A naturally occurring sugar in red meat may explain why consumption of these foods is associated with a higher risk of type 2 diabetes. Preliminary results from a large observational study suggest that people who consume the most of this sugar are at a much higher risk of developing the disease, potentially due to its effects on the immune system and chronic inflammation.
Sugar, known as N-glycolylneuraminic acid (Neu5Gc), is particularly present in beef and lamb. Researchers found that participants consuming the most meat-derived Neu5Gc had a 63% higher risk of developing type 2 diabetes (T2D) compared to those consuming the least.
The association remained statistically significant after researchers took into account several established risk factors for diabetes, including physical activity, general diet, smoking and existing health conditions. It weakened after body mass index (BMI) was also taken into account, but it remained significant.
The findings were presented at the annual meeting of the European Association for the Study of Diabetes (EASD) in Milan, Italy.
“Our findings support chronic inflammation as a specific mechanism linking red meat consumption to T2D, partly beyond the amount of red meat a person consumes and partly independent of body fat,” said lead author Dr Léopold Fezeu of Université Sorbonne Paris Nord, Bobigny, France.
The researchers also observed that the risk of diabetes generally increased with increased consumption of meat-derived Neu5Gc, especially among those at highest risk.
“Although we do not know exactly what levels of Neu5Gc trigger an immune response, our data suggest that higher consumption of meat-derived Neu5Gc is associated with progressively higher risk of T2D.”
Why sugar in red meat can trigger inflammation
Neu5Gc is produced naturally by most mammals, but humans lost the ability to make it following an ancient mutation in the CMAH gene. Despite this evolutionary change, sugar can still enter the human body through food.
It is found in red meat (especially beef and lamb), and in smaller quantities also in dairy products.
Once Neu5Gc is consumed, the body absorbs it and can incorporate it into human tissues. Because humans do not naturally produce the molecule, the immune system may recognize it as foreign. Scientists classify it as a xenoautoantigen, a foreign substance that incorporates into the body’s tissues and can cause an immune response.
In response, the immune system produces antibodies against Neu5Gc. The resulting prolonged immune activity, called xenosialitis (xenosialitis), has previously been linked to cardiovascular disease and cancer.
The researchers suspect that this persistent inflammatory response could also contribute to type 2 diabetes. However, prior to this investigation, no large prospective studies had examined whether dietary Neu5Gc could promote diabetes through chronic inflammation.
Nearly 90,000 adults studied for several years
To study this possible link, scientists analyzed diet and health information from 89,953 adults participating in NutriNet-Santé, a large French observational study that follows people over time to examine how nutrition and lifestyle influence health.
Participants were on average 42 years old and 79% were women. None had type 2 diabetes or cancer when they entered the study.
Each person completed three 24-hour food records. The research team then used a validated dietary database to calculate the likely amount Neu5Gc participants were consuming based on measured amounts of sugar in different foods.
The analysis covered a wide range of red meats, such as beef, lamb, pork, rabbit, goat and game. Processed meats (such as bacon, sausages and cold cuts) were evaluated in a separate category, while dairy products were analyzed independently.
Using dietary information, researchers estimated total Neu5Gc intake from all reported foods. They then categorized participants separately by gender based on their consumption of meat-derived Neu5Gc and divided them into five equal-sized groups (quintiles).
Diabetes risk was compared between these groups, using those with the lowest intake as a reference.
During a median follow-up period of 7.2 years, researchers recorded 966 new cases of type 2 diabetes.
Higher consumption of sugar in red meat linked to 63% higher risk of diabetes
The results showed a significant relationship between meat-derived Neu5Gc consumption and the likelihood of developing type 2 diabetes. The association became particularly pronounced among participants with the highest estimated consumption.
Compared to the low consumption group, individuals in the highest group had a 63% higher risk of developing the disease. People in the second highest group had a 41% higher risk (men and women combined).
These estimates took into account potentially influential factors including age, gender, exercise habits, overall dietary quality, smoking, and existing health conditions.
The researchers also looked at how much meat the participants typically ate.
Among men in the highest Neu5Gc consuming group, the median red meat consumption was 97 grams per day (136 g, including processed meat). For women, the corresponding amount was 73 grams (96 g).
In comparison, men in the lowest intake group consumed an average of just 5 grams of red meat per day (21 g), while women consumed 0 grams (9 g).
The relationship between Neu5Gc and diabetes was observed in both sexes, with no statistically significant evidence that it differed between men and women (see tables in notes to editors).
The results were also consistent when differences in total caloric intake were taken into account.
The researchers noted that the increase in diabetes risk was particularly strong at higher levels of Neu5Gc exposure. One possible explanation is that the immune system begins to respond more strongly after enough foreign sugar has accumulated in body tissues, although this proposed threshold mechanism has not been confirmed.
Importantly, when the analysis also took into account the total amount of red meat consumed, the relationship between Neu5Gc and diabetes weakened and was no longer statistically significant. However, the direction of the association remains the same.
This means that researchers cannot determine whether Neu5Gc itself (rather than other components of red meat) is responsible for the increased risk. The results suggest that this could contribute to this relationship, but they do not establish that sugar acts independently of red meat consumption.
Diabetes risk may extend beyond weight gain
Another notable finding is that obesity appears to explain only a relatively small part of the association.
Obesity accounted for about 13% of the relationship between meat-derived Neu5Gc consumption and type 2 diabetes, the researchers estimated.
This suggests that factors unrelated to excess body weight may contribute substantially to the observed link.
One possibility is that immune reactions to Neu5Gc produce chronic inflammation that interferes with insulin-producing cells or tissues that normally respond to insulin. Such effects could potentially increase the risk of developing type 2 diabetes, even without substantial weight gain.
However, further studies are needed to determine whether these inflammatory processes actually explain this association.
Why Dairy Products Showed Different Results
Although Neu5Gc is present in both red meat and dairy products, researchers found an important difference between these food sources.
Higher consumption of Neu5Gc from dairy products was not associated with increased risk of type 2 diabetes.
This finding may reflect the relatively low amounts of Neu5Gc in cow’s milk compared to red meats like beef and lamb. The generally lower amounts of Neu5Gc consumed in dairy servings may also contribute to the difference.
When the scientists took into account Neu5Gc intake from all food sources combined, participants in the highest intake group had a 37% higher risk of developing type 2 diabetes compared to those in the lowest group.
This association appears to be mainly due to Neu5Gc obtained from red meat.
“Together, these results suggest that the association between Neu5Gc and T2D may depend on its dietary source, with meat-derived Neu5Gc showing a stronger association with T2D risk than total dietary Neu5Gc,” Dr. Fezeu said. “There may be differences between sources, or other components of red meat may contribute.”
Could changing protein sources reduce diabetes risk?
The results raise the possibility that reducing dietary exposure to meat-derived Neu5Gc could eventually become an approach to reducing diabetes risk.
However, the researchers emphasize that studies are still needed to determine whether replacing Neu5Gc-rich foods with other protein sources would actually produce measurable health benefits.
“Given the frequency of red meat in the Western diet, the strong association between meat-derived Neu5Gc risk and T2D risk is an important finding. Future research should explore whether reducing exposure to meat-derived Neu5Gc, for example by favoring poultry or plant-based proteins over beef and lamb, which have the highest Neu5Gc content, could help prevent T2D. Studies directly measuring the Anti-Neu5Gc antibodies in large cohorts would also help directly test the xenosialitis mechanism in humans.
The research team plans to study how Neu5Gc interacts with other substances found in red meat, including heme iron (a form of dietary iron), and how these components may collectively be linked to diabetes risk.
They also intend to directly measure antibodies against Neu5Gc. This could help determine whether the proposed immune response is an important biological mechanism linking red meat consumption to type 2 diabetes.
Important limitations of the results
The researchers warn that their…
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