Orianne Villard1,2, Jean Frédéric Brun3,4, Lisa Bories5, Nicolas Molinari6, Pierre Yves Benhamou7,8, Thierry Berney9, Anne Wojtusciszyn1,2,5. 1. Laboratory of Cell Therapy for Diabetes, Institute of Regenerative Medicine and Biotherapy, University Hospital of Montpellier, Saint Eloi Hospital, Montpellier, France. 2. Institut National de la Santé et de la Recherche Médicale U1191, Institute of Functional Genomics, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5203, Montpellier University, Montpellier, France. 3. Unité Mixte de Recherche, Centre National de la Recherche Scientifique 9214, Institut National de la Santé et de la Recherche Médicale U1046, Physiologie et Médecine Experimentale du coeur et des muscles, Montpellier University, Montpellier, France. 4. Department of Clinical Physiology, Metabolic Explorations, University Hospital of Montpellier, Montpellier, France. 5. Department of Endocrinology, Diabetes and Nutrition, University Hospital of Montpellier, Lapeyronie Hospital, Montpellier, France. 6. Department of Medical Information, University Hospital of Montpellier, La Colombière Hospital, Montpellier, France. 7. Department of Diabetology, Pôle DigiDune, Grenoble University Hospital, Grenoble Alpes University, Grenoble, France. 8. Grenoble Alpes University, Institut National de la Santé et de la Recherche Médicale U1055, Laboratory of Fundamental and Applied Bioenergetics, Grenoble, France. 9. Visceral and Transplant Surgery, Department of Surgery, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland.
Abstract
Context: Islet transplantation (IT) can treat patients with severely unstable type 1 diabetes. Prehepatic kinetics of insulin secretion (ISec) in two phases can be calculated by C-peptide levels during meal tests. We proposed to describe the ISec profile after a mixed-meal tolerance test (MMTT) in IT recipients and to determine whether the calculated ISec indexes can predict graft outcome. Methods: We analyzed 34 MMTT among 11 patients who underwent IT between 2011 and 2016 and compared them with healthy controls and patients with type 2 diabetes (T2D). ISec indexes and insulin sensitivity were calculated from models of Van Cauter, Breda, and Mari after MMTT. Graft success was defined by total insulin independence without any criteria for diabetes. Results: In patients with successful IT, the first- and second-phase ISec indexes were lower than those of controls (P < 0.001) and did not differ from those of the T2D group. Nevertheless, insulin sensitivity of IT recipients was similar to that of the control group and higher than that of the T2D group. The index of the second phase of ISec ɸS was correlated with total infused islet equivalents (IEQs), was a good predictor of diabetes (re)occurrence, and allowed us to calculate 9500 IEQ/kg as the minimum needed to reach insulin independence. Conclusion: We showed that indexes from the first and second phases of ISec are altered in insulin-independent IT recipients. Higher sensitivity distinguishes them from patients with T2D. Even in insulin-independent patients, IT remains a marginal mass model. Moreover, ɸS can estimate transplanted islet mass and predict IT recipient outcomes.
Context: Islet transplantation (IT) can treat patients with severely unstable type 1 diabetes. Prehepatic kinetics of insulin secretion (ISec) in two phases can be calculated by C-peptide levels during meal tests. We proposed to describe the ISec profile after a mixed-meal tolerance test (MMTT) in IT recipients and to determine whether the calculated ISec indexes can predict graft outcome. Methods: We analyzed 34 MMTT among 11 patients who underwent IT between 2011 and 2016 and compared them with healthy controls and patients with type 2 diabetes (T2D). ISec indexes and insulin sensitivity were calculated from models of Van Cauter, Breda, and Mari after MMTT. Graft success was defined by total insulin independence without any criteria for diabetes. Results: In patients with successful IT, the first- and second-phase ISec indexes were lower than those of controls (P < 0.001) and did not differ from those of the T2D group. Nevertheless, insulin sensitivity of IT recipients was similar to that of the control group and higher than that of the T2D group. The index of the second phase of ISec ɸS was correlated with total infused islet equivalents (IEQs), was a good predictor of diabetes (re)occurrence, and allowed us to calculate 9500 IEQ/kg as the minimum needed to reach insulin independence. Conclusion: We showed that indexes from the first and second phases of ISec are altered in insulin-independent IT recipients. Higher sensitivity distinguishes them from patients with T2D. Even in insulin-independent patients, IT remains a marginal mass model. Moreover, ɸS can estimate transplanted islet mass and predict IT recipient outcomes.
Authors: Petr Ježek; Blanka Holendová; Martin Jabůrek; Jan Tauber; Andrea Dlasková; Lydie Plecitá-Hlavatá Journal: Antioxidants (Basel) Date: 2021-01-29