Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2005) 9 P8

BES2005 Poster Presentations Diabetes and metabolism (35 abstracts)

Hyperinsulinaemia associated endotoxaemia and its relationship to Type 2 diabetes mellitus

SJ Creely 1 , PG McTernan 1 , AL Harte 1 , J Farmer 2 & S Kumar 1


1Department of Diabetes and Metabolism, University of Warwick Medical School, Coventry, UK; 2University of Coventry and Warwickshire Hospital Trust, Coventry, UK.


Type 2 diabetes mellitus (T2DM) is associated with insulin resistance/ hyperinsulinaemia and chronic sub-clinical inflammation that is considered important in the pathogenesis of macrovascular disease. We propose activation of the innate immune system, a biologically conserved first line immune response, within adipose tissue by endotoxaemia secondary to hyperinsulinaemia as one of the causes of this phenomenon. Hyperinsulinaemia may lead to altered gut permeability and resultant endotoxaemia and thereafter activation of the innate immune system. Therefore we investigated whether T2DM patients had higher circulating endotoxin levels to account for the associated chronic inflammation by determining serum endotoxin levels in healthy lean non-diabetic (ND) subjects (Age: 36.8plus/minus 11.5yrs; BMI: 26.5plus/minus 4.4 kg/m2; n=22) compared with T2DM subjects with no major diabetic co-morbidity or other inflammatory conditions (Age: 51.3plus/minus 12.6yrs; BMI: 37.2plus/minus 8.9kg/m2; n=30) using a Limulus Amoebocyte Lysate (LAL) gram negative endotoxin ELISA. We also evaluated the levels of soluble CD14 (an immunological receptor involved in the presentation of LPS to the innate immune system) using a sCD14 ELISA. We then determined the correlation between endotoxin and fasting insulin levels.

Circulating endotoxin levels were significantly higher in T2DM than controls (T2DM: 0.96plus/minus 0.36IU/mL; ND: 0.78plus/minus 0.26IU/mL; p<0.05). A similar pattern was identified for CD14 (T2DM: 2816.7plus/minus1011.6ng/mL; ND: 1326.3plus/minus351.3ng/mL; p<0.001). Insulin levels correlated significantly with endotoxin in our ND population (r=0.55; p<0.05). In T2DM the levels of both insulin and endotoxin were found to be raised.

Taken together, these data and the correlation between endotoxin and insulin levels support our hypothesis of relationship between hyperinsulinaemia and endotoxamia. This relationship could therefore be a potential mediator of chronic inflammation and T2DM.

Volume 9

24th Joint Meeting of the British Endocrine Societies

British Endocrine Societies 

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