Hyperleptinemia as a risk factor for post-transplant diabetes mellitus development after kidney transplantation
Karol Graňák1, Matej Vnučák1, Monika Beliančinová1, Margaréta Pytliaková2, Ivana Dedinská1.
1Transplant Center, University hospital Martin, Jessenius Medical Faculty of Comenius University, Martin, Slovakia (Slovak Republic); 2Clinic of Gastrointestinal Internal Medicine, University hospital Martin, Jessenius Medical Faculty of Comenius University, Martin, Slovakia (Slovak Republic)
Background and Aims: Adipose tissue, as an endocrine organ, is involved in the synthesis of hormones that are involved in several processes, including the regulation of food intake, the control of insulin sensitivity or as mediators of inflammatory processes. The aim of this study was to determine the importance of leptin, adiponectin, interleukin 6 and interleukin 10 levels for the development of post-transplant diabetes mellitus (PTDM) 1 year after kidney transplantation (KT).
Methods: In the prospective analysis, the studied sample (n = 104) was divided into three groups: 1. control group, 2. patients who developed a pre-diabetic condition after KT (impaired glucose tolerance, fasting hyperglycemia) and 3. patients who developed de novo PTDM. Pre-transplantation and subsequently at 3, 6 and 12 months after KT, we recorded the basic characteristics of the donor and recipient, including parameters reflecting graft function, metabolic (lipid profile, glucose metabolism parameters) and anthropometric parameters. At the same time, we monitored the levels of adipocytokines (adiponectin, leptin) and interleukins (IL-6, IL-10) during the monitored period (Table 1).
Results: The level of leptin in the post-transplant period had a continuously decreasing tendency in the control group with a significantly lower level 12 months after KT (P = 0.0078). On the other hand, after transient decrease, leptin level remained high in 12 months after KT in the group with prediabetes (P = 0.0343) and PTDM (insignificant) (Figure 1). In contrast, adiponectin levels showed a significant decrease after 12 months in the group with prediabetes (P = 0.0009) and PTDM (P <0.0001), while it increased in the control group. IL-6 decreased significantly in the control group (P = 0.0023), with prediabetes (P = 0.0061) and PTDM (P = 0.0499). After adjusting for differences in the baseline donor and recipient characteristics, we found risk factors for PTDM 12 months after KT in a univariate analysis: baseline hyperleptinemia (P = 0.0458) and at 12 months (P = 0.0464), low adiponectin levels at 12 months (0 = 0.0108), low IL-6 baseline (P = 0.0180), IL10 at 6 months (P = 0.0271) and 12 months (P = 0.0397). Using multivariate analysis, we identified hyperleptinemia 12 months after KT as an independent risk factor for PTDM development 1 year after KT [OR 1.0320; 95% Cl 0.9785-1.0884 (P = 0.0038)] (Table 2).
Conclusion: We confirmed that elevated leptin level 12 months after KT is associated with the development of PTDM. Levels of inflammatory process mediators (IL-6 and IL-10) did not correlate with an increased incidence of metabolic complications. Their importance seems to apply in the event of acute rejection, which requires further investigation.
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