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. 2016 Aug;6(4):289-300.
doi: 10.1159/000446294. Epub 2016 May 18.

Association of Inflammation prior to Kidney Transplantation with Post-Transplant Diabetes Mellitus

Maria P Martinez Cantarin  1 , Scott W Keith  2 , Zhao Lin  3 , Cataldo Doria  4 , Adam M Frank  4 , Warren R Maley  4 , Carlo Ramirez  4 , Costas D Lallas  5 , Ashesh Shah  4 , Scott A Waldman  2 , Bonita Falkner  1
Affiliations

Association of Inflammation prior to Kidney Transplantation with Post-Transplant Diabetes Mellitus

Maria P Martinez Cantarin et al. Cardiorenal Med. 2016 Aug.

Abstract

Background/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).

Conclusion: 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.

Keywords: Adiponectin; Cytokines; Diabetes; Kidney transplantation.

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Figures

Fig. 1
Fig. 1
Visceral fat cytokine expression in ESRD participants versus controls. mRNA expression of TNFα was assessed in visceral adipose tissue of ESRD participants and compared with controls with normal kidney function. TNFα mRNA fold change: 1.33; * p < 0.05.
Fig. 2
Fig. 2
Visceral fat mRNA expression of cytokines in ESRD participants. TNFα, adiponectin (ADIPOQ), adiponectin receptor 1 (ADIPOR1), and adiponectin receptor 2 (ADIPOR2) mRNA expression from visceral adipose tissue was assessed in ESRD participants that developed PTDM versus ESRD patients that did not. TNFα mRNA fold change: 1.42, ADIPOQ mRNA fold change: 0.48, * p < 0.05; ADIPOR1 mRNA fold change: 0.89, p = 0.33; ADIPOR2 mRNA fold change: 0.86, p = 0.49.
Fig. 3
Fig. 3
Glucose uptake by 2-NBDG in C2C12 cells. C2C12 cells were treated with ascending doses of globular adiponectin (0, 1, and 2 µg/ml) and TNFα (0, 1, and 5 ng/ml) for 48 h. * p < 0.01, ** p < 0.05.
See this image and copyright information in PMC

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