Two “biomarkers” that could help determine whether an Emirati is more or less susceptible to obesity and diabetes have been identified in early evidence from a pilot study of the local population.
Researchers are trying to use biological characteristics of molecules or genes, known as biomarkers, to predict the genetic likelihood of UAE nationals ending up with the conditions and have examined the relationship between AGE and RAGE biomarkers, something that has not been done before in the Arab population in a cohort study. RAGE is an acronym of receptor for advanced glycation end-products, while AGE stands for advanced glycation end products.
The AGE-RAGE Axis in an Arab Population study is part of the wider UAE Healthy Future Study and it involved 517 Emiratis who had no evidence of any serious disease. Of the participants, 33 were found to have diabetes, and researchers found a link between the levels of the two biomarkers and the two conditions.
Dr Ann Marie Schmidt, professor of medicine at New York University School of Medicine, and a senior author of the study, said: "We found even in just the 517-subject pilot study that there was an association that was statistically significant between the levels of two kinds of biomarkers and the obesity markers and diabetes marker in the Emirati subjects. These people have to be looked at again, serially over time, to determine if that initial association is maintained.
"As the study progresses we want to see if there is variation in the biomarker composition in the UAE cohort. At this point it's amazing that even with only 517 people, we are already seeing statistically significant differences. The AGE-RAGE levels are associated with diabetes and obesity markers.”
The researchers want to repeat these tests every 5 years to tests levels of AGE and RAGE and check people's obesity status and if they develop diabetes. After doing multiple measurements they will analyse if there was anything in those blood tests that predicted a high chance of developing obesity and diabetes.
Biomarkers can be useful as a reliable one could take about five years to introduce, while drugs typically take 10 to 20 years to develop.
The research involved taking blood samples from a cohort and measuring the biomarkers. The academics involved will be following the participants over time and will be checking if the pattern of the AGE-RAGE molecules can predict who was going to develop diabetes.
Dr Ravichandran Ramasamy, associate professor of medicine at NYU School of Medicine and a senior author of the study, explained how the biomarkers work.
"If we go crazy consuming sugar, the sugar can modify the proteins and the modification over a period of time becomes irreversible. This modification happens in diabetic people,” he said.
Dr Schmidt discovered a receptor that binds to this sugar-modified end product in 1992.
"The consequence is that this receptor derails cells into processes and reactions, which lead to inflammation. We believe that the initial high levels of glucose triggering this kind of unchallenged process is triggering the complications,” Dr Ramasamy added.
The academics believe this may be a key driver of diabetic complications, cardiovascular complications and eye and kidney complications that accompany long-term diabetes.
"As the study progresses we want to see if there is variation in AGE composition in the UAE cohort. We are heading towards developing the means to track these measurements but we are not there yet,” said Dr Ramasamy.
Whether the biomarkers can identify potential obesity and diabetes or not, it is important to maintain a healthy diet and lifestyle, the researchers said.
"If our work eventually discovers that the AGE-RAGE markers can predict people's vulnerable to obesity and diabetes, and even if it does not, it is always good practice to maintain healthy diet and lifestyle, including exercise,” said Dr Schmidt. “If this work showed that the AGE-RAGE biomarkers predicted obesity and diabetes then very early intervention could be instituted to maintain maximum healthy diet and calorie counting as well as physical activity to work towards prevention.”
Dr Job Simon, consultant endocrinologist at Burjeel Hospital in Abu Dhabi, believes it is even more important to maintain a healthy lifestyle if someone is predicted to be at risk of developing diabetes.
“None of the biomarkers predict diabetes with 100 per cent accuracy, and one can mitigate the risk with healthy choices,” he said.
Dr Simon said that in the Diabetes Prevention Programme, a major multicentre clinical research study in the US, patients with pre-diabetes who undertook lifestyle changes, including 30 minutes of daily exercise and eating a healthy diet, had a 58 per cent reduction in the risk of developing diabetes. Similar findings were reported from trials in India and China and the benefits were still present in those with high genetic risk, he said.
The plan is to enroll 20,000 Emirati volunteers in the UAE Healthy Future Study with a view to understand the reasons behind the rising numbers of obesity, diabetes and heart disease cases.
The International Diabetes Federation estimates that there are more than one million diabetics in the UAE and obesity is believed to increase the risk of the condition by 40 times.