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 ofNODAT and specificmarkers for β- cell dysfunction may have additive value for predictingNODAT 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. Research design andmethods-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 506 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. © 2013 by the American Diabetes Association.