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Glycemic variability indices can be used to diagnose islet transplantation success in type 1 diabetic patients

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Abstract

Aims

High glycemic variability (GV) is the major indication for islet transplantation (IT) in patients with type 1 diabetes (T1D). The actual criteria used to assess graft function do not consider GV improvement. Our study aimed to describe GV indices’ evolution in T1D patients who benefited from IT during the TRIMECO trial and to evaluate if thresholds might be defined to diagnose IT success.

Methods

We collected data from 29 patients of the TRIMECO trial, a clinical trial (NCT01148680) comparing the metabolic efficacy of IT with intensive insulin therapy. Based on CGM data, we analyzed mean glucose level and four GV indices (standard deviation, coefficient of variation, MAGE and GVP) before (M0) and 6 months (M6) after IT.

Results

Each GV index decreased significantly between M0 and M6: SD 53.9 mg/dL [44.6–61.5] versus 20.1 mg/dL [13.5–24.3]; CV 35.2% [30.6–37.7] versus 17.3% [12.0–20.5]; MAGE 134.9 mg/dl [111.2–155.8] versus 51.9 mg/dL [32.4–62.4]; GVP 35.3% [24.9–47.2] versus 12.2% [6.2–18.8] (p ≤ 0.0001). Thresholds diagnosing IT success at 6 months post-transplant were an SD at 22.76 mg/dL (sensibility 88.89%, specificity 80.00%), a CV at 17.47% (sensibility 88.89%, specificity 70.00%), a MAGE at 54.81 mg/dL (sensibility 88.89%, specificity 80.00%) and a GVP at 12.27% (sensibility 88.89%, specificity 70.00%).

Conclusions

This study confirms a positive impact of IT on GV. The proposed thresholds allow an easy evaluation of IT success using only CGM data and may be a clinical tool for the follow-up of transplanted patients.

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Abbreviations

CGM:

Continuous glucose monitoring

CV:

Coefficient of variation

GV:

Glycemic variability

GVP:

Glycemic variability percentage

HbA1c:

Glycated hemoglobin

IT:

Islet transplantation

MAGE:

Mean amplitude glycemic excursion

ROC curve:

Receiver operating characteristic curve

SD:

Standard deviation

Se:

Sensibility

Spe:

Specificity

T1D:

Type 1 diabetes

TIR:

Time in range

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Funding

This work was supported by a Research Year Scholarship from Grenoble Alpes University.

Author information

Authors and Affiliations

  1. Department of Endocrinology, Diabetes and Nutrition, Grenoble Alpes University Hospital, CS10217, 38043, Grenoble, France

    Manon Jalbert, Pierre-Yves Benhamou & Sandrine Lablanche

  2. Inria, CNRS, Grenoble INP, LJK, Grenoble Alpes University, Grenoble, France

    Fei Zheng, Florence Forbes & Stéphane Bonnet

  3. Department of Endocrinology, Diabetes and Nutrition, Montpellier University Hospital, Montpellier, France

    Anne Wojtusciszyn

  4. CEA LETI, DTBS, Univ. Grenoble Alpes, Minatec Campus, Grenoble, France

    Fei Zheng, Florence Forbes & Stéphane Bonnet

  5. Department of Public Health, Grenoble Alpes University, Grenoble, France

    Kristina Skaare

Authors
  1. Manon Jalbert
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  2. Fei Zheng
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  4. Florence Forbes
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  7. Pierre-Yves Benhamou
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  8. Sandrine Lablanche
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Consortia

TRIMECO Study Group

  • S. Lablanche
  • , P.-Y. Benhamou
  • , J.-L. Bosson
  • , K. Skaare
  • , R. Tetaz
  • , S. Logerot
  • , H. Egelhofer
  • , M.-C. Vantyghem
  • , J. Kerr-Conte
  • , K. Benomar
  • , F. Kessler
  • , A. Wojtusciszyn
  • , E. Renard
  • , S. Borot
  • , C. Thivolet
  • , C. Colin
  • , Gwen Grguric
  • , C. Camillo-Brault
  • , E. Morelon
  • , F. Buron
  • , L. Badet
  • , S. Girerd
  • , D. Bosco
  • , T. Berney
  • , G. Grguric
  •  & A. Penfornis

Corresponding author

Correspondence to Manon Jalbert.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standard

The institutional review board approved the study (French Committee for the Protection of Persons participating in biomedical research “Sud-Est V”; no 09-CHUG-21) and Clinical Trial Authorization was obtained from the French National Competent Authority (ANSM-no 2008-A01554-51).

Informed consent

Informed consent was obtained from the patients included in this study.

Additional information

Managed by Massimo Federici.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Members listed in the appendix are belongs to TRIMECO Study Group.

Appendix

Appendix

Department of Endocrinology, Diabetes, and Nutrition (Lablanche MD, Prof P-Y Benhamou MD), French National Center for Scientific Research (Prof J-L Bosson MD, K Skaare PhD), Department of Nephrology (R Tetaz MD), Department of Clinical Trial Surveillance, Direction of Clinical Research and Innovation (S Logerot PharmD), and Cellular Therapy Unit, National Blood Service Rhône-Alpes (H Egelhofer PhD), Grenoble University Hospital, and Department of Public Health (Prof J-L Bosson, K Skaare), Grenoble Alpes University, Grenoble, France; Inserm U1055, Laboratory of Fundamental and Applied Bioenergetics Grenoble, Grenoble, France (S Lablanche, Prof P-Y Benhamou); Laboratoire des Techniques de l’Ingénierie Médicale et de la Complexité–Informatique, Mathématiques et Applications de Grenoble, Grenoble, France (Prof J-L Bosson, K Skaare); Department of Endocrinology, Diabetes, and Nutrition, C Huriez Hospital, Lille University Hospital, Lille, France; Inserm 1190, European Genomic Institute for Diabetes, Lille, France (Prof M-C Vantyghem MD, Prof J Kerr-Conte PhD, K Benomar MD, Prof F Pattou MD); Hôpitaux Universitaires de Strasbourg, Service d’Endocrinologie Diabète et Maladies Métaboliques, and Equipe d’Accueil 7293, Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg, Strasbourg, France (Prof L Kessler MD); Department of Endocrinology, Diabetes, and Nutrition, Montpellier University Hospital, and Laboratory of Cell Therapy of Diabetes, Institute of Functional Genomics, Mixed Research Unit, French National Center for Scientific Research 5203, Inserm U1191, University of Montpellier, Montpellier, France (Prof A Wojtusciszyn MD, Prof E Renard MD); Centre Hospitalier Universitaire Jean Minjoz, Service d’Endocrinologie-Métabolisme et Diabétologie-Nutrition, Besançon, France (S Borot MD); Service d’Endocrinologie Diabète Nutrition (Prof C Thivolet MD) Pôle de Santé Publique Service Evaluation Economique en Santé (Prof C Colin MD, Gwen Grguric PhD, C Camillo-Brault PharmD), Service de Transplantation, Néphrologie et Immunologie Clinique (Prof E Morelon MD, F Buron MD), and Service d’Urologie et de Chirurgie de la Transplantation (Prof L Badet MD), Hospices Civils de Lyon, Groupement Hospitalier Centre, Université de Lyon, Lyon, France; Service de Néphrologie, Centre Hospitalier Universitaire de Nancy, Nancy, France (S Girerd MD); Department of Surgery, Islet Isolation, and Transplantation, Geneva University Hospitals, Geneva, Switzerland (D Bosco PhD, Prof T Berney MD); F-69003, EA 7425 Health Services and Performance Research, Public Health Service and Health Economic Evaluation, Claude Bernard University Lyon 1, Lyon, France (Prof C Colin, G Grguric, C Camillo-Brault); Department of Diabetes, Sud-Francilien Hospital, Corbeil-Essonnes, France (Prof A Penfornis MD); and Université Paris-Sud, Orsay, France (Prof A Penfornis).

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Jalbert, M., Zheng, F., Wojtusciszyn, A. et al. Glycemic variability indices can be used to diagnose islet transplantation success in type 1 diabetic patients. Acta Diabetol 57, 335–345 (2020). https://doi.org/10.1007/s00592-019-01425-3

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