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Tacrolimus decreases insulin sensitivity without reducing fasting insulin concentration: a 2-year follow-up study in

Qing-Jie Chen1, Jing Li, Shan-Ru Zuo

  • 1Clinical Pharmacy and Pharmacology Research Institute, The Third Xiangya Hospital of Central South University , Changsha, Hunan , PR China .

Renal Failure
|February 4, 2015
PubMed

Insights

New Onset Diabetes after Transplantation (NODAT) is primarily caused by insulin resistance, not specific gene variations in IRS-1 or IRS-2. Tacrolimus treatment in kidney transplant patients showed elevated insulin levels in NODAT patients, indicating resistance as the main driver.

Area of Science:

  • Nephrology
  • Endocrinology
  • Immunology

Background:

  • New Onset Diabetes after Transplantation (NODAT) is a significant complication in transplant recipients.
  • Tacrolimus, a common immunosuppressant, is associated with increased NODAT risk.
  • Understanding the mechanisms behind NODAT is crucial for patient management.

Purpose of the Study:

  • To investigate the impact of tacrolimus on insulin secretion and sensitivity in kidney transplant recipients.
  • To determine the association between NODAT and single-nucleotide polymorphisms (SNPs) in IRS-1 and IRS-2 genes.
  • To identify the primary cause of tacrolimus-induced NODAT.

Main Methods:

  • A cohort study involving 158 kidney transplant patients treated with tacrolimus.
  • Division of patients into NODAT and non-NODAT groups.
  • Measurement of plasma fasting insulin and C-peptide levels.
  • Genotyping of IRS-2 Gly1057Asp and IRS-1 Gly972Arg polymorphisms using PCR fragment length polymorphism.

Main Results:

  • Patients with NODAT and non-NODAT groups treated with tacrolimus exhibited higher fasting insulin and C-peptide levels than healthy volunteers.
  • Fasting plasma insulin levels were significantly higher in the NODAT group compared to the non-NODAT group.
  • No significant differences were observed in C-peptide levels or in the allele/genotype frequencies of IRS-2 Gly1057Asp and IRS-1 Gly972Arg between NODAT and non-NODAT patients.

Conclusions:

  • Insulin resistance is the principal factor contributing to tacrolimus-induced NODAT.
  • The studied genetic variations in IRS-2 and IRS-1 do not appear to be associated with the development of NODAT in this cohort.
Keywords:
IRS-1IRS-2PTDMSNPTAC

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