Once again, a high intake of protein — animal protein in particular — has been linked with an increased risk of type 2 diabetes, especially among obese women, according to an article published online this week in Diabetes Care.

Monique van Nielen, PhD, from the division of nutrition, Wageningen University, the Netherlands, and colleagues conducted a prospective analysis as part of the European Prospective Investigation into Cancer and Nutrition-InterAct case-control study (EPIC-InterAct).

The goal of InterAct is to investigate how both genetic and lifestyle factors cause diabetes in European countries.

The current analysis included 10,901 incident type 2 diabetes cases and a subcohort of 15,352 participants, including 736 diabetes cases, with a mean follow-up of 12 years. The study covers cases occurring in EPIC cohorts between 1991 and 2007 in 8 countries.

Previous studies have also examined a potential link between meat consumption and diabetes risk. In the current analysis, researchers used food frequency questionnaires to determine participants' eating habits. They categorized estimated protein intake by quintile of grams per day consumed. They then used Cox proportional hazard models, stratified by country, to estimate the association between protein intake and diabetes incidence.

Estimated total protein (mainly animal) intake was 90.4 g/day for men and 91.0 g/day for women. Spain had the highest intake of 102.5 g/day; Germany (80.0 g/day) and Sweden (80.8 g/day) had the lowest. In order of consumption, animal protein sources were meat, dairy, and fish; plant protein sources were bread, pasta, rice, potatoes, and other vegetables.

More Meat, More Diabetes

The researchers found that, overall, high total protein intake was associated with a 13% higher incidence of diabetes for every 10-g increment after adjusting for energy intake, center, sex, diabetes risk factors, and dietary factors (hazard ratio [HR], 1.13; 95% confidence interval [CI], 1.08 – 1.19). The HR for animal protein alone was 1.12.

In women, the confirmed association between total and animal protein intake and increase in diabetes incidence was 10% (P < .001). Obese women had a 19% increased incidence compared with normal-weight women. Researchers found no confirmed association in men.

The researchers found no significant association between diabetes incidence and intake of dairy, fish, or plant proteins.

"Our study, the largest of its kind in terms of sample size, number of cases, and follow-up years, is the first to investigate the association between type 2 diabetes incidence and protein intake at a general European level," the researchers write.

"Overall, we conclude that a greater intake of total protein is associated with a higher type 2 diabetes incidence in European populations, but the effect of protein intake is small, and known type 2 diabetes risk factors are also important," they continue. "Our results show that protein of animal origin is largely responsible for the association — not plant protein."

Potential Mechanisms

In an email to Medscape Medical News, study coauthor Edith J. M. Feskens, PhD, professor of nutrition at Wageningen University, elaborated on possible mechanisms for the association.

"Red meat contains iron and saturated fatty acids, [and] we think that may be a reason why it is associated with an increased risk of type 2 diabetes," she said. "The plant protein may be associated with more fiber and hence can be beneficial from that point of view. However, more studies on the exact role of protein quality (and amino-acid content) and diabetes are warranted."

Of all the risk factors for diabetes, overweight is the most important, she added. "Diet plays a role in contributing to overweight. In addition, smaller independent dietary effects are seen, just as in this case [showing] the small elevated risk from animal protein."

Why the confirmed positive association appears for women and not men is unknown, she said. "Hormonal factors may be involved, and we certainly are going to look into that. We are conducting an intervention with soy in women."

InterAct is funded by several government and other agencies, as well as NovoNordisk for some investigators. None of the authors have reported any other relevant financial interests.

Diabetes Care. Published online April 10, 2014. Abstract