Post-transplant diabetes mellitus in patients with solid organ transplants

Abstract

Solid organ transplantation (SOT) is a life-saving procedure and an established treatment for patients with end-stage organ failure. However, transplantation is also accompanied by associated cardiovascular risk factors, of which post-transplant diabetes mellitus (PTDM) is one of the most important. PTDM develops in 10–20% of patients with kidney transplants and in 20–40% of patients who have undergone other SOT. PTDM increases mortality, which is best documented in patients who have received kidney and heart transplants. PTDM results from predisposing factors (similar to type 2 diabetes mellitus) but also as a result of specific post-transplant risk factors. Although PTDM has many characteristics in common with type 2 diabetes mellitus, the prevention and treatment of the two disorders are often different. Over the past 20 years, the lifespan of patients who have undergone SOT has increased, and PTDM becomes more common over the lifespan of these patients. Accordingly, PTDM becomes an important condition not only to be aware of but also to treat. This Review presents the current knowledge on PTDM in patients receiving kidney, heart, liver and lung transplants. This information is not only for transplant health providers but also for endocrinologists and others who will meet these patients in their clinics.

Key points

  • Post-transplant diabetes mellitus (PTDM) is mostly studied in recipients of kidney transplants, but risk factors for development of PTDM seem to be similar in recipients of heart, liver and lung transplants.

  • PTDM develops in 10–40% of patients during the first year after a solid organ transplant and is a major risk factor for cardiovascular disease and death.

  • Major risk factors for development of PTDM are metabolic adverse effects of immunosuppressive drugs, post-transplant viral infections and hypomagnesaemia, in addition to the traditional risk factors seen in patients with type 2 diabetes mellitus.

  • Prevention of PTDM can be achieved by tailoring the immunosuppressant regimen and probably also by lifestyle intervention; however, this intervention is not well studied.

  • Patients with PTDM should be treated with hypoglycaemic agents that have been tested for efficacy and safety regarding drug–drug interactions, immunosuppressant drugs and organ function.

  • Large-scale long-term studies on new glucose-lowering drug classes that have shown cardiovascular protection in high-risk patients with type 2 diabetes mellitus (for example, glucagon-like protein 1 (GLP1) receptor agonists and sodium/glucose cotransporter 2 (SGLT2) inhibitors) are also warranted in patients with PTDM.

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Fig. 1: Acknowledged contributors of hyperglycaemia in PTDM.
Fig. 2: Incidence of PTDM after renal transplantation.
Fig. 3: Effects of immunosuppressive agents on β-cells and insulin-sensitive tissues that promote PTDM.
Fig. 4: The incidence of early PTDM and impaired glucose tolerance over the past 20 years in a national cohort of recipients of kidney transplants.
Fig. 5: Long-term outcomes of recipients of different organ transplants according to their PTDM status.
Fig. 6: A suggested algorithm for glucose lowering in PTDM, drawn from our experience of treating recipients of renal transplants.

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Nature Reviews Endocrinology thanks L. Rostaing, A. Secchi and other anonymous reviewer(s) for their contribution to the peer review of this work.

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Both authors contributed to researching the data for the article, discussion of content, writing the article and reviewing and/or editing the manuscript.

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Correspondence to Trond Jenssen.

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T.J. has received lecture honoraria from AstraZeneca, Boehringer Ingelheim, Merck Sharpe and Dohme and Novo Nordisk. He also has received an unrestricted research grant from Boehringer Ingelheim Norway. A.H. has received lecture honoraria from AstraZeneca.

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Jenssen, T., Hartmann, A. Post-transplant diabetes mellitus in patients with solid organ transplants. Nat Rev Endocrinol 15, 172–188 (2019). https://doi.org/10.1038/s41574-018-0137-7

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