Diabetic Complications

Head – Merlin Thomas

The growing epidemic of diabetes already affects over 1.3 million Australians and twice that number again is at risk of developing diabetes in the next 5–10 years. Despite the clear and present danger of diabetes, the role of high sugars in causing blindness, kidney failure and heart disease is poorly understood. Merlin is working on breaking the links between sugar and the damage it causes.

Merlin's team's research has concentrated on Advanced Glycation End-products (AGEs), formed when sugars bind to protein, making it sticky, sweet and brown. In food like chocolate and caramel, this reaction is appetizing. But when sugar accumulates in diabetes, this same process contributes to blindness, kidney failure and heart disease. Merlin’s research has shown that this reaction leads to changes in the shape and function of AGE modified proteins. In the same way that lamb is more tender than mutton, AGE-modified proteins tend to be inelastic. This means that AGEs gradually build up in tissues, making them in turn more stiff; literally ‘hardening’ the arteries. Where the sugar concentration is high, AGEs accumulate much more quickly.This is one reason why strong sugar control is so important in diabetes. For Merlin and his team, the best way of reducing the impact of diabetes is to break the link between high sugar levels and the damage they cause because even with the best treatment, patients can suffer from kidney failure, amputations and blindness from their diabetes.

AGEs are one of those links. For the millions with diabetes who struggle to control their sugars every day, an understanding of this pathway will provide an important advance to their care.

Another key focus of the Biochemistry of Diabetic Complications lab is the renin angiotensin system (RAS), a pivotal element of vascular function in both health and disease. Many patients with diabetes are already taking drugs that block the RAS, in an attempt to prevent some of the complications of diabetes. However, these agents are only partly effective. Merlin and his team are working to define novel regulators of the RAS, using unique methods to disrupt the RAS, with the aim of making current interventions for diabetes even more effective.

This group is also coordinating the NEFRON study, the largest study of patients with type 2 diabetes across Australia. NEFRON is a collaborative effort of Baker IDI, Kidney Health Australia and Servier Australia, that aims to define the prevalence and severity of complications of diabetes in Australian general practice. Already this study has been able to show that every second individual with type 2 diabetes in Australian currently has chronic kidney disease, with clear potential to influence their health and wellbeing, as well as contribute to premature mortality.