title: Pancreatic β-cell dysfunction and risk of new-onset diabetes after kidney transplantation.
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 β-cell dysfunction may be crucial to the pathophysiology of NODAT and specific markers for β-cell dysfunction may have additive value for predicting NODAT in this population. Therefore, we prospectively investigated whether proinsulin, as a marker of pancreatic β-cell dysfunction, is associated with future development of NODAT and improves prediction of it.
  
  
  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 β-cell dysfunction in the pathophysiology of NODAT and indicate the potential value of proinsulin for identification of RTR at increased risk for NODAT.
authors: Department of Nephrology, University Medical Center Groningen, Groningen, The Netherlands. d.m.zelle@umcg.nl
authors: Dorien M
authors: DM
authors: Zelle
authors: Eva
authors: E
authors: Corpeleijn
authors: Jolijn
authors: J
authors: Deinum
authors: Ronald P
authors: RP
authors: Stolk
authors: Rijk O B
authors: RO
authors: Gans
authors: Gerjan
authors: G
authors: Navis
authors: Stephan J L
authors: SJ
authors: Bakker
mesh_terms: D000328:Adult; D003920:Diabetes Mellitus / Q000503:physiopathology* / Q000601:surgery; D005215:Fasting / Q000097:blood; D006801:Humans; D050417:Insulin-Secreting Cells / Q000502:physiology*; D053208:Kaplan-Meier Estimate; D016030:Kidney Transplantation; D008875:Middle Aged; D011384:Proinsulin / Q000097:blood; D011446:Prospective Studies
chemical_list: D011384:Proinsulin
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