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Decreased insulin secretion in patients receiving tacrolimus as GVHD prophylaxis after allogeneic hematopoietic SCT

Bone Marrow Transplantation volume 45, pages 405–406 (2010)Cite this article

As it has been reported that hyperglycemia is associated with a higher risk of non-relapse mortality after allogeneic hematopoietic SCT (HSCT), the efficient control of hyperglycemia has become an important consideration for safer HSCT.1, 2, 3 A characteristic feature of this field is the use of calcineurin inhibitors, including tacrolimus (TAC), which may cause hyperglycemia as suggested in organ transplant settings, possibly by decreasing insulin secretion.4 To evaluate this possibility, we serially monitored fasting glucose levels and serum immunoreactive insulin, and calculated homeostasis model assessment (HOMA)-IR and HOMA-β with the HOMA model5 as recommended by Wallace et al.6 HOMA-IR reflects insulin resistance and HOMA-β reflects the insulin secretion status.5 If HOMA-IR increased after the administration of allogeneic HSCT, drugs that reduce insulin resistance, such as metformin or pioglitazone, might theoretically be effective. In contrast, if HOMA-β decreased, drugs that increase insulin secretion, such as glucagon-like peptide-1 analog or sulfonylureas, might be effective. The data from this study may help us to better understand how we should control glucose levels after HSCT.

Data obtained from 43 adult patients who received allogeneic HSCT from October 2006 to December 2007 were included in the analysis. The median age of the patients was 48 years (range: 19–66 years). When patients were not receiving s.c. long-acting insulin, systemic corticosteroid or parenteral nutrition, blood samples were obtained 1–2 months after HSCT. GVHD prophylaxis was started using CsA-based (n=13) or TAC-based regimens (n=30), with an additional short course of MTX in 35 patients. At the time of subsequent blood sampling, 15 patients were receiving CsA and 28 patients were receiving TAC, with no significant difference in various factors including age, gender, disease and intensity of the conditioning regimen (conventional vs reduced intensity), except that the TAC group included more HSCT with unrelated BM than the CsA group (89 vs 27%, respectively). The results regarding fasting glucose level, immunoreactive insulin and the HOMA model are summarized in Table 1.

Table 1 Pretransplant and posttransplant glycemic status
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Acknowledgements

This study was supported in part by grants from the Ministry of Health, Labor and Welfare, Japan, and the Advanced Clinical Research Organization.

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Authors and Affiliations

  1. Division of Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan

    S Fuji, S-W Kim, S Mori, R Tanosaki, Y Heike, Y Takaue & T Fukuda

  2. Division of Laboratory Medicine, National Cancer Center Hospital, Tokyo, Japan

    K Furuta

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  1. S Fuji
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  2. S-W Kim
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  3. S Mori
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  8. T Fukuda
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Correspondence to T Fukuda.

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Fuji, S., Kim, SW., Mori, S. et al. Decreased insulin secretion in patients receiving tacrolimus as GVHD prophylaxis after allogeneic hematopoietic SCT. Bone Marrow Transplant 45, 405–406 (2010). https://doi.org/10.1038/bmt.2009.154

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