Abstract
New-onset diabetes after transplantation (NODAT) is a frequent complication in renal transplant recipients (RTR). Although oxidative stress has been associated with diabetes mellitus, data regarding NODAT are limited. We aimed to prospectively investigate the long-term association between the oxidative stress biomarker malondialdehyde (measured by high-performance liquid chromatography) and NODAT in an extensively phenotyped cohort of non-diabetic RTR with a functioning graft ≥1 year. We included 516 RTR (51 ± 13 years-old, 57% male). Median plasma malondialdehyde (MDA) was 2.55 (IQR, 1.92–3.66) µmol/L. During a median follow-up of 5.3 (IQR, 4.6–6.0) years, 56 (11%) RTR developed NODAT. In Cox proportional-hazards regression analyses, MDA was inversely associated with NODAT, independent of immunosuppressive therapy, transplant-specific covariates, lifestyle, inflammation, and metabolism parameters (HR, 0.55; 95% CI, 0.36–0.83 per 1-SD increase; p < 0.01). Dietary antioxidants intake (e.g., vitamin E, α-lipoic acid, and linoleic acid) were effect-modifiers of the association between MDA and NODAT, with particularly strong inverse associations within the subgroup of RTR with relatively higher dietary antioxidants intake. In conclusion, plasma MDA concentration is inversely and independently associated with long-term risk of NODAT in RTR. Our findings support a potential underrecognized role of oxidative stress in post-transplantation glucose homeostasis.
Highlights
New-onset diabetes after transplantation (NODAT) is a major metabolic complication of solid organ transplantation, with a reported incidence of up to 50% [1]
Consequences of NODAT are detrimental for renal transplant recipients (RTR) as it is associated with reduced recipient survival, increased rate of cardiovascular events, and impaired graft survival in the long term [2,3]
In order to improve the outcomes of RTR, it is of great interest to know which factors contribute to this long-term NODAT development and maintenance [2]
Summary
New-onset diabetes after transplantation (NODAT) is a major metabolic complication of solid organ transplantation, with a reported incidence of up to 50% [1]. With new cyclosporine-based and tacrolimus-based regimens [1,4], it is well-documented that the largest number of incident cases of NODAT occurred, after the first year of transplantation [4,5], and other agents potentially involved in the long-term pathogenesis of the disease remain to be elucidated. A developing body of evidence has linked oxidative species with insulin signaling [10,11,12,13], and it has been postulated that diabetes mellitus is—to a considerable extent—caused by a failure of the organism to create enough oxidative redox potential [14]. To the extent of our knowledge, no longitudinal studies have aimed to study the association between OS biomarkers and long-term incidence of diabetes, which makes it difficult to foresee whether OS biomarkers may prospectively be associated with positive or negative outcomes regarding glucose metabolism outcomes
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