Over 350 million individuals worldwide currently live with pre-Type 2 diabetes (prediabetes), defined as impaired glucose tolerance (IGT) or impaired fasting glucose (IFG). This number is projected to approach 548 million by 2045. Nearly half of them (48.1%) are under the age of 50, and one third (28.3%) are in the age group of 20-39 years, thus likely to spend many years at high risk of developing severe outcomes. In the face of the currently available treatment protocols, conversion rate of prediabetes to full Type 2 Diabetes (T2D) is substantial: 5-10% of prediabetics progress each year, with as many as 70% developing T2D during their lifetime3. The consequences are harmful, including blindness, kidney failure, cardiovascular disease, stroke, and limb amputations. More than 3 million people die annually from the disease and its complications. The global economic burden exceeds €1 trillion per year, ranking among the greatest health-related challenges worldwide.
Early treatment of the people at risk with available medications, combined with lifestyle modifications, can reduce progression risk and improve survival by 40-70%. These interventions are most effective when implemented before the onset of metabolic deterioration, manifested as impaired glucose metabolism (IGT, IGF). However, by the time prediabetes can be identified through currently available tests, both insulin resistance and β-cell damage are already present, resulting in severe insulin sensitivity and secretion problems, with limited treatment abilities. This inability to detect those at risk early enough is a direct driver of an enormous burden on individuals, communities, and governments (Figure 1).
Our long-term goal is to develop an effective, simple, blood-based test of the risk of young individuals with normal glucose levels to develop prediabetes during their life. Based on the results of a former ERC-funded research program, we developed a new class of epigenetic biomarkers that capture the earliest shifts in gene regulation, and therefore, may provide far greater predictive power than existing approaches. In this Proof-of-Concept research we have validated the prediction power of this novel biomarkers in identifying the people at risk. This new ability to identify the people at risk, and provide them with effective treatments in time, may dramatically improve the way we are dealing with these harmful diseases.
