Diabetes is often accompanied by chronic low-grade inflammation. Recent research indicates that inflammation may be linked to molecules derived from bacteria.
It has been hypothesized that bacterial endotoxins, lipopolysaccharides (LPS) located on the outer membrane of Gram-negative bacteria, can increase the risk for type 2 diabetes by activating components of the immune system which promote insulin resistance and other metabolic abnormalities.
In this large prospective study from last year:
Endotoxemia Is Associated With an Increased Risk of Incident Diabetes, Diabetes Care, February, 2011
Endotoxemia was associated with an increased risk for type 2 diabetes. Notably, the increased risk was independent of established diabetes risk factors such as blood glucose, serum lipids, C-reactive protein (CRP), and body mass index (BMI). The risk was also independent of factors known to affect serum endotoxin activity, such as total cholesterol, triglyceride levels, HDL cholesterol levels, and smoking.
"Our results indicate for the first time that endotoxemia is a key player in the pathogenesis of diabetes and that microbes may have a central role."
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This study from last month:
High Fat Intake Leads to Acute Postprandial Exposure to Circulating Endotoxin in Type 2 Diabetic Subjects, Diabetes Care, December 2011
Found that a high-fat meal elevated levels of endotoxins, especially in people with diabetes.
"These studies have highlighted that exposure to a high-fat meal elevates circulating endotoxin irrespective of metabolic state, as early as 1 h after a meal. However, this increase is substantial in IGT and type 2 diabetic subjects, suggesting that metabolic endotoxinemia is exacerbated after high-fat intake.
In conclusion, our data suggest that, in a compromised metabolic state such as type 2 diabetes, a continual snacking routine will cumulatively promote their condition more rapidly than in other individuals because of the greater exposure to endotoxin."
Previous studies implicated dietary fat in levels of endotoxins (LPS):
"In mice fed a high-carbohydrate diet, the increase in plasma LPS was blunted compared with mice fed a high-fat diet."
...
"In this large sample of healthy men from a population-based sample, we found a link between food intake and plasma LPS. Experimental data suggest that fat was more efficient in transporting bacterial LPS from the gut lumen into the bloodstream."
- Energy intake is associated with endotoxemia in apparently healthy men, American Journal of Clinical Nutrition, May 2008
How does dietary fat assist endotoxin absorption? It's been proposed that fat-soluble endotoxins mix with and are absorbed in conjunction with the fat contained in a meal:
"Dietary fat is incorporated from the gut into triglyceride-enriched lipoproteins, chylomicrons, whose formation promotes LPS absorption."
- Endotoxemia Is Associated With an Increased Risk of Incident Diabetes, Diabetes Care, February, 2011
Another hypothesis is that the absorption of endotoxins is assisted by inflammation present in the gut. This novel study found that orange juice, taken with a meal, could lower levels of circulating endotoxins:
"Whether this increase of endotoxemia is due to the lipid solubility of endotoxin and its absorption into the circulation with the fat contained in the meal or is secondary to other factors such as the inflammation of the intestinal epithelium is not clear. If it is secondary to other factors, the potential antiinflammatory effect of orange juice intake could lower postprandial endotoxin increase."
- Orange juice neutralizes the proinflammatory effect of a high-fat, high-carbohydrate meal and prevents endotoxin increase and Toll-like receptor expression, American Journal of Clinical Nutrition, April 2010
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The following study found a strong correlation between endotoxins and features of the Metabolic Syndrome (in line with the findings of the study at the top of this post which found an association between endotoxins and type 2 diabetes):
Bacterial Endotoxin Activity in Human Serum Is Associated With Dyslipidemia, Insulin Resistance, Obesity, and Chronic Inflammation, Diabetes Care, August 201
It is known that HDL cholesterol assists in the elimination of endotoxin from the circulation. (In healthy individuals, endotoxins are bound mainly to HDL). This study found that diabetic patients with low HDL often had high endotoxin activity.
"Of all the tested clinical variables, the strongest correlation was observed between the LPS/HDL ratio and serum triglyceride concentrations. High fasting concentrations of triglycerides predict postprandial hypertriglyceridemia and the development of insulin resistance."
The study also found an inverse correlation between serum LPS activity and insulin sentitivity in both diabetic and nondiabetic groups. High endotoxin activity was linked to insulin resistance.
The contribution of a high-fat diet was also noted:
"Human and animal studies have both highlighted the importance of the composition of the diet for its influence on the endotoxin absorption process. Consumption of an energy-rich high-fat diet may result in increased levels of gut-derived bacterial endotoxins in circulation."
The authors concluded:
"Taken together, these data show that endotoxins derived from gram-negative bacteria are strongly associated with the MetS variables in vivo. These observations may have clinical implications, because high LPS activity is more often found in subjects who show signs of dyslipidemia, insulin resistance, overweight, and inflammation—factors that increase the risk for diverse micro- and macrovascular complications."
Two recent studies find no benefit to the heart from supplementing with vitamin D.
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