Hyperglycemia in pediatric liver transplantation

Introduction: After liver transplant (LT), hyperglycemia (HG) is a common complication and is associated to an unfavorable prognosis, a persistent diabetes onset and an increased cardiovascular event. However, in pediatric LT, incidence of HG, its occurrence, persistence, and predispositions remain understudied. Objectives: Therefore, the objectives of our study were the characterization and evolution of hyperglycemia in children with LT and the analysis of their glycemic profile. Methods: We collected 7-years data about 195 children with LT in Brussels to characterize hyperglycemia and associated risk factors in multivariate analyses, and we followed five children with LT during the most critical moment of HG to analyze their glycemic profile. Hyperglycemia was defined as a glycemia exceeded 200 mg/dL, for at least two measurements separated by 24 hours, outside the day of LT. Results: Our retrospective study showed that 24% of LT children presented hyperglycemia and its onset was between 0 and 14 days after transplant. Multivariate analysis showed that children with LT who benefited of steroids (OR 2,51) for a graft rejection and/or had a virus infection (OR 2,05) were more at risk to develop hyperglycemia. Glucose sensors showed that HG was present in the post-prandial afternoon for all LT children. Conclusions: Our study shows that children with LT were more at risk of developing hyperglycemia when they required the use of steroids or when they had a viral infection, and that the measurement of blood glucose during the first month posttransplantand in the post-prandial period is essential to detect glycemic abnormalities

Probiotic Escherichia coli Nissle 1917 activates DC and prevents house dust mite allergy through a TLR4-dependent pathway.

Experimental animal and human studies have demonstrated that probiotic strains have beneficial effects on allergy. Here we report that the probiotic Escherichia coli Nissle 1917 strain (EcN) is able to activate DC, as shown by important cytokine synthesis together with up-regulation of membrane expression of CD40, CD80 and CD86. This EcN-induced DC activation was strictly dependent on the TLR4 signaling pathway and was also associated with stimulation of NF-kappaB and MAPK. We next investigated the prophylactic potential of i.n. co-administration of EcN with a recombinant form of Der p 1 (ProDer p 1) in a murine model of mite allergy. I.n. vaccinations with EcN plus ProDer p 1 prevented the subsequent allergic response following Der p 1 sensitization and airway challenge with aerosolized mite extracts through the induction of an allergen-specific IgG2a response, the prevention of specific IgE production and a strong reduction of IL-5 secretion by allergen-restimulated splenocytes. EcN alone or in combination with ProDer p 1 inhibited the development of airway eosinophilia and neutrophilia. This in vivo protective effect of EcN was, in part, mediated by TLR4 signaling. Our results suggest that EcN represents an efficient adjuvant to prevent allergic responses.Journal ArticleResearch Support, Non-U.S. Gov'tFLWINSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Characterization, evolution and risk factors of diabetes and prediabetes in a pediatric cohort of renal and liver transplant recipients

Background: Hyperglycemia (HG) and prediabetes are rarely sought in pediatric liver (LT) and renal (RT) transplantation, yet their presence indicates a high risk of diabetes and cardiovascular disease. The objectives of our DIABGRAFT study were to retrospectively (rDIABGRAFT) and longitudinally (pDIABGRAFT) characterize HG and (pre)diabetes in a cohort of children with LT or/and RT. Methods: We retrospectively analyzed risk factors of HG from 195 children with LT from 2012 to 2019 and twenty children with RT from 2005 to 2019 at Cliniques universitaires Saint-Luc. In addition, we prospectively followed four LT and four RT children to evaluate the evolution of their glucose metabolism. Results: Our rDIABGRAFT study showed that 25% and 35% of LT and RT children respectively presented transient HG and 20% of RT developed diabetes. The occurrence of HG was associated with the use of glucocorticoids and with acute events as graft rejection and infection. In our pDIABGRAFT cohort, biological markers of diabetes were in the normal range for HbA1C, fasting glucose and insulin levels. However, oral glucose tolerance test and glucose sensors showed insulin resistance, impaired glucose tolerance and HG in the post-prandial afternoon period. Conclusion: Our study shows that children with LT and RT were more at risk of developing HG when glucocorticoids were required and that HbA1C and fasting glucose lack sensitivity for early detection of glucose intolerance. Also, measurement of glycemia immediately after the transplantation and in postprandial period is key to detect dysglycemia since insulin resistance prevailed in our cohort