Presentation on theme: "Update on Artificial Pancreas Project"— Presentation transcript:
1 Update on Artificial Pancreas Project Are We There Yet?Eda Cengiz, MD, MHSAssistant Professor of PediatricsYale University School of Medicine
2 Artificial Pancreas / Bionic Pancreas ? utilizing electronic devices and mechanical parts to assist humans in performing difficult, dangerous, or intricate tasks, as by supplementing or duplicating parts of the bodyArtificial intelligence runs the algorithm
3 The Promise of Artificial Pancreas Glucose SensorAlgorithmInsulin Pump & InsulinSensor signals transmitted to a laptop computer that displays the sensor glucose and calculates rate of insulin deliveryRate of insulin delivery is transmitted to the insulin pumpDetermine insulin requirement real time, deliver proper insulin to achieve euglycemia.
4 Medtronic Closed-loop System c. 2011 CGMInsulin PumpLaptopControllerWe brought 17 teenagers into the inpatient HRU for 36 hours of closed loop control. As you can see, they had two sensors placed, and a standard insulin pump capable of receiving RF signals. We used a laptop to run the algorithm. The next round of studies will use the smaller transmitter and also a smaller handheld PDA-like device. We had IVs placed so we could measure venous blood glucose levels every minutes during the study.
5 When is it going to be ready? During a Typical Clinic Visit at Yale Diabetes Center…How is it going with the Artificial Pancreas Dr. C?When is it going to be ready?What is taking so long ?
6 Challenges & Solutions: Artificial Pancreas (Closed-Loop System) Glucose SensorsInsulin Delivery AlgorithmInsulin PumpsInsulin (ultrafast action)Progress to datePitfallsSolutionsFuture closed-loop studies(hot off the press!)
7 JDRF Road Map to Artificial Pancreas What is the plan?JDRF Road Map to Artificial Pancreas
8 Do we need to wait until we have the Fully Automated Artificial Pancreas?
9 Progress to dateArtificial PancreasSENSOR-AUGMENTEDPUMP THERAPY
10 CGM improved A1c, but not in everyone JDRF CGM Study Group. N Engl J Med 2008; 359:
11 Average Days of CGM Use by Age Group JDRF CGM Study Group. N Engl J Med 2008; 359:11
12 Medtronic STAR 3 Sensor-Augmented Pump Trial 3/27/2017Medtronic STAR 3 Sensor-Augmented Pump TrialThe SAP group achieved a greater A1C reduction vs. MDI at 3 months and sustained it over 12 monthsA1C Reduction for SAP and MDI Groups∆ -0.2- 0.6P<0.001- 0.6P<0.001∆ -0.8= MDI= SAPn = 244n = 241Values are means ± SE. Comparisons between SAP group and MDI group are significant for each time period (P<0.001).1212
13 A1C Reduction Correlates to Increased Sensor Use 3/27/2017A1C Reduction Correlates to Increased Sensor UseThe majority of patients used sensors ≥61% of the timePatients who used sensors ≥81% of the time reduced their mean A1C by 1.2% at 1 year vs. baselinen =27n =46n =108n =56Values are the difference between the means ± SE. p=0.003 for association between sensor wear and A1C reduction at 1 year. Only 7 participants had sensor use of 20% or less, with a change in A1C of at 1 year vs. baseline.13
14 DirecNet / TrialNet Metabolic Control Study Does the rapid normalization of BG levels at the time of diagnosis of diabetes, followed by super- intensive control of BG levels, help to preserve residual beta-cell function?Use of an artificial pancreas in subjects AT DIAGNOSIS for 3-4 days to rapidly normalize BG levels, followed by sensor-augmented pump therapy x 2 years
19 Progress to Date Artificial Pancreas PUMP SUSPENSION FOR ACTUAL HYPOGLYCEMIASENSOR-AUGMENTEDPUMP THERAPY
20 Prevention of Hypoglycemia with AP Insulin suspension prevented low BG (<60mg/dl) in 78% of the suspensions.Non resulted in hyperglycemiaReduction in CGM hypoglycemia alarms
21 A Semi-Closed-Loop System: The Paradigm® Veo™* Integrated sensorImproved Calibration RoutinesGlucose trendAlarmsOutside target zonePredictiveMissing insulin bolusMinimum basal rate of U/hHypoglycemia suspendSuspend for 2 hoursRe-suspend after 4 hours if neededKeenan et al., J. Diabetes Sci. Tech., 2010; 4(1):Buckingham et al., Diabetes Technol. Ther., 2009; 11:93-97Attia et al., Diabetes Care, 1998; 21:Guerci et al., J Clin Endocrinol Metab, 1999; 84:Zisser, Diabetes Care, 2008; 31:* Investigational device. Limited by U.S. law to investigational use.
22 Automatic Low-Glucose Suspend LGS offLGS onMean Glucose (mg/dL)145 ± 23148 ± 19Time < 70 per day (min)101 ± 6858 ± 33 *Time > 140 per day (min)651 ± 240639 ± 182* p=0.002Number of excursions < 70 and < 40 mg/dL reduced with LGSDanne T, Diabetes Technol Ther 2011; 13:
24 Automatic pump suspension for predicted hypoglycemia
25 Exercise AP Study objective To evaluate whether use of a AP system reduces the risk of delayed (nocturnal) hypoglycemia following antecedent daytime exercise
26 Exercise Study Protocol Schematic 48-hour evaluation period2 overnights48-hour evaluation period2 overnightsClosed-LoopClosed-LoopSubject recruitment, consent, enrollment(n = 12)Open-LoopOpen-LoopPlasma BG q30 min, insulin q30 min x meals
27 Nocturnal Hypoglycemia All Nocturnal Hypo114Night FollowingExercisep=0.0625222015Closed LoopNumber of Treatments GivenOpen Loop1053p=0.05
28 Glucose Frequency Distribution Night after sedentary condition 1 %99 %0%3 %90 %7 %The benefits of CL control following a sedentary day are even more pronounced when our target blood glucose is widened to mg/dL as 99% of CL reference blood glucose values fall within this range.P<0.0001
29 Glucose Frequency Distribution Night following afternoon exercise 3 %93 %4 %8 %76 %16 %When we expand our target range to mg/dL we see that 93% of our reference blood glucose fall within this range during the closed loop condition. The distribution of reference blood glucose levels closely follows the set point of our closed loop system.P<0.0001
37 Progress to date Artificial Pancreas CLOSED-LOOP MULTIHORMONAL FULL CLOSED-LOOP CONTROLCLOSED-LOOP MULTIHORMONALCLOSED-LOOP BASALMANUAL MEALSBASAL/BOLUS ACTIVATIONFOR HYPERGLYCEMIAPUMP SUSPENSION FORPREDICTED HYPOGLYCEMIAPUMP SUSPENSION FORACTUAL HYPOGLYCEMIASENSOR-AUGMENTEDPUMP THERAPY
38 AP Multi-hormonal Approach Can the addition of pramlintide improve the performance of a CL system by reducing the peak post-prandial glucose excursions?
39 Pramlintide Analog of human amylin Co-secreted with insulin from -cellUsed as adjunct to insulin in T1D to reduce post-prandial glycemic excursionsDelay gastric emptyingSuppress endogenous glucagon
40 Closed-Loop + Pramlintide Pramlintide Study Protocol Schematic24-hour evaluation period3 meals (BF, L, Din)24-hour evaluation period3 meals (BF, L, Din)Closed-LoopClosed-LoopSubject recruitment, consent, enrollment(n = 8)Closed-Loop + Pramlintide(30 mcg per meal)Closed-Loop +Pramlintide(30 mcg per meal)Plasma BG q30 min, insulin q30 min x meals
42 Summary and conclusions Pramlintide had modest effect on prandial glucoseWould require manual injection or at best, manual bolusFaster insulin absorption / action clearly needed
43 ? Progress to date Artificial Pancreas FULL CLOSED-LOOP CONTROL CLOSED-LOOP MULTIHORMONALCLOSED-LOOP BASALMANUAL MEALSBASAL/BOLUS ACTIVATIONFOR HYPERGLYCEMIAPUMP SUSPENSION FORPREDICTED HYPOGLYCEMIAPUMP SUSPENSION FORACTUAL HYPOGLYCEMIASENSOR-AUGMENTEDPUMP THERAPY
44 What do we need to achieve AP? Glucose SensorsInsulin Delivery AlgorithmInsulin PumpsInsulin (ultrafast action)Better accuracy, user interface, reliability.Better algorithmOne site for CGM & Insulin
45 Single Port, Multiple Sensor One site, two catheters for insulin infusion and glucose sensingSingle port for CGM and insulinCGM with an optic sensor back up
46 What do we need to achieve AP? Glucose SensorsInsulin Delivery AlgorithmInsulin PumpsInsulin (ultrafast action)Better accuracy, user interface, reliability.Better algorithmOne site for CGM & InsulinFaster acting insulin
47 Dangerous Delays in Insulin Action after SC Injection Delays due to the chemical properties of insulin.Tissue delays
49 InsuPatchTemp. SensorThe InsuPatchTM device applies controlled heat around the insulin infusion site.
50 Peak aspart insulin action curve shifted to the left . The Effect of InsuPatch on Insulin Actionwith InsuPatch activation:Aspart insulin bolus maximum effect was 35 min earlier compared to the same dose bolus without InsuPatch activation .Peak aspart insulin action curve shifted to the left .
51 Hyaluronidase Mechanism of Action LAN030408ZXW ZXWHyaluronidase Mechanism of Action5151
52 DiaPortThe Accu-Chek DiaPort is a port system for continuous intraperitoneal insulin infusion.Fixation discPort bodyPolyester FeltMembraneCatheterInfusion set with ball cannulaThe catheter tip is placed in the peritoneal cavity where the insulin is directly infused.
53 Pathway to Closed-Loop (CL) InsuPatchClosed Loop studies at YaleDiaPortCL studies in France,? in USHyaluronidase(rhUPH20)CL studies are planned.
54 Platform and Connectivity for Ambulatory StudiesPump
55 ? Progress to date Artificial Pancreas Outpatient studies FULL CLOSED-LOOP CONTROLOutpatient studies?CLOSED-LOOP MULTIHORMONALCLOSED-LOOP BASALMANUAL MEALSBASAL/BOLUS ACTIVATIONFOR HYPERGLYCEMIAPUMP SUSPENSION FORPREDICTED HYPOGLYCEMIAPUMP SUSPENSION FORACTUAL HYPOGLYCEMIASENSOR-AUGMENTEDPUMP THERAPY