LISBON – Snacking throughout the day might not be the best way to help control type 2 diabetes, especially if the snacks contain much fat.
A high-fat meal in people with diabetes and impaired glucose tolerance appears to trigger the passage of bacterial endotoxins through the intestinal wall, adding to the load of inflammatory cytokines that have already been implicated in the disease, Alison Harte, Ph.D., said at the annual meeting of the European Association for the Study of Diabetes.
Because people with diabetes are often counseled to consume food in smaller, but more frequent, meals, this "leaky gut" effect could be compounded by this eating pattern, building up more and more of the lipopolysaccharide endotoxin – the main component of a gram-negative bacterium’s cell membrane – in the blood.
"Our data highlight that these people can be exposed to as much as 126% more circulating lipopolysaccharide after a high-fat meal," said Dr. Harte of the University of Warwick (England). "A continual grazing routine will cumulatively promote their pathogenic condition more rapidly than other individuals’ due to the elevated exposure to endotoxin."
Dr. Harte and her colleagues tested this hypothesis in 54 participants: 9 nonobese controls, 15 obese subjects, 12 with impaired glucose tolerance, and 18 with type 2 diabetes. The mean body mass index was 25 kg/m2 in the normal controls, 33 kg/m2 in the obese subjects, 32 kg/m2 in those with impaired glucose tolerance, and 30 kg/m2 in those with type 2 diabetes.
Each of the subjects ate a high-fat meal composed of 75 g of fat, 5 g of carbohydrate, and 6 g of protein after an overnight fast. Blood was drawn at baseline and at 1, 2, 3, and 4 hours after eating.
At baseline, lipopolysaccharide was already significantly higher in obese subjects and those with diabetes and impaired glucose tolerance (mean of 5.7 endotoxin units [EU]/mL), compared with the control subjects (mean of 3.5 EU/mL).
The high-fat meal caused a significant jump in lipopolysaccharides among those with diabetes and impaired glucose tolerance. By 4 hours, those with diabetes had a mean lipopolysaccharide load of 17 EU/mL. The load increased to 8 EU/mL in those with impaired glucose tolerance. At 4 hours after the meal, the obese controls had a nonsignificant increase but still had a mean of 22% more circulating lipopolysaccharide than the normal controls. This group had a slight, nonsignificant increase in the endotoxin.
Triglycerides followed a parallel course, she said, increasing over the 4-hour period significantly more in those with type 2 diabetes, impaired glucose tolerance, and obesity, compared with the controls.
"A high-fat diet raises endotoxin and triglycerides over 4 hours, and this increase could be further compounded by subsequent eating during the day, potentially resulting in continually raised levels," Dr. Harte said. "The fasting studies that we do might actually be masking the true impact of these circulating endotoxins and lipids."
Research confirms that obesity, diabetes, and cardiovascular disease all have an element of systemic inflammation. Dr. Harte said that her research suggests this inflammatory insult could arise, in part, from a compromised gut mucosa that allows bacterial endotoxins to enter the circulation and initiate a systemic inflammatory response.
Dr. Harte reported no financial conflicts.