Diabetes Metab J.  2012 Jun;36(3):199-206. 10.4093/dmj.2012.36.3.199.

Post-Renal Transplant Diabetes Mellitus in Korean Subjects: Superimposition of Transplant-Related Immunosuppressant Factors on Genetic and Type 2 Diabetic Risk Factors

• Lee HC

• KMID: 2281400
• DOI: http://doi.org/10.4093/dmj.2012.36.3.199

Abstract

Postrenal transplantation diabetes mellitus (PTDM), or new-onset diabetes after organ transplantation, is an important chronic transplant-associated complication. Similar to type 2 diabetes, decreased insulin secretion and increased insulin resistance are important to the pathophysiologic mechanism behind the development of PTDM. However, beta-cell dysfunction rather than insulin resistance seems to be a greater contributing factor in the development of PTDM. Increased age, family history of diabetes, ethnicity, genetic variation, obesity, and hepatitis C are partially accountable for an increased underlying risk of PTDM in renal allograft recipients. In addition, the use of and kinds of immunosuppressive agents are key transplant-associated risk factors. Recently, a number of genetic variants or polymorphisms susceptible to immunosuppressants have been reported to be associated with calcineurin inhibition-induced beta-cell dysfunction. The identification of high risk factors of PTDM would help prevent PTDM and improve long-term patient outcomes by allowing for personalized immunosuppressant regimens and by managing cardiovascular risk factors.

Keyword

Diabetes mellitus; Immunosuppressive agents; Polymorphism, genetic; Risk factors; Transplantation

MeSH Terms

Calcineurin
Diabetes Mellitus
Genetic Variation
Hepatitis C
Humans
Immunosuppressive Agents
Insulin
Insulin Resistance
Obesity
Organ Transplantation
Polymorphism, Genetic
Risk Factors
Transplantation, Homologous
Transplants
Calcineurin
Immunosuppressive Agents
Insulin

Figure

• 

  Fig. 1 Schematic representation of vesicular zinc transporter-8 (ZnT-8) expression and R325W polymorphism in pancreatic islet β-cells. The single-nucleotide polymorphism rs13266634 of SLC30A8 is associated with postrenal transplantation diabetes mellitus (PTDM) in renal allograft recipients, as demonstrated by Kang et al. [59]. SLC30A8 encodes ZnT-8, which is specifically expressed in β-cells. ZnT-8 promotes zinc accumulation in secretory vesicles, and vesicular zinc is important for the formation of the zinc-insulin hexamer. Calcineurin is the intracellular target of the immunosuppressive drugs CsA and tacrolimus, and calcineurin activity is known to play a role in insulin gene transcription through the regulation of NFATc activity (Reproduced from Kim I, et al. Pharmacogenomics J 2011;11:191-8, with permission from Nature Publishing Group, a division of Macmillan Publishers Limited) [29].

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