The novel effects of anti-dibetic therapies on inflammatory mediators of type 2 diabetes mellitus

Journal Article
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Supplement 1
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Publication Abstract: 

Chronic low-grade inflammation is a significant factor in the development of obesity associated diabetes. This is supported by recent studies suggesting that endotoxin, derived from gut flora, may be key to the development of inflammarion by stimulating the secretion of an adverse cytokine profile from adipose tissue. The study investigated the relationship of endotoxin on several metabolic parameters of diabetic patients. It also determined if various anti-diabetic therapies exerted a significant effect on endotoxin levels and the adipocytokine profiles of Type 2 diabetes mellitus (T2DM) patients. Fasting blood samples were collected from consenting Saudi Arabian subjects (BMI:30.2 Kg/M²±5.6, n=413), consisting of non-diabetics (NDs, n=67) and T2DM subjects (n=346). The diabetics were divided into 5 subgroups based on their 1 year treatment regimes: diet-control (n=36), insulin (n=47), metformin (n=141), rosiglitazone (RSG, n=22) or a combined fixed dose of metformin/rosiglitazone (Avandamet n=100). Lipid profiles, fasting plasma 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 (TGs, r²=0.40; p<0.0001); total cholesterol (r²=0.10; p<0.0001), glucose (r²=0.14; p<0.0001) and insulin (r²0.12; p=0.01). Endotoxin showed a strong inverse correlation with HDL (r²=0.10; p<0.0001) and was elevated in all of the treated diabetic subgroups compared with NDs. Only circulating endotoxin levels of the RSG treated diabetics were comparable to ND controls (Control:4.2±1.7, RSG:5.6±2.2 EU/mL). Both the Avandamet and RSG treated groups had the highest adiponectin levels. In summary, sub-clinical inflammation in T2DM may be mediated by endotoxin in serum. Furthermore, 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. In addition, a positive association between endotoxin, serum insulin and TGs was noted 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.