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 type 2 diabetes 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 diabetes risk 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 insulin resistance, 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 amino acids 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.
These studies were performed in close collaboration with Clary Clish, PhD, director of Metabolite Profiling of the Broad Institute. Additional co-authors of the Nature Medicine report are Susan Cheng, MD, Elizabeth McCabe, MS, and Gregory Lewis, MD, MGH Cardiology; Eugene Rhee, MD, MGH Renal Unit; Vamsi Mootha, MD, and Jose Florez, MD, PhD, MGH Center for Human Genetic Research and the Broad Institute; Martin Larson, ScD, Ramachandran Vasan, MD, Christopher O'Donnell,MD, and Caroline Fox, MD, MPH, Framingham Heart Study; Paul Jacques, DSc, Tufts University; Celine Fernandez and Olle Melander, MD, PhD, Lund University, Malmo, Sweden; and Stephen Carr, PhD, and Amanda Souza, Broad Institute.
The study was supported by grants from the National Institutes of Health, the Leducq Foundation, the Donald W. Reynolds Foundation, and the American Heart Association. The Framingham Heart Study of the National, Heart, Lung and Blood Institute and Boston University is supported by a contract from the National Institutes of Health.
Celebrating the 200th anniversary of its founding in 1811, Massachusetts General Hospital is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of nearly $700 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, reproductive biology, regenerative medicine, reproductive biology, systems biology, transplantation biology and photomedicine.
Marty Ray | EurekAlert!
Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute
Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water
In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...
The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.
Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
02.12.2016 | Medical Engineering
02.12.2016 | Agricultural and Forestry Science
02.12.2016 | Physics and Astronomy