Long-Term Insulin Independence Achieved by a Multimodal Approach to Beta-Cell Replacement in Patients with Type I Diabetes

M. Nunez¹, S. Wisel², J. Gardner³, G. Worner⁴, G. Roll⁵, S. Syed³, G. Szot¹, M. Tavakol¹, K. Johnson¹, A. Posselt⁴, P. Stock⁶

¹Surgery, University of California, San Francisco, San Francisco, CA, ²Cedars-Sinai Medical Center, Los Angeles, CA, ³University of California, San Francisco, San Francisco, CA, ⁴University of California San Francisco, San Francisco, CA, ⁵UCSF Medical Center, San Francisco, CA, ⁶Univ of California-San Francisco, San Francisco, CA

Meeting: 2022 American Transplant Congress

Abstract number: 1149

Keywords: Immunosuppression, Islets, Pancreas transplantation, Tolerance

Topic: Clinical Science » Pancreas » 65 - Pancreas and Islet: All Topics

Session Information

Session Name: Pancreas and Islet: All Topics

Session Type: Poster Abstract

Date: Sunday, June 5, 2022

Session Time: 7:00pm-8:00pm

Presentation Time: 7:00pm-8:00pm

Location: Hynes Halls C & D

*Purpose: Long-term insulin independence in beta-cell replacement, via islet or pancreas transplant, remains limited by the toxic effects of calcineurin inhibitors (CNI) on beta cells and renal function. Here, we report a multimodal approach including islet and pancreas after islet (PAI) transplant utilizing CNI-free immunosuppression (IS) regimens based on Belatacept (BELA) and Efalizumab (EFA).

*Methods: Ten patients with severe Type 1 diabetes (T1D) received their first islet transplant between 2007 and 2009 with CNI-sparing IS based on BELA (n=5) or EFA (n=5). Patients were monitored for a mean of 12.9±1.1 years for beta cell function and renal function. Following islet failure, patients were considered for repeat islet infusion and/or PAI transplant. Circulating immunologic phenotype was characterized in the first year.

*Results: Seven of 10 patients (70%) maintained insulin independence (3 BELA, 4 EFA) at 10 years from islet transplant; four patients (2 EFA, 2 BELA) after one islet infusion and three patients (2 EFA, 1 BELA) following PAI transplant (Fig 1 and 2). Six of 10 (60%) remain insulin independent at a mean follow-up of 13.3±1.1 years. Eight of 10 patients maintain renal function with less than 30% decrease in GFR (Figure 2B). Patients receiving EFA demonstrated profound expansion of circulating CD4+Foxp3+ regulatory T cells (Tregs). One patient (EFA-4) with peak Tregs comprising 68% of all circulating CD4+ T cells remains insulin independent despite discontinuing all IS, demonstrating operational tolerance.

*Conclusions: Our results describe a multi-modal, personalized approach to beta-cell replacement in T1D. In our series, repeat islet transplant is ineffective at restoring insulin independence. PAI results in durable insulin independence but was associated with impaired renal function in 1/3 of recipients secondary to CNI dependence.

To cite this abstract in AMA style:

Nunez M, Wisel S, Gardner J, Worner G, Roll G, Syed S, Szot G, Tavakol M, Johnson K, Posselt A, Stock P. Long-Term Insulin Independence Achieved by a Multimodal Approach to Beta-Cell Replacement in Patients with Type I Diabetes [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/long-term-insulin-independence-achieved-by-a-multimodal-approach-to-beta-cell-replacement-in-patients-with-type-i-diabetes/. Accessed December 3, 2024.

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