Supplemental Islet Infusions Restore Insulin Independence After Graft Dysfunction in Islet Transplant Recipients

Koh, Angela; Imes, Sharleen; Kin, Tatsuya; Dinyari, Parastoo; Malcolm, Andrew J.; Toso, Christian; Shapiro, A. M. James; Senior, Peter

doi:10.1097/tp.0b013e3181bcdbe8

Cited by 35 publications

(22 citation statements)

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“…Subjects were eligible for further transplant if by the end of the fourth week after the first islet infusion or by the end of the fourth week after the second islet infusion they do not meet insulin-independence criteria [21], or HbA1c increased over 6.5% (47.5 mmol/mol) [22] (three patients required a supplemental islet infusion after the initial study period). Two immunosuppressive protocols were utilized in this clinical trial, as outlined in Figure 1A.…”

Section: Methodsmentioning

confidence: 99%

Five-year follow-up of patients with type 1 diabetes transplanted with allogeneic islets: the UIC experience

Kinzer

Danielson

et al. 2014

Acta Diabetol

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This report summarizes a 5-year phase 1/2 allogeneic islet transplantation clinical trial conducted at the University of Illinois at Chicago (UIC). Ten patients were enrolled in this single center, open label, and prospective trial in which patients received 1–3 transplants. The first four subjects underwent islet transplantation with the Edmonton immunosuppressive regimen and the remaining six subjects received the UIC immunosuppressive protocol (Edmonton plus etanercept and exenatide). All 10 patients achieved insulin independence after 1–3 transplants. At five years of follow-up, six of the initial 10 patients were free of exogenous insulin. During the follow-up period, 7 of the 10 patients maintained positive C-peptide levels and a composite hypoglycemic (HYPO) score of 0. Most patients maintained HbA1c levels < 6.0% (42.1 mmol/mol) and a significantly improved β-score. In conclusion, this study demonstrated long-term islet graft function without using T-cell depleting induction, with an encouraging outcome that includes 60% of patients remaining insulin independent after five years of initial transplantation.

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Section: Methodsmentioning

confidence: 99%

Five-year follow-up of patients with type 1 diabetes transplanted with allogeneic islets: the UIC experience

Kinzer

Danielson

et al. 2014

Acta Diabetol

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“…Supplemental islet infusions have also been shown to be a safe and effective means to restore insulin independence in subjects who have had to resume insulin therapy after a period of insulin independence (32).…”

Section: Recent Progress and Refinements In Islet Transplantationmentioning

confidence: 99%

Islet Transplantation at the University of Alberta: Status Update and Review of Progress over the Last Decade

Senior

Kin

Shapiro

et al. 2012

Canadian Journal of Diabetes

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Keywords: islet transplant type 1 diabetes hypoglycemia immunosuppressionMots clés: transplantation d'îlots diabète de type 1 hypoglycémie immunosuppression a b s t r a c tThe general perception of islet transplantation among the diabetes community is somewhat negative, as insulin independence was maintained in only a small minority and there are fears about the safety of lifelong immunosuppression. There has been substantial progress in refining the islet transplant procedure to enhance its safety, reduce the toxicity of immunosuppression and improve long-term graft function. Longer-term follow-up studies have clarified the indications for islet transplantation; frequent, severe hypoglycemia, hypoglycemia unawareness and glycemic lability; facilitated informed consent and provided a framework for more realistic expectations, and suggest beneficial effects on microvascular complications. One hundred thirty-eight individuals have undergone islet transplantation at the University of Alberta over the last 12 years. Of these, 109 (79%) have full or partial graft function. Patient survival is 96% with no deaths due to transplantation. Three subjects have been hospitalized because of severe opportunistic infection and 3 have progressed to require renal replacement therapy. Current protocols are able to achieve insulin independence rates of 60% beyond 4 years. Safer and more effective islet transplantation, along with refinements in immunosuppressive therapy, make islet transplantation a more attractive option for a subset of persons with type 1 diabetes who suffer from frequent, severe hypoglycemia, lability and/or hypoglycemia unawareness, and resulting in excellent glycemic control and freedom from hypoglycemia.Ó 2012 Canadian Diabetes Association r é s u m é L'opinion générale de la communauté diabétique sur la transplantation d'îlots est quelque peu négative, comme l'insulino-indépendance est maintenue par un petit nombre seulement et qu'il y a des craintes concernant l'innocuité de l'immunosuppression permanente. Des progrès considérables quant au raffinement de la technique de transplantation d'îlots ont eu pour effet d'améliorer son innocuité, de réduire la toxicité de l'immunosuppression et d'améliorer le fonctionnement du greffon à long terme. Les études de suivi à plus long terme ont précisé les indications de la transplantation d'îlots (hypoglycémie grave et fréquente, ignorance de l'hypoglycémie et instabilité glycémique), facilité le consentement informé et fourni un cadre pour des attentes plus réalistes, et elles laissent entrevoir des effets bénéfiques concernant les complications microvasculaires. Cent trente-huit individus (138) ont subi une transplantation d'îlots à l'Université de l'Alberta au cours des douze dernières années. Parmi eux, 109 (79 %) ont un fonctionnement du greffon complet ou partiel. La survie des patients est de 96 % sans décès attribués à la transplantation. Trois (3) sujets ont été hospitalisés en raison d'infection opportuniste grave et 3 ont évolué vers la thérapie de remplacem...

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“…In islet cell transplantation, peri‐transplant insulin therapy has been associated with higher rates of insulin independence after islet transplantation but these observational data are far from conclusive regarding clinical benefits of intervention in this setting . Nonetheless, intensive insulin therapy to achieve normoglycaemia in the peri‐transplant period has become standard of care.…”

Section: Insulin Therapy and Transplantationmentioning

confidence: 99%

Insulin therapy in organ donation and transplantation

Shapey

Summers

Yiannoullou

et al. 2019

Diabetes Obesity Metabolism

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Hyperglycaemia is common in hospitalized individuals, and is often caused by physiological stress associated with critical illness or major surgery. Insulin therapy is an established treatment for hyperglycaemia and acute hyperkalaemia, and has also been used for myocardial dysfunction resistant to inotropic support. Insulin is commonly used in both organ donors and transplant recipients for hyperglycaemia, but the underlying knowledge base supporting its use remains limited. Insulin therapy plays an important yet poorly understood role in both organ donation and transplantation. Tight glycaemic control has been extensively studied in critical care over the past 15 years; however, this has not yet translated into the field of transplantation, where patients are more unwell and where improved outcomes remain an ongoing challenge. Insulin therapy and optimization of glycaemic control represent important areas for future hypothesis‐driven research into organ donation and transplantation, such as amelioration of ischaemia‐reperfusion injury, rejection and infection.

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Supplemental Islet Infusions Restore Insulin Independence After Graft Dysfunction in Islet Transplant Recipients

Abstract: Using current protocols, SII in the absence of exenatide results in impressive insulin-independence rates and the durability of insulin independence seems to be promising. However, a beneficial effect of exenatide should not be discounted until tested in randomized controlled studies.

Cited by 35 publications

References 10 publications

Five-year follow-up of patients with type 1 diabetes transplanted with allogeneic islets: the UIC experience

Five-year follow-up of patients with type 1 diabetes transplanted with allogeneic islets: the UIC experience

Islet Transplantation at the University of Alberta: Status Update and Review of Progress over the Last Decade

Insulin therapy in organ donation and transplantation

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