Diabetes through my eyes Rick Mauseth, M.D. W.A.D.E. April 2013
Ant hills
Total Available Glucose utilized Two drops of urine in test tube Add 10 drops of water Added tablet Foamed and got hot Compared to color chart Calculated glucose concentration/100ml times urine volume giving amout of glucose unutilized
Total Available Glucose Add up Carbohydrates Determine grams of protein as 40% Determine grams of fat as 10% Subtract urinary losses Gave you grams utilized Adjusted insulin accordingly
Physiological and Psychological effects of one versus two shots/day 1. Regular/nph 2. 2/3 in am, 1/3 in pm 3. TAG system 4. Two to three days prior to q 3 month visits
Chemstrip Bicolored strips Compare to container Took 2 minutes if high Could cut in quarters Teenagers
Humalog Insulin Number of people with diabetes increasing Pork consumption decreasing Potential shortage of insulin??faster insulin
DCCT study 1. 1441 patients 2. 13-39 years old 3. 6/7 disqualified 4. A1c <12 in control group 5. Adults 7.4% 6. Adolescents 8.3% 7. ADA goals 8. Control does make difference
DCCT results 76% reduction risk for progression of retinopathy 54% reduced clinical albuminuria 60% decrease in risk of neuropathy Cost for decreased risk was higher risk of hypoglycemia
2003 in Woodinville
Edmonton Protocol 1. Transplants 2. Immunosuppression 3. Funding 4. Didn t last and not enough islets
Pumps and meters 1. smaller 2. better 3. more user friendly 4. bolus calculators
Sensors Originally long needle Lots of Noise Lag period for blood sugar to venous sugar Biofowling Short duration
Participating JDRF/NIH AP Sites 17 sites worldwide running clinical trials, providing engineering resources, or doing both: Dose Safety Oregon W. Ontario Mayo Boston Yale Cambridge W. Australia Stanford Rensselaer Harvard Colorado Virginia Montpellier Pavia/Padova UCSB/Sansum Israel
Controllers 1. Proportional Integral Derivative 2. Model Predictive Controller 3. Fuzzy logic
Fuzzy logic Thermostat picture
Fuzzy Logic Response to Rising BGL D A B C E F G H BGL Rate (mg/dl/min): Very Negative, Negative, Zero, Positive, Very Pos. BGL Accel: (mg/dl/min/min) Negative, Zero Positive VN: < -2.50 N: -1.25 Z: 0.0 P: 1.25 VP: > 2.5 N Z P N Z P N Z P N Z P N Z P BGL Trajectory >250 mg/dl G H F E 180-250 mg/dl 120-180 mg/dl 80-120 mg/dl A B D C < 80 mg/dl
JDRF Innovative Technology Grant 2008 Diabetes Technology meeting In silico testing Economy and JDRF funds
2:09 PM 2:29 PM 2:49 PM 3:09 PM 3:29 PM 3:49 PM 4:14 PM 4:34 PM 4:44 PM 5:04 PM 5:24 PM 5:44 PM 6:04 PM 6:24 PM 6:44 PM 7:04 PM 7:24 PM 7:39 PM 7:59 PM 8:19 PM 8:39 PM 8:59 PM 9:19 PM 9:39 PM 9:59 PM 10:19 PM 10:44 PM 11:04 PM 11:24 PM 11:44 PM 12:04 AM 12:24 AM 12:44 AM 1:04 AM 1:24 AM 1:44 AM 2:04 AM 2:24 AM 2:49 AM 3:14 AM 3:34 AM 3:54 AM 4:14 AM 4:34 AM 4:54 AM 5:14 AM 5:34 AM 5:54 AM 6:14 AM 6:34 AM 6:54 AM 7:14 AM 7:39 AM 7:59 AM Units of insulin 2:09 PM 2:29 PM 2:49 PM 3:09 PM 3:29 PM 3:49 PM 4:14 PM 4:34 PM 4:44 PM 5:04 PM 5:24 PM 5:44 PM 6:04 PM 6:24 PM 6:44 PM 7:04 PM 7:24 PM 7:39 PM 7:59 PM 8:19 PM 8:39 PM 8:59 PM 9:19 PM 9:39 PM 9:59 PM 10:19 PM 10:44 PM 11:04 PM 11:24 PM 11:44 PM 12:04 AM 12:24 AM 12:44 AM 1:04 AM 1:24 AM 1:44 AM 2:04 AM 2:24 AM 2:49 AM 3:14 AM 3:34 AM 3:54 AM 4:14 AM 4:34 AM 4:54 AM 5:14 AM 5:34 AM 5:54 AM 6:14 AM 6:34 AM 6:54 AM 7:14 AM 7:39 AM 7:59 AM mg/dl 75 gm meal 30 gm snack Dosing 400 350 300 250 200 150 100 Picture of CGMS and dosing- a good patient- 50 Subject 204V1 Gender: Female, TDD: 30.8, PF: 5, IC: 10, CF: 40, BMI: 29.6 CGM 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 Commanded Doses Dose
Protocol Pilot Study 26 hours Subject Give 75% bolus Subject Arrives Closed Loop Started Breakast 30g CHO Pilot Lunch 60g CHO End of Study 5:00p 6:00p 8:00p 8:00a 2:00p 8:00p Equipment: Omnipod insulin pump Dexcom Seven+ CGM UCSB ver 2.9 APS System Laptop PC Version 1.5 FL Controller YSI 2300 Plus Glucose Analyzer Enrollment: Initiation No pre-meal bolus or announcement Totally automated
Endpoints by time period (n=8) YSI Endpoints All Time Periods Hyperglycemia correction Diurnal Variation Small Meal Moderate Meal 8p-8p 8p-2a 2a-8a 8a-2p 2p-8p Average BG (mg/dl) 165.1 159.7 129.7 174.9 195.2 Lowest BG (mg/dl) 68.0 82.0 68.0 88.0 88.0 Highest BG (mg/dl) 342.0 342.0 215.0 255.0 266.0 Time BG 70-200 mg/dl (%) 76.3% 79.8% 97.6% 72.6% 55.4% Time BG < 70 mg/dl (%) 0.1% 0.0% 0.6% 0.0% 0.0% Time BG >200 mg/dl (%) 23.5% 20.2% 1.8% 27.4% 44.6% Low blood glucose index (LBGI) 0.2 0.2 0.6 0.0 0.0 High blood glucose index (HBGI) 7.1 6.5 2.2 8.0 11.3 Area above curve <70 mg/dl*min 4.3 0.0 4.3 0.0 0.0 Area under curve >200 mg/dl*min 11817.3 4236.4 122.1 2941.6 4517.1
Overnight Endpoints (n=8) Overnight YSI Endpoints Midnight - 7:30a Midnight - 8:00a 9:30p to - 8:00a Time BG < 70 mg/dl (%) 0.0% 0.4% 0.3% Time BG 70-144 mg/dl (%) 62.4% 62.1% 58.8% Time BG 70-180 mg/dl (%) 91.9% 92.0% 84.4% Time BG >180 mg/dl (%) 8.1% 7.6% 15.3% Time BG >200 mg/dl (%) 6.2% 5.8% 10.0%
BG (mg/dl) Average Time Histories (n=8) 350 300 Sensor BG Avg YSI BG Avg 250 200 150 100 50 0 20:00 22:00 0:00 2:00 4:00 6:00 8:00 10:00 12:00 14:00 16:00 18:00 20:00
In-silico Version 2.1 15 0 18 1 Version 2.0 11 5 13 8 16 3 Version 2.1 95
Our present system
Personalization factor 1. Can adjust for individuals 2. Can change for different circumstances, Thanksgiving, marathons 3. Designing to manage 95% of time 4. No premeal bolus, totally automated 5. Will be able to learn
Protocol High Carb Pizza Study Equipment: Omnipod insulin pump Dexcom Seven+ CGM UCSB APS System Laptop PC Version 2.0 FL Controller YSI 2300 Plus Glucose Analyzer Enrollment: Initiation No pre-meal bolus or announcement Totally automated
Selecting PF Selec ng PF PF5 No Low Low 1 st Test BGavg<160 BGavg>160 Done (Use PF5) PF4 PF6 No Low BGavg<160 Low No Low Low 2 nd Test BGavg>160 Done (Use PF4) Done (Use PF5) Done (Use PF6) PF3 PF7 No Low Low No Low Low BGavg>160 PF2 (if possible) BGavg<160 Done (Use PF3) Done (Use PF4) Done (Use PF7) PF8 (if possible) 3rd Test
Delta BG mg/dl (YSI) High Carb Study Summary (n=9) 300 250 200 Subject 201 202 203 150 PF5 PF4 100 PF3 50 0 0.80 1.00 1.20 1.40 1.60 1.80 2.00 Normalized Insulin use (PF 5, 4, 3)
Protocol Exercise Study Equipment: Omnipod insulin pump Dexcom Seven+ CGM UCSB APS System Laptop PC Version 2.0 FL Controller YSI 2300 Plus Glucose Analyzer Enrollment: Initiation No pre-meal bolus or announcement Totally automated
Exercise Study Result (n=2) Blood Glucose History (mg/dl) 204 205 Starting BG (2:00p) 145 111 Pre-Exercise BG 163 109 Post exercise BG 154 120 Pre-dinner BG 167 119 Nocturnal hypoglycemia no no Ending BG (8:00a) 150 154
Pizza and exercise on different days Pizza- blood sugar rise Difficult May need to modify need for temporary Change in PF Exercise for 30 minutes moderate exercise Works Marathons??
Bihormonal APS
Utilize technology from worldwide artificial pancreas program for camp study University of Virginia Diabetes Assistant (DiAs) hardware used for closed loop research Android smart phone computational and communication platform Could the remote monitoring component of the DiAs system be used to reduce severe hypoglycemia at diabetes camps? University of Virginia DiAs on Sony Ericsson smartphone
Remote Monitoring on ipad at Night
Computer screen display of Dexcom G4/UVa remote monitoring system: 10 campers (11 sensors)
Australian Patient
Duration of Events Below Thresholds Remote Monitoring Control Nights Number of Nights 161 179 <70 mg/dl <50 mg/dl >1 hour 7 33 > 2 hours 0 12 > 30 minutes 0 9 > 1 hour 0 6
Future systems 1. Android or I-phone 2. Sensor and patch pump in one device 3. Redundant sensor (one or two types) 4. Online transmission 5. GPS device 6. Motion sensor 7. Real time transmission to medical staff 8. Parents monitoring 9. Bipolar proteins 10. Single catheters 11. Faster insulin
Impact on Personnel Automated downloads Who s going to check download? Will this be reimbursed? Are you in control or is patient responsible? Will need to get hospital administrators and insurance companies to Buy In To idea May be more work less patient contact
When??? 1. Pizza (now) 2. Exercise (now) 3. Ad lib living in CRC (start July) 4. Remotely monitored in resort (January 2014) 5. Outpatient with daily transmissions automatically to medical staff (July 2014) 6. FDA approval, commercially available?????
Pathway to Prevention Did you know that your risk of type 1 diabetes is 15 x greater if you have a relative with t1d? Your risk can be determined through a simple blood test and follow up The risk test is available at no cost to family members of people with type 1 diabetes Three prevention trials are now open