Doctors 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 by measuring the levels of small molecules in the blood.In a report 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, an MGH cardiologist and associate professor of medicine at Harvard Medical School (HMS). “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 more insight into the metabolic status of patients. Because 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 that in smaller studies were found 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 senior author Robert Gerszten, associate professor of medicine at HMS and director of clinical and translational Research for the MGH Heart Center. “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.”
Would you like to read more?Register for free to finish this article.Sign up now for the following benefits:Four FREE articles of your choice per monthBreaking news, comment and analysis from industry experts as it happensChoose from our portfolio of email newsletters To access this article REGISTER NOWWould you like print copies, app and digital replica access too? SUBSCRIBE for as little as £5 per week.
“UK pension scheme assets benefited from positive equity and credit returns this month, though this was partly offset by an increase in liabilities as inflation expectations rose,” he said.“Though March was generally positive for markets as central bank action, positive economic data and rising oil prices bolstered investor sentiment, clouds remain on the horizon – most noticeably the prospect of market volatility in the event of a ‘Brexit’, which extended sterling’s weakening against the euro in March.”At the end of March, the PPF 7800 universe covered schemes with liabilities of £1.59trn, slightly down by £5.5bn compared with February.In other news, a working group founded by leading employer covenant advisers has published a list of principles to guide stakeholders during the valuation of defined benefit funds.The Employer Covenant Working Group (ECWG) said the publication of its principles was necessitated as The Pensions Regulator (TPR) “consistently raised the bar” on what was expected of trustees and employers, while individual advisers had developed their own approach to valuing covenant strength.“With this in mind,” a statement said, “the ECWG has been formed to address the need for greater consistency, recognised leading practice and improved standards in covenant advisory work.”Gary Squires, chair of the ECWG, noted that employers would not want to risk schemes becoming reliant on the PPF.“Given the scale of the challenge, it’s clear there is a need for a consistent approach to addressing funding deficits, and the members of the ECWG’s work assisting trustees, scheme sponsors and regulators in considering an employer’s ability to pay contributions into the future is vitally important to help secure the retirement of millions of people.”The principles detail a sponsor’s legal obligation, how to best value a scheme’s position and how to assess a sponsor’s ability to support a fund, among other areas.Finally, Willis Towers Watson has developed a new longevity model to improve the accuracy of assumptions by drawing on medical data, better predicting how many pension fund members will go on to develop diabetes, for example.PulseModel was designed as the consultancy was concerned mortality models failed to incorporate medical information, Matthew Edwards, head of mortality at Willis Towers Watson, said.James Brown, lecturer in ageing metabolism at the Aston Research centre for Healthy Ageing in Birmingham, said the emergence of type 2 diabetes was “one of the gravest health issues” for the coming century.“This model represents a potential step-change in our ability to accurately predict outcomes based upon the likely future trends in diabetes incidence,” he said.“More importantly, it provides quantifiable predictions of the potentially dramatic implications diabetes might have on mortality and life expectancy.” Funding among the UK’s defined benefit (DB) funds rose towards the end of the financial year, as the aggregate deficit reported by the Pension Protection Fund (PPF) fell to £302bn (€384bn).Overall funding levels stood at 81% at the end of last month, according to the PPF 7800 Index, while the deficit across the 5,945 schemes captured fell by £20bn compared with February.However, despite the improved ratio, funding remained down compared with March 2015, when it stood at 84.2%, accounting for a deficit of £244bn.Andy Tunningley, head of strategic clients at BlackRock in the UK, noted that March had been a “positive month” for the sector.