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2	"`In the past we..." `In the past we had a light that flickered, in the present, a light that flames, and in the future we will have a light that shines over all the land and the sea’ Winston Churchill
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4	Limitations/Challenges to Better Glycemic Control A1c’centric Hypoglycemic Risk Glucose excursions above and below what the HbA1c average represents may be more important than HbA1c Inadequate Postprandial Glucose Control Weight Gain
5	Obstacles in Glycemic Control Invasive glucose monitoring devices-owie!!!!! Limited availability of reliable continuous glucose monitoring Lack of alternate routes of insulin delivery.
6	Alternate Site Glucose Testing (Forearm, Thighs, Abdomen vs. Fingers) Rubbing/exercising/suction does not uniformly increase the blood flow but glucose values may be better correlated to fingers. At extremes of glucose values fingerstick testing is mandatory for confirmation. Rapid changes in glucose values, fingers are the best
7	Alternate Site Glucose Measurements
8	MAJOR RESEARCH CHALLENGES? CLINICALLY Development of new methods for achieving tight control without hypoglycemia RESEARCH Development of methods for replacing beta cell function (islet cell transplantation, artificial pancreas) Enhanced understanding of immunopathogenesis (interaction of genes, environment and immune system) allowing for more effective preventative therapies
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10	TOWARDS CLOSED LOOP DELIVERY
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15	"Why do we need Glucose..." Why do we need Glucose Sensors?
16	Model of Multihormonal Regulation of Glucose Homeostasis
17	Excessive 24-Hour Glucose Fluctuations in Type 1 Patients with Mean A1C of 6.7%
18	Intensively-treated T1DM: Diurnal Glucose Fluctuation and Nocturnal Hypoglycemia
19	Blood Glucose Values (SMBG) Needed to Attain Different HbA_1C Values
20	Need for Continuous glucose monitoring Direction Magnitude Duration Frequency Cause of fluctuation Alerts/Alarms Improve therapeutics decisions
21	Glucose Sensors Continuous Glucose Monitoring System (CGMS) GlucoWatch Automatic Biographer Navigator Near-InfraRed (NIR) Implantable glucose sensors-Dexcom Optical sensors Ultrasonic sensors
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23	MiniMed^® Continuous Glucose Monitoring System (CGMS)
24	GlucoWatch^® Biographer
25	Schematics of the Autosensor & Biographer
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28	Sensors in Development
29	"Role of Frequent Glucose Monitoring" Role of Frequent Glucose Monitoring
30	More Frequent Testing Improves HbA_1cin Type 1 Patients
31	Current Medical Practice
32	With the GlucoWatch® Biographer
33	Measurement of Blood Glucose Conventional Blood Glucose Meters
34	Continuous Subcutaneous Glucose Monitoring in a Subject with Type 1 Diabetes
35	Technical Aspects of Continuous Glucose Monitoring Interstitial vs. Blood glucose –reported Lag of few seconds to 15 minutes High frequency of measurements Signal Stability –Quick and over time Calibration Issues Duration of Sensor application
36	Limitations with Current Technologies SMBG Solitary Data points with no trend information CGMS No real time feedback, 4T/day calibration Unreliable data, size of the needle GlucoWatch - Prospective data but too many skips,12 hr.sensor - Skin irritation, Sweating,Temperature changes * HbA1c and Fructosamine Assay Purely retrospective No immediate Feedback
37	Device Description: Sensor DexCom G1 Sensor Subcutaneous implant in the abdominal wall Multi-layer membrane system Measures glucose every 30 seconds Wireless transmission to receiver
38	Device Description: DEXCOM Receiver Long Or Short Term Use
39	Profile With Continuous Glucose Sensor in Patients With Insulin-requiring Diabetes
40	Slicing the Pie from DCGM Sensor Downloads Blinded vs. Unblinded phases (n=14)
41	Results (G2)
42	Results (G2)
43	Closing the Loop: The Artificial Pancreas Accurate, reliable continuous glucose monitoring systems, in progress Algorithms to incorporate glucose trend data into proper dose adjustments External or internal insulin pump systems
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46	Until the Cure-The Realities: Learn to manage glucose TRENDS rather than isolated numbers Minimize the moodiness associated with wide glucose excursions Understand glucose profiles over extended time Improve implementation of new regimens Knowledge and acceptance of inaccuracies and data interpretation
47	Conclusions Continuous glucose monitoring promises the goal of normalization of blood sugars while minimizing risk of hypoglycemia The result of full implementation will be normal HbA1c with further reduction in complications of diabetes A closed loop, artificial pancreas either externally or internally based is now on the horizon
48	Implantable pump Implanted under the skin of the abdomen through a minor surgical procedure. Controlled today by hand-held radio frequency telemetry. Delivers short, frequent pulses of insulin into the peritoneal cavity. Designed to be refilled in a physician’s office every 3 months. Projected 10 year battery life. Hypoglycemic events reduced 400%.
49	Out-takes from a Web Blog Of RT User “Now, I never look at a single reading. I check my NOW number and then quickly scroll back in time using the down arrow button. Five minutes per click. I usually glance at half an hour…I think about what I’m looking at. Direction? Is the BG going up or down? Or is it fairly stable? Speed? Speed I’m not always so good at, because that takes mental mathematics, which is my weak spot. That said I can get a rough idea of how fast things are moving.”
50	THE RUB Even if the continuous sensors are refined, reimbursement for the devices as well as for providers’ time to help analyze data remains a problem. As things now stand, relatively few doctors and nurses have the time or expertise to assess the log records of individual glucose readings.
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