New Genetic Markers Discovered for Diabetes Traits

The work of an international team of scientists has helped unravel the biological blueprint of type 2 diabetes (T2D). Funded in part by the EU, the two major parallel studies were conducted by researchers representing more than 100 institutes and using genetic data from over 100,000 individuals. The discovery of common genetic variants associated with T2D risk and blood glucose levels is published in two corresponding reports in Nature Genetics.

Between 170 million and 285 million people worldwide are afflicted with diabetes. A staggering 95% of sufferers have T2D, which is characterised by a chronic state of elevated blood sugar levels. T2D usually affects people over the age of 30, but is becoming increasingly prevalent in children. If the disease is not addressed properly, the World Health Organization (WHO) warns that deaths caused by diabetes could double in the next decade.

The two current studies were conducted by the Meta-analyses of glucose and insulin-related traits consortium (MAGIC) and represent an impressive feat of collaboration on a European and international scale.

Professor Nick Wareham from the University of Cambridge's Institute of Metabolic Science in the UK explained that traits associated with diseases like T2D are so common that it is extremely difficult for scientists to discover the genetic regions underlying the physical features and make a foolproof connection. "In the face of common diseases, we need to work together in large teams to share and analyse the vast suites of data available," he said.

For the first study, the team performed a meta-analysis of fasting glucose levels in thousands of participants of European descent. They identified nine genetic variants that influence fasting glucose levels (many of which are linked to an increased risk of T2D), and one influencing fasting insulin and HOMA-IR (homeostasis model of insulin resistance).

In the parallel study, the team analysed the participants' blood sugar levels two hours after an oral glucose challenge (a common test for T2D where the blood is tested after a sweet liquid containing glucose is consumed) and identified three new genetic variants that are associated with raised levels of glucose.

Dr Inês Barroso from the Wellcome Trust Sanger Institute in the UK said she and the team were delighted with the results but surprised that only one strong association with insulin levels was found. "We don't think this is a technical difference, but that genetics is telling us that the two measures, insulin and glucose, have different architectures with fewer genes, rarer variants or greater environmental influence affecting insulin resistance," Dr Barroso added.

The consortium's findings provide knowledge on new loci associated with glucose levels and diabetes risk, and, importantly, provide insight into biological pathways that could ultimately result in diabetes. "Our knowledge of T2D is slowly being added to with these genetic studies," noted Professor Mark McCarthy of Oxford University in the UK, "as we are beginning to unravel the complex pathways that lead to the common endpoint of disease."

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