Neu5Gc in Red Meat: 63% Higher Diabetes Risk

A study presented today at the congress of the European Association for the Study of Diabetes (EASD) in Milan links higher intake of a sugar called N-glycolylneuraminic acid (Neu5Gc), common in red meat, to a 63 percent higher risk of developing type 2 diabetes. The findings were presented by a team of French researchers led by Dr. Leopold Fezeu of Sorbonne Paris Nord University in Bobigny. The EASD congress runs from September 28 to October 2, and the finding was presented on the first day of the meeting.

Neu5Gc is a sugar produced by most mammals, but not by humans. People lost the ability to produce it through an ancient mutation of the CMAH gene. When the sugar is consumed through food, it becomes incorporated into tissues, and the body recognizes it as foreign, a so called xenoautoantigen. The immune system then produces antibodies against it, and the resulting chronic immune activation, known as xenosialitis, has previously been linked to cardiovascular disease and cancer. Until now, no large prospective study had examined whether Neu5Gc can trigger chronic inflammation and drive type 2 diabetes.

The researchers analyzed data from 89,953 adults in the French NutriNet-Santé cohort, with an average age of 42, of whom 79 percent were women. None of the participants had type 2 diabetes or cancer at the start of the study. Diet was recorded through three 24 hour dietary records per participant. Follow up lasted a median of 7.2 years, during which 966 new cases of type 2 diabetes were recorded. Neu5Gc intake from meat covered beef, lamb, pork, rabbit, goat and game, while processed meat and dairy products were analyzed separately.

Participants were divided into five equal groups, called quintiles, based on Neu5Gc intake from meat, calculated separately for men and women. The group with the highest intake had a 63 percent higher risk of type 2 diabetes compared with the group with the lowest intake, and the association remained statistically significant after adjusting for age, sex, physical activity, diet quality, smoking and existing health conditions. The second highest intake group had a 41 percent higher risk. In the highest intake group, men ate a median of 97 grams of red meat a day, or 136 grams including processed meat, while women ate 73 grams, or 96 grams including processed meat. In the lowest intake group, men ate 5 grams of red meat, or 21 grams including processed meat, while women ate no red meat at all, or 9 grams including processed meat.

After adjusting for body mass index, the association weakened but remained statistically significant. The researchers estimate that obesity accounts for about 13 percent of the association, indicating that most of it operates through mechanisms independent of weight gain. When the researchers also adjusted for total red meat intake, the association weakened further and was no longer statistically significant, though it remained in the same direction. This suggests that Neu5Gc itself, not necessarily other components of red meat, explains part, but not all, of the relationship between red meat and type 2 diabetes.

When Neu5Gc from all dietary sources, not just meat, was taken into account, the group with the highest total intake had a 37 percent higher risk of type 2 diabetes compared with the group with the lowest intake. Neu5Gc from dairy products, unlike Neu5Gc from meat, showed no significant link to disease risk.

Dr. Fezeu explained the mechanism behind the findings. He said:

“Our findings support chronic inflammation as a specific mechanism linking red meat consumption to type 2 diabetes, partly independent of the amount of red meat a person eats and partly independent of body fat.”

He added that the association rises progressively with intake:

“While we do not know exactly which levels of Neu5Gc trigger an immune response, our data indicate that higher intake of Neu5Gc from meat is followed by a progressively higher risk of type 2 diabetes.”

Fezeu also pointed out that the dietary source of Neu5Gc plays a role:

“Together, these findings suggest that the association between Neu5Gc and type 2 diabetes may depend on the dietary source, with Neu5Gc from meat showing a stronger link to diabetes risk than total dietary Neu5Gc.”

The study’s authors say further research will track how Neu5Gc and other components of red meat, such as heme iron, jointly relate to type 2 diabetes risk, and will measure antibodies to Neu5Gc to directly test the proposed mechanism.

The authors themselves note the study’s limitations. The results are preliminary, have not yet been peer reviewed or published in a scientific journal, and the estimates may change once the analysis is finalized. This is an observational study, meaning it does not prove causation, only that two phenomena are linked. The researchers could not rule out the influence of other lifestyle and social factors they did not measure, and estimating Neu5Gc intake from dietary records, without tracking dietary changes over the follow up period, may have introduced measurement error.