Endocrine Abstracts

Obesity-mediated diabetes is associated with insulin resistance/hyperinsulinaemia and chronic sub-clinical inflammation. Recent studies have highlighted fatty liver

(steatosis) as a risk factor for diabetes. Fatty liver disease (FLD) progresses through fatty liver, necro-inflammation (non-alcoholic steatohepatitis, NASH) and fat

with fibrosis. In addition, hepatic steatosis per se can lead to hepatic insulin resistance/hyperinsulinaemia which may contribute significantly to the development of T2DM. Previousin vitro studies indicate liver may initiate an innate immune response which may be due to increased gut permeability through

hyperinsulinaemia leading to increased bacterial absorption. However, to date no study has confirmed whether there is a causal link between increased endotoxin

levels and the progression of fatty liver, in vivo. Therefore in this study we (a) investigated the impact of FLD (Age:36.8plus/minusSD 11.5yrs; BMI:26.5plus/minusSD4.4kilograms per meter ²; n=44), and diabetic status compared to case controls (CC):36.83plus/minusSD 6.2yrs; BMI:26.97plus/minusSD 4.5kilograms per meter ²; n=23; LERC approved), (b) assessed inflammatory markers including soluble CD14 (an immunological receptor involved in the presentation of LPS to the TLRs), TNFRII and the anti-inflammatory cytokine adiponectin. The findings showed that endotoxin levels were significantly higher in all patents with fatty liver disease compared with CC (FLD: 8.52plus/minus(meanplus/minusSEM)0.56International Units per millilitre; CC:0.82plus/minus0.07International Units per millilitre, pless than0.001). T2DM status in FLD caused an aggravation in endotoxin level (FLD: T2DM: 6.61plus/minus0.83International Units per millilitre; Non-diabetic:6.0plus/minus0.07International Units per millilitre, pequals0.003). Furthermore, CD14 and TNFRII were both raised in FLD subjects (pless than0.05) whilst the anti-inflammatory adiponectin was reduced in FL compared with CC (FLD: 11.62plus/minus0.60micrograms per millilitre

vs CC: 23.00plus/minus4.15micrograms per millilitre,pequals0.034). In summary, our results suggest that fatty liver disease is associated with a 7 fold higher level of

endotoxaemia compared with CC, exacerbated by diabetic status. Therefore fatty liver which is associated with hyperinsulinaemia/T2DM may mediate increased gut permeability and hence endotoxaemia. As such impaired liver metabolism may interfere with portal circulation, metabolic clearance and pre-dispose to diabetes.