March 23/Boston/The Diabetes Report -- A team led by Massachusetts General Hospital (MGH) researchers has found that levels of five amino acids not only indicated increased type II diabetes risk in a general population, but could also differentiate, among individuals with traditional risk factors such as obesity, those most likely to actually develop diabetes.

The team believes that measuring the levels of these amino acids may be able to identify individuals at elevated risk of developing type II diabetes as much as a decade before symptoms of the disorder appear.

Some earlier studies had found elevated levels of certain amino acids in individuals with obesity or insulin resistance, but no previous investigation had examined whether levels of these or other metabolites predicted the future development of diabetes in currently healthy individuals.

The present trial, details of which were reported in the March 20 online issue of Nature Medicine (10.1038/nm.2307), began with an analysis of data from the Framingham Offspring Study. Out of 2,400 study participants who entered the study in 1991 and 1995, approximately 200 developed Type II diabetes during the following 12 years. Using the baseline blood samples, the MGH team measured levels of 61 metabolites in 189 participants who later developed diabetes and 189 others (matched for age, sex and diabetes risk factors) who remained diabetes free.

This analysis found that elevations in isoleucine, leucine, valine, tyrosine and phenylalanine were significantly associated with the later development of type II diabetes. Several of these amino acids were the same ones found in smaller studies to be elevated in individuals with obesity or insulin resistance, and other evidence has suggested that they may directly affect glucose regulation. The association of levels of these five amino acids with future diabetes development was replicated in 326 participants in the Malmo Diet and Cancer Study.

The investigators then found that measuring combinations of several metabolites, as opposed to a single amino acid, improved risk prediction. Overall, in individuals closely matched for traditional risk factors for type II diabetes, those with the highest levels of the three most predictive amino acids had a four- to five-times greater risk of developing diabetes than did those with the lowest levels.

Additional basic investigations should reveal whether these metabolites play a role in the process leading to diabetes and if there are ways that such damage can be stopped.

From the April 4, 2011, Prepared Foods E-dition