Defining outcomes for β-cell replacement therapy in the treatment of diabetes: a consensus report on the Igls criteria from the IPITA/EPITA opinion leaders workshop

Michael R Rickels¹, Peter G Stock², Eelco J P de Koning³, Lorenzo Piemonti⁴, Johann Pratschke⁵, Rodolfo Alejandro⁶, Melena D Bellin⁷, Thierry Berney⁸, Pratik Choudhary⁹, Paul R Johnson¹⁰, Raja Kandaswamy¹¹, Thomas W H Kay¹², Bart Keymeulen¹³, Yogish C Kudva¹⁴, Esther Latres¹⁵, Robert M Langer¹⁶, Roger Lehmann¹⁷, Barbara Ludwig¹⁸, James F Markmann¹⁹, Marjana Marinac¹⁵, Jon S Odorico²⁰, François Pattou²¹, Peter A Senior²², James A M Shaw²³, Marie-Christine Vantyghem²⁴, Steven White²³

Affiliations

¹ Department of Medicine, Division of Endocrinology, Diabetes & Metabolism, Institute for Diabetes, Obesity & Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
² Department of Surgery, Division of Transplantation, University of California at San Francisco, San Francisco, CA, USA.
³ Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands.
⁴ Diabetes Research Institute, San Raffaele Scientific Institute, Milan, Italy.
⁵ Department of Surgery, Charité Medical School, Berlin, Germany.
⁶ Department of Medicine, Division of Endocrinology, Diabetes & Metabolism, Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL, USA.
⁷ Department of Pediatrics, Division of Endocrinology, Schulze Diabetes Institute, University of Minnesota, Minneapolis, MN, USA.
⁸ Department of Surgery, Division of Transplantation and Visceral Surgery, Geneva University Hospital, Geneva, Switzerland.
⁹ Diabetes Research Group, King's College London, London, UK.
¹⁰ Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.
¹¹ Department of Surgery, Division of Transplantation, Schulze Diabetes Institute, University of Minnesota, Minneapolis, MN, USA.
¹² Department of Medicine, St. Vincent's Hospital, St. Vincent's Institute of Medical Research, University of Melbourne, Melbourne, Vic., Australia.
¹³ Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium.
¹⁴ Department of Internal Medicine, Division of Endocrinology, Diabetes, Metabolism & Nutrition, Mayo Clinic, Rochester, MN, USA.
¹⁵ JDRF International, New York, NY, USA.
¹⁶ Ordensklinikum Elisabethinin Hospital, Linz, Austria.
¹⁷ Department of Endocrinology and Diabetology, University Hospital Zurich, Zurich, Switzerland.
¹⁸ Department of Medicine III, Division of Endocrinology and Diabetes, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany.
¹⁹ Department of Surgery, Division of Transplantation, Massachusetts General Hospital, Boston, MA, USA.
²⁰ Department of Surgery, Division of Transplantation, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
²¹ Department of General and Endocrine Surgery, Centre Hospitalier Universitaire de Lille, Inserm, Université de Lille, Lille, France.
²² Department of Medicine, Division of Endocrinology & Metabolism, University of Alberta, Edmonton, AB, Canada.
²³ Institute of Transplantation, The Freeman Hospital, Newcastle University, Newcastle upon Tyne, UK.
²⁴ Department of Endocrinology, Diabetology and Metabolism, Centre Hospitalier Universitaire de Lille, Inserm, Université de Lille, Lille, France.

PMID: 29453879
PMCID: PMC5867272
DOI: 10.1111/tri.13138

Review

Defining outcomes for β-cell replacement therapy in the treatment of diabetes: a consensus report on the Igls criteria from the IPITA/EPITA opinion leaders workshop

Michael R Rickels et al. Transpl Int. 2018 Apr.

. 2018 Apr;31(4):343-352.

doi: 10.1111/tri.13138.

Authors

Affiliations

¹ Department of Medicine, Division of Endocrinology, Diabetes & Metabolism, Institute for Diabetes, Obesity & Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
² Department of Surgery, Division of Transplantation, University of California at San Francisco, San Francisco, CA, USA.
³ Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands.
⁴ Diabetes Research Institute, San Raffaele Scientific Institute, Milan, Italy.
⁵ Department of Surgery, Charité Medical School, Berlin, Germany.
⁶ Department of Medicine, Division of Endocrinology, Diabetes & Metabolism, Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL, USA.
⁷ Department of Pediatrics, Division of Endocrinology, Schulze Diabetes Institute, University of Minnesota, Minneapolis, MN, USA.
⁸ Department of Surgery, Division of Transplantation and Visceral Surgery, Geneva University Hospital, Geneva, Switzerland.
⁹ Diabetes Research Group, King's College London, London, UK.
¹⁰ Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.
¹¹ Department of Surgery, Division of Transplantation, Schulze Diabetes Institute, University of Minnesota, Minneapolis, MN, USA.
¹² Department of Medicine, St. Vincent's Hospital, St. Vincent's Institute of Medical Research, University of Melbourne, Melbourne, Vic., Australia.
¹³ Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium.
¹⁴ Department of Internal Medicine, Division of Endocrinology, Diabetes, Metabolism & Nutrition, Mayo Clinic, Rochester, MN, USA.
¹⁵ JDRF International, New York, NY, USA.
¹⁶ Ordensklinikum Elisabethinin Hospital, Linz, Austria.
¹⁷ Department of Endocrinology and Diabetology, University Hospital Zurich, Zurich, Switzerland.
¹⁸ Department of Medicine III, Division of Endocrinology and Diabetes, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany.
¹⁹ Department of Surgery, Division of Transplantation, Massachusetts General Hospital, Boston, MA, USA.
²⁰ Department of Surgery, Division of Transplantation, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
²¹ Department of General and Endocrine Surgery, Centre Hospitalier Universitaire de Lille, Inserm, Université de Lille, Lille, France.
²² Department of Medicine, Division of Endocrinology & Metabolism, University of Alberta, Edmonton, AB, Canada.
²³ Institute of Transplantation, The Freeman Hospital, Newcastle University, Newcastle upon Tyne, UK.
²⁴ Department of Endocrinology, Diabetology and Metabolism, Centre Hospitalier Universitaire de Lille, Inserm, Université de Lille, Lille, France.

PMID: 29453879
PMCID: PMC5867272
DOI: 10.1111/tri.13138

Abstract

β-cell replacement therapy, available currently as pancreas or islet transplantation, has developed without a clear definition of graft functional and clinical outcomes. The International Pancreas & Islet Transplant Association (IPITA) and European Pancreas & Islet Transplantation Association (EPITA) held a workshop to develop consensus for an IPITA/EPITA Statement on the definition of function and failure of current and future forms of β-cell replacement therapy. There was consensus that β-cell replacement therapy could be considered as a treatment for β-cell failure, regardless of etiology and without requiring undetectable C-peptide, accompanied by glycemic instability with either problematic hypoglycemia or hyperglycemia. Glycemic control should be assessed at a minimum by glycated hemoglobin (HbA_1c ) and the occurrence of severe hypoglycemia. Optimal β-cell graft function is defined by near-normal glycemic control [HbA_1c ≤ 6.5% (48 mmol/mol)] without severe hypoglycemia or requirement for insulin or other antihyperglycemic therapy, and with an increase over pretransplant measurement of C-peptide. Good β-cell graft function requires HbA_1c < 7.0% (53 mmol/mol) without severe hypoglycemia and with a significant (>50%) reduction in insulin requirements and restoration of clinically significant C-peptide production. Marginal β-cell graft function is defined by failure to achieve HbA_1c < 7.0% (53 mmol/mol), the occurrence of any severe hypoglycemia, or less than 50% reduction in insulin requirements when there is restoration of clinically significant C-peptide production documented by improvement in hypoglycemia awareness/severity, or glycemic variability/lability. A failed β-cell graft is defined by the absence of any evidence for clinically significant C-peptide production. Optimal and good functional outcomes are considered successful clinical outcomes.

Keywords: Outcome; islet clinical; pancreas clinical.

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Conflict of interest statement

The authors declare no conflicts of interest relevant to this work.

References

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Defining outcomes for β-cell replacement therapy in the treatment of diabetes: a consensus report on the Igls criteria from the IPITA/EPITA opinion leaders workshop

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Defining outcomes for β-cell replacement therapy in the treatment of diabetes: a consensus report on the Igls criteria from the IPITA/EPITA opinion leaders workshop

Authors

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Conflict of interest statement

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