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

Endocrine Abstracts (2008) 16 P225

Circulating endotoxin as a potential biomarker and mediator of inflammation: influenced by diabetic therapies

Nasser Al-Daghri1, Khalid Al-Rubeaan2, Omar Al-Attas1, Nancy da Silva3, Shaun Sabico1, Sudhesh Kumar3, Philip Mc Ternan3 & Alison Harte1

1King Saud University, Riyadh, Saudi Arabia; 2Diabetes Research Center, Riyadh, Saudi Arabia; 3University of Warwick, Birmingham, UK.

Recent studies suggest that endotoxin from gut flora, may be key to development of inflammation by stimulating the secretion of an adverse cytokine profile from adipose tissue. The study investigated the relationship between endotoxin and various metabolic parameters of diabetic patients to determine if anti-diabetic therapies exerted a significant effect on endotoxin levels and adipocytokine profiles of T2DM subjects. Fasting blood samples were collected from consenting Saudi Arabian patients (BMI: 30.2± (S.D.) 5.6 kg/m2, n=413), consisting of non-diabetics (controls, n=67) and T2DM subjects (n=346). The diabetics were divided into 5 subgroups based on 1 year treatment regimes: dietcontrol (n=36), metformin (n=141), rosiglitazone (RSG, n=22), a combined fixed dose of metformin/rosiglitazone (Avandamet n=100) and insulin (n=47). Lipid profiles, fasting serum glucose, insulin, adiponectin, resistin, TNF-α, leptin, C-reactive protein (CRP) and endotoxin concentrations were determined. Regression analyses revealed significant correlations between endotoxin levels and triglycerides (r2=0.42; P<0.0001); total cholesterol (r2=0.10; P<0.001), glucose (r2=0.076; P<0.0001) and insulin (r2=0.032; P<0.001). Endotoxin showed strong inverse correlation with HDL-cholesterol (r2=0.055; P<0.001). Endotoxin levels were elevated in all of the treated diabetic subgroups compared with control, but only RSG group did not differ significantly from control (Control: 4.2±1.7 EU/ml, RSG: 5.6±2.2 EU/ml). Both Avandamet and RSG treated groups had significantly higher adiponectin levels than all the other groups, with RSG group expressing the highest levels overall. In conclusion, sub-clinical inflammation in T2DM may, in part, be mediated by circulating endotoxin. Furthermore, that whilst the endotoxin and adipocytokine profiles of diabetic patients treated with different therapies were comparable, the RSG group demonstrated significant differences in both adiponectin and endotoxin levels. We confirm an association between endotoxin and serum insulin and triglycerides and an inverse relationship with HDL. Lower endotoxin and higher adiponectin in the groups treated with RSG may be related and indicate another mechanism for the effects of RSG on insulin sensitivity.

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