Recent evidence suggests that diet-induced inflammation in the small intestine is linked to obesity and insulin resistance. Long-chain omega-3 polyunsaturated fatty acids (LCn-3PUFA) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been shown to have anti-inflammatory effects by down-regulating inflammatory gene expression in adipocytes and mononuclear cells. However, the extent to which EPA and DHA may exert their anti-inflammatory effects by down-regulating inflammation in the gut is unknown. The objective of the study was to investigate the impact of EPA+DHA supplementation on the expression of inflammatory genes in the small intestine of patients with type 2 diabetes. A total of 12 men with type 2 diabetes were recruited in this placebo-controlled randomized crossover study. After a 4-week run-in period, patients received in random sequence 5 g/d of fish oil providing 3 g of EPA+DHA or placebo (corn and soybean oil) for 8 weeks, each separated by a 12-week washout period. Gene expression was assessed by real-time PCR in duodenal biopsy samples obtained in the fasted state at the end of each treatment phase. Intestinal mRNA expression levels for interleukin(IL)-6 and tumor-necrosis factor(TNF)-α were hardly detectable after either treatment (< 100 copies/10^5 copies of the reference gene ATP synthase O subunit, ATP5o). Intestinal mRNA expression of IL-18 and of the transcription factor STAT3 (signal transducer and activator of transcription 3) was higher (> 5000 copies/10^5 copies ATP5o) but still relatively low and EPA+DHA supplementation had no impact on any of these levels (P ≥ 0.73 between treatments). Plasma C-reactive protein (CRP) concentrations after supplementation with EPA+DHA (5.2 ± 4.5 mg/L) were not significantly different than values measured after placebo (8.0 ± 10.8 mg/L, P = 0.2). In conclusion, these data suggest that gene expression of pro-inflammatory cytokines and STAT3 in duodenal cells is low in patients with type 2 diabetes and not affected by EPA+DHA supplementation.
Benfotiamine and Long-Chain Omega-3 and Omega-6 Polyunsaturated Fatty Acids in Treatment of Cardiac Autonomic Neuropathy in Patients with Type 2 Diabetes Mellitus