1. 1
Type 1 Diabetes:
Progress Toward its Prevention,
Treatment, and Cure
Julia Greenstein
JDRF VP Cure therapies
jgreenstein@JDRF.org
April 9, 2013

2. JDRF Mission: Cure, Treat, and Prevent T1D
Cure T1D by removing the
disease from the lives of our
loved ones
CureCure
Better ways to Treat T1D so
people can live healthier
lives more conveniently
TreatTreat
Prevent T1D from occurring
& stopping it early
Prevent

3. 3
Our Goal: Life Changing Therapies…
Leading to a World Without T1D
Clinical
Development
Regulatory
ADVOCACY
RESEARCH
ADVOCACY
RESEARCH
ADVOCACY
RESEARCH
Delivery
to Patients
Discovery
Research
 Proactively accelerate the discovery, development, and
delivery of drugs and devices to cure, better treat, and
prevent type 1 diabetes and its complications.

4. JDRF Partners
4
 Proactively accelerate the discovery, development, and
delivery of drugs and devices to cure, better treat, and
prevent type 1 diabetes and its complications.

5. JDRF Mission: Cure, Treat, and Prevent T1D
Cure T1D by removing the
disease from the lives of our
loved ones
CureCure
Better ways to Treat T1D so
people can live healthier
lives more conveniently
TreatTreat
Prevent T1D from occurring
& stopping it early
Prevent

6. Cadaver Islet Transplantation
Limitations
•Islet source
•Immunosuppression
Success
•50–60% 5-yr insulin independence;
•80–90% reversal of hypoglycemia
unawareness

7. Human Embryonic Stem Cell-Derived Islet
Sources: Progenitors Mature to Islets In-Vivo

8. • Physical barrier to protect islets from immune responses
• Barrier should allow islets to survive and function, sensing glucose
and releasing insulin physiologically
Dr. Tejal A. Desai UCSF
Encapsulation of Islet or Islet Precursor for
Immunoisolation

9. Diabetes 50:2020 (2010)
In this individual, after more than 50 years of type 1 diabetes,
•every islet had at least one insulin positive beta cell (left)
•replicating beta cells cells were also found (right)
After 50 years of type 1 diabetes, beta cells can
still be present

10. Beta Cell Regenerating Therapy
SurvivalSurvivalReplicationReplicationNeogenesisNeogenesis
Progenitor
cell
De-differentiated
beta cell
Alpha cell
Reprogramming-
TransdifferentiationRedifferentiation
Differentiation

11. JDRF Mission: Cure, Treat, and Prevent T1D
Cure T1D by removing the
disease from the lives of our
loved ones
CureCure
Better ways to Treat T1D so
people can live healthier
lives more conveniently
TreatTreat
Prevent T1D from occurring
& stopping it early
Prevent

12. 12
0
10
20
30
40
50
60
70
1950 1960 1970 1980 1990 2000
Finland
Sweden
Colorado
Germany
Cases/100,000/yr
in children 0-14 yrs
T1D Incidence (# new cases/yr) is doubling
every 20 yrs (~3-4% annual increase)
Burden: Increasing Incidence of T1D

13. Relative Percent Increase of
Type 1 Diabetes Incidence in
Finland 1965-1996 (32 yrs)
Type 1 Diabetes is Occurring Earlier in Life
Projected Age-Incidence of T1D
from 2006-2020 in Finland
Lancet: 371:1777, 2008

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Rationale for T1D Prevention
 Risk of developing T1D can
be diagnosed
 T1D develops with a relatively
predictable course with
variable rate of progression
 Rate of progression to insulin
dependence can be predicted
Adapted from Eisenbarth
100%
0%
FunctionalBetaCell
Mass
At Risk Pre-Diabetes
Recent
Onset Established Diabetes
Diagnosis
Time
Genetic
Risk +
Environmental
Etiologies
Beta Cell
Autoimmunity
Beta Cell
Loss
Glucose
Intolerance
Insulin
Dependence

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T1D Prevention Interventions
Adapted from Eisenbarth
100%
0%
FunctionalBetaCell
Mass
At Risk Pre-Diabetes
Recent
Onset Established Diabetes
Diagnosis
Time
Beta Cell
Autoimmunity
Beta Cell
Loss
Glucose
Intolerance
InsulinInsulin
Dependence
Primary
Prevention
Secondary
Prevention
Genetic
Risk +
Environmental
Etiologies

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Approaches to Prevent T1D
 Primary Prevention
Viral vaccines: Enteroviral vaccine
Microbiota-induced immunoregulation related
“vaccines”
Beta cell autoantigen tolerogenic vaccines
 Secondary Prevention
Beta cell autoantigen tolerogenic vaccines
Beta cell survival agents

17. JDRF Mission: Cure, Treat, and Prevent T1D
Cure T1D by removing the
disease from the lives of our
loved ones
CureCure
Better ways to Treat T1D so
people can live healthier
lives more conveniently
TreatTreat
Prevent T1D from occurring
& stopping it early
Prevent

18. Mean
HbA1c
 2011-2012 data
 67 Clinics
 n = 24,116
Poor Glucose Control in T1D in USA
Despite Care at State-of-the-Art Clinics
(HbA1c should be <7.0% to avoid complications)
Goal: HbA1C <7.5% Goal: HbA1C <7%
18

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Closed Loop Artificial Pancreas Systems:
Simulate a normal pancreas
• Requires:
- Improved glucose sensors
- Improved Insulins + other
drugs (glucagon)
- Improved control software
- Dual/multi-chamber pumps

20. 20
11
Very Low Glucose
Insulin Off Pump
Pump Shuts off
when user not
responding to
low-glucose alarm
22
Hypoglycemia
Minimizer
Predictive
hypoglycemia
causes alarms
followed by
reduction or
cessation of
insulin delivery
before someone
gets low
33
Hypoglycemia/
Hyperglycemia
Minimizer
Same as Product
#2 but added
feature allowing
insulin dosing
above high
threshold
(e.g., 200mg/dl)
44
Automated
Basal/Hybrid
Closed Loop
Closed loop at
all times with
meal-time manual
assist bolusing
55
Fully Automated
Insulin Closed
Loop
Manual meal-
time bolus
eliminated
66
Fully Automated
Multi-Hormone
Closed Loop
First
Generation
Second
Generation
Third
Generation
Progression to Artificial Pancreas Systems
There Will Be Multiple Generations: Each Becoming More Automatic

21. Overnight Closed-Loop Control will be Early Success
and Important (55-75% of Severe Hypoglycemia at Night)
• Lowers glucose variability
• Controls to a tight range (71% vs 43% in range)
• Reduces extreme hyperglycemia and
hypoglycemia (2.1% vs 4.1% <70mg/dl).

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Thank you!