A sugar in red meat that the human body recognizes as foreign may help explain the food’s link to type 2 diabetes.
Preliminary findings from a French study of nearly 90,000 adults linked higher intake of a meat-derived sugar called N-glycolylneuraminic acid (Neu5Gc) with a greater risk of developing type 2 diabetes (T2D). Participants with the highest intake had a 63% higher risk than those with the lowest intake, although the observational research cannot establish that the sugar caused the disease.
The findings were presented at the Annual Meeting of the European Association for the Study of Diabetes (EASD). Researchers are investigating whether an immune response to Neu5Gc could help explain why red meat consumption has been associated with diabetes.
“Our findings support chronic inflammation as a specific mechanism linking red meat consumption with T2D, partly beyond the amount of red meat a person eats and partly independent of body fat,” said lead author Dr. Leopold Fezeu of Université Sorbonne Paris Nord in Bobigny, France.
Why the Body Recognizes This Sugar as Foreign
Most mammals naturally produce Neu5Gc, but an ancient mutation in the CMAH gene left humans unable to make it. We nevertheless encounter it in food, particularly beef and lamb, with smaller amounts in dairy products.
After consumption, Neu5Gc can enter human tissues. Its presence creates an unusual situation: a foreign molecule becomes incorporated into the body’s own cells. Scientists describe it as a xeno-autoantigen, against which the immune system produces antibodies.
The resulting persistent immune activity (xenosialitis) has previously been linked to cardiovascular disease and cancer. The researchers wanted to explore whether a similar process might contribute to diabetes, a question that had not previously been examined in a large prospective study.
Tracking Diet and Diabetes Over Time
The analysis drew on 89,953 participants in NutriNet-Santé, a long-term French study of diet, lifestyle, and health. Their average age was 42, 79% were women, and none had diabetes or cancer at enrollment. During a median follow-up of 7.2 years, 966 developed T2D.
Participants completed three 24-hour dietary records. Researchers used a validated database of measured Neu5Gc concentrations in foods to estimate how much each person consumed and whether it came from meat or dairy.
The meat analysis included beef, lamb, pork, rabbit, goat, and game. Processed meat products (such as bacon, sausages, and cured meats) were recorded as a separate food group, and dairy products were analyzed separately.
Men and women were each divided into five equally sized groups (quintiles) according to meat-derived Neu5Gc intake. The researchers then compared diabetes risk across these groups, using the lowest-intake group as the reference.
Higher Intake Was Linked to Higher Risk
The highest-intake group had a 63% higher diabetes risk, while the second-highest group had a 41% higher risk (men and women combined). These are relative increases compared with the lowest-intake group, not the percentages of participants who developed diabetes.
The association remained after accounting for age, sex, physical activity, diet quality, smoking, and underlying health conditions. It appeared in both men and women, with no statistically detectable difference between them, and was consistent regardless of total energy intake.
The groups also differed substantially in meat consumption. In the highest-intake group, men ate a median of 97 grams (3.4 ounces) of red meat daily and women 73 grams (2.6 ounces). Including processed meat brought those amounts to 136 grams (4.8 ounces) and 96 grams (3.4 ounces), respectively. In the lowest-intake group, the corresponding totals were just 21 grams (0.74 ounces) for men and 9 grams (0.32 ounces) for women.
The risk rose particularly sharply at higher Neu5Gc intakes. Researchers suggested that this could reflect a threshold at which its accumulation in tissues provokes a stronger immune response, but the study did not identify or establish such a threshold.
Separating the Sugar From the Meat
“Although we do not know exactly what levels of Neu5Gc trigger an immune response, our data suggest that higher intakes of meat-derived Neu5Gc are associated with a progressively higher risk of T2D,” Fezeu said.
Accounting for body mass index (BMI) weakened the association, but it remained statistically significant. The researchers estimated that obesity explained approximately 13% of the association and proposed that inflammation affecting insulin-producing cells and insulin-sensitive tissues might help explain the rest. Those mechanisms still require investigation.
However, when researchers also adjusted for total red meat consumption, the association weakened and was no longer statistically significant. Although it continued to point toward higher risk, this result makes it difficult to separate Neu5Gc’s possible contribution from that of other substances in meat.
Dairy-derived Neu5Gc showed no association with diabetes. The researchers considered this consistent with the lower concentrations in cow’s milk compared with beef and lamb, and with smaller serving sizes typically consumed. Across all food sources combined, the highest Neu5Gc intake was associated with a 37% higher diabetes risk, largely driven by meat.
What Researchers Want To Test Next
“Together, these findings 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,” Fezeu said. “There may be differences between sources, or other components of red meat may contribute.”
He added, “Given how common red meat is in Western diets, the strong association between meat-derived Neu5Gc 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 anti-Neu5Gc antibodies in large cohorts would also help to directly test the xenosialitis mechanism in humans.”
The team plans to investigate Neu5Gc alongside other red meat components, including heme iron (a form of dietary iron). Measuring antibodies against Neu5Gc would also provide a more direct test of the proposed immune mechanism than dietary estimates alone.
Preliminary Findings Leave Important Questions
The results have not yet been validated, and the estimates could change when the analysis is finalized. The study identifies an association but cannot determine what caused the higher diabetes risk or establish that reducing Neu5Gc intake would prevent the disease.
Although researchers adjusted for several major risk factors, unmeasured lifestyle and social differences could still have influenced the findings. Food records can also misrepresent actual intake, and the analysis did not track dietary changes during follow-up.
Meeting: Annual Meeting of the European Association for the Study of Diabetes (EASD)
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