17. Future Pump Features How A Setting Change Will Impact the TDD (&BG) Temp Basal + Bolus Doses Super Bolus Meal Size Boluses Excess BOB Alert Exercise Compensator Infusion Set Monitor Automated Bolus and Basal Testing Multistep Temp Basals

18. Super Bolus For A High GI Meal Shifts Basal To Bolus Future Feature: Super Bolus shifts part of the next 2 to 3.5 hrs of basal insulin into the bolus with less risk of a low later. 1,2 1 J. Walsh: http://www.diabetesnet.com/diabetes_presentations/super-bolus.html September, 2004http://www.diabetesnet.com/diabetes_presentations/super-bolus.html 2 J. Bondia, E. Dassau, H. Zisser, R. Calm. J. Vehí, L. Jovanovic, F.J. Doyle III, Coordinated basal-bolus for tighter postprandial glucose control in insulin pump therapy, Journal of Diabetes Science and Technology, 3(1), 89-97, 2008 A Super Bolus helps when eating more than 30 or 40 grams of carb, esp. high GI meals like cereal. Max carbs/meal = Wt(lb) X 0.36 2 to stay in control

19. Insulin Pump + CGM Full BG record lets basals and boluses be adjusted for optimal energy flow Optimal health, better growth, better work and school performance

20. CGMs

21. Components Sensor Receiver Transmitter

22. CGM Systems Abbott FreeStyle Navigator ® DexCom ™ SEVEN ® PLUS Medtronic MiniMed Paradigm ® REAL-Time* * Medtronic Guardian ® REAL-Time and I-Port also available.

23. CGM And Pump Choices Pump: Animas* Insulet* Medtronic AccuCk Combo* CGM: Dexcom 7+ Navigator Paradigm RT AccuCk Combo * Not yet available

24. CGM Benefits Increased security Immediate feedback – look and learn BG trend provides more info than static readings Control + safety

25. Trends Better Than Points Photo courtesy Bernard Farrell No clue what to do Insight

26. Dosing For Success 1.Stop lows first 2.Find the True TDD – good A1C, stable readings, with basal/carb bolus balance 3.Set & test basals – do overnight readings stay level? 4.Set & test carb boluses – fine-tune premeal BGs 5.Lower post meal BGs – give boluses early, low GI foods, Symlin, etc. 6.Set & test corr. boluses – bring highs down safely Enjoy good control or return to #1 Brittle diabetes or frequent highs = wrong doses (usually)

27. Find The True TDD If it ain’t broke, don’t fix it – current doses are great if A1c and avg. meter BG are good with few lows If not, adjust the current TDD: 1.Lower the TDD by about 5% for: Frequent lows Or highs AND lows IF lows come first 2.Raise the TDD, using the True TDD Table on next slide to adjust for high A1c or high meter average Keep basal and carb bolus totals balanced Avg BG on pumps is 184.5 mg/dl (10.2 mmol) – most need more insulin

28. The True TDD Table If frequent lows are main problem, lower current TDD by 5% or more If frequent highs are main problem, increase current avg. TDD from recent A1c or a 14 day BG average J Walsh and R Roberts: Pumping Insulin (5th ed), 2010

29. Basal / Carb Bolus Balance Keep basal rates and carb boluses balanced For frequent lows, lower the higher one. For frequent highs, raise the lower one Basal = 48.1% of TDD Carb Bolus = 42.8% of TDD Correction Bolus = 8.98% of TDD J Walsh and R Roberts: Pumping Insulin (5th ed), 2010 Best control tertile: 135 of 405 pumps Avg BG 146

30. Smart Pumps Arrive Dumb Basal rates, carb factor, correction factor, and DIA must be individualized For accurate boluses, a bolus calculator needs Current BG Accurate CHO count Don’t depend too much on bolus calculator Use temp basals and combo boluses appropriately

31. Does Your Pump Have The Right Settings?

32. Pump Autopsies – Carb Factor in Pump 1 Carb factors from pumps are not physiologically distributed. Less accurate “magic” numbers – 5, 10, 15, and 20 g/unit – are preferred. 7 10 115 20 1 Carb factor settings from pumps 5 10 15 20 R2 = 0.40

33. Pump Autopsies – Carb Factors Used 1 Despite pump’s Carb Factor, users in good control adapt – changing carb count or ignoring bolus recommendation. Those in poor control don’t. 7 10 15 20 1 Carb Factors actually used – avg carbs/avg carb bolus per day R2 = 0.76

34. How A CarbF Adjustment Changes Glucose * Calculated as carbs in meal – carbs in meal X 1900 new carb factor old carb factor TDD ** Larger meals have greater impact on glucose 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 Meal SizeFall in BG for 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

35. Easy And Accurate Carb Factors Carb Factor = 10.46 g/u x Wt (lbs) TDD x 4.17 = 2.5 x Wt(lbs)/TDD* Carb factor = average carb factor times individual’s insulin sensitivity Replaces 450/500 Rule J Walsh and R Roberts: Pumping Insulin (5th ed), 2010 * Best calculated from a True TDD

36. Test The Carb Factor Eat carbs = half wt (lbs) in grams Peak glucose doesn’t matter unless excessive Glucose back to target by end of DIA time No lows for 5 hrs after the bolus Clearout No bolus in last 5 hrs No carbs in last 3 hrs 2 4 3 1

37. Basal Rates & Correction Factors J Walsh and R Roberts: Pumping Insulin (5th ed), 2010 Basal = ~ 48% of TDD Corr. Factor = 1900 / TDD* *Corr Factor Rule # from 135 well- controlled pumpers (lower tertile) with avg BG of 145 (avg. of 365 readings per pump)

38. Test The Correction Factor & DIA Time Glucose CGM helps check both correction factor and DIA time Glucose near target by end of DIA time No lows for 5 hrs after bolus Clearout No bolus in last 5 hrs No carbs in last 3 hrs 2 4 3 Give corr. bolus for BG (over 250 mg/dl) 1

39. Infusion Sets – The Weak Link in Pumps and Patch Pumps May cause unexplained highs due to: Poor design Not taping the infusion line down Problems during insertion (bent Teflon, auto inserters) Inadequate training “You may have scarring” = blame shifting

40. Pump Autopsies – What Affects Control? LowMiddleHigh Avg BG146.6181.6229.3 BGs/day4.744.524.22 Blocks/mo1.363.043.57 Stops/mo8.0110.3211.7

41. Occlusions / Blockages Should rarely happen! More than once a month? Change infusion set brand (usually) Or change insulin brand

42. Do You Have An Infusion Set Problem? Do your sites often “go bad” Do you have “unexplained” highs? Do the highs correct when you change your infusion set? Yes? Anchor your infusion line with tape Review site technique Switch to a different infusion set

43. Infusion Set Failure On CGM Bad infusion set?

44. Never Stop A Pump! You may forget to turn it back on It’s rarely needed It doesn’t help when low A temp basal reduction for 30 to 60 min. will restart at an appropriate time

45. New Pump Styles Styling is becoming competitive for pumps But never give up function for styling

46. Communication – Pump + Phone Some pumps and meters transfer glucoses to phone via Bluetooth or attached meter Great for parents, spouses, and children of elderly Plus food databases, carb counters, apps, and eventually management on cell phone

47. Diabetes Phone Apps Many apps are becoming available for I–Phones, Pre, and Blackberry Aids for dosing, logging, carb counting

48. Diabetes Phone Devices Many companies are developing meters for I–Phones, Pre, and Blackberry Aids dosing, logging, carb counting Rapid alerts for young, elderly, those with hypo unawareness

49. Data Analysis Wanted: a pump that Recognizes glucose patterns Alerts user and provider about helpful basal or bolus setting adjustments Simplifies and speeds up data collection and analysis Thinks and learns “Why can’t my smart pump learn?” John Rodosevich, President of SD Pump Club

50. Future Pump Modifications Dual chamber pumps that deliver glucagon, amylin, or GLP-1 agonists along with insulin New Infusion Sets  Safer and more reliable  May also act as glucose sensors? Smart phones  That control pump, show sensor data, act as BG meter, and analyze data in a single device

51. Pumps Require Wise Users Many things change the glucose:  exercise, heat, bolus size, GI index of foods, prior experience, stress, infection, context around high BG, etc. A pump cannot monitor these The wise user can and does

52. How long a bolus lowers the glucose Setting Duration Of Insulin Action (DIA)

53. Duration Of Carb Action (Digestion) Most carbs affect the BG only 1 to 2.5 hours Slower digestion with complex carbs, more fiber, more fat, etc BG impact varies considerably Thanks to Gary Scheiner, MS, CDE

54. Duration Of Insulin Action (DIA) 4 hrs 6 hrs 2 hrs 0 Accurate boluses require an accurate DIA Glucose-lowering Activity DIA times shorter than 4.5 to 6 hrs will hide BOB and its glucose lowering activity

55. Bolus Early To Stop Meal Spiking Figure shows rapid insulin injected 0, 30, or 60 min before a meal Normal glucose and insulin profiles shown in the shaded areas Best glucose profile when bolus is given 60 min ahead, but too risky to recommend!!!

56. Insulin Activity Times – Large Doses Large dose (0.3 u/kg = 15 u for 110 lbs) of “rapid” insulin in 18 non- diabetic, obese people Med. dose (0.2 u/kg = 15 u for 165 lb) Note little activity in first 30 min Apidra product handout, Rev. April 2004a Human Regular

57. A short DIA hides true BOB and Causes “unexplained” lows Leads to incorrect adjustments in basal rates, carb factors, and correction factors to compensate for excess boluses Makes user ignore their “smart” pump’s advice Select DIA from real insulin action time Don’t change DIA to fix a control problem! A Short DIA Hides Bolus Activity

58. Recommended DIA Times Set DIA to 4.5 to 6 hrs for accurate calculation of BOB and bolus doses 5 hr Linear 5 hr Curvilinear From Pumping Insulin, 4th ed., adapted fom Mudaliar et al: Diabetes Care, 22: 1501, 1999

59. DIA Tips Current research suggests that DIA times are NOT different between children and adults If the pump does not “give enough bolus insulin”, do NOT shorten the DIA to get larger boluses. Look for the real reason:  a basal rate that is too low  or carb factor that is too high  Temporary factors can shorten insulin action time:  Activity and exercise  Hot weather Don’t shorten DIA for temporary factors

60. Bolus insulin still active from previous boluses Bolus On Board (BOB)

61. Bolus On Board (BOB) 1 Glucose-lowering activity that remains from recent boluses An accurate BOB Prevents Insulin stacking Improves bolus accuracy Reveals current carb or insulin deficit when BG test is done (HypoManager) Requires an accurate DIA Basal insulin is NOT included in BOB! aka: insulin on board, active insulin, unused insulin* 1 Introduced as The Unused Insulin Rule in Pumping Insulin, 1st ed, 1989, Chap 12, pgs 70-73

62. BOB Helps Prevent Insulin Stacking When the bedtime BG is 173 mg/dl, is there an insulin or a carb deficit? 6 pm8 pm10 pm12 am Dinner Dessert Correction Bedtime BG = 173 mg/dl

63. The 1–Hour BOB Blind Spot 1 hour after a meal & meal bolus is a blind spot – it takes an hour for most carbs to be digested but insulin action is just beginning. A BG check during this time cannot measure what impact a bolus will have on the carbs eaten: Ignore BOB when covering a desert within an hour after a meal bolus Use of Symlin or Byetta-like meds, the presence of gastroparesis, and eating low GI meals can all slow digestion and make BOB estimates inaccurate. Boluses can start to be evaluated about 60 to 90 minutes later.

64. Bolus Recommendations Differ BOB = 3.0 u 30 gr. of carb will be eaten at each BG level Carb factor = 1u / 10 gr Corr. Factor = 1 u / 2.2 mmol over 5.5 Target BG = 5.5 TDD = ~ 50 u units mg/dl Omnipod bolus cannot be determined - it counts only correction bolus insulin as BOB Graphic shows how widely bolus recommendations vary from one pump to another for the same situation.

65. 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 InjectionsNo Animas PingYes No*Yes Deltec CozmoYes Insulet OmnipodNoYesNo**Yes Medtronic ParadigmYes NoYes * Except when BG below target BG ** Except when BG is below target and reverse correction is turned on YES = Safer

66. Example: BOB Calcs From Different Pumps TDD = 38u, corr factor = 10 g/u, corr factor = 65 mg/dl 65 mg/dl x 6.35 u = 413 mg/dl (13 mmol) fall in BG following other pump’s advice How Bolus Recommendations Differ Between Pumps TimeBG Carbs Eaten Carb Bolus Other Pump Cozmo Dose Difference 6:54 am111 (6.2)160No bolus0 9:52 am174 (9.7)03.0 u *4.3 u 0 10:35 am140 (7.8)505.0 u 2.15 u+ 2.85 u 11:58 am117 (6.5)404.0 u 0.5 u+ 3.5 u 1:12 pm137 (7.6)000 uEat 19 g 6.35 more units recommended by other pump in 6 hours!

67. CGMs

68. CareLink™ Personal Online Reports Sensor daily overlay Sensor overlay by meal MiniMed Paradigm ® & Guardian ® REAL-Time

69. Navigator CoPilot Weekly View Same person – Daily values: Wed: 103 mg/dl (5.7), TDD 59u, carbs 330 g, corr boluses = 0.85 u Thur: 217 (12.1) mg/dl, TDD 70u, carbs 170 g, correction boluses = 23.75 u NOT a TDD problem!

70. Don’t Stack Rapid (Slow) Insulin

71. Stay Between The Lines As readings improve, gradually lower the upper target.

72. Quick CGM Analysis TDD too low High avg BG Night basal too low Rising trend

73. Bolus Timing Carb factor appears OK – PP spikes probably caused by bolusing just before eating. 3.5 hrs 3.75 hrs

74. Self-Learning First 3 days Next 3 days

75. Glucose Distribution Graph 75.2% between 71 (4) and 160 (8.9) 5.3% below 55 (3) 5.3% of 24 hrs = 73 min/day spent below 55 mg/dl (3 mmol)

76. CGM Tips Wear all the time Look at it 1-2 times an hour Look for trend not accuracy Rapid rises usually require more insulin Validate with meter before dosing Balance CGM BG with BOB Don’t over-react and stack Calibrate when flat

77. For Answers To Your Questions Available at www.diabetesnet.com or 800-988-4772www.diabetesnet.com