Abstract
Over the years, new research has elucidated the importance of the very fast formation of AGEs by the highly reactive methylglyoxal (MGO). It has become clear that MGO triggers maladaptive responses in vascular tissue. To counteract the deleterious effects of MGO, organisms have an enzymatic glyoxalase defence system in which MGO is converted to d-lactate, with glyoxalase 1 (GLO1) as the key enzyme in this system. Significant progress has been made towards the understanding of the MGO–GLO1 pathway in the pathogenesis of vascular disease in diabetes. This commentary highlights some lines of current research and future perspectives. The work conducted so far is only the starting point—in the coming 50 years, the MGO–GLO1 pathway will be the subject of intensified research, with special focus on pathophysiological pathways, the use of this system for early screening and risk prediction, and the development of intervention strategies for preventing vascular complications in people with and without diabetes. This is one of a series of commentaries under the banner ‘50 years forward’, giving personal opinions on future perspectives in diabetes, to celebrate the 50th anniversary of Diabetologia (1965–2015).
Highlights
Over the years, new research has elucidated the importance of the very fast formation of AGEs by the highly reactive methylglyoxal (MGO)
The latest estimates from 2013 show that 382 million people worldwide are suffering from diabetes and this is expected to rise to 592 million by 2035 [1]
The increased formation of AGEs has been proposed as one mechanism that could explain the much faster development of vascular complications in diabetic than in non-diabetic individuals
Summary
With increasing incidence of diabetes, the early detection of vascular disease continues to be a great challenge for clinicians in the 21st century. Despite the development of integrated risk scores for vascular disease, it is still very difficult to precisely estimate which individuals will develop vascular disease and which individuals will remain event-free. Even the extent to which high glucose levels in diabetic patients, as estimated by measuring HbA1c levels, contributes directly
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