Metabolite levels may be able to improve diabetes risk prediction

Mar 20, 2011

Measuring the levels of small molecules in the blood may be able to identify individuals at elevated risk of developing type 2 diabetes as much as a decade before symptoms of the disorder appear. In a report receiving advance online release in Nature Medicine, a team led by Massachusetts General Hospital (MGH) researchers describes finding that levels of five amino acids not only indicated increased diabetes risk in a general population but also could differentiate, among individuals with traditional risk factors such as obesity, those most likely to actually develop diabetes.

"These findings could provide insight into metabolic pathways that are altered very early in the process leading to diabetes," says lead author Thomas Wang, MD, of the MGH Cardiovascular Research Center (CVRC) and Division of Cardiology. "They also raise the possibility that, in selected individuals, these measurements could identify those at highest risk of developing diabetes so that early preventive measures could be instituted."

New technologies to measure levels of metabolites -- small molecules produced by metabolic activities and released into the bloodstream -- are giving investigators increased insight into an individual's metabolic status. Since the diagnosis of marks the culmination of a years-long breakdown of the body's system for metabolizing glucose, the ability to detect that breakdown at a stage when lifestyle changes could halt the process may significantly reduce the incidence of the disease. Known risk factors such as obesity and elevated glucose levels often signify that diabetes actually is present, so earlier identification of at-risk individuals is critical to more effective preventive measures, the authors note.

Some earlier studies had found elevated levels of certain amino acids in individuals who are obese or have insulin resistance, a condition that precedes full-blown type 2 diabetes. But no previous study examined whether levels of these or other metabolites predicted the future development of diabetes in currently healthy individuals. The current study began with an analysis of data from the Framingham Offspring Study, which follows a group of adult children of participants in the original Framingham Heart Study. Out of 2,400 study participants who entered the study in 1991 and 1995, about 200 developed type 2 diabetes during the following 12 years. Using the baseline blood samples, the research team measured levels of 61 metabolites in 189 participants who later developed diabetes and 189 others -- matched for age, sex and factors such as obesity and fasting glucose levels -- who remained diabetes free.

This analysis found that elevations in five amino acids -- isoleucine, leucine, valine, tyrosine and phenylalanine -- were significantly associated with the later development of type 2 diabetes. Several of these amino acids were the same ones found in smaller studies to be elevated in individuals with obesity or , and other evidence has suggested 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 2 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.

"Several groups have suggested that these can aberrantly activate an important metabolic pathway involved in cellular growth or can somehow poison the mitochondria that provide cellular energy," says Robert Gerszten, MD, director of Clinical and Translational Research for the MGH Heart Center, the paper's senior author. "From a clinical perspective, we need to see if these markers, which we found using data from only about 1,000 individuals, do identify truly high-risk individuals who should be triaged to early preventive treatment and intensive lifestyle interventions. Additional basic investigations can reveal if these metabolites play a role in the process leading to diabetes and if there are ways we can stop the damage." Gerszten and Wang are both associate professors of Medicine at Harvard Medical School.

Explore further: Vietnam battles fatal measles outbreak

Related Stories

Fatty liver may herald impending type 2 diabetes

Feb 24, 2011

A recent study accepted for publication in The Endocrine Society's Journal of Clinical Endocrinology & Metabolism (JCEM) found that individuals with fatty liver were five times more likely to develop type 2 diabetes than t ...

Recommended for you

US orders farms to report pig virus infections

15 hours ago

The U.S. government is starting a new program to help monitor and possibly control the spread of a virus that has killed millions of pigs since showing up in the country last year.

Foreigner dies of MERS in Saudi

16 hours ago

A foreigner has died after she contracted MERS in the Saudi capital, the health ministry said on announced Friday, bringing the nationwide death toll to 73.

Vietnam battles fatal measles outbreak

19 hours ago

Vietnam is scrambling to contain a deadly outbreak of measles that has killed more than 100 people, mostly young children, and infected thousands more this year, the government said Friday.

New clues on tissue scarring in scleroderma

20 hours ago

A discovery by Northwestern Medicine scientists could lead to potential new treatments for breaking the cycle of tissue scarring in people with scleroderma.

User comments : 0

More news stories

Treating depression in Parkinson's patients

A group of scientists from the University of Kentucky College of Medicine and the Sanders-Brown Center on Aging has found interesting new information in a study on depression and neuropsychological function in Parkinson's ...

Health care site flagged in Heartbleed review

People with accounts on the enrollment website for President Barack Obama's signature health care law are being told to change their passwords following an administration-wide review of the government's vulnerability to the ...

Airbnb rental site raises $450 mn

Online lodging listings website Airbnb inked a $450 million funding deal with investors led by TPG, a source close to the matter said Friday.