Pancreatic beta-Cell Dysfunction and Risk of New-Onset Diabetes After Kidney Transplantation

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Abstract

OBJECTIVE-Chronic exposure to calcineurin inhibitors and corticosteroids poses renal transplant recipients (RTR) at high risk for development of new-onset diabetes after transplantation (NODAT). Pancreatic beta-cell dysfunction may be crucial to the pathophysiology of NODAT and specific markers for beta-cell dysfunction may have additive value for predicting NODAT in this population. Therefore, we prospectively investigated whether proinsulin, as a marker of pancreatic beta-cell dysfunction, is associated with future development of NODAT and improves prediction of it.

RESEARCH DESIGN AND METHODS-All RTR between 2001 and 2003 with a functioning graft for >= 1 year were considered eligible for inclusion, except for subjects with diabetes at baseline who were excluded. We recorded incidence of NODAT until April 2012.

RESULTS-A total of 487 RTR (age 50 +/- 12 years, 55% men) participated at a median time of 6.0 (interquartile range [IQR], 2.6-11.5) years after transplantation. Median fasting proinsulin levels were 16.6 (IQR, 11.0-24.2) pmol/L. During median follow-up for 10.1 (IQR, 9.1-10.4) years, 42 (35%) RTR had development of NODAT in the highest quartile of the distribution of proinsulin versus 34 (9%) in the lowest three quartiles (P <0.001). In Cox regression analyses, proinsulin (hazard ratio, 2.29; 95% CI, 1.85-2.83; P <0.001) was strongly associated with NODAT development. This was independent of age, sex, calcineurine inhibitors, prednisolone use, components of the metabolic syndrome, or homeostasis model assessment.

CONCLUSIONS-In conclusion, fasting proinsulin is strongly associated with NODAT development in RTR. Our results highlight the role of beta-cell dysfunction in the pathophysiology of NODAT and indicate the potential value of proinsulin for identification of RTR at increased risk for NODAT.

Original languageEnglish
Pages (from-to)1926-1932
Number of pages7
JournalDiabetes Care
Volume36
Issue number7
DOIs
Publication statusPublished - Jul-2013

Keywords

  • INSULIN-RESISTANCE INDEXES
  • INTACT PROINSULIN
  • RECIPIENTS
  • TACROLIMUS
  • CYCLOSPORINE
  • MELLITUS
  • IMMUNOSUPPRESSION
  • PREDICTION
  • SECRETION
  • MORTALITY

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