title: Association of Inflammation prior to Kidney Transplantation with Post-Transplant Diabetes Mellitus.
abstract: OBJECTIVE
  Post-transplant diabetes mellitus (PTDM) is both common and associated with poor outcomes after kidney transplantation. Our objective was to examine relationships of uremia-associated inflammation and adiponectin with PTDM.
  
  
  METHODS
  Nondiabetic kidney transplant patients were enrolled with donor controls. Inflammatory cytokines and adiponectin were measured before and after transplantation. Adipose tissue was obtained for gene expression analysis. Glucose transport was quantified in vitro in C2C12 cells following cytokine exposure. The patients were monitored up to 12 months for PTDM.
  
  
  RESULTS
  We studied 36 controls and 32 transplant patients, of whom 11 (35%) developed PTDM. Compared to controls, plasma TNFα, IL-6, MCP-1, and CRP levels were higher in transplant patients (p < 0.01). In multivariable analysis, TNFα plasma levels before transplantation were associated with development of PTDM (OR = 2.03, p = 0.04). Visceral adipose tissue TNFα mRNA expression was higher in transplant patients than controls (fold change 1.33; p < 0.05). TNFα mRNA expression was also higher in patients who developed PTDM than in those who did not (fold change 1.42; p = 0.05), and adiponectin mRNA expression was lower (fold change 0.48; p < 0.05). The studies on the C2C12 cells demonstrated an increase in glucose uptake following exposure to adiponectin and no significant change after exposure to TNFα alone. Concomitant TNFα and adiponectin exposure blunted adiponectin-induced glucose uptake (11% reduction; p < 0.001).
  
  
  CONCLUSIONS
  Our in vitro and clinical observations suggest that TNFα could contribute to PTDM through an effect on adiponectin. Our study proposes that inflammation is involved in glucose regulation after kidney transplantation.
authors.affiliation: Division of Nephrology, Department of Medicine, Thomas Jefferson University Hospital, Pa., USA.
authors.forename: Maria P Martinez
authors.initials: MP
authors.lastname: Cantarin
authors.affiliation: Division of Biostatistics, Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, Pa., USA.
authors.forename: Scott W
authors.initials: SW
authors.lastname: Keith
authors.affiliation: Kimmel Cancer Center, Department of Medical Oncology, Thomas Jefferson University, Philadelphia, Pa., USA.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Division of Transplantation, Department of Surgery, Thomas Jefferson University Hospital, Pa., USA.
authors.forename: Cataldo
authors.initials: C
authors.lastname: Doria
authors.affiliation: Division of Transplantation, Department of Surgery, Thomas Jefferson University Hospital, Pa., USA.
authors.forename: Adam M
authors.initials: AM
authors.lastname: Frank
authors.affiliation: Division of Transplantation, Department of Surgery, Thomas Jefferson University Hospital, Pa., USA.
authors.forename: Warren R
authors.initials: WR
authors.lastname: Maley
authors.affiliation: Division of Transplantation, Department of Surgery, Thomas Jefferson University Hospital, Pa., USA.
authors.forename: Carlo
authors.initials: C
authors.lastname: Ramirez
authors.affiliation: Department of Urology, Thomas Jefferson University Hospital, Pa., USA.
authors.forename: Costas D
authors.initials: CD
authors.lastname: Lallas
authors.affiliation: Division of Transplantation, Department of Surgery, Thomas Jefferson University Hospital, Pa., USA.
authors.forename: Ashesh
authors.initials: A
authors.lastname: Shah
authors.affiliation: Division of Biostatistics, Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, Pa., USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Waldman
authors.affiliation: Division of Nephrology, Department of Medicine, Thomas Jefferson University Hospital, Pa., USA.
authors.forename: Bonita
authors.initials: B
authors.lastname: Falkner
keywords: Adiponectin; Cytokines; Diabetes; Kidney transplantation