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Clinical islet Clinical islet transplantationtransplantationStephanie A Amiel, BSc, MD, FRCP
RD Lawrence Professor of Diabetic MedicineKing’s College London School of Medicine
Diabetes Research Group
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Treatment of organ failure?
• Renal failure
• Liver failure
• Heart failure
• Islet failure
• Kidney transplant
• Liver transplant
• Heart transplant
INSUU100
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Case Histories
1. Born 1944; T1DM 1966; keen runner
2. Born 1965; T1DM 1987; HCA on locked ward
3. Born 1985; T1DM 1994; mother of two
“afraid to be in charge of my granddaughter”
“threatened with medical redundancy”
“you just drove across a red light, Mummy”
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GLUCOSE-GLUCOSE-RESPONSIVERESPONSIVE
INSULIN DELIVERYINSULIN DELIVERYBionics vs nature?
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Nature – whole pancreas or islets?
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Islet TransplantationIslet Transplantation• 1998 established laboratory• 2000 proof of concept• 2002 1st UK patient• 2008 NCG funded programme
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Insulin Independence, Insulin Dependence, Graft failure
*C-peptide data not available at Day 75
**Year 3 status independent of re-infusion
CITR Islet Alone Recipients outcomeFrom all infusions
Recipient Status Insulin IndependentInsulin Dependent with Detectable Fasting C-peptideNo Detectable Fasting C-peptideMissing Data
Per
cent
of R
ecip
ient
s
0
10
20
30
40
50
60
Month 6N=249
Year 1N=225
Year 2N=169
Year 3N=129
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No severe hypoglycemic episodesSevere hypoglycemic episodeMissing data for recipient without islet graft functionMissing data for recipient with islet graft function
Per
cent
of R
ecip
ient
s
0
10
20
30
40
50
60
70
80
90
100
Pre Inf 1N=262
Day 30N=262
Month 6N=249
Year 1N=225
Year 2N=169
Year 3N=129
CITR 2007
SEVERE HYPOGLYCEMIA FOLLOWING LAST TRANSPLANT
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• 1 person with 4% reduction in HbA1c• 2 people back in work• 1 woman resumed running and
babysitting her grandchildren• 2 children safely back on school run
• 3 people achieved insulin independence
Clinical Outcomes: Diabetes UK patients
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UK ITC
Shaw, Manus, Amiel, Huang
NCG:April 20082 isolation centres6 Transplant centres
Intractable hypoglycaemiaIslet after kidneyLocal and remote
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Problems to be solved
• Current• Organ supply/distribution• Sub-optimal immunosuppression
• Research• Prevent loss of islets on administration• Improve immunosuppression• Make new islets to give greater loads and
re-transplant if required
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Meanwhile
• Whatever cell therapy we devise, it will need to be safer than insulin therapy
• For a small number of patients, it already is