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UCLA researchers identify markers that may predict diabetes in still-healthy people

In the first large scale, multiethnic study of its kind, researchers at UCLA have confirmed the role played by three particular molecules known as cytokines as a cause of Type 2 diabetes, and further, have identified these molecules as early biological markers that may be used to more accurately predict future incidences of diabetes among apparently healthy individuals.

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Keywords: ucla, researchers, identify, markers, predict, diabetes, still-healthy, people, researcher, marker, diabete, still, healthy

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1. Advance in understanding of blood pressure gene could lead to new treatments
   02-04-2007 · EurekAlert!
   Research by scientists at UCL (University College London) has clearly demonstrated for the first time the structure and function of a gene crucial to the regulation of blood pressure. The discovery could be important in the search for new treatments for illnesses such as heart disease, the UK's biggest killer. In a paper published online today in Nature Medicine, the team, led by Professor Patrick Vallance and Dr James Leiper, UCL Department of Medicine, reveal the role of the human gene dimethylarginine dimethylaminohydrolase (DDAH), showing that loss of DDAH activity disrupts nitric oxide (NO) production. NO is critical in the regulation of blood pressure, nervous system functions and the immune system. The role of DDAH is to break down modified amino acids (Asymmetric dimethylarginine (ADMA) and monomethyl arginine (L-NMMA)) that are produced by the body and have been shown to inhibit NO synthase. These molecules accumulate in various disease states including diabetes, renal failure and pulmonary and systemic hypertension, and their concentration in plasma (the fluid component of blood) is strongly predicative of cardiovascular disease and death. In a healthy human body, the majority of ADMA is eliminated through active metabolism by DDAH. Scientists have hypothesised that if DDAH function is impaired, NO production is reduced, and that this could be an important feature of increased cardiovascular risk. To examine this pathway in more detail, the researchers deleted the DDAH gene in mice. These mice went on to develop hypertension, or high blood pressure. They also designed specific inhibitors (small molecules) which bind to the active site of human DDAH. These small molecule inhibitors also induced hypertension in mice, confirming the importance of DDAH in the regulation of blood pressure. Dr Leiper, UCL Medicine, said: “These genetic and chemical approaches to disrupt DDAH showed remarkably consistent results, and provide compelling evidence that loss of DDAH function increases the concentration of ADMA and thereby disrupts vascular NO signalling. “There has been considerable scientific interest in this pathway and the role of ADMA as a novel risk factor, but so far there's been little evidence to support the idea that it's a cause of disease, rather than just a marker. Genes and their pathways are crucial to our understanding of cardiovascular disease and a better understanding of DDAH-1 could lead to important new treatments. “It could help us to establish if genetic variation predisposes certain people to these diseases, or whether environmental factors exert some of their effects through modulation of DDAH activity. “Our research also shows that this pathway could be harnessed therapeutically to limit production of NO in certain situations where too much nitric oxide is a bad thing; for example, hypotension and septic shock. These are some of the biggest problems in intensive care medicine and there is a huge unmet need for drug treatments.” The study, which was carried out at UCL's Rayne Institute, was funded by grants from the British Heart Foundation, the Wellcome Trust and the Medical Research Council. Professor Jeremy Pearson, Associate Medical Director of the British Heart Foundation, said: "The unexpected finding in the 1980s that a simple gas, nitric oxide (NO), is made by cells in the blood vessel wall and is a powerful control of blood vessel relaxation led to the award of the Nobel Prize in 1998 to its discoverers. "More recently, there has been increasing evidence that impairment of NO production is likely to be an important factor in the development of heart and circulatory disease, but the mechanisms responsible are not fully understood. "This study suggests for the first time that the loss of the activity of the enzyme DDAH-1 leads to reduced NO production and may cause heart and circulatory disease. These findings are likely to be important in the search for new ways to optimise the health of our blood vessels." ### Notes for Editors 1. For more information, please contact Ruth Metcalfe in the UCL Media Relations Office on tel: +44 (0)20 7679 9739, mobile: +44 (0)7990 675 947, out of hours: +44 (0)7917 271 364, e-mail: r.metcalfe@ucl.ac.uk2. 'Disruption of methylarginine metabolism impairs vascular homeostasis' is published in the February issue of the journal Nature Medicine. Advance online publication is embargoed to 18.00 GMT (13.00 US Eastern) Sunday 4 February 2007. Journalists can obtain copies of the paper by contacting the UCL Media Relations Office.3. The study was funded by the British Heart Foundation, the Wellcome Trust and the Medical Research Council. About UCL Founded in 1826, UCL was the first English university established after Oxford and Cambridge, the first to admit students regardless of race, class, religion or gender, and the first to provide systematic teaching of law, architecture and medicine. In the government's most recent Research Assessment Exercise, 59 UCL departments achieved top ratings of 5* and 5, indicating research quality of international excellence. UCL is the fourth-ranked UK university in the 2006 league table of the top 500 world universities produced by the Shanghai Jiao Tong University. UCL alumni include Mahatma Gandhi (Laws 1889, Indian political and spiritual leader); Jonathan Dimbleby (Philosophy 1969, writer and television presenter); Junichiro Koizumi (Economics 1969, Prime Minister of Japan); Lord Woolf (Laws 1954, Lord Chief Justice of England & Wales); Alexander Graham Bell (Phonetics 1860s, inventor of the telephone), and members of the band Coldplay.
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2. New genetic biomarkers could predict coronary heart disease
   03-31-2007 · EurekAlert!
   New genetic markers may be able to predict whether a person is likely to have coronary heart disease (CAD) in the future. Research shows that people who are pre-diabetic or who have Type 2 diabetes have much shorter telomeres (ends of the chromosome) and, since these people are prone to CAD, an early test could indicate their susceptibility and help them to alter their lifestyle to avoid or delay the onset of the disease.
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3. Research team identifies new Alzheimer's gene
   06-06-2007 · EurekAlert!
   A study comparing more genetic markers in the DNA of people with and without Alzheimer's disease than ever before enabled researchers to identify a common gene that appears to increase one's risk for developing Alzheimer's disease. The finding by researchers at the Translational Genomics Research Institute, Banner Alzheimer's Institute, Kronos Science Laboratory and their collaborative partners, suggests that the gene -- called GAB2 -- modifies an individual's risk when associated with other genes, including APOE4.
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4. Individual differences in a clock gene predict decline of performance during sleep deprivation
   03-08-2007 · EurekAlert!
   People are known to differ markedly in their response to sleep deprivation, but the biological underpinnings of these differences have remained difficult to identify. Researchers have now found that a genetic difference in a so-called clock gene, PERIOD3, makes some people particularly sensitive to the effects of sleep deprivation.
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5. Mayo Clinic study predicts cardiovascular disease risk for rheumatoid arthritis patients
   11-07-2007 · EurekAlert!
   People with rheumatoid arthritis have a higher risk for developing heart disease than the general population; however, it is difficult to identify which patients are at increased risk. Researchers at Mayo Clinic have developed a simple approach to predict heart disease in these patients within 10 years of their initial diagnosis of rheumatoid arthritis.
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6. Blood markers predict risk for recurrent stroke and mortality
   10-24-2006 · EurekAlert!
   People who have just suffered their first ischemic stroke, a blood clot in the brain, often have elevated inflammatory biomarkers in their blood that indicate their likelihood of having another stroke or an increased risk of dying, according to Columbia University Medical Center researchers at New York-Presbyterian Hospital.
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7. Early indicator of kidney disease may also predict risk of pre-diabetes
   07-02-2007 · EurekAlert!
   A blood component called cystatin C, used to test for early-stage kidney impairment, also may be a very early marker for those at risk of developing a condition known as pre-diabetes, a study conducted by researchers at the University at Buffalo has shown.
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8. Researchers identify gene associated with severe kidney failure in diabetes
   01-09-2007 · EurekAlert!
   A research team at Wake Forest University Baptist Medical Center and the University of Heidelberg has proven that a gene protects some people with diabetes from developing severe kidney failure or "end-stage renal disease."
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9. UCLA/Toronto researchers unlock key to memory storage in brain
   04-19-2007 · EurekAlert!
   Scientists know little about how the brain chooses cells to encode and store memories. Now a UCLA-University of Toronto team has discovered that a protein called CREB controls the odds of a neuron participating in memory formation. The April 20 edition of Science reports the findings, which suggest a new approach for preserving memory in people suffering from Alzheimer's or other brain injury. Memories could be guided into healthy cells and away from sick cells in dying regions of the brain.
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10. Researchers identify key indicators for activity-friendly communities
    10-31-2006 · EurekAlert!
    There is no doubt that people can benefit from regular physical activity. Advocates, community leaders and researchers lack the tools needed to assess local barriers to and opportunities for more active, healthy lifestyles. In a study published in the December 2006 issue of the American Journal of Preventive Medicine, researchers used a systematic review process to identify key indicators of activity-friendly communities that can be used to assess and improve opportunities for regular physical activity.
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