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treatment strategy in non-obese diabetic patients requiring
insulin regardless of type of diabetes.
S09-3
Pancreas transplant
–
Taipei Veterans General Hospital
experience
Yi-Ming SHYR
1
, Shin-E WANG
1
.
1
Division of General Surgery,
Departments of Surgery, Taipei Veterans General Hospital, National
Yang Ming University, Taipei, Taiwan
Type 1 diabetes eventually leads to nephropathy, neuropathy,
retinopathy and angiopathy after 10
–
30 years. Currently, pan-
creas transplant is the treatment of choice in tight control of
blood sugar for IDDM patients, and further to stabilize, prevent
or even to reverse the diabetic complications.
We will present our experience in pancreas transplant which
was initiated on September 19, 2003. From September 2003 to
June 2016, there were 126 pancreas transplants performed
for 120 patients at Taipei Veterans General Hospital, with 36
SPK, 15 PAK, 57 PTA and 18 PBK. Most (78.5%) of our pancreas
transplants were for IDDM patients. The blood sugar usually
returned to normal level within 5 hours (median) after
revascularization of the pancreas grafts. The fasting blood
sugar maintained within normal range thereafter throughout
the whole clinical course in most cases. There were 2 surgical
mortality. The technical success rate was 96%. Excluding the 4
cases with technique failure, overall 1-year pancreas graft
survival is 98.5% and 5-year is 94.1%, with 100% 1-year for SPK,
97.1% 1-year for PTA, 100% 1-year for PAK and 100% 1-year for
PBK.
In conclusion, pancreas transplant provided an ideal insulin-
free solution for IDDM and selected NIDDM. Pancreas trans-
plant could be performed with similar successful rate irre-
spective of the type of pancreas transplant at our hospital.
Islet Transplantation
S16-1
Current status of clinical islet transplantation
Philip J. O
’
CONNELL
1
.
1
National Pancreas Transplant Unit,
University of Sydney at Westmead Hospital, Sydney, Australia
Islet transplantation is a promising therapy for patients with
type 1 diabetes and severe hypoglycemia. Several studies have
shown that high levels of insulin independence and good
control of hypoglycemia can be achieved in the short term.
However, long term results are not as good and five year
insulin independence rates although improving show pro-
gressive loss of function over time. In two recent multicenter
trials
–
one in North America and one in Australia- similar
results were achieved. Approximately 85% of patient achieved
the primary end point of HbA1c <7.0% and absence of
hypoglycemia in presence of detectable c-peptide. With
multiple transplants approximately 60% were insulin inde-
pendent. Over time there was a progressive deterioration in
function. In the North American study graft function had
dropped from 87% to 72% by 24 months. Whereas, in the
Australian study, graft survival was 64% at 5 years after
transplantation. Patients with acceptable graft function have
a remarkable improvement in their diabetic control and
complete resolution of difficult to control hypoglycemia. As a
result there is a profound improvement in quality of life and
many recipients are able to return to work. Islet transplant-
ation does come with its own problems particularly regarding
complications and tolerability of immunosuppression. In
a study where continuous insulin infusion (CSII) was com-
pared with islet transplantation for severe repeated hypo-
glycemia the data suggested that in subjects with severe
hypoglycemia, CSII was an appropriate therapy, which sub-
stantially reduced the frequency and severity of hypoglycemia
but did not remove the need for islet transplantation in the
majority of individuals. CSII reduced duration of time with
blood glucose <4 mmol/L and significantly improved gly-
cemic variation as compared with MDI, the latter potentially
accounting for reduced frequency of severe hypoglycemia.
However, islet transplantation eliminated hypoglycemia
regardless of whether insulin independence was achieved.
Frequency, severity and risk of hypoglycemia as measured by,
respectively, CGM percentage of time in hypoglycemia,
HYPOscore, and glycemic variability at 12 months post islet
transplantation all returned to levels as good as, or better than,
those reported in type 1 diabetes without problems with
hypoglycemia. Transplantation reduced HbA1c and mean
glucose at 12 months, benefits that were not seen with
changing to CSII. The study provided further evidence that in
appropriately selected patients with severe hypoglycemiawith
large glycemic variability, islet transplantation provides
superior glycemic control and reduction in hypoglycemia
over and above that achieved with CSII.
S16-2
Clinical islet transplantation from allogeneic toward
xenogeneic
Shinichi MATSUMOTO
1
*.
1
Otsuka Pharmaceutical Factory INC,
Japan
In 2014, opinion leaders of beta cell replacement therapy
discussed the current status and future of the therapy at
the Oxford University. At the meeting, it was revealed that
approximately one-eighth of type 1 diabetic patients with
prolonged diabetic history (>20 years) suffered unaware
hypoglycemia and 7
–
10% of cause of death of type 1 diabetes
was hypoglycemia. Beta-cell replacement therapy including
pancreas and islet transplantation is the best treatment
for preventing severe hypoglycemia, however due to donor
shortage, only at most only 0.1% of type 1 diabetic patients can
receive beta-cell replacement therapy. Donor shortage is the
most serious issue.
To alleviate donor shortage, we have conducted islet trans-
plantation using non-heart beating donor, living donor islet
transplantation and improving the efficacy of islet transplant-
ation. However, none of them can solve the issue of donor
shortage.
Establishment of islet transplantation using non-human
pancreas donor (bio-artificial islet transplantation) can solve
the donor shortage issue. Three major resources of islets for
bio-artificial islets are porcine islet, ES cell derived islet and iPS
cell derived islets. Among them porcine islets have several
advantages including previous clinical experiences, clean and
healthy islets from healthy designated pathogen free donor,
possible gene modification to improve clinical outcomes.
Encapsulated neonatal porcine islet transplantation has been
conducted under comprehensive New Zealand regulation.
The study had four different dose groups: 5,000 IE/kg (n = 4),
10,000 IE/kg (n = 4), 15,000 IE/kg (n = 4), and 20,000 IE/kg (n = 2).
There were four serious adverse events related to the pro-
cedure, which were resolved without residual effects. Tests for
PERV DNA and RNA were negative in the blood of all patients.
In terms of efficacy, the number of episodes of unaware
hypoglycemia was reduced 1 year after transplantation in all
dose groups.
To improve the clinical outcome, the Ricordi isolation method
and injection of ETK solution into pancreata were introduced,
which resulted in a high islet yield (approximately 180,000
IE/piglet). Next clinical trial was performed in Argentina.
Subanalysis of the efficacy dataset demonstrated that when
a dose of 10,000 IE/kg was transplanted twice, HbA1c levels
<7% for more than 2 years, with a significant reduction of in
the number of episodes of unaware hypoglycemia.
Speech Abstracts / Diabetes Research and Clinical Practice 120S1 (2016) S1
–
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