1. Research & Development Type 1 & Type 2 Diabetes
technology is transforming how we manage diabetes, the way we check and track blood glucose, the way give insulin, all changing super fast.
Advancement of technology are making diabetes management not only easier and convenient but also more effective and safe.
Amrit Bhangoo, MD
Division of Pediatric Endocrinology
Children’s Hospital Orange County
May 14th, 2016

2. Diabetes Mellitus in USA
Diabetes affects 25.8 million people
(#1.25 million type1 - 1:4000)
8.3 % of US population has diabetes
If current trends continue, 1 of 3 U.S. adults will have diabetes by 2050
Total estimated diabetes type 1 related cost is $14 billion, 174 billion for all diabetes
JDRF website

3. Monitoring glycemic control: early history
From appearance, color,
sediment and often taste
In 1954 Glucotest/Testape roll
1960’s the “dipstix”
Not until early 19 century (1838) excess sugar was identify in the blood in diabetes patient by George Rees at Guy’s hospital in London
Pre and 50’s qualitative urinalysis by reducing property of glucose of alkaline cupric sulphate to colored cuprous oxide
60’s semi-quantitative Blood glucose
70’s quantitative first generation blood glucose meter. Digital read out meter – needed 40 sec to 2 min
80’s second generation meter, required less blood volume by capillary filling, less pain, better accuracy

4. Insulin delivery NovoPen Echo® Insulcheck
Pen offer greater accuracy especially in lower dose requirement. Improve portability, adherence, reduce complexity of insulin therapy and increase QOL.
NovoPen Echo® provides both precise half-unit dosing and a memory function that records the dose and time passed since the last injection.
Insulcheck has created an insulin pen attachment that tracks when you last injected insulin from your pen.
Insulcheck

5. Quest for Cure of Diabetes
Biological cure
Islet cell transplantation
Stem cell development
Immunomodulation
BCG
Technological Cure
Hybrid approach

6. The Natural History of Type 1 Diabetes
Inductive Event
eg. Coxsackie virus
Metabolic Derangements
FPIR to IVGTT
Impaired OGTT
Elevated fasting glucose
Genetic Predispositions
HLA-DR/DQ
? A.B.C
VNTR INS.
CTLA-4
Others
Islet Antigens IAA, GAD65A, IA-2A, IA-2bA, Glima-38A
Cell Mediated response to islet antigens
Islet Cell Mass
Diabetes Onset
IL-12 / INF-g
Lack of environmental protection from NK-T cells / CD25+ T cells
Honeymoon
Phase
9 months – 3 years
months to years
months

7. Immunotherapy AntiCD3 monoclonal antibody (mAb)
Otelixizumab
Low doses did not change c-peptide, HbA1c, insulin dose and glucose
Only beneficial in high doses
Adverse effects
Teplizumab
Patients were still insulin dependent
Expert Opin Biol Ther. 2016 Jun;16(6): doi: /
Diabetes Care. 2014 Oct;37(10): doi: /dc Epub 2014 Jul 10.
Lancet. 2011 Aug 6;378(9790): doi: /S (11) Epub 2011 Jun 28.

8. Oral Insulin - Prevention
Genetically susceptible to type 1 diabetes 
CD4+ T-cell proliferative responses 
Autoantibodies to GAD-65 or IA2 antigen
Diabetes Prevention Trial of Type 1 (DPT-1) -Phase 3
Trialnet Oral Insulin study
Pre-Pilot study

9. Newly diagnosed – Stem cell therapies
 Multipotent mesenchymal stromal cells (MSCs)
Adult stem cells residing in bone marrow, adipose tissue, umbilical cord blood
Migrate to injured areas
Tissue generation
T1D-MSCs were able to reverse hyperglycemia in murine diabetes models
Lowered ICA, GAD-65 and insulin antibodies of 2 patients in 12 months
Stem Cell Res Ther Jan 18;7:14. doi: /s , Med Sci Monit 19: ,

10. Stem cell / MSCs Drawbacks
Mild therapy
“homing” factors toward pancreas
Pulmonary first pass effect
Contamination
Tumorigenicity and immunogenicity
Cost-effectiveness

11. Generation of stem cell-derived β-cells from patients with type 1 diabetes
Stem cell-derived β-cells from type 1 diabetic patients can be used for treatment of diabetes
β cells in vitro
 Secrete quantities of insulin comparable to adult β cells
response to multiple sequential glucose challenges in vitro
Nat Commun May 10;7: doi: /ncomms11463
Cell Oct 9;159(2): doi: /j.cell

12. Islet Cell Technology Islet cell encapsulation
Natural means, e.g., seaweed
Artificial membranes
Trying to eliminate the need for chronic immunosuppressant therapy
Implantable cell therapy - UCSD conducting First ever clinical trial of a stem cell-derived therapy
Many non-immunological and immunological factors such as biocompatibility, reduced immunoprotection, hypoxia, pericapsular fibrotic overgrowth, effects of the encapsulation process and post-transplant inflammation hamper the successful application of this promising technology.

13. Clinical Islet Transplantation (CIT) Consortium
University of Miami Miami, Florida
University of Minnesota Minneapolis, Minnesota
University of Pennsylvania Philadelphia, Pennsylvania
Emory University Atlanta, Georgia
Northwestern University Chicago, Illinois
University of Alberta Edmonton, Alberta, Canada
University of California San Francisco, California
University of Illinois at Chicago Chicago, Illinois
University of Wisconsin Madison Wisconsin
Uppsala University Uppsala, Sweden
University Hospital Rikshospitalet Oslo, Norway
Karolinska University Stockholm, Sweden
Massachusetts General Hospital Boston, Massachusetts

15. Collaborative Islet Transplant Registry Data 2010
571 pancreatic islet allo-transplants
90 with kidney transplant
One or two infusions of islets
Average number of islets received per infusion was 463,000.
1st year - 60 % insulin independence (no insulin for at least 14 consecutive days)
2nd year - 50 % insulin independence
Better outcome
age—35 years or older
lower pre-transplant triglyceride, or blood fat, levels
lower pre-transplant insulin use
Collaborative Islet Transplant Registry seventh annual report. Collaborative Islet Transplant Registry website.  Updated December 30, Accessed July 23, 2013.

16. ViaCyte Inc - Pancreas in a Capsule Encapsulation Research
University of California, San Diego School of Medicine, in partnership with ViaCyte, Inc., a San Diego-based biotechnology firm specializing in regenerative medicine, have launched the first-ever human Phase I/II clinical trial of a stem cell-derived therapy for patients with Type 1 diabetes.
The initial clinical trials of ViaCyte’s experimental therapy called VC-01TM recently began at the University of California at San Diego. This product concept encapsulates immature human pancreatic cells derived from stem cell source in an immune-protective device called the Encaptra® system. It is the first ever use of stem cell-derived islets for people with T1D.
Phase 1/2 trial called STEP ONE, or Safety, Tolerability, and Efficacy of VC-01 Combination Product in Type One Diabetes.  
UCSDSchool of Medicine, in partnership with ViaCyte, Inc

17. Technological “Cure”
Self Monitoring & Self Management of Diabetes

18. Blood Glucose Meters iBG Star meter/app (Sanofi Aventis, available)
OneTouch® Verio®Sync
Frequent blood glucose monitoring is critical in diabetic management to maintain blood glucose within physiological range. That is the only way a diabetic can lead healthy lifestyle avoiding life-threatening complications of poorly controlled diabetes form hyperglycemia as well as hypoglycemia.
LG Glucophone: In an unusual, but sensible, marriage of technologies, LG has released the KP8400 cellphone that doubles as a blood test for diabetics.  The phone includes a tester into which users can place a blood test drop on a strip, place the strip in a special reader on the phone (located near the phone's battery pack), and get insulin and blood readings on the phone display.  Readings can then be uploaded to an online database for retrieval later on.  Because of the added technology the rest of the phone isn't anything to write home about, but it's more than sufficient: 262k color TFT display, CIF camera, and 64 voice polyphonic sound. Not yet for sale in the US?
iBG Star: meter attachment for iPhone/iTouch systems microliter, 6 second test # memory. Diabetes Management App that goes with it.
Freestyle InsuLinx: The InsuLinx System is the first blood glucose monitoring device from Abbott that includes a mealtime (bolus) insulin calculator for calculating suggested insulin doses. The new system also offers several additional features, including a touch screen interface, automated logbook, personalization preferences and USB connectivity for plug-and-play reports via the new FreeStyle Auto-Assist data management software.
Verio®Sync: The meter that automatically sends your blood sugar results wirelessly to your iPhone, using the OneTouch® Reveal™ mobile app. Also works with your iPad® or iPod touch. 500 results and automatically sends them to your iPhone whenever you open the OneTouch® Reveal™ mobile app. Plus, it is simple to use with an easy to read screen and test strip port light for testing in the dark.
Easy, One-Step™ testing with the press of one button
No hassling with individual test supplies
Self-contained for discreet testing and disposal
Fast, four second countdown
Tiny blood sample (250 nanoliters)
No coding required
USB port for fast data upload
Freestyle InsuLinx
(Abbott)
Accu-Chek ® Aviva Expert Bolus Advisor System
LG KP8400 cell phone (Korea, 2002);
Infopia LG Glucophone/JVAGO 5965 (US, 2008)

21. Continuous Subcutaneous Glucose Monitoring

22. The first Glucose Sensors
Glucowatch Biographer
FDA approval
Reverse iontophoresis
Cyngnus/Animas
CGM Gold
Enzyme tipped catheter
1999
Medtronic Guardian
Real time
2004
Freestyle navigator
Dexcom STS 2006
2000 3rd gen CGM
4th non invasive CGM

23. How Does CGM Work?
Glucose in the interstitial fluid hits the sensor causing an glucose-oxidation reaction to occur

24. Sensor Glucose (SG) vs. Blood Glucose(BG)
During rapid states of change, SG and BG may differ more than 20%
The CGM needs calibrations a minimum of twice a day (once every 12 hours)

25. Todays Glucose Sensors – U.S.
Dexcom G4: 1198 $ for sensor and daily cost 6.70 $ from sensor
Guardian 1400 CGM and 50 $/sensor
Free style navigator 1000 CGM and 375 for pack of 6 sensor
Sensitivity for hypoglycemia is only 39%; specificity is 96%
"lag time" of between 5 and 20 minutes reported by the various CGM devices because the blood glucose reading is taken from interstitial fluid and does not reflect actual blood sugar concentration that is found in standard fingerstick blood samples drawn from capillary blood. Trend is the keyword to keep in mind about the advantage of the CGM devices not individual number
“Tracking and trending” purpose only in USA. Capilary BG should be used to guide the therapy. CGM has not been associated with improvement of QOL in randomized trial (Langendam M, Cochrane database syst review 2012)- less than 10% T1D are CGM users.

26. CGM Parts
Dexocm
Enlite
Sensors
Transmitters
Receivers
Inserters

27. Sensor Sites Change every 6-7 days, per manufacturer guidelines
Discuss with your healthcare provider if sites can be worn for longer periods of time
Check sites daily and remove if reddened, inflamed and/or irritated or infected
Adhesive wipes (Skin Tac, IV Prep) and tapes (Tegaderm, IV 3000) may be helpful to keep the sites
For pain with insertion, try numbing with EMLA/Lidocaine cream or the Synera patch – ask MD/NP for prescription

28. Dexcom Share and Dexcom G5
Dexcom receiver that has Share blue-tooth capability built-in so you will not have to have a cable and phone attached to receiver
Must have iPhone, iPod touch, or iPad with internet connection close to Dexcom receiver
Dexcom Share app
Real-time data available to 5 users on their iPhone, iPad or iPod touch

29. Sensor Glucose vs. Meter Glucose mean absolute relative difference (MARD)
Meter MARD
FreeStyle Lite %
FreeStyle Freedom Lite %
Accu-Chek Aviva %
Contour %
OneTouch UltraEasy %
Sensor MARD
Dexcom <10%
Enlite %
J Diabetes Sci Technol. A comparative effectiveness analysis of three continuous glucose monitors: the Navigator, G4 Platinum, and Enlite.2014 Jul;8(4):
Accuracy Evaluation of Five Blood Glucose Monitoring Systems Obtained from the Pharmacy: A European Multicenter Study with 453 Subjects Apr; 14(4): 330–337

30. MiniMed Connect
MiniMed Connect is available for iPhone® or iPod touch®. If you have a MiniMed® 530G or a MiniMed Paradigm® RevelTM insulin pump
Friends and family can view online with CareLink®

31. Glucose Sensors (contd.)
Navigator Libre – Approved in Europe
Medtronic Enlite sensor: Medtronic reckon its 17% better overall and 26% better when it comes to low blood sugars. More accurate. Lag seemed less. Lasts for 6 days. 6 hour time-point calibration has been removed.
Glucose Biosensor: with fluorescence or amperometric signals microns = mm
Tattoo glucose sensor: Researchers at Draper Laboratory are developing a tattoo-like implant that senses glucose levels and fluoresce different colors in response.
Medtronic & Ford Motor Company
glucose monitoring on the go
Glucose
Tattoo

32. Future Non invasive glucose monitoring
Non-invasive continuous glucose monitoring 1. transdermal and 2. optical using spectroscopy, thermal infrared technology
GlucoTrack Ear Meter: made by Integrity Applications, an Ashkelon, Israel firm. Uses ultrasound, conductivity and heat capacity in an ear clip sensor to take glucose readings in a matter of seconds. Integrity recently received European approval (2009) for the GlucoTrack and is now waiting for FDA’s blessings to market in the US. Not as consistently accurate as current fingerstick meters.
Symphony waiting for FDA approval for clinical trial likely in the Prelude® SkinPrep System, as a platform technology to enhance drug delivery of topical pharmaceuticals.
expects to begin clinical trials for FDA approval for its GlucoTrack model DF-F device in 2014.
PEC costs $100; replaced every 6 months vs Invasive measurement costs $1.00 each
Glucotrach: Ultrasonic, electromagnetic and heat capacity technique, compatible with glucometer but currently on hold by the company for further improvement and better calibration
GlucoTrack Ear Lobe Meter
(Approved in Europe 2009, awaiting FDA approval)
Symphony® CGM
Needle free transdermal sensor

33. Non invasive glucose monitoring
The lenses use a minuscule glucose sensor and a wireless transmitter
Occlusion near infrared spectroscopy
OrSense: Occlusion near
infrared spectroscopy

34. First Combined Glucose Sensor and Insulin Infusion Set
Combined infusion set and sensor electrode
MiniMed® Duo(TM) launched in Europe in June 2014.
change one device every 3-days

35. Asante Solutions’ Pearl/Snap Pump
Insulin Pumps
Asante Solutions’ Pearl/Snap Pump
FDA approved May 2011
Now Bigfoot
Tandem’s t:slim pump
FDA approved spring 2012
Pearl Pump: only pump that uses a pre-filled 300 unit insulin cartridge. Wired pump.
Tandem t:slim pump: Patented system of insulin delivery, 25% thinner than current pumps (size of a credit card), USB-rechargeable battery, looks like a smartphone, high contrast color touch screen, holds 300 units of insulin
OmniPod

36. Insulin Pump Comparison
Medtronic Revel/Medtronic 530G
Animas Ping/Animas Vibe
Tandem t-slim/t:slim G4
Omnipod
Starting Minimum Basal Rate (units/hour)
0.025
0.025 increments
0.100
0.01 increment >0.1unit/hour
0.05
0.05 increments
Reservoir Volume (units)
180 or 300
200
300 or 450 (t-Flex)
(minimum fill is 100 units)
(minimum fill is 85 units)
Linked Meter/Remote
Linked meter – Bayer Contour Next Link
Meter/Remote One Touch Ping
No meter/remote with Vibe No
Meter/Remote uses Freestyle strip
CGM Integration
Yes
Enlite sensor and Low Threshold Suspend with 530G only
No CGM with Ping
Yes, Vibe integrated with Dexcom G4 CGM
No CGM with t-slim
Yes, t-slim G4 integrated with Dexcom G4 CGM
Battery
1 AAA, meter is charged via USB
1 AA (can use lithium) for pump, 2 AAA for Ping meter/remote
Must charge min daily via USB
2 AAA
Waterproof
Protected against water immersion
waterproof, 12’ for 24 hours; meter/remote not waterproof
Watertight
Pod is waterproof; PDM is not waterproof
Max Bolus 25 35
25/ T-Flex 60 30
Downloading at home
Carelink (web-based)
Diasend (web-based)
T-Connect(web-based)
Omnipod Partner (web-based)
Tubeless/Infusion Sets
Not tubeless; variety of sets, tubing and cannula lengths
Not tubeless; variety of types, tubing and cannula lengths
Pod – one size only
Only Tubeless pump

37. Medtronic’s 670G Phase 3 Clinical Trial
“hybrid-closed loop” system with Enlite 3 CGM sensor
Software automatically increases/decreases insulin delivery to target a blood glucose of 120 mg/dl
Give bolus for meals
Notify - exercise

38. Future Patch Pumps JewelPUMPTM
The JewelPUMP2 is opening entirely new possibilities for Diabetic Type 2 patients, including improved convenience of use, very easy programming with simplified basal-bolus selection and automatic Meal correction, as well as real-time remote communication and assistance.
Debiotech Jewel: Pod portion is relatively flat and looks comfortable. Has a bladder of insulin that will hold up to 450 units. No separate controller – will be controlled by an Android-platform smartphone. “controller app” disables other functions of your phone while you are programming your pump. PIN-code locked. Detachable. Expected to be ready for market in 2011, pending FDA approval.
Debiotech’s Nanopump: volumetric membrane pump, with a pair of check valves, integrated in a MEMS chip. The chip is a stack of 3 layers bonded together: a silicon on insulator (SOI) plate with micromachined pump-structures and two Pyrex cover plates with through-holes. More info is available at .
**Animas/Lifescan went into licence and development agreement with Debiotech in 2004.**
The JewelPUMPTM is a miniaturized Patch-pump with 500U insulin for up to 7 days use. The disposable unit is filled once and discarded entirely after use, while the controller unit (incl. the electronics) can be used for 2 years, making it the most cost effective and environmental friendly disposable pump for diabetes care.
Debiotech Jewel
Micro-chip
7 day wear
500 IU of insulin
Clinical trials in France
(FDA application filed 2014?)

39. Patch Pumps Cellnovo France & UK Medingo Solo Roche
(FDA approved in July 2009)
Medingo Solo: patch pump with disposable and reusable parts, detachable from the site. Has bolus buttons on the pump itself. Holds 200 units of insulin. Has pediatric approval (Jan. 2010). Medingo was acquired by Roche in April The Solo is expected to launch sometime in 2012.
Calibra Finesse: simple to use and elegant insulin dispensing device. Does not contain any electronics. Holds 200 units of insulin. Each button push corresponds to either 1 or 2 units per press. Working on 5 units/press for T2DM and 0.5 units/press for peds. Can be worn for 2-3 days. Device works well under extreme cold conditions.
Valeritas V-Go: the first simple, fully disposable device for the delivery of basal-bolus insulin therapy for adults with diabetes. Designed for T2DM. Not electronic. for the continuous subcutaneous delivery of insulin in preset basal rates and with on-demand bolus dosing for adult patients requiring insulin. V-Go devices will be available in a preset basal rate to deliver 20, 30, or 40 Units of insulin in one 24-hour period (0.83 U/hr, 1.25 U/hr or 1.67 U/hr, respectively) and on-demand bolus dosing in 2 Unit increments (up to 36 Units per one 24-hour time period). The V-Go offers a simple way to deliver basal-bolus therapy.
Valeritas V-Go
(FDA approved in Dec. 2010)
Preset basal rate to deliver 20, 30, or 40
Bolus dosing in 2 Unit increments up to 36 Units
Calibra Finesse
(FDA approved in Jan. 2010)
Launch in 2016
200 units of insulin
Bolus only pump 1-2 units of Insulin / unit boluses )

40. Insulin types

41. New Insulins/ Alternate Routes of Insulin Delivery
Viaject (in Phase III development) – works faster than all existing insulins, mimics first-phase insulin response
Afrezza Technosphere inhaled insulin (MannKind) – works like first-phase insulin response (FDA approved – Adults)
Oral-lyn buccal spray insulin
SmartInsulin (SmartCells, Inc.)
Insulin Patch (PassPort)

42. VIAject™
Closely mimics natural spike of first-phase insulin release in non-diabetics
Lower dose of insulin required to adequately cover a meal compared to Humalog®,
Reduces the amount of insulin that remains in the bloodstream several hours after a meal
May prevent weight gain

43. Inhaled insulin AFREZZA® Exubera
Peak insulin levels are achieved within 12 to 15 minutes of administration. Dry particle Proprietary Technosphere particle.
T(max) for insulin – mins
Duration of action 2-3 hours
Proven reductions in HbA1c
A reduced risk of hypoglycemia vs. rapid-acting analogs
Less weight gain vs. rapid-acting analogs
Injection-free insulin deliver
In clinical trials of up to two years duration in Type 1 and Type 2 adult patients with diabetes, observed changes in lung function were small, did not progress and resolved when AFREZZA treatment was discontinued. The most common respiratory side effect experienced with AFREZZA in trials was a mild, transient, non-productive cough. Discontinuation due to cough was uncommon.
Small decline in FEV1 after 24 months of continues treatment from baseline. Difference disappear one month after d/c.
The FDA now has until July 15, 2014 to make a decision on Afrezza
Exubera was withdrawn from the U.S. market in 2007 due to lack of consumer demand for the product
Exubera

44. Smart insulin Patch Glucose-responsive insulin.
Microneedles
Glucose-responsive insulin.
Glucose sensing enzymes
Studied in animal models
Used for 9 hrs
Courtesy: Zhen Gu. Ph. D NC State University

45. 2011
U.S. Senators, Clinicians and People with Type 1 Diabetes Urge FDA to Issue Clear and Reasonable Guidance on Artificial Pancreas
In Just 23 Days, Over 100,000 Individuals Sign Petition for the FDA to Advance, Not Delay, the Development of an Artificial Pancreas

46. Closed-Loop Systems – Hypoglycemia Prevention
Most of the severe hypoglycemic events occur at night 1
75% of hypoglycemic seizures in children 2
6% of the deaths (T1DM aged <40 yr) were due to “dead-in-bed” syndrome 3
Hypoglycemia occurred 8.5% of nights on open CGM 4
71% of youth didn’t respond to glucose sensor alarms during the night 5
Insulin + glucagon
Bolus and then suspend basal
Medtronic MiniMed 530G pump – auto-shutoff for lows (2 hour suspend) FDA approved
1 The DCCT , NEJM; 329(14):977-86,1993
2 Davis et al, Diabetes Care; 20(1):22-5,1997
3 Sovik and Thordarson, Diabetes Care; 22(l2):B40-2,1999
4 JDRF CGM Study group , Diabetes Care; 33:1004-8, 2010
5 Buckingham et al, Diabetes Technol Ther; 7:440-7,2005

47. Sensor Augmented Insulin Pumps (SAP)
Medtronic MiniMed 530G system
Threshold Suspend automatically stops insulin delivery when your sensor glucose values reach a preset low threshold giving you increased confidence for better control.
CGM integration provides readings every five minutes. Allowing you to identify trends and make adjustments to your lifestyle or treatment
Predictive alerts notify you up to 30 minutes before you reach a certain sensor glucose level. Helping you to react sooner to low and high sensor glucose levels
Accurate Enlite sensor features a 31% improvement in overall accuracy versus Sof-sensor® glucose sensor5,6.
More reliable detection of high and low glucose levels
Bolus Wizard calculates an insulin bolus amount with minimal button pushes, making life easier and helping prevent calculation errors.
Enlite sensor detects up to 93 percent of hypoglycemia episodes when predictive and threshold alerts are on
Animas Vibe system )

48. Sensor-Augmented Pump Therapy for A1C Reduction (STAR 3) Study
45% of SAP achieved HbA1c targets
20% on MDIs
HbA1C reduction of 1.2 percent
No increase in the rate of hypoglycemia
Slover RH at el. Effectiveness of sensor-augmented pump therapy in children and adolescents with type 1 diabetes in the STAR 3 study. Pediatr Diabetes Feb;13(1):6-11.
NEJM 2010– Medtronic sponsored trial

49. Counter regulatory delivery
Day and night use of bihormonal artificial pancreas system has been shown to reduce both mean glycemia and hypoglycemia.

50. Ilet –”Bionic Pancreas”

51. Bionic Pancreas – the iLet Dual Chamber pump Glucagon and Insulin Reservoir

52. iLet – Carb entry feature

53. Bi-hormonal pump CGMS - Case Study

54. The burden of diabetes: so much to consider
What affects my diabetes and what I need to know:
– Blood glucose
--HbA1c
– Food
– Activity
– Insulin
– Illness
– Stress level
What I need to carry:
– Insulin pump
– Blood glucose meter
– CGM
– Computer
– Internet access
– Mobile phone
– Instruction manuals
--Too much information!
-- Too many devices!

55. The burden of diabetes Who needs to know about my diabetes?
– The hospital doctors
– PCP
– CDE/ diabetes nurses
– The dietitian
– The family
- School
– The pharmacy
– The pump supplier
Too many people!

56. Nightscout – CGM in the Cloud
Allows real time access to a Dexcom G4 CGM from web browsers via smartphones, computers, tablets, and the Pebble smartwatch
You can see your child’s real-time sensor readings while they are away from you
Requires cable, dedicated Android phone
iPad, iPhone, Pebblewatch set-up info

57. OPEN APS
The Open Artificial Pancreas System project is an open and transparent effort to make safe and effective basic Artificial Pancreas System (APS) technology widely available to more quickly improve and save as many lives as possible and reduce the burden of Type 1 diabetes.

58. OPEN APS Insulin pump and CGM
Centralized controller - Raspberry Pi mini-computer
USB or Bluetooth connection capability
Translator device such as a Carelink USB
Wireless Internet connection

59. OPEN APS /DoItYourself
 Parents/Friends/Patients – Coders/programmer
Algorithms based on
CGM
Insulin on board
Carbohydrate decay
 Calculated on active insulin
 Real-time predictive alerts for future high or low BG states (hours in advance)
 Continually updated recommendations for required insulin or carbs
DIYPS (the Do-It-Yourself Pancreas System)

60. Have a app for that Diasend Glooko Logbook - Free
dLife Diabetes Companion
MyNetDiary™
Moves
Ontrack
Glucose buddy
Insulincalc
Diasend

61. Glooko
Compatible with 50+ Meters, Insulin Pumps and CGMs, Paid service for patients and HCP

62. Downloading and Interpreting Data
Dexcom Clarity
Medtronic Carelink Personal
Software downloaded from website
Iphone PC compatible
Uses USB cable
Sensor data
Can reports
Diasend, GlooKo, Tidepool
Web-based
PC and MAC compatible
Use USB cable
Sensor Data
Can have linked to CHOC database
Web-based
PC and MAC compatible
Uses Carelink USB or Bayer Contour Link USB
Sensor and Pump data combined
Can have data linked to MD Office database

63. TidePool – platform that will allow you to download all of your devices to one place and view all of the data on one report Animas, Asante, Dexcom, OmniPod, Tandem, and Abbott

64. Developments in Type 2 Diabetes Mellitus

65. Traditional Oral Medications
Metformin – Insulin Sensitizing agent
Before starting metformin, obtain the patient’s eGFR.
Contraindicated in patients with an eGFR below 30
eGFR between 30 and 45 mL/minute/1.73 m2 is not recommended.
Obtain an eGFR at least annually
Sulfonylureas - Stimulate insulin release
Cardiovascular mortality was lower in those taking metformin vs sulfonylureas.
Metformin-containing drugs: Drug safety communication - revised warnings for certain patients with reduced kidney function [news release]. Silver Spring, MD: FDA; April 8,

66. Sodium Glucose Co transporter -2 SGLT2 inhibitors
FDA warning regarding increased Ketoacidosis
Others
dehydration
kidney problems
Hypoglycemia
Increased cholesterol
Yeast infections

67. SGLT2 inhibitors
SGLT2 inhibitors lower blood sugar by causing the kidneys to remove sugar from the body through the urine.
Generic
Brand name
Canagliflozin
Invokana
Canagliflozin and metformin
Invokamet
Dapagliflozin
Farxiga
Dapagliflozin and metformin extended-release
Xigduo XR
Empagliflozin
Jardiance
Empagliflozin and linagliptin
Glyxambi

68. Glucagon like peptides GLP-1 agonists
Generic
Brand name
exenatide
Byetta/ Bydureon (ER)
liraglutide
Victoza, Saxenda (Obesity)
albiglutide
Tanzeum
dulaglutide
Trulicity
Stimulates insulin secretion
Inhibits glucagon secretion
Lowering blood sugar
Shorter-acting agonists
lowering post-meal glucose spikes
Long-acting
Effect both post-meal and fasting glucose levels

69. GLP-1 agonists CI:- MEN 2 SYNDROME Medullary thyroid carcinoma
personal or family history
Pancreatitis
Gallbladder disease
Renal impairment
Suicidal thoughts

70. DPP-4 Inhibitors Inhibits enzyme DPP-4 Increases GLP-1
Stimulates insulin production
Lowers glucagon  
Generic
Brand Name
Alogliptin
Nesina
Linagliptin
Tradjenta
Saxagliptin
Ongglyza
Sitagliptin
Januvia
Increased risk of hospitalization for heart failure

71. TZDs activate a protein PPAR g decreasing insulin resistance.
Generic Name
Brand Name
pioglitazone
Actos
rosiglitazone
Avandia
activate a protein PPAR g
decreasing insulin resistance.
Lower BG levels
Needs to monitor LFTs

73. Summary
Immune therapies to slow or alter the autoimmune process are Evolving
Pump and Sensor technologies are evolving rapidly
Closed loop systems will be leading the future
Insulin only algorithms
Insulin + Glucagon (bi-hormonal)
Diabetes providers would need more exposure to newer technologies
Tech savvy parents or patients will be expecting more from providers, drug & device manufacturers and FDA
Type 2 Diabetes Mellitus – Much more treatment options
In Pediatrics – Insulin & Metformin

74. Questions?