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P501 Abdominal obesity in Paediatric Crohn’s disease is associated with adipokine dysregulation

D. Thangarajah*1, K. E. Chapell1, S. Mandalia1, G. Frost2, J. M. Fell3

1Imperial College, Section of Academic Neonatal Medicine, London, United Kingdom, 2Imperial College, Nutrition and Dietetic Research Group, Faculty of Medicine, London, United Kingdom, 3Chelsea and Westminster Hospital NHS Foundation Trust, Department of Paediatric Gastroenterology, London, United Kingdom

Background

We have shown that paediatric Crohn’s disease (CD) is associated with a distinct obesity phenotype with both visceral and abdominal subcutaneous adipose tissue expansion, as defined by MRI.1 Abdominal obesity is associated with metabolic syndrome, chronic inflammation, and adipokine dysregulation. The aim of this study was to investigate disease specific determinants of abdominal obesity, and define the metabolic and adipokine profile in our cohort of children with CD.

Methods

Children (7–18 years) with CD had visceral adipose tissue (VAT), subcutaneous adipose tissue (SCA) volumes (l) quantified from MRI as per our previous study.1 All children had blood analysed for CRP, ESR, albumin, fasting insulin, fasting glucose, and lipid profile. Serum adipokines (adiponectin, leptin, visfatin, and resistin) were measured using the Bio-Plex Pro Human Cytokine 27-plex Assay (Bio-Rad, Hemel Hempstead, United Kingdom) according to the manufacturer’s instructions. Analysis: Univariate and linear regression analysis was used to identify factors (disease duration, disease site, disease activity, active therapy, CRP, ESR, albumen, fasting insulin, fasting glucose, lipid profile, and adipokines), associated with the dependent variable (VAT or SCA volume). All variables found to be significantly associated with dependent variable (p < 0.2) were used to derive multivariable linear regression model, where significance level was p < 0.05. All factors were adjusted for sex, weight z score, time, and whether children had received active therapy in the multivariable model.

Results

In total, 25 children with CD (16 males) were recruited, with a median PCDAI of 30 (15 to 42.5). In CD, VAT was found to be significantly positively associated with leptin levels p < 0.05. No significant association was observed between VAT and PCDAI score, disease site, active therapy, lipid profile, fasting glucose, and insulin. VAT was positively associated with longer duration of disease in the univariate model only, p < 0.05. In CD SCA was found to be significantly positively associated with leptin levels, CRP, active disease (PCDAI score >11), visfatin, and steroid therapy p < 0.05. There was a predominance to VAT being higher on the left side in all participants regardless of disease site.

Conclusion

For the first time in children with CD, we have shown that visceral obesity was not associated with current inflammation, but maybe associated with longer disease duration. On the contrary, SCA is associated with markers of inflammation. This pattern of expanded abdominal VAT and SCA is strongly associated with leptin and less so with adiponectin levels. These adipokines play a pertinent role in VAT and SCA deposition, insulin sensitivity and the inflammatory cascade.

References:

[1] Thangarajah D., Chappell K.E., Frost, G, et al. Aberrant adipose tissue partitioning with abdominal obesity, defined by MRI, is a hallmark of paediatric Crohn’s Disease, A-1331. Working paper 2015. [Abstract submitted to ECCO 2016].