Role of dipeptidyl peptidase-4 inhibitors in new-onset diabetes after transplantation

Abstract

Despite strict pre- and post-transplantation screening, the incidence of new-onset diabetes after transplantation (NODAT) remains as high as 60%. This complication affects the risk of cardiovascular events and patient and graft survival rates. Thus, reducing the impact of NODAT could improve overall transplant success. The pathogenesis of NODAT is multifactorial, and both modifiable and nonmodifiable risk factors have been implicated. Monitoring and controlling the blood glucose profile, implementing multidisciplinary care, performing lifestyle modifications, using a modified immunosuppressive regimen, administering anti-metabolite agents, and taking a conventional antidiabetic approach may diminish the incidence of NODAT. In addition to these preventive strategies, inhibition of dipeptidyl peptidase-4 (DPP4) by the gliptin family of drugs has recently gained considerable interest as therapy for type 2 diabetes mellitus and NODAT. This review focuses on the role of DPP4 inhibitors and discusses recent literature regarding management of NODAT.

Keywords: Dipeptidyl-peptidase IV inhibitors; Kidney transplantation; New-onset diabetes after transplantation.

Figure 1.

Effect of MK-0626 on apoptosis and islet viability in tacrolimus-induced pancreatic and renal injured experimental rats. (Aa, Ba, Ca) In situ TdT-mediated dUTP-biotin nick end labeling (TUNEL) assay in pancreatic islets. (Ab, Bb, Cb) Acridine orange/propidium iodide staining of isolated islets. (Ac, Bc, Cc) TUNEL assay in renal tissues. The tacrolimus group (B) combined with the MK-0626 group (C) reduced apoptosis. (A) is the vehicle group (×400). Adapted from Lim et al. [36], with permission from Nature Publishing Group and Jin et al. [35].

Figure 2.

Effect of MK-0626 on oxidative stress and apoptotic gene expression in tacrolimus (TAC)-induced pancreatic and renal injured experimental rats. (A) Immunoblot analysis of manganese superoxide dismutase (MnSOD), heme oxygenase-1 (HO-1), Bcl-2, active caspase-3, and β-actin. 8-Hydroxy-2'-deoxyguanosine (8-OHdG) levels in serum (B) and 24-hour urine (C). Adapted from Lim et al. [36], with permission from Nature Publishing Group and Jin et al. [35]. ^ap < 0.05 vs. vehicle (VH) group or VH + M groups; ^bp < 0.05 vs. TAC group.

Figure 3.

Paradigm of dipeptidyl peptidase-4 (DPP4) inhibitors actions on new-onset diabetes after transplantation (NODAT). DPP4 inhibitors exert antidiabetic effect dependent on the regulation of glucagon-like peptide-1 (GLP-1) and/or glucose inhibitory peptide (GIP) pathway. However, DPP4 inhibitors may also exert pleiotropic actions dependent or independent on GLP-1 and/or GIP pathway.