A clue about the blood chemistry of obese people who develop insulin resistance, a precursor to diabetes, has been confirmed in animal studies at the Duke University Medical Center.

Obese people have been found to harbor proteins called branched-chain amino acids (BCAAs) at far higher levels than non-obese people. The suspicion has been that these amino acids, in combination with a high-fat diet, contribute to insulin resistance. The team found that the BCAA signature in obese humans consisted of the branched-chain amino acids themselves, plus a cluster of several products related to the bodys breakdown processes for BCAA.

In the case of the amino acids, we also are finding increased levels of their metabolic breakdown products, which suggests the whole system for handling the amino acid metabolic process has been overloaded, said senior author Christopher Newgard, Ph.D., director of the Sarah W. Stedman Nutrition and Metabolism Center and W. David and Sarah W. Stedman Distinguished Professor at Duke. Our rat studies show that this overload causes changes at the cellular level that can lead to insulin resistance.

To determine whether the BCAA signature in obese humans might signal that their intake is harmful, the scientists performed a feeding study in rats that showed an independent contribution of BCAAs to insulin resistance.

These findings, however, would need to be confirmed in studies with people before any dietary recommendations could be issued, said Laura Svetkey, M.D., director of the Duke Hypertension Center, director of clinical research at the Sarah W. Stedman Nutrition and Metabolism Center, and co-senior author of the study, published in Cell Metabolism.

“Insulin resistance occurred in animals with a diet high in the branched-chain amino acids, but only if they were ingested along with a high level of fat in the diet, Newgard said. Because obese humans tend to ingest high-fat diets, the combination of high-BCAA and high-fat intake might contribute to insulin resistance in obese humans, but additional studies are needed. BCAAs constitute as much as 25 percent of amino acids in dietary protein, and are particularly enriched in diets high in animal (meat) proteins.

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