Blood endotoxin raised after high fat meals

New research identifies a higher inflammatory response to high fat meals in people with type 2 diabetes, a factor which could contribute to many of the disease’s complications. The findings, presented at the Society for Endocrinology annual meeting in Harrogate, show that all people display increased blood levels of endotoxin following a high fat meal, and that those with type 2 diabetes are exposed to over twice as much endotoxin per high fat meal than those without.

Previous research shows people with type 2 diabetes have raised baseline levels of endotoxin, a bacterial fragment which enters the bloodstream from the gut and is associated with inflammation and heart disease. Dr Alison Harte from the University of Warwick, UK, and colleagues from the UK, Spain and Saudi Arabia investigated the effect that a high fat meal might have on endotoxin levels in people with diabetes. The team gave 54 people (15 obese, 12 with impaired glucose tolerance (‘pre-diabetes’), 18 with type 2 diabetes and 9 non-obese controls) high fat meals after an overnight fast. They monitored their blood levels of endotoxin for four hours, comparing these to levels before eating (baseline).

Mean circulating endotoxin levels increased significantly after the high fat meal in all participants over the four hour time period compared to baseline values: obese baseline: 5.1±0.94 EU/ml; 4 hr: 7.7±0.58 EU/ml (p<0.01), pre-diabetes baseline: 5.7±0.10 EU/ml; 4 hr: 7.5±0.20 EU/ml (p<0.05) and type 2 diabetes subjects baseline: 5.3±0.54 EU/ml; 4 hr: 14.2 ±3.0 EU/ml (p<0.01). In the non-obese control group, whilst there was a rise in circulating endotoxin (baseline 3.3±0.15 EU/ml; 4hr 6.3±1.4 EU/ml) this did not reach significance past 1hr. Most importantly, these data show a large, long lasting and significant rise in endotoxin levels (to approximately 125.4% of that of controls) amongst subjects with type 2 diabetes.

Inflammation is a reaction mediated by the immune system in response to a physical stressor, for example a wound or infection. In normal circumstances it is a temporary measure which aids healing. However, if inflammation is long-term, it can be damaging. In obesity and type 2 diabetes there is widespread inflammatory damage to blood vessels and other tissues, contributing to many associated conditions such as heart disease (which as many as 80% of type 2 diabetics die from1).

This study could explain one mechanism by which obesity can lead to inflammatory damage, and help researchers develop new preventative measures. If confirmed in larger studies, it suggests that the high fat, low carbohydrate diets currently promoted to aid weight loss and control of blood sugar may be harmful to diabetics. Also, altering the size and timing of meals (i.e. infrequent, large meals versus a continual grazing routine) may help to control the chronic inflammation and resulting damage.

Dr Alison Harte, lead investigator and Post-Doctoral Research Fellow at the University of Warwick said:

“Our study shows for the first time that eating a high fat meal is rapidly followed by an increase in blood endotoxins, which are bacterial fragments that can provoke inflammation. Patients with type 2 diabetes show this response to a greatly enhanced degree, over twice that of controls.

“High fat, low carbohydrate diets are often promoted to patients with type 2 diabetes as they have been suggested to aid weight loss and control blood sugar, but if confirmed in larger studies our data show that being healthy is not just about losing weight, as these particular diets could increase inflammation in some patients and with it the risk of heart disease.
“The next phase of our research is to understand the effects of small, frequent meals versus large, infrequent meals on endotoxin levels in type 2 diabetics. We’d also be interested to find out the effects of meals of different fat and carbohydrate contents.”