RUT

1. Managing Curing Type 1 Diabetes
Jeremy Warshauer, PGY-2
Internal Medicine
UT Southwestern

2. Objectives
• Overview of type 1 diabetes
• Bionic Pancreas
• Islet Transplantation
• Stem Cell Therapy

3. Prevalence
• In 2012, 29.1 million Americans, or 9.3% of
the population, had diabetes
– 1.25 million American children and adults have
type 1 diabetes
• $245 billion in 2012 impact on economy

4. Normal Islet Cells
http://www.britannica.com/EBchecked/topic/329670/islets-of-Langerhans

5. T1DM
α-cell dysfunction
autoimmune β-cell destruction  insulin deficiency

6. T1DM
α-cell dysfunction
autoimmune β-cell destruction  insulin deficiency
• Beta cell regeneration
and transplantation
• Immune research

7. T1DM
α-cell dysfunction
autoimmune β-cell destruction  insulin deficiency
Artificial or bionic pancreas

8. “Insulin is not a cure for
diabetes; it is a treatment. It
enables the diabetic to burn
sufficient carbohydrates, so
that proteins and fats may be
added to the diet in sufficient
quantities to provide energy
for the economic burdens of
life.”
– Sir Frederick Grant Banting
during his Nobel lecture on
September 15, 1925.

9. From JDRF

11. Bionic Pancreas
• Addresses dysfunctional alpha cells and insulin
deficiency
• Embraces technology: CGMS, insulin and
glucagon pumps

12. α-cell dysfunction
Diabetes Care Volume 37, May 2014

13. 4-10x
Old way

14. Bionic Pancreas
288x

15. Bionic Pancreas: Setup

17. Bionic Pancreas: improved glucose
control

18. How much did the bionic pancreas
help?
• Average blood glucose reduced
– 159 mg/dL to 133 mg/dL (A1C = 6.2)
• Hypoglycemia reduced
– 3.7% to 1.5% of the time with a blood glucose
<60mg/dL

19. How much did they improve?

20. Is this really a cure?

21. Problems with Bionic Pancreas
• Invasive
• Possibility of technology malfunction
• No stable preparation of glucagon
• Insulin time of onset
• Not physiologic

22. α-cell dysfunction

23. Underlying problem with insulin
injections

25. Islet transplantation

26. Edmonton Protocol -
immunosuppresion
• Glucocorticoid-free immunosuppressive
therapy
• Daclizumab
• Tacrolimus
• Sirolimus

27. 􏰡􏰡􏰡􏰡􏰡􏰡􏰡􏰡􏰡􏰡􏰡􏰡􏰡􏰡􏰡􏰡􏰡􏰡􏰡􏰡􏰡􏰡􏰡􏰡􏰡􏰡􏰡􏰡􏰡􏰡􏰡􏰡􏰡􏰡􏰡􏰡􏰡􏰡􏰡􏰡

28. Edmonton Protocol – a long term
solution?

29. Why doesn’t everybody get this?
• Patient needs unstable glycemic control that
cannot be corrected by standard conventional
and intensive insulin therapies.
• Remaining challenges:
– expansion of the islet donor supply
– improving islet isolation techniques
– strategies to improve engraftment
– mediating the anti-inflammatory response post-
transplant
– improving recipient immunosuppression regimens.

30. Prevelancess Islet transplantation for typ
80
60
Edmonton
North America
International
40
20
Year
Islet transplant recipients per
year registered with CITR
Numberofislettransplantrecipients
0
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
2011
2012
2013
umber of islet transplant recipientsfrom 1999–2013 in Edmonton, North Americaand International Islet Transplant Centers.
From the Clinical Islet Transplantation (CIT) Consortium

31. Stem cell Therapy
• 2 Key features:
– Ability to renew themselves through cell division
while remaining undifferentiated.
– When given the appropriate signals, stem cells can
differentiate into many specialized cell types.

38. Encapsulation
• Protect against immune rejection – Encaptra
device by Viacyte.
http://viacyte.com/products/vc-01-diabetes-therapy/

39. Conclusions
• A cure is in site, but there are several
obstacles that still must be overcome
– Immune modulation
– Not enough supply

40. References
• Bruni, A., et al. (2014). "Islet cell transplantation for the treatment of type 1 diabetes: recent
advances and future challenges." Diabetes Metab Syndr Obes 7: 211-223.
• Derr, R., et al. (2003). "Is HbA(1c) affected by glycemic instability?" Diabetes Care 26(10): 2728-
2733.
• Kudva, Y. C., et al. (2014). "Closed-loop artificial pancreas systems: physiological input to enhance
next-generation devices." Diabetes Care 37(5): 1184-1190.
• Peyser, T., et al. (2014). "The artificial pancreas: current status and future prospects in the
management of diabetes." Ann N Y Acad Sci 1311: 102-123.
• Pagliuca, F. W., et al. (2014). "Generation of functional human pancreatic beta cells in vitro." Cell
159(2): 428-439.
• Russell, S. J., et al. (2014). "Outpatient glycemic control with a bionic pancreas in type 1 diabetes."
N Engl J Med 371(4): 313-325.
• Shapiro, A. M., et al. (2006). "International trial of the Edmonton protocol for islet transplantation."
N Engl J Med 355(13): 1318-1330.
• Unger, R. H. and L. Orci (2010). "Paracrinology of islets and the paracrinopathy of diabetes." Proc
Natl Acad Sci U S A 107(37): 16009-16012.
• Unger, R. H. and A. D. Cherrington (2012). "Glucagonocentric restructuring of diabetes: a
pathophysiologic and therapeutic makeover." J Clin Invest 122(1): 4-12.