This article isThis article by protected copyright. All rightsreserved. 10.1111/ctr.13153doi: differences to lead between the of thisversion c and Version Record.Please copyediting, paginationbeen throughthe andproofreadingtypesetting, process,may which This article acceptedhas been for publication andundergone fullpeer review buthasnot failure after pancreas transplantation Islet Running 3 2 Switzerland 1 Oberkofler Christian Zue A. Gerber Philipp avoid severe hypoglycemia Islet transp Article :Original Article type 0000 ID : (Orcid GERBER A DR. PHILIPP Accepted Switzerland Zurich, Hospital Surgery, University of Transplant Division Zurich, Switzerland Hospital University of Radiology, Division Zurich, Hospital University Nutrition, Clinical and Diabetes of Endocrinology, Division Article llig 1 , PhD, Title
lantation
Oliver 1 , MD, 3
Tschopp , MD,G as safe and and safe as
Michel Hochuli Michel
iatgen iatgen 1 after donor organ failure in pancreas pancreas in failure organ donor after , MD, efficacious - A. 0002 Michael Glenck Michael Spinas 1 ,
- MD, 2476
1 Bara D. Benediktsdottir Bara - , MD, 7076)
method to restore glyc torestore method
2 and R , MD,
oger Olivier de Rougemont de Olivier
Lehmann 1 , transplantation MD,
emic control control emic 1 , MD ite thisarticle as R ichard A ichard
3 , MD, MD, . and to and
This article isThis article by protected copyright. All rightsreserved. Acceptedtransplantation of rate a with declined (eGFR) (n=7) group transplantation follow after patients end transplantation pancreas re pancreas receiving failure, graft pancreas with patients of group control a to compared were failure organ failure pancreas after institution our organ at transplantation subsequent with transplantation pancreas and safety assess to was study this of aim The Abstract Transplant Clin Articleavoid severe hypoglycemia after donor organ failure inpancreas transplantation safeand Islet transplantationas R: Lehmann GAand Spinas C, O, Oberkofler Rougemont M,Benediktsdottir Hochuli PA, Gerber phone: +4144 255 362 Zurich Hospital University Gerber Philipp ad Corresponding - on o HAc <7 HbA1c of point In .
sulin requirement was reduced by 50% after islet transplantation. Kidney function function Kidney transplantation. islet after 50% by reduced was requirement sulin , , which which ,
MD d , MSc , ress: - up bt y oe f h ptet i te group the in patients the of none by but , - transplantation 0 ad reo o svr hpgyei ws e b 9 u o 10 of out 9 by met was hypoglycemia severe of freedom and .0% tended to be be to tended 0
after islet transplantation and in in and transplantation islet after
, , , failed Division of Endocrinology, of Endocrinology, Division FAX +41 44 255 44 47, 44 255 44 FAX +41 Raemistrasse 100 Raemistrasse -
1. and were followed for a median of 51 months. The primary primary The months. 51 of median a for followed were and 0 efficaci ml± . 10 patients underwent islet transplantation after initial initial after transplantation islet underwent patients 10 .
1 BD, Zuellig RA, Tschopp O, Glenck M,de O, Glenck Tschopp RA, BD, Zuellig lwr hn n h group the in than slower . 2
ml/min/1.73m o us , but without islet transplantation islet without but 8091 Zurich
method to restore glycemic control and to to and control glycemic torestore method efficacy e - mail: mail: Diabetes 2
per year during follow during year per [email protected]
, Switzerland; all of
islet transplantation after initial initial after transplantation islet ptet i te aces re pancreas the in patients 3
. and Clinical Nutrition Clinical and Patients undergoing islet islet undergoing Patients
ihu re without ihu retransplan without
- and to a group group a to and transplantation - up
, after islet islet after
tation -
This article isThis article by protected copyright. All rightsreserved. Acceptedcare glyc patients, most transplantation kidney transplantatio pancreas transplanted the of function 60 in present indepen insulin in nowadays achieved routinely However, achieved. not often was independence me been has transplantation pancreas organ Whole Introduction phone: +4144 255 3620, FAX44 25547, +41 e Switzerland; Zurich, 8091 100, Zurich, Raemistrasse Hospital University a Diabetes of Endocrinology, MSc, Division MD, Gerber, Philipp Articleaddress: Corresponding insulin mellitus, type1 diabetes transplantation, pancreas transplantation, Islet words Key ofexogenousthe need additional insulin. after as control glycemic similar establish thus, and hypoglycemia severe of incidence the reduce and control glycemic improve safely can that (p=0.07) lts n re t rsoe glyc restore to order in llitus
itnieisln treatment) insulin (intensive . Islet transplantation after after transplantation Islet .
n should be recommended, in particular in patients after combined pancreas combined after patients in particular in recommended, be should n - 0 o ptet 5 er atr transplantation after years 5 patients of 70% emic control worsens again again worsens control emic
with a functioning kidney graft kidney functioning a with the majority of patients after after patients of majority the
emic control for 50 years years 50 for control emic . However, there are also factors that that factors also are there However, . deceased donor deceased
,
the question remains whether whether remains question the after pancreas failure failure pancreas after performed performed -
mail: mail: pancreas pancreas initial initial
and continued continued and aces rnpatto and transplantation pancreas
[email protected] pancreas transplantation, despite despite transplantation, pancreas [1] in patients with type 1 diabetes diabetes 1 type with patients in
transplant Iiily long Initially, . nd Clinical Nutrition, Nutrition, Clinical nd [2] .
n ains ih os of loss with patients In despite optimal optimal despite immunosuppression
may failure is a method method a is failure
-
prohibit whole whole prohibit lasting insulin insulin lasting pancreas pancreas
dence is is dence medical medical is . In . still still re - - This article isThis article by protected copyright. All rightsreserved. Acceptedtransplantation. hypoglycemia) severe to was study this of aim The may con be and transplantation pancreas initial after transplantation islet Thus, consid comp of rate lower much glyc transplantation islet Article2000 steroid a using independence insulin cent many by implemented was transplantation whole to alternative an is transplantation Islet about is transplantation pancreas rate. complication transp kidney to contrast in transplantation, Pancreas surgery abdominal previous after patients in of risk the from suffer may and transplantation, re organ emic control comparable to whole to comparable control emic [4] erably improved in recent years years recent in erably improved . While insulin independence insulin While . - transplantation re sidered as an alternative to re to anas alternative sidered - transplantation. transplantation.
h rpre rt o r of rate reported The [5]
of islet transplantation after donor donor after transplantation islet of s oprd o aces rnpatto i ms centers most in transplantation pancreas to compared as because , lications lications evaluate In addition, addition, In 30 [6, 7] [6,
- 40% ofpatients
- ains r odr hn t h tm o te first the of time the at than older are patients is generally achieved achieved generally is - the safety and and safety the organ transplantation can be routinely achieved with a with achieved routinely be can transplantation organ diinl adoaclr complicati cardiovascular additional [8, 9] re muoupeso pooo wr pbihd in published were protocol immunosuppression free .
In addition, the results of islet transplantation have have transplantation islet of results the addition, In - re transplantation of the whole organ. of thewhole transplantation lprtm de o opiain a te ie of site the at complications to due elaparotomy . -
transplantation may be may transplantation
and e - ra taslnain Ti mdlt of modality This transplantation. organ rs mainly after after mainly rs with with
[3] efficacy lantation, is an intervention with a high a with intervention an is lantation, .
oe dacd aclr disease vascular advanced more in a lower number of cases after after cases of number lower a in
(HbA1c <7.0% and freedom of of freedom and <7.0% (HbA1c pancreas the technically technically pancreas
eut o consistent of results failure in pancreas pancreas in failure ons that increase increase that ons
more difficult difficult more organ failure failure organ good , . This article isThis article by protected copyright. All rightsreserved. care) medical best for selection Patient transplantation for selection Patient were patients 2008, fromstu obtained was consent After informed Written Study. Centre. Cohort Transplant Swiss the Transplantation in included simultaneously Zurich of Hospital University w protocol study The 2008 by in ourgroup as suggested events hypoglycemic end primary The patients who received apancreas retrospectively and 2000 after prospectively collected was transplantation pancreas after follow of Data the patient’s pancreas possible regarding decision institution our at transplantation initial after failure organ donor pancreas from suffering group re study the in included between December Zurich Hospital University the at (SIK) islet transplantation simultaneous or (ITA) alone transplantation islet underwent who patients All design Study Patients -
Accepted Articletransplantation Te poss The . and
31
prefere
st Methods -
up after islet transplantation was collected collected was transplantation islet after up 2015 after initial pancreas transplantation with with transplantation pancreas initial after 2015 blt o pancreas of ibility -
point was the achievement of HbA1c < 7.0% and freedom from severe severe from freedom and 7.0% < HbA1c of achievement the was point and
nce as well as age and comorbidity. age and as well nce as was performed after careful evaluation of possible advantages and and advantages possible of evaluation careful after performed was , as well as well as , as reviewed and approved by members of the board of trustees of the the of trustees of board the of members by approved and reviewed as islet dy participants prior to surgery/intervention to prior participants dy three patients who received pancreas re pancreas received who patients three
- after - aces rnpatto (s pnra re pancreas (vs. transplantation pancreas
7 graft before 2000graftbefore
- patients with pancreas organ failure b failure organ pancreas with patients
r se re islet or -
or islet or - re - rnpatto ws icse wt patient with discussed was transplantation - transplantation was made was transplantation .
[10] prospectively;
and used in in CITTrials the used and pancr - . transplantation
aur 1 January eas
organ fail organ -
ut no consecutive consecutive no ut rnpatto or transplantation aa f follow of data after considering considering after
st as a control control a as
2000 and and 2000 ure were were ure - kidney kidney . The . [9] - for for up .
s
This article isThis article by protected copyright. All rightsreserved. HDL Switzerland). Roche, analyzer, lab AcceptedP (modular hydrolysis enzymatic after chloride iodonitrotetazolium with reaction colorimetric c using test colorimetric enzymatic an by measured was Cholesterol pmol/l. 12 of detection of limit lower intra Internat Bio CIS (Technogenetics, C Plasma instructions. manufacturer’s the to according USA) Elkhart, Diagnostics, (Bayer 2000 DCA the with measured was HbA1c analyses Biochemical perso another was hypoglycemia Severe history, patient by assessed results. angiography and examination physical was disease Macrovascular Germany). Wetzlar, GmbH, rate heart of analysis computer included which examination, Article clinical and history the by diagnosed was neuropathy Autonomic cases. atypical in testing (MNSI, Instrument Screening Neuropathy Michigan the using examination, clinical by defined was neuropathy Peripheral d was Retinopathy factors risk and cardiovascular complications related diabetes of Assessment modalities both pro risk higher comorb and age to regard special with disadvantages, eue f se taslnain while transplantation, islet of cedure - sa ad inter and assay for holesterol esterase and cholesterol oxidase, triglycerides were determined by a by determined were triglycerides oxidase, cholesterol and esterase holesterol
n to treat n to intra
(islet transplantation or pancreas re pancreas or transplantation (islet efined according to the diagnosis made by ophthalmological examination. examination. ophthalmological by made diagnosis the to according efined - operative complications were preferentially assigned to the less invasive invasive less the to assigned preferentially were complications operative -
sa cefcet f aito o 47 ad .% rsetvl, n a and respectively, 5.6%, and 4.7% of variation of coefficient assay
or loss of consciousness or loss defined as any hypoglycemic event that required assistance from from assistance required that event hypoglycemic any as defined [11] ), monofilament pressure sensation and electrodiagnostic electrodiagnostic and sensation pressure monofilament ), ional, Schering, Baar, Switzerland) with a local laboratory laboratory local a with Switzerland) Baar, Schering, ional,
only
cholesterol -
etd ws esrd ih n RA kit IRMA an with measured was peptide younger and healthier patients were offered offered were patients healthier and younger .
- transplantation)
was measured by a homogeneous homogeneous a by measured was idities. Patients considered being considered Patients idities.
aiblt (rSiad CPS (ProSciCard, variability .
at at This article isThis article by protected copyright. All rightsreserved. Accepted 720 of doses in daily twice adapted weight administered were tacrolimus thymoglobuline with later basiliximab, with initially performed [15] initial after Immunosuppression Immunosuppression >8%. HbA1c C as defined was failure organ Pancreas (IEQ) equivalents islet as given trans a by conducted was transplantation previously transpla and Preparation Article compatibility not or transplantation list waiting transplantation closest the by given was relatives. consent informed Written Switzerland. in hospitals different brain from obtained were pancreata and Kidneys and procurement Organ concentration lab Integra (Cobas test enzymatic
n mcpeoae mofetil mycophenolate and Panel reactive antibodies (PRA) were measured measured were (PRA) antibodies reactive Panel [13]
were was calculated was Taslne ilt wr nt utrd eoe transplantation. before cultured not were islets Transplanted . initially initially
considered as minimal requirements for transplantation for requirements minimal as considered
. A negative serum cross serum negative A transplantation procedure transplantation
10 tto o te acetc ses ee efre as performed were islets pancreatic the of ntation and included in the decision whether to accept a certain organ for organ certain a accept to whether decision the in included and -
5 μg/l 15 with the Friedewald formula formula Friedewald the with [14] pancreas transplantation included transplantation pancreas
[16] and islet number islet and
ad long and , analyzer, Roche, Switzerland) and and Switzerland) Roche, analyzer, a , - peptide (stimulated) of less than 100pmol/l, and/or and/or 100pmol/l, than less of (stimulated) peptide wl a pensn. nuto teay was therapy Induction prednisone. as well s eai pruaeu approach. percutaneous hepatic - match between donor and recipient and and recipient and donor between match - em 6 term
- ed multi dead .
- -
1440mg. 8ug/l [12] at the time of activation for the the for activation of time the at . Mycop . -
org [17]
an a regimen with tacrolimus tacrolimus with regimen a . Target trough levels for for levels trough Target . deceased deceased eoae oei was mofetil henolate .
LDL
Islet volume is is volume Islet donors from from donors cholesterol cholesterol described described
AB0 AB0 Islet Islet This article isThis article by protected copyright. All rightsreserved. person another of Accepted assistance consciousness of requirement the with episode insulin. with treated was 6.5% ≥ transplantation. before as intensity and regimen same the with out carried was necessary, if transplantation, after treatment insulin particular, In guidelines. according treated were patients All control. glycemic to addition HDL both and cholesterol total triacylglycerols, necessary if therapy insulin of every least Collaborat Epidemiology Disease Kidney Chronic min) 180 for min the by GFR estimated and by creatinine serum assessed was function Renal transplantation. 30 every measurements protein; 17% test tolerance meal was secretion peptide insulin exogenous for need and measurement follow During ArticleFollow transplantation) 10 after and 2, 7 day 25mgon transplantation; before addition, In afterwards. basiliximab and before), used not was day) last the on 25mg of dosage a to intervention, the before prednisone 500mg of bolus a with sirolimus for reported effects side of as regimen same the to 2012 after changed Edmonton the to according Switzerland), Zug, Pharma, (Wyeth sirolimus was immunosuppression the transplantation, islet For .
For induction, thymoglobuline was used for the first transplantation (if thymoglobuline thymoglobuline (if transplantation first the for used was thymoglobuline induction, For - up
after transplantation after 3
months for evaluation of transplant function and adverse events andadverse function transplant of evaluation for months - ) up .
If HbA1c levels above 7% persisted, and / or in case of recurrent severe severe recurrent of case in or / and persisted, 7% above levels HbA1c If
fe transplantation after 6 clk bd w body kcal/kg (6 assessed assessed
. For assessment of cardiovascular risk, blood pressure, pressure, blood risk, cardiovascular of assessment For . nptet atr se transplantation islet after patients in
eee h Severe [5] eigh , now including the use of steroids for 4 days (starting (starting days 4 for steroids of use the including now , , transplant transplant , , en t, for ypoglycemia was defined as a hypoglycemic hypoglycemic a as defined was ypoglycemia
(insulin requirement U/kg of body weight) body of U/kg requirement (insulin pancreas transplantation pancreas ry ore: 4 croyrts 2% fat, 29% carbohydrates, 54% sources: ergy - n LDL and ion carried out out carried function was assessed by HbA1c HbA1c by assessed was function formula formula
- cholesterol were measured, in in measured, were cholesterol
Every patient with an HbA1c HbA1c an with patient Every [19] etanercept was used (50mg (50mg used was etanercept at least every year after after year every least at initially Ptet wr se at seen were Patients .
to current international international current to
[18]
only
due to the high rate high the to due with tacrolimus and and tacrolimus with (including .
protocol uig mixed a during
and adaptation adaptation and
os of loss [4] , but but , . C . - - This article isThis article by protected copyright. All rightsreserved. ( loss the lost 0 (range: 3 group ( was failure organ pancreas and transplantation pancreas between Time re pancreas analysis the in after failure pancreas with transplanted of total A Patient Results 2 Version software Statistics significa considered was p < 0.05 of value applied. were procedures probability exact Fisher and χ2 the data, frequency categorical the groups independent of comparison o comparison are Data analysis Statistical was hypoglycemia 4 median;
Accepted, 2 Article
offered to the patient. the to offered in the in and and transplant and transplant
organ within the first month after transplantation after month first the within organ range: 0 range: 1 presented presented
three patient 10 - transplantation transplantation pancreas f continuous variables in two in variables continuous f
after islet transplantation islet after
ains eevd se taslnain fe ogn ucin failure function organ after transplantation islet received patients gop 2) (group
groups groups - -
6.9 years) 6.9 0.8 in the 3 groups, respectively the3groups, in
s means as
characteristics years after S after were acute rejection ( rejection acute were .
S ute data Further was also was ; ns ; P 4 ,
K 11 months in group 2 (range: 0 (range: 2 group in months 11 P (IBM, Armonk, USA). Armonk, (IBM,
K transplantation (group 1) (group transplantation K transplantation, but without re without but transplantation, )
. ± Two
SD
included in the analysis.
patients mda ad range, and median , , the , of Kruskal nt. All calculations were performed using SPSS using performed were calculations All nt. related a
possibility of an additional islet transplantation transplantation islet additional an of possibility small ) and vascular causes (5 causes vascular ) and 1 in - patient Wallis
group 1 and 2, an one patient in patient one an 2, and 1 group groups er
ru (n=3 group
et a used was test in group in
. the Wilcoxon test was applied was test Wilcoxon the
. The reasons for pancreas organ organ pancreas for reasons The
For comparison, comparison, For -
5.9 years; years; 5.9 -
transplantation, were included included were transplantation, r eaie rqece. For frequencies. relative or
gop 3 group , 1 and 2 and 1 . For the analysis of of analysis the For . , ns 4 2 months 2
), chronic rejection rejection chronic ), and 1 ) o patient of ) , and and , seven patient). 2 months in months 2
in group 1 1 group in
patients group of the the of s with with s
, for ,
A 3 ®
This article isThis article by protected copyright. All rightsreserved. Peripheral 1 groups P related Diabetes 2 in group 11.0) to (5.1 years 9.0 1 group in years) 31.7 to 6.8 range (median, years 11.8 was transplantation pancreas initial re pancreas after months 34 and f Mean 61 in 0% ≥ measured were (PRA) antibodies reactive Panel kg/m 3, group in years transplantation: of age an donors The transplantation (IEQ/kg volume T patients group) transplantation 1 of out re pancreas was transplantation islet B ransplant characteristics ransplant roliferative retinopathy was present in in present was retinopathy roliferative characteristics aseline
Accepted%) Article 16 2
at thetime of (for
ollow islet donors donors islet 0
(2 in the pancreas re pancreas (2 inthe
,
patients presented with an HbA1c > 7.0% > HbA1c an with presented patients
pancreas re pancreas 2 and -
- transplantation 1.1 years (0.5 (0.5 years 1.1 transplantation up after up n 3 and s /or
36.1
was 1.6±was 1.
and
ns autonomic neuropathy were neuropathy autonomic body weight) weight) body respectively , waiting had a mean age of age had a mean . 52.6% 52.6% .
macrovascular complications macrovascular ± 12.7 ± islet transplantation was was transplantation islet 38.9 - , and the occurrence of severe hypoglycemia was registered in in registered was hypoglycemia severe of occurrence the and , transplantation donors: 66.7% females, BMI 24.5 BMI24.5 66.7% females, donors: transplantation of patients patients of 6.1
- including list activation for activation list
± of years ( years 3 years -
transplantation group) transplantation per patient. per islet islet . years 5.1
- and 4.1years (3.0to 9.6) in group 3 transplantation ( transplantation (ns)
are in group 1, 27.0 ± 11.3 years in group 2 group in years 11.3 ± 27.0 1, group in are described in table 1. table in described are
median, median, donors donors number of islet islet of number
Al ains ufrd rm end from suffered patients All . 56.8 ±10.1 56.8 also
80
– were (p<0.01)
islet transplantation islet range: range: % 7.7 years 7.7 shown in in shown 10 and 100% , 51 present in in present females;
months ( months 30 to 36 months, ns) months, 36 to 30 , hypertension, smoking , hypertension,
years 1. . D . infusions
(3 out of 3 patients in the the in patients 3 of out (3 9 )
. –
onor age of the initial pancreas pancreas initial the of age onor At the time of islet transplantation, transplantation, islet of time the At
, the 3 pancreas (re , the3pancreas 29
2 al 1 table BMI of BMI 90
median, median, of the 1 the of .4 100% D % , transplanted ,
uration between pancreas and and pancreas between uration years) , 100% , .
islet islet .
of 0 range 7 to 142 months) 142 to 7 range The mean number of of number mean The
, between pancreas an pancreas between , islet recipients islet ains t aeie in baseline at patients
donors was 28.1 ± 5.7 ± 28.1 was donors ( - and 100% 100% and . ns stage renal disease. disease. renal stage
± Total follow Total ).
0.4
islet islet -
transplantation) transplantation) and kg/m pancreas re pancreas number and and number
of patients of 42.3 2
). - (7 up after up
% and and % ±
9.0 9.0 d 7 9 - , ,
This article isThis article by protected copyright. All rightsreserved. C stimulated C being total) stimulated maximally became patients 2 in achieved was independence Insulin of follow end the at ±0.7% 5.9 of a value re pancreas follow during 8% above remained with achieved be not could HbA1c du stable transplantation, it However, (ns). 3 group 2 group 0.9%in baseline G patients a (p<0.001) was follow hypoglycemia severe of freedom and 7.0% by met successfully < HbA1c of point end primary The and control Glycemic patients ingroup 2were cardiovascular the in
Accepted hemoglobin lycated Article per day per - up (group 1), but by none of the patients patients the of none by but 1), (group up -
three peptide positive (> 100 pmol/l)) 100 (> positive peptide (8. ring follow ring eesr i a in necessary . fter re
n ru 3 pnra re (pancreas 3 group In 5 - - transplantation (group 3), HbA1c decreased from 8.2 ± 0.7% to 5.6 ± 0.3%, with with 0.3%, ± 5.6 to 0.7% ± 8.2 from decreased HbA1c 3), (group transplantation
peptide were peptide
± and
groups
- 1. disease (p< HbA1c decreased from decreased HbA1c transplantation and at the end offollow end and at the transplantation 8 129 ± 223 223 ± 129 %) - both) for 0.05 up all
incidence of incidence
C to 6.0 ± 0. ± 6.0 to
(HbA1c) (HbA1c) (HbA1c at the end of follow of end the at (HbA1c (ns)
-
patient p smoker (ns) ll eptide levels levels eptide 0.
. recipients
28 i , pmol/l before islet transplantation islet before pmol/l cesd gi atr aces transplant pancreas after again ncreased 7 s 7 0
± 0.2 ±
s 0 % 3 after islet transplantation transplantation islet after decreased decreased . , %
- % hypoglycemia 7% n 67% and 70% , up and by 2.6% from baseline (7.7 (7.7 baseline from 2.6% by and , best medical treatment medical best - 100% in group 1 group in transplantation), the primary end point was met by all all by met was point end primary the transplantation), 3 , and was 8. was and ,
U/kgBW/d t h ed f follow of end the at were .
- 8.0 After islet transplantation, insulin requirements and and requirements insulin transplantation, islet After up. and 67% 67% and
± 1. ± after pancreas transplantation transplantation pancreas after 0.6 ,
by 2 4
(19.9 ± 20.2 ± (19.9 3
% to 6. to % 0.1 ± % at the end of follow of end the at % 2.0 -
up: 6. up: after islet islet after
% from baseline ( baseline from % had in without - up. 8
0 2 ± 0.8%), whereas a reduction of reduction a whereas 0.8%), ± 2 h three the
U/kg body weight weight body U/kg
at
in group 2, where HbA1c values values HbA1c where 2, group in arterial ± 0.5% 0.5% ± -
1 year an year 1 up. Insulin requirements and and requirements Insulin up.
U
(with only 2 out of out 2 only (with re infusion
total) - rnpatto (ru 2) (group transplantation
± (p<0.001) (p<0.001)
hypertension
1.7%) to 5.1 5.1 to 1.7%)
groups groups a , but insulin therapy therapy insulin but , nd d 7.8
- 90% at the end of end the at 90% up
failure. failure. 1444
± 1.1% ±
(figure 1). (figure (41.2 ± 19.5 19.5 ± (41.2 by suffered from from suffered and remained remained and
±
10 2. 922 (ns) After ± ) to 5.8 ± 5.8 to ) 5
% from from % patients 0.4% in in 0.4%
. pmol/l pmol/l
After After Two Two islet U
This article isThis article by protected copyright. All rightsreserved. re pancreas of rate a with declined eGFR was transplantation of transplantation year of rate a with declined eGFR of terms in function Kidney follow of (end 2. table in shown are levels S lipid serum and pressure blood function, kidney Weight, Cardiovasc to 0per100years patient islet The follow during follow of end the until preserved was independency insulin re pancreas after independent insulin became patients all 3, group In up: 0.74± 0.49U/kg U/kg were requirements insulin contrast, In patients were stillC C stimulated in increase the and total) follow during
Acceptedchange ignificant Article
frequency frequency /d transplantation during and
body weight, 48.8 ± 20.3 ± 48.8 weight, body 840 ular risk factors ular risk
- transplantation. - - follow - up up, and and up, up) and and up)
of severe hypoglycemia decreased from 1 from decreased hypoglycemia severe of ±
as described above described as 775 48.2 - s up
-
( - /d p observed occurring occurring 2.7
eptide positive eptide at the end of follow of end the at
mll fgr 2). (figure pmol/l
of triglyceride levels of triglyceride body weight, body fe ilt transplantation islet after
± ± 2.3 ± 14.1 after pancreas re pancreas after
and kidney function function kidney and
ml/min/1.73m after islet transplantation transplantation islet after in one patient with negative C negative with patient one in ml/min/1.73m
- U . ± 1.7 ± 1.2 - peptide (p=0.02) were statistically significant. significant. statistically were (p=0.02) peptide
total) and remained high during follow during high remained and total)
46.9 ±27.4 46.9 ; HbA1c ; HbA1c (>100pmol/l)
high in group 2 after pancreas failure (0.75 ± 0.39 0.39 ± (0.75 failure pancreas after 2 group in high Both the decrease of insulin requirement (p<0.001) (p<0.001) requirement insulin of decrease the Both - up they were they up
(initially after transplantation). (initially after -
transplantation 2 ml/min/1.73m one 2
. per year during follow during year per
h dcieo eF i gop wt n re no with 2 group in eGFR of decline The during follow during
U , with with ,
year after transplantation year after
at theend of follow total , ns a starting eGFR at the time of islet islet of time the at eGFR starting a 0.3
were 20 ). 2 8 .
-
- up - e ya drn follow during year per ± 0.2 ±
1. up - to Peptide
0
reductions of LDL cholesterol cholesterol LDL of reductions (
5 with a with l ± ml
8 per 100 patient years after years patient 100 per
U/kg - up - ) ( ) up. 1.2 mean HbA1c HbA1c mean
p - (p=0.07) BW
rnpatto, and transplantation, =0.03
- ml/min/1.73m :
up (end of follow of (end up 5. /d 7
(26.6 ± 25.7 ± (26.6 )
, and from 70 70 from and , ± 0. .
9 In group 3, group In
4 out - % up of < 6% 6% < of )
. of
2 after after
per per 10
U - -
This article isThis article by protected copyright. All rightsreserved. survival 14.5 versus transplantation) graft a with conclusion, similar a to came 1149 and transplants primary 19705 including database (UNOS) Sharing transplants) fourth and third (for 2.42 and transplants) second (for 1.78 of ratio hazard a in result to number transplant pancre in failure re (415 cohort Minnesota large transplantation transplantations function re pancreas of outcome the on Studies initiall ofthe function of failure after transplantation re follow pancreas combined after function organ pancreas evaluated study Our Discussion re pancreas after performed. be to had hematoma to due laparatomy) patients three the of one In therapy) (induction no patients after intervention surgical for need no was There effects Side -
Accepted pancreas after transplantation Article short - up of up
- received immunosuppression primarily for the transplanted kidney transplanted the for primarily immunosuppression received ae eeld ofitn dt. oe tde i small in studies Some data. conflicting revealed have term
of islet transplantation of islet more than 4 than more side effects that could be attributed to the change in immunosuppression immunosuppression in change the to attributed be could that effects side compared to compared :
as re as 18 .
-
37) 37) - the transplantation; a multivariate analysis revealed increasing pancreas pancreas increasing revealed analysis multivariate a transplantation;
years. reported effect % (re
the [23]
-
initial transplantation transplantation initial Th transplantations) demonstrate transplantations) . - of organ transplantation) transplantation) Also
is islet transplantation in a cohort of patients with failed failed with patients of cohort a in transplantation islet a
cohort was compared to a second cohort receiving no receiving cohort second a to compared was cohort , analys , similar rate of graft graft of rate similar failure - transplantation transplantation , and to three patients receiving pancreas re pancreas receiving patients three to and , is of data from the United Network for Organ Organ for Network United the from data of is [24] y transplanted pancreas y transplanted -
any of the the of any kidney kidney - transpla [20 .
ae t yas f 69.2 of years 5 at rate
- 22] fe fiue f panc of failure after transplantation transplantation . However, a recent stud recent a However, . tto, eiin ugr (re surgery revision ntation, d uvvl fe pnra re pancreas after survival islet islet
an increased increased an
oot (ubr f re of (number cohorts infusion infusion
re .
ih long a with -
transplantations transplantations and there were were there and procedures rate rate (prima % reas organ organ reas of organ organ of y
in the the in - term .
All All ry ry - - - - This article isThis article by protected copyright. All rightsreserved. optimal even hand, other the On control. glycemic good achieve to order in necessary seen transplantation before than transplantation. pancreas organ whole to compared pr and control 10 insulin endogenous of levels exogenous transplantation own our patient hypoglyc re pancreas after transpla pancreas initial after those to similar levels to HbA1c Importantly in disease cardiovascular established and transplantation these in procedure here, demonstrated As of mean age safe be to considered as is it Thus, well transplantation. as problems technical increase may increased the re pancreas after transplantation first the increased as safe as procedure a not were failure technical large the in transplantation and mortality patient As
Accepted Article patients mean recipient age in this cohort was was cohort this in age recipient mean
as part of a multimodality approach, and and approach, multimodality a of part as s
cohort cohort receiving intensive or intensive receiving emia by more than than more by emia disease burden and frequency and burden disease , with a mean of 1.6 islet transplantations per per transplantations islet 1.6 of mean a with , ) are sufficient to support exogenous exogenous support to sufficient are ) insulin in all patients all in insulin more than more than vn svr hypoglyc severe event
as as [26] - transplantation in the third group) group) third the in transplantation described here described ,
10 where where
also also islet transplantation islet 52 older patients, with with patients, older
presently not not presently
years. Minnesota cohort Minnesota HbA1c levels were levels HbA1c at the the at n ol in
20 as observed in our cohort our in observed as even less less even fold to fold der
. at the end of follow of end the at
end of follow of end This improvement was observed observed was improvement This recipients li recipients emia a rate rate a known, whether pancreas re pancreas whether known,
intensive insulin treatment in the DCCT DCCT the in treatment insulin intensive of cardiovascular morbidity and vascular disease, disease, vascular and morbidity cardiovascular of
by more than than more by less than less after , a that that pancreas re pancreas - substantially substantially diabetes [23] up optimal support regarding insulin therapy is is therapy insulin regarding support optimal e h one the ke insulin therapy in order to facilitate glucose facilitate to order in therapy insulin failed failed was was .
. However, it is important to point out that that out point to important is it However, . the Of course, islet transplantation has to be be to has transplantation islet course, Of
and to reduce reduce to and The insulin requirement was was requirement insulin The - 45 years. years. 45 up. much lower lower much
pancreas transplantation was a safe safe a was transplantation pancreas opiain ik n aces re pancreas in risk complication (positive C (positive
uain of duration 7 - recipient Thus transplantation can be considered considered be can transplantation 95
out s higher than in patients after islet islet after patients in than higher
% evaluated evaluated , obtaining similar results as as results similar obtaining , of 1 , we conclud we , ntation Higher patient age, with an an with age, patient Higher , it was possible to lower lower to possible was it , than the one reported for for reported one the than - 0 peptide despite a despite
the incidence of sever of incidence the more patients. - transplantation can be can transplantation (and similar to those those to similar (and in our study, with a a with study, our in hn 40 than
response e
need for some some for need that even low low even that
38 [25] years
% less less % in
or in in or 9
of at e - -
This article isThis article by protected copyright. All rightsreserved. 5.5 around levels with compared up, coh reveals centers other our in achieved re pancreas were receiving patients of those that with transplantation levels HbA1c of comparison Further follow >0% levels PRA with 6. of (HbA1c transplantation pancreas after islet with here transplantati the to compared When isletsby rejection. transplanted of loss of amount higher a thus, and rejection) to due organ the of function lost who patients some a to of due proportion higher be also might this IEQ, transplanted of amount lower the Besides trial. CIT the d insulin failure. pancreas after transplantation islet without group control the in patient any in 7% study. our in weight patient Consortium ( hypoglycemia avoid and 7%) < (HbA1c control glycemic good of point end primary The insulin production. endogenous of amount certain a by supported not when control glycemic good achieve to conservative Accepted Article90 %) - up (6.6% vs. 6.1%), but the low number of these patients prohibits any conclusions. any prohibits patients these of number low the but 6.1%), vs. (6.6% up that was was that osage that was necessary after transplantation was higher in our study compared to to compared study our in higher was transplantation after necessary was that osage
n t u center our at on 8% f patients) of (88% therapy (as provided to the group without re without group the to provided (as therapy one year after transplantation transplantation after year one similar
sensitization only only showed
earlier published results of the of results published earlier
to
slightly higher HbA1c values (HbA1c of around 6% during follow during 6% around of (HbA1c values HbA1c higher slightly the
In contrast, it was not possible to possible not was it contrast, In
[7]
a [9] primary outcome of the the of outcome primary
, glycemic control was slightly better in patients patients in better slightly was control glycemic ,
tendency towards a towards tendency in patients after pancreas transplantation (in pa (in transplantation pancreas after patients in , with a slightly lower number of IEQ transplanted per kg kg per transplanted IEQ of number lower slightly a with , % described in[22]). % described
a ahee i a in achieved was
somewhat higher HbA1c at the end of of end the at HbA1c higher somewhat
whole cohort of patients receiving islet islet receiving patients of cohort whole
eety ulse til f h CIT the of trial published recently - transplantation) was not sufficient sufficient not was transplantation) 2 - v. 6.5%). vs. % transplantation in cohorts from from cohorts in transplantation achieve HbA1c levels below below levels HbA1c achieve high proportion of patients patients of proportion
The two patients patients two The ance of severe severe of ance r atr islet after ort rticular with with rticular described described
The - -
This article isThis article by protected copyright. All rightsreserved. Accepted need alonger observation time. follow the within assessed be not could therapy, induction tha to be mentioned has it Nonetheless, and safety demonstrate to to up of time transplantation islet and pancreas performing centers most in small be to believe we which disease), heart coronary to due risk cardiovascular perioperative re and failure re organ (pancreas of population issue the address to importance of is it that believe we limitation, clear a represent studied recipients islet of number small the Although transplantation. islet after stable fac risk cardiovascular and weight Body significant). statistically not (albeit Article higher was decline eGFR transplantation, islet without institut our at transplantation pancreas in of eGFR in decline with study, this prog the evaluate not did we baseline, at complications diabetes nephropathy i that shown previously was It transplantation. organ whole for used preferentially are donors younger of organs where Switzerland, in criteria donors) organ whole the to (compared Further, 12 4
years go guoe oto cud e achieved be could control glucose good a yea rs might be considered relatively short, we have we short, relatively considered be might rs [27]
and a long duration after kidney transplantation, kidney after duration long a and the
and neuropathy neuropathy and - xeto o rnl function renal of exception 1.
0
ml/min/1.73m efficacy
slet transplantation transplantation slet [28]
2 f se taslnain fe pnra ogn failure organ pancreas after transplantation islet of
. . The older donor age donor older The . per year, year, per t some possible side possible t some n h lgt f t of light the In ion os sbod rsue n srmlpd remained lipids serum and pressure blood as tors - rnpatto a rltvl hg age high relatively at transplantation [7]
as well as by other groups groups other by as well as f h taslne kidney transplanted the of which is similar to similar is which
- a so dw te rgeso of progression the down slow may rnpatto fr this for transplantation ept a relative a despite he high rate of already established established already of rate high he
- up of our study since this would this since study our of up - effects, e.g. long e.g. effects,
ind is
which which
mainly ividual observation time observation ividual ression of complications in in complications of ression the rate that is observed observed is that rate the . is
E due to the allocation allocation the to due likely to be to likely e i te follow the if ven ly high donor age age donor high ly W observe We . [29] - term effects of term effects
. ey specific very
In the group group the In ,
with high high with sufficient sufficient s d -
up up
of a .
This article isThis article by protected copyright. All rightsreserved. Accepted Zurich. Hospital attheUniversity Research Foundation Promedica the by supported was Gerber Nutrition Clinical and Diabetology thank We Acknowledgements occu transplantation islet after insulin exogenous Articleglyc 7%) < transplantation pancreas initial we summary, In efficacy study after glucose blood high persistent showed patient this and years), (52 patient older one patients transplanted 3 only included transplantation) islet after pancreas as well (as transplantation results reported publication recent A emic control as after initial pancreas transplantation (despite the need of additional additional of need the (despite transplantation pancreas initial after as control emic
rrence of diabetic nephrop rrence of diabetic islet
xed te urn kolde with knowledge current the extends and
of islet after pancreas transplantation also in transplantation pancreas after of islet
transplantation (HbA1c transplantation reduce the inc the reduce . Bernhard E. were able to able were
- Roth, Roth, idence of severe hypoglyc severe of idence
demonstrate demonstrate athy. is a method that can safely can that method a is . Kehret I.
, University Hospital Zurich) Hospital University , 12.1% at the end of follow of end the at 12.1%
with a younger mean age (39.7 years). There was only only was There years). (39.7 age mean younger a with of islet after combined or sequential pancreas sequential or combined after islet of
and ) and to protect to and ) study this in important information regarding regarding information important
. Seiler H. emia a
cohort o
that islet transplantation after transplantation islet that .
and the Foundation of Diabetes Diabetes of Foundation the and
It improve
the transplanted kidney kidney transplanted the ( is all -
up). Thus, we believe that our our that believe we Thus, up). for their assistance. their for
f older patients. f older able to establish establish to able Division of Endocrinology, Endocrinology, of Division
[30]
glycemic control glycemic . However, this study study this However, . the
comparable safety and and safety
Philipp A. Philipp
from re from (HbA1c (HbA1c -
kidney kidney levels levels failed failed -
This article isThis article by protected copyright. All rightsreserved. Accepted of the paper writing of performance design, Research Lehmann: Roger of paper the writing design, Research A. Spinas: Giatgen discussion research, the of Performance Oberkofler: Christian discussion research, the of Performance Rougemont: de Olivier Article Performance Glenck: Michael discussion research, the of Performance Oliver Tschopp: discussion research, the Performanceof Zuellig: A. Richard paper of the writing analysis, data research, of Performance D. Benediktsdottir: Bara research, of Performance Hochuli: Michel of the paper writing discussion, analysis, data research, the of performance design, Research A. Gerber: Philipp Author contributions
of theresearch, discussion data analysis, discussion analysis, data the research, data analysis, discussion, discussion, analysis, data research, the
This article isThis article by protected copyright. All rightsreserved. 8. 7. 6. 5. 4. 3. 2. 1. References
Accepted Article Transplant long promotes immunotherapy induction Potent al. A,et Heitman FB, MD,Barton Bellin 13 Pancreas Versus Kidney Islet Simultaneous in Control Glycemic al. et J, J, Brockmann Graziano R, Lehmann Diabetologia me diabetes in type1 transplantation kidney al. N,et V,Demartines Pavlicek PA, Gerber transplantation. islet for Ricordi AM, Shapiro Med J Engl a glucocorticoid using mellitus diabetes type 1 with patients in seven transplantation Islet al. JR,RyanEA,et Lakey AM, Shapiro transplantation. kidney al. CE,et Ber T, M,Rimmele Page Endocrinol Rev transplantation. ofpancreas state current AC.The Gruessner RW, Gruessner 1967; nephropathy. in diabetic thekidney with along andduodenum pancreas FC. Y,Goetz Idezuki FK, RC,Merkel WD,Lillehei Kelly - Year Follow Year -
term insulin independence after islet transplantation in type 1 diabetes. typein 1diabetes. transplantation islet after independence term insulin 61 : 827 . 2012; . 2000; . 2008; - 37. - . 2013; up.
12 343
Diabetes Care Diabetes 51 C, Hering BJ, et al. International trial of the Edmonton protocol protocol the of Edmonton trial International al. et BJ, C, Hering : 1576 : 110 : 230 9 Transplantation N Engl J Med J N Engl : 555 - Kidney Transplantation in Type 1 Diabetes: A Prospective AProspective 1Diabetes: inType Transplantation Kidney - - - 83. 9. 8. - 62.
. 2015; Early relaparotomy after simultaneous pancreas simultaneous after relaparotomy Early . 2006; . 2012; 38 llitus: a 5 year single centre follow centre single a5year llitus: : 752 Simultaneous islet Simultaneous 355 - 94 free immunosuppressive regimen. regimen. freeimmunosuppressive : 159 : 1318
- 9.
- 64. - Allotransplantation of the the of Allotransplantation 30.
- kidney vspancreas kidney Surgery Am J - Nat up. . N - - - This article isThis article by protected copyright. All rightsreserved. 16. 15. 14. 13. 12. 11. 10. 9.
Accepted Article
transplantation. transplantation. kidney after simultaneous rejection allograft renal acute of prevention for azathioprine versus mofetil mycophenolate of trial prospective Randomized, RJ. DE, Taylor Sutherland HW, Sollinger JS, ML, Melzer Henry RM, Merion trial. multicenter 1 alarge at year of results pancreas primarysimultaneous in cyclosporine Land W,Malaise Sandberg J, J,Langrehr J,Group ES. Tacrolimus versus animals large manand in assessment isolation al. et Islet BJ, Gray C, DW,Hering Ricordi Transplant steroid a using transplantation M,Bert Weber R, Lehmann ultracentrifuge. the preparative of use plasma,without in cholesterol lipoprotein density low of concentration of the DS.Estimation Fredrickson Levy WT, RI, Friedewald neuropathy. of diabetic staging and two DA. Apractical N, Greene MB, Canal PK,Brown Thomas MJ, Stevens EL, Feldman transplanta islet humanin goals fornew come time M.Has Weber W, GA,Moritz Spinas R, Lehmann 2016; Hypoglycemia. bySevere Complicated Diabetes inType1 Islets WR, Clarke BJ, Hering - step quantitative clinical and electrophysiological assessment for the diagnosis diagnosis the for assessment electrophysiological and clinical quantitative step 39 . : 1230 Acta Diabetol Lat Acta Diabetol . 2004; - Clin Chem Clin tion? tion? 40. Transplantation 4
: 1117 Am JTransplant Bridges ND, et al. Phase 3 Trial of Transplantation of Human of Transplantation of 3Trial Phase al. ND,et Bridges - . 1972; . 1990; 23. hold P, et al. et al. P, hold
- free immunosuppression: two immunosuppression: free . 2000; 18 27 Diabetes Diabetes : 499 : 185 . 2008; 70 Successful simultaneous islet simultaneous Successful - - : 105 502. 95. Transplant P Transplant
Care 8
: 1096 - - 11. kidney transplantation: preliminary preliminary transplantation: kidney
. 1994;
- 100. roc 17
. 2002; : 1281 - year follow Diabetes Care Diabetes - 34 9. -
: 1911 pancre - kidney kidney - up. - 2. Am J as as
. - This article isThis article by protected copyright. All rightsreserved. Accepted25. 24. 23. 22. 21. Article20. 19. 18. 17.
and Complications Trial Research Group. Group. Trial Research Complications and long The effectof treatment intensive onthe ofdiabetes development of andprogression database. Sharing al withpoor associated is retransplantation al. Pancreatic V, et C,Jayaschandaran E, Maloney Siskind retransplantation. pancreas of Outcomes TB. DE,Dunn R, Sutherland N, Kandaswamy EB,Chandolias Finger EN, Rudolph alone. transplantation kidney kidney simultaneous after retransplantation pancreas of al.Outcomes et J, M,Laurence Selzner J, Seal Transplant retransplantation. pancreas Late etal. JM, RS, Chen Mangus JA, Fridell patients? diabetic for chance second O,Demuylder Thaunat F, Buron rate. filtration glomerular to estimate equation Anew al. et CH, Schmid LA, Stevens Levey AS, and etanercept. exenatide under infusion islet after supplemental secretion insulin in improvement Long al. S, et Messinger T, RN,Tharavanij Faradji andlong graftfunction, rejection, kidney forsimultaneous therapy induction basiliximab versus Thymoglobulin MU,etal. M, Boehnert F, Selzner Bazerbachi - term complications ininsulin term complications . 2015; Ann Intern Med Intern Ann Transplantation 29 Pancreas - : 1 pancreas transplantation are comparable to pancreas after after pancreas to are comparable transplantation pancreas lograft survival: an update of the United Network for Organ Organ for Network United ofthe update an survival: lograft - 8.
. 2015; . 2009; Transplantation . 2008; - - Mischler S, et al. Pancreas retransplantation: a a retransplantation: et al.Pancreas S, Mischler - term dependent diabetes mellitus diabetes dependent 44 150 Transplantation : 769 outcome. outcome. 86 : 604 Transplantation - : N Engl J Med J N Engl pancreas transplantation: impact on on impact transplantation: pancreas 1658 - 72. . 2015; - 12.
- Transplantation 65.
- term insulin independence and and independence term insulin
99 . 2013; : 623 . 1993; . 2015; - 95 8. . The Diabetes Control Control Diabetes . The
: 347 329 . 2011; 99 : 977 : 367 - 52. 92
- - Clin Clin 86. 74. : 1039
- 43.
This article isThis article by protected copyright. All rightsreserved. Accepted 30. 29. Article28. 27. 26.
Islets diabetes. control to strategies rescue complementary Two transplantation: islet failed A, Livingston Andres 2357 and function better than transplantation ofkidney alone. long preserves transplantation andkidney pancreas Lindahl JP, Reinholt FP, Eide 3063 analysis. longitudinal skin biopsy and neurophysiological 1 diabetic kidney transplantpatients and effects of islettransplantation: P, Amadio Fiorina U, Carro Del transplants. kidney and mellitus diabetes typeI with patients uremic among function renal of improvement with associated is Islet transplantation G,etal. Zerbini F, P, Folli Fiorina 2174 IsletTransplantation. for List TherapyWaiting and Insulin Islet Simultaneous RA,et al. R,Zuellig Locher PA, Gerber - - - . 2016; . 2016; 65. 9. 80.
7 : e1126036. - Kidney or Islet After Kidney Transplantation Versus Intensiv Versus Transplantation Kidney After KidneyIslet or e S, Kin T, et al. Islet et al. T, Kin e S, J Am Nephrol J Soc
IA, et al. In patients with type 1 diabetes simultaneous simultaneous diabetes type1 with patients In al. IA, et S, et al. al. S, et Glycemia, Hypoglycemia, and Costs of Costs and Hypoglycemia, Glycemia, Evaluation of polyneuropathy markers in type in markers polyneuropathy of Evaluation - . 2003; . 2003; after - failed
14 - : 2150 term kidney graft ultrastructure ultrastructure graft term kidney - pancreas and pancreas and pancreas Diabetologia Diabetes Care Diabetes Transplantation - 8.
. 2014; . 2007; . 2015; 57 - after e : 30 99 : - : This article isThis article by protected copyright. All rightsreserved. di statistical re failure pancreas and pancreas with Patients 3: group with Patients 2: group organfailure, pancreas as given are Data (IEQ) weight body kg per equivalent islet Total (n) weight body numberkg islet per Total (n) transplantations islet Number of (y) at Age (y) transplantation at pancreas Age (y) diagnosis at diabetes Age (%) Female patients Number of Characteristic Table 1: Tables
Accepted Article
islet Patient Patient
fference between the the between fference (pancreas re (pancreas
and transplantation transplantation and Mean ± SD or %. Group 1: Patients with islet transplantation after after islet with transplantation 1: Patients Group Mean ±SDor%.
- )
transplantation transplantation
three
c groups. haracteristics
9676 ±9785 9676 ±9547 9405 41.0 ±10.6 41.0 52.2 ±6.0 52.2 ±7.3 12.1 pancreas failure but without re without but failure pancreas 1.6 ±1.3 1.6 Group 1 .
30.0 10
-
transplantation
41.4 ±2.7 41.4 9.7 ±5.3 9.7 Group 2 42.9 n/a n/a n/a n/a 7
. p:p 38.4 ±6.7 38.4 ±9.5 35.6 ±1.1 12.8 Group 3 - - transplantation value for for value 100 n/a n/a n/a 3
, 0.03 0. 0. 0.10
p 59 67
This article isThis article by protected copyright. All rightsreserved. islet before (p<0.05). PT (mmHg) blood pressure Diastolic (mmHg) pressure blood Systolic (mmol/l) Triglycerides (mmol/l) HDL cholesterol (mmol/l) LDL cholesterol (mmol/l) cholesterol Total eGFR (ml/min/1.73m BMI (kg/m Parameter Table
Accepted transplantation; PL: pancreas Article 2 :
BMI, † 2 Significantly different compared with levels before pancreas transplantation (p<0.05). (p<0.05). transplantation pancreas before levels with compared different Significantly
) (or pancreas re (or pancreas
Kidney function, cardiovascular riskfactors cardiovascular function, Kidney 2
)
- ) transplantation (p<0.05). transplantation Group 3 Group 2 Group 1 Group 3 Group 2 Group 1 Group 3 Group 2 Group 1 Group 3 Group 2 Group 1 Group 3 Group 2 Group 1 Group 3 Group 2 Group 1 Group Group 3 Group 2 Group 1 Group 3 Group 2 Group 1 Group ITPL: islet transplantation ITPL: islet
Before PTPL Before 10.0 ±7.0 14.0 21.2 ±3.2 23.4 23. 1.8 155 ±36 155 ±23 148 0.9 ±0.4 1.4 ±0.8 2.1 ±0.3 1.1 ±0.4 1.5 2.2 ±0.7 2.3 ±0.1 2.0 4.3 ±0.7 4.2 ±1.0 4.5 ±4.6 9.4 80 ± 18 80 ± 15 87 148 88 5
± ± ± ± ± ± ± ± 4.
± 0.7 1.1 1.3 0.1 4 5.7 1.3 4
5
; PRTPL: pancreas re ; PRTPL: pancreas 77.6 ±31.1 77.6 ±21.0 60.5 After PTPL 64.5 21.3 ±2.5 22.6 ±6.1 24.3
1.0 ±0.3 1.0 1.7 133 ±16 137 ±20 146 ±1.1 2.0 ± 1.7 1.4 ±0.1 1.6 2.3 ±0.9 2.5 ±1.7 2.4 4.5 ±1.0 4.4 ±2.1 4.3 83 ± 14 83 ± 11 86 85
± ± ± ± ± ± ± ±
0.6 0.2 0.7 0.1 1.0 7 11 0.7 1.5
*
† †
75.4 ±30.3 75.4 ±14.6 51.1 After PTPL 56.5 21.7 ±2.6 23.2 ±5.6 24.2 153 ±11 144 ±24 134 1.8 ±1.0 2.3 ±0.8 1.7 2.0 ±0.1 0.9 ±0.6 1.5 2.6 ±1.0 2.7 ±1.1 2.1 5.3 ±1.2 4.6 ±1.8 4.8 - 83 ± 18 83 ± 14 83 Failure transplantation
± ± ± ± ± ± ± ±
11 1.3 0.4 0.1 0.1 11 4.9 1.5
† †
Before ITPL Before . 48.2 ±14.1 48.2 § * Significant difference between groups betweengroups difference * Significant
63.5 21.7 ±5.0 24.2 Significantly diff Significantly 132 ±25 132 1.7 ±1.3 1.9 2.0 ±0.6 1.4 2.6 ±0.7 2.4 5.0 ±1.1 4.7 77 ± 16 77 140 PRTPL 83
± ± ± ±
± ± ±
± 1.3 0.4 0.1 0.5 4 3.5 1.8 7
†
†
/ 47.2 ±18.2 47.2 After ITPL erent compared with levels levels with compared erent 62.5 21.8 23. 1.4 ±0.9 1.4 133 ±24 139 1.3 1.9 ±0.5 1.5 2.4 ±0.7 2.0 5.0 4. PRTPL 80 ± 8 81 3 8
± ± ± ± ± 1.4
± ± ± ± ± 4.
0.3 0.1 0.1 0.4 7 11 3.5 1.7
6 §
† /
End of follow End of 57.5 ±27.4 57.5 ±19.8 43.2 21.9 ±3.0 24.1 ±5.4 24.1 1.8 ±0.8 1.8 140 ±19 140 ±13 130 1.0 ±1.1 1.8 ±0.9 1.7 1.8 ±0.4 1.1 ±0.5 1.3 2.4 ±0.5 2.3 4.8 ±1.0 4.7 ±1.5 4.1 59 125 78 ± 7 83 ± 8 75
± ± ± ± ± ± ±
±
1.4 0.4 0.4 0.5 0.1 4 2.0 7 * * *
§
† † -
up
This article isThis article by protected copyright. All rightsreserved. Accepted and before Article 2. Figure p<0. groups, between transplantation pancreas PTPL: bars) 1, (group with transplantation, 1. Figure legends Figure , as well as well as , as
Median Median after islet transplantation islet after bright bright . *=
after after transplantation; ITPL: islet transplantation ITPL: islet transplantation; in
HbA1c (%, (%, HbA1c C patients with pancreas re pancreas patients with significantly significantly - p grey pancreas failure failure pancreas eptide levels (A) and insulin requirement (B) 0 1 .
bars) and without without and bars) 1./3. Quartile, Range Quartile, 1./3.
different from baseline, p<0.05. p<0.05. baseline, from different
(ITPL) and during . * = different from baseline, p<0.05. p<0.05. from baseline, . *=different consecutive islet transplantation islet consecutive - transplantation (group 3, dark grey bars) grey dark 3, (group transplantation
follow ) before and and before - up
; PRTPL: pancreas re ; PRTPL: pancreas afterre after pancreas pancreas after †
= significant difference difference = significant - (1./3 transplantation . Quartile, Range) Range) . Quartile,
(group 2, white 2, white (group
-
in patients in patients . This article isThis article by protected copyright. All rightsreserved. Accepted Article
This article isThis article by protected copyright. All rightsreserved. Accepted Article