Purity of islet preparations and 5-year metabolic outcome of allogenic islet transplantation

Benomar, Kanza; Chetboun, Mikaël; Espiard, Stéphanie; Jannin, Arnaud; Mapihan, Kristell Le; Gmyr, Valéry; Caïazzo, Robert; Torres, F.; Raverdy, Violeta; Bonner, Caroline; d’Herbomez, Michèle; Pigny, Pascal; Noël, Christian; Kerr–Conte, Julie; Pattou, François; Vantyghem, Marie-Christine

doi:10.1111/ajt.14514

Cited by 25 publications

(16 citation statements)

References 30 publications

(61 reference statements)

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“…After islet transplantation, 5-year insulin independence might be as high as 50% (table 1). 9,14,[34][35][36]48,49 A quarter of patients can remain insulin independent, with HbA 1c concentrations of less than or equal to 6•5% (48 mmol/mol), for at least 10 years, with either islet transplantation alone or islet-after-kidney transplantation. 14…”

Section: What Can Be Expected From Islet Transplantation?mentioning

confidence: 99%

“…Compared with patients on optimised insulin therapy, patients who have had islet transplantation alone have a reduced risk for progression of retinopathy. 48,49 Nevertheless, in patients with high HbA 1c concentrations before islet transplantation, rapid improvement in glycaemic control poses a risk for early vitreal haemorrhage after transplantation. Several studies 60,61 have shown stabilisation or improvement of diabetic peripheral sensory neuropathy after islet transplantation compared with before islet transplantation.…”

Section: Diabetes Complicationsmentioning

confidence: 99%

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Advances in β-cell replacement therapy for the treatment of type 1 diabetes

et al. 2019

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The main goal of treatment for type 1 diabetes is to control glycaemia with insulin therapy to reduce disease complications. For some patients, technological approaches to insulin delivery are inadequate, and allogeneic islet transplantation is a safe alternative for those patients who have had severe hypoglycaemia complicated by impaired hypoglycaemia awareness or glycaemic lability, or who already receive immunosuppressive drugs for a kidney transplant. Since 2000, intrahepatic islet transplantation has proven efficacious in alleviating the burden of labile diabetes and preventing complications related to diabetes, whether or not a previous kidney transplant is present. Age, body-mass index, renal status, and cardiopulmonary status affect the choice between pancreas or islet transplantation. Access to transplantation is limited by the number of deceased donors and the necessity of immunosuppression. Future approaches might include alternative sources of islets (eg, xenogeneic tissue or human stem cells), extrahepatic sites of implantation (eg, omental, subcutaneous, or intramuscular), and induction of immune tolerance or encapsulation of islets.

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Section: What Can Be Expected From Islet Transplantation?mentioning

confidence: 99%

Section: Diabetes Complicationsmentioning

confidence: 99%

Advances in β-cell replacement therapy for the treatment of type 1 diabetes

et al. 2019

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“…Islet purity, defined as the proportion of islet cells relative to other pancreatic cell types such as the exocrine and ductal cells, is another aspect worth considering in every islet preparation [24]. Similar to islet counting, islet purity is assessed following DTZ staining to determine the ratio of islets to the exocrine portion.…”

Section: Puritymentioning

confidence: 99%

“…Although high islet purity is generally preferred for islet transplantation, any correlation between islet purity and clinical outcome has not been clearly established yet. On the contrary, studies have indicated that transplantation of islets with lower purity may unexpectedly yield better clinical outcomes for T1D patients, as non-islet cells may have beneficial effects on islet graft function [24,25]. In the context of basic research, islets are often manually hand-picked to ensure a pure islet population.…”

Section: Puritymentioning

confidence: 99%

Human Islet Isolation and Distribution Efforts for Clinical and Basic Research

Ng¹,

Wei²,

Koh³

et al. 2019

obm transplant

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The ability to routinely and reproducibly obtain purified human islets has facilitated substantial progress in providing a safe and reliable treatment option for adult patients of type 1 diabetes. The availability of human islets for basic research has also significantly improved the understanding of the biology of human islets, and consequently the pathophysiology of diabetes. Presently, about 70 human islet isolation centers are known to exist around the world, in addition to multiple coordinated human islet distribution programs, that facilitate the exchange of knowledge and sharing of this precious resource. This review summarizes the steps involved in the isolation and dissemination of human islets, and discusses key considerations with respect to the major challenges faced during this

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“…Intrahepatic ITx can achieve short‐term insulin independence in almost all cases. Factors promoting ITx success include islet number and purity, but long‐term insulin independence is difficult to maintain . Attrition in graft function is well recognized although poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Comparison of metabolic responses to the mixed meal tolerance test vs the oral glucose tolerance test after successful clinical islet transplantation

Forbes

Lam

Koh

et al. 2018

Clinical Transplantation

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Following islet transplantation, mixed meal tolerance tests (MMTs) are routinely utilized to assess graft function, but how the 90-minute MMTT glucose value relates to a 120-minute glucose concentration of ≥11.1 mmol/L used to diagnose diabetes following a standardized 75 g-OGTT, is not known. We examined this relationship further. Thirteen subjects with Type 1 diabetes and stable transplant grafts, not on exogenous insulin with HbA1c < 7% (53 mmol/mol), were studied on 17 occasions with paired OGTTs and MMTTs. Receiver operating characteristic (ROC) curves were constructed to derive the 90-minute MMTT glucose threshold associated with a 120-minute glucose concentration following a 75 g-OGTT (OGTT ) ≥11.1 mmol/L and their diagnostic accuracy. Studies with OGTT ≥11.1 mmol/L (n = 5) had diminished C-peptide: glucose, greater integrated glucose and diminished insulin: glucose area under the curve (AUC) ratios (0-120 minutes) and disposition indices; all P < .05, contrasting with MMTTs where no difference in the 90-minute glucose concentrations, C-peptide:glucose, integrated glucose, C-peptide and C-peptide: glucose AUCs (0-90 minutes) was seen; all P > .05. A 90-minute MMTT glucose concentration ≥8.0 mmol/L demonstrated a sensitivity and specificity of ≥80% for the diagnosis of OGTT ≥11.1 mmol/L; area under ROC curve (mean ± SEM) 73 ± 13%. A 90-minute MMTT glucose ≥8.0 mmol/L, identifies islet transplant recipients who may require closer monitoring for graft dysfunction.

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Purity of islet preparations and 5-year metabolic outcome of allogenic islet transplantation

Abstract: Am J Transplant. 2018;18:945-951. amjtransplant.com | 945

Cited by 25 publications

References 30 publications

Advances in β-cell replacement therapy for the treatment of type 1 diabetes

Advances in β-cell replacement therapy for the treatment of type 1 diabetes

Human Islet Isolation and Distribution Efforts for Clinical and Basic Research

Comparison of metabolic responses to the mixed meal tolerance test vs the oral glucose tolerance test after successful clinical islet transplantation

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