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Combating a Silent Killer

Type 2 diabetes has long been a concern amongst medical professionals, but recent evidence suggests that the disease is reaching epidemic proportions worldwide. However, Professor Clifford Bailey and colleagues at Aston University are taking a unique approach by tackling the disease on multiple fronts.

Cliff Bailey

Diabetes is a condition that arises when the body doesn't produce enough insulin and therefore struggles to regulate blood sugar levels. As opposed to Type 1 diabetes, which generally appears in childhood, adolescence and very early adulthood, Type 2 was traditionally a condition associated with the over 40s, although is now appearing in younger people. In the UK alone, over 90 per cent of all cases of diabetes are Type 2, which is treated initially by dietary means, then by a range of orally-taken drugs, and eventually by insulin or insulin plus. Obesity is a major risk-factor, but certain sub-groups, like members of the Asian community, are also especially prone to it. An alarming figure is that 25 per cent of Asian men over the age of 60 have Type 2 diabetes.

“If that doesn’t scare you enough,” remarks Clifford Bailey, Professor of Clinical Science at Aston University, “the number of people in the world at the moment with Type 2 diabetes overall is somewhere in the region of 385 million and the likelihood is that by the year 2035 it will be well over 500 million. Most of the estimates that have been produced in the past have turned out to be underestimates, however extravagant they may have looked at the time. We are now seeing even teenagers and people in their 20s developing this condition, so we suspect that it’s going to be a rather grim future for diabetes.”

One of the reasons that medical professionals are so concerned about the disease is because it can lead to a range of complications. An individual may go for a long time without diabetes having been diagnosed, and for the most part, it may not seem to be causing them any trouble. However, warns, Professor Bailey, it will be surreptitiously stacking up damage to the body. When that damage comes to light - perhaps ten or 20 years in the future - it can affect everything from kidney and neural function to eyesight, and - especially with Type 2 diabetes - can lead to heart attacks and strokes.

“For example, when you look at the kidney dialysis register, the largest single group of people on that register will be people with long-term diabetes. You look at the main cause of people going onto the blind register of working age - diabetes. This disease is now believed to cost in the region of ten per cent of the direct healthcare NHS budget, so it causes a disproportionately greater cost than the healthcare costs in general.”

Metformin

Tackling Diabetes

So how can it be tackled? With such a complicated condition, approaches need to be made on several different fronts ranging from health education to the development of new agents to improve insulin action and reduce obesity. As Professor Bailey explains, one of the biggest hurdles is actually one of perception.

“You have to ask people to change their lifestyle for a condition that doesn’t hurt them and at the current time doesn’t appear to be encumbering them a great deal. So in order to do this you require the buy-in of the patient and that requires considerable inputs of time, and it also requires a certain amount of monitoring in the hope that they are following your advice.

“The next major challenge is identifying who to screen. You can’t screen everyone because there aren’t the resources, so you have to find ways of narrowing down that population. The next thing that we have to face is, as the disease is progressive, you need to get in early and try to treat it effectively. But as it gets worse, it gets more difficult to control because these various comorbidities occur - renal functions becomes impaired; neural functions become impaired; heart disease and vascular disease become more prevalent - and each of these is an additive problem to the treatment. It’s not uncommon for someone with Type 2 diabetes to be taking five medications and we have plenty of examples of people who are taking as many as 20 tablets a day.”

Aston University has been at the forefront of diabetes research for many years, but its methodology is relatively unique, in that it has combined basic scientific research with applied and clinical approaches. The result has been a handful of major treatments which have emerged over the last few decades. One important contribution has been the drug Metformin, which was developed in the 1950s but which fell into disrepute and was eventually sidelined. However, academics at the Aston diabetes research group reappraised the drug and were instrumental in bringing it out of the shadows to become accepted worldwide (it is now a primary agent for the treatment of Type 2 diabetes).

More recently, Aston has been involved in SGLT2 inhibitors: a new class of diabetes medications. SGLT2 is a protein in humans that facilitates glucose reabsorption in the kidney. SGLT2 inhibitors work by effectively blocking this reabsorption process, which causes excess glucose to be eliminated through the urine instead. Aston has mainly been involved in clinical trials for an agent called Dapagliflozin, which has also become widely accepted as an effective treatment.

Given the complexity of the condition, it is clear that there will be no ‘magic bullet’ for diabetes even in the distant future, but Professor Bailey is convinced that a holistic approach is the way forward.

“We need to identify the people who are developing diabetes as early as possible to implement the treatment early, and - as the complications develop - to modify the therapy to try to reduce the impact of the complications as well as control the disease,” he says. “We often need to use combinations of agents - sometimes tablets and injections - and we are busy at Aston trying to look at how we can leverage the value of treatment by looking at all the components that are actually responsible for the pathogenesis of this disease.”

This article first appeared in the Sep 2015 edition of Aston in Touch >>

  • Metformin:Research carried out at Aston between the end of the 1970s and the 1990s identified how this drug worked and why it deserved wider usage. Having been studied in some detail in the USA, and subsequently adopted throughout North America, it has now become the main preferred first-line treatment for Type 2 diabetes worldwide.
  • GLP1: Work undertaken at Aston on what was known as the entero-insular axis played an important part in the identification of a group of hormones called incretins, one of which, GLP1, now forms the template for several therapies used principally in Type 2 diabetes.
  • Sibutramine: Aston had a very considerable role in the development of an anti-obesity agent called Sibutramine. It is not continually prescribed now because it was intended for short-term use and has some known side-effects. A problem with Sibutramine, as with other anti-obesity agents, is that patients are often tempted to take the medication beyond the prescribed period, even when they know it might be harmful to do so.
  • Dapagliflozin: Recently Aston has been involved in developing the drug Dapagliflozin which works by inhibiting the subtype 2 of the sodium-glucose transport proteins (SGLT2). Dapagliflozin has now been approved in the UK, Europe, America, Australia and a large number of other countries around the world, particularly in Asia.

Find out more about Professor Clifford Bailey

Find out more about Professor Clifford Bailey
You can’t screen everyone because there aren’t the resources, so you have to find ways of narrowing down that population.