Endocrine Abstracts (2012) 28 OC3.2

Post-prandial high fat intake leads to acute exposure to circulating endotoxin in type 2 diabetes mellitus subjects

Alison Harte1, Madhusudhan Varma1, Gyanendra Tripathi1, Kirsty McGee1, Nasser Al-Daghri2, Omar Al-Attas2, Shaun Sabico2, Joseph O'Hare1, Antonio Ceriello3, Ponnusamy Saravanan1,4, Sudhesh Kumar1 & Philip McTernan1


1Division of Metabolic and Vascular Health, University of Warwick, Coventry, United Kingdom; 2Biomarkers Research Program and Center of Excellence in Biotechnology Research, King Saud University, Riyadh, Saudi Arabia; 3Insititut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) and Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas, Barcelona, Spain; 4Clinical Sciences Research Laboratories, Warwick Medical School, University of Warwick & George Eliot Hospital, Coventry, United Kingdom.


Habitual post-prandial absorption of saturated fatty acids (SFAs) increases systemic atherogenic lipoproteins and a pro-inflammatory response, a condition exacerbated by obesity, insulin resistance (IR) and type 2 diabetes mellitus (T2DM). Also, gut derived bacteria (endotoxin) is absorbed coupled to damaging lipoproteins as it crosses the mucosa, which could directly impact on adipose tissue, as our previous studies suggest. The current studies addressed whether a SFA rich meal increases circulating endotoxin absorption and whether this is dependent on disease state. Subjects (n=58) with and without T2DM were given a high-fat meal (meal: 75 g fat, 5 g carbohydrate, 6 g protein) following an over-night fast [non-obese controls (NOC): age: 39.8 (Mean±S.E.M)11.2 yr, BMI: 25.3(mean±S.D.)3.3 kg/m2; n=10; Obese: age: 43.8±9.5 yr; BMI: 33.3±2.6 kg/m2; n=15; impaired glucose tolerance (IGT): age: 41.7±3.3 yr; BMI: 32.0±4.5 kg/m2; n=12; T2DM: age: 46.4±9.6 yr; BMI: 30.1±5.2 kg/m2; n=21]. Baseline (0 hr) and post-prandial sera (1–4 hr) were taken from subjects and endotoxin, inflammatory cytokines and lipid levels measured. Baseline circulating endotoxin was significantly higher in the T2DM, IGT and obese subjects compared with NOC (Baseline endotoxin: T2DM:5.73 (mean±S.E.M) 0.85 EU/mL*; Obese:5.75±1.45 EU/mL*; IGT:5.83±0.45 EU/mL* Vs NOC:3.55±0.50 EU/mL; *P<0.05). The high fat meal led to a significant rise in endotoxin levels in T2DM and IGT subjects over the post-prandial time period compared with baseline. The findings also showed that, at 4 hr post-feed, T2DM subjects exhibited a mean endotoxin level 118.5% higher than that of the NOC. A strong positive correlation between increasing BMI and log endotoxin was noted in the non-obese and obese cohorts (r value=0.501** and 0.301*, respectively; **P<0.001, *P<0.05). These studies highlight that post-prandial exposure to a high-fat meal elevates circulating endotoxin, with T2DM subjects exposed to as much as 119% more circulating endotoxin post-prandially, per high-fat meal. Therefore a continual grazing routine will cumulatively promote their pathogenic condition more rapidly than other individuals, due to the exposure to elevated endotoxin.

Declaration of interest: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Funding: No specific grant from any funding agency in the public, commercial or not-for-profit sector.