ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2006) 11 P370

Increased sub-clinical inflammation and markers of vascular injury in obese children

AL Harte1, AR Baker1, ML Hill1, L Gilardini2, A Girola2, NF da Silva1, C Invitti2, S Kumar1 & PG McTernan1

1Unit for Diabetes and Metabolism, Warwick Medical School, University of Warwick, Coventry, United Kingdom; 2Unit for Diabetes and Metabolic Diseases, Instituto Auxologico Italiano, Milan, Italy.

Childhood obesity and its later progression to Type 2 Diabetes (T2DM) are known to be associated with sub-clinical inflammation; although the underlying cause for this is unclear. However, studies suggest that bacterial endotoxin (LPS) derived from commensal bacteria in the human gastrointestinal tract may contribute directly to sub-clinical inflammation. Human adipose tissue expresses toll like receptors that induce an inflammatory cascade in the presence of endotoxin. Hence, with increasing adiposity the inflammatory response is exacerbated producing inflammatory adipocytokines, such as plasminogen activator inhibitor type-1 (PAI-1), IL-6 and TNF-α. This study investigated the pathogenesis of the metabolic syndrome in obese children and its’ association with inflammation, with LERC approval. In particular, we examined the role of endotoxaemia in childhood obesity through the application of multiplex cardiovascular disease (CVD) biomarker immunoassays to investigate the levels of a range of inflammatory and CVD risk markers. Serum was obtained from children with varying degrees of obesity; age±S.D.:13.9±2.3 yr; BMI±S.D.:35.1±5.2 Kg/m2; n=60. All children underwent an OGTT; insulin resistance was measured by homeostasis model assessment (HOMA-IR) and insulin secretion by Stumvoll index (ISI). BMI correlated strongly with some, but not all, of the inflammatory markers. However, endotoxin levels demonstrated a significant and positive correlation with the majority of markers for vascular injury and atherogenesis (TNF-α, myeloperoxidase; P<0.05; PAI-1, matrix metalloproteinase-9, monocyte chemotactic protein-1, soluble intercellular adhesion molecule type-1, vascular endothelial growth factor; P<0.01), as well as blood pressure. These relationships remained significant following adjustment for sex, BMI and HOMA-IR. Therefore, we conclude that sub-clinical inflammation in obesity and T2DM may be mediated by endotoxin in serum. Furthermore, that children as young as 11 exhibit the same inflammatory profiles as identified in obese adults and may, as a result of long-term sub-clinical inflammation, have increased risk of diabetes and CVD at an earlier age.

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