Diabetes feature

By Tanya Hollis
Monday, 15 July, 2002


Attend any major meeting on diabetes around the world and chances are there will be a fair contingent of Aussies in attendance. Australian researchers are renowned for their work in all facets of the disease, which experts say has now burgeoned to epidemic proportions.

"Internationally, there is an enormous amount of work going on and Australia is fairly prominent in that," said National Diabetes Strategy Group (NDSG) chairman and Garvan Institute head of diabetes research Prof Don Chisholm.

From education and awareness programs aimed at reducing the incidence of diabetes risk factors, to stem cell work and genomics looking at new treatments, the approaches to the disease are as vast as Australia itself. Literally hundreds of programs are underway across most of Australia's teaching hospitals and research institutes, and within companies including Autogen, Metabolic and Cardia Technologies.

Even the new $43 million Biotechnology Centre of Excellence Centre for Stem Cells and Tissue Repair has a diabetes project, led by Prof Bernie Tuch. "Diabetes is a growth industry, unfortunately, and the pharmaceutical industry is becoming more interested in it," Chisholm explained.

Juvenile (type 1) diabetes, in which the sufferer's body is insulin deficient, affects about 100,000 Australians, mostly children. Adult onset (type 2) diabetes, characterised by insulin insufficiency or resistance, by contrast affects about 800,000 Australians - about half of whom do not know they have it. There are also less common forms of the disease including gestational diabetes, which occurs in 4 to 6 per cent of pregnancies.

Research efforts are currently focused on prevention, whether that is through medication and/or lifestyle changes, as well as better treatments and possible cures for both major forms of the disease. While it is difficult to accurately pinpoint the amount of money going into the disease, it is roughly estimated at almost $20 million a year -- about a third of which comes from the Federal government.

According to St Vincent's Institute of Medical Research director Prof Tom Kay, about $6 million comes from government, $1 million comes from Diabetes Australia and $12 million comes from the US-based Juvenile Diabetes Research Fund.

Money also comes from the National Health and Medical Research Council, (NHMRC) which in 2000 spent about 3.6 per cent of its research budget on diabetes, although Kay points out that it is sometimes difficult to determine at what point funding for diabetes becomes funding for obesity, cardiovascular disease or other related illnesses.

"I don't think diabetes research is over-funded, but it's not desperately under-funded either," Kay said. "But I think the important thing for us as diabetes researchers to remember is if we don't keep up the advocacy campaign there's a risk of falling behind, but I don't think we're way behind where we should be."

Keeping political interest in diabetes on the boil is a major concern for everyone working in the sector, particularly since the federal health portfolio was passed from Dr Michael Wooldridge - a vocal supporter of the cause - to current Health Minister Kay Patterson. A member of the NDSG and the Assoc Prof of Concord Hospital's department of endocrinology, John Carter, said that in 1993 the Australian Diabetes Association began lobbying the government for a national action plan on diabetes to be formulated.

"It lobbied the government for support and for it to understand there was an epidemic and that something needed to be done now to reduce the burden of diabetes personally and financially in the next couple of decades," Carter said. "Fortunately the message was received by Minister Wooldridge."

In 1996, under Wooldridge's leadership, state and territory health ministers agreed to make diabetes a national priority area "in recognition of the impact that diabetes has on the Australian community, and the potential for improved health outcomes". Wooldridge earmarked $7.7 million over three years to be directed towards diabetes strategies and set up the Commonwealth Ministerial Advisory Committee on Diabetes (MACOD), chaired by Carter, which subsequently morphed into the National Diabetes Taskforce and now the NDSG.

And while politics appears to be playing a major role in the direction of national strategies dealing with the identification, management and reduction of high-risk individuals, the clinical research side of the disease continues to make quiet inroads. Obviously, it is not possible to list every participant in diabetes research. But highlighting a few helps create a picture of Australia's activity in the field.

In Melbourne, St Vincent's Institute of Medical Research has chosen to make diabetes the key focus of the centre, recruiting leading researchers, including Tom Kay, in areas including immunotherapy, kidney complications, islet transplantation, lipids and cardiovascular disease.

Kay's previous home, the Walter and Eliza Hall Institute, also has a prominent spot on the nation's diabetes research map, with a team led by Prof Len Harrison examining immunotherapy techniques in the prevention and treatment of type 1. The search for a diabetes vaccine will also be the focus of the world's first Diabetes Vaccine Development Centre, a joint effort between the NHMRC and the JDRF that will pour $13.5 million into type 1 over five years.

Scientists say stem cells offer another exciting avenue for type 1 research, with groups such as that led by Prof Bernie Tuch at the University of NSW looking at the possibility of engineering the cells to produce insulin. Chisholm said that while the concept sounded simple enough, it would in reality prove extremely difficult to engineer cells not just to produce insulin, but to do so at rapidly changing levels in response to blood sugar levels.

"My feeling is that probably within the foreseeable future, 20 years or so, it is likely that prevention of type 1 will be achieved," Chisholm said. "In terms of curing it, although there is a lot of exciting stuff is going on, I think it will be a lot more difficult."

In the case of the more common type 2 disease, opinion is mixed on the possibilities of medical prevention and cure. Animal studies are finding that existing drugs, such as metaformin, when used before the onset of full-blown diabetes could delay the disease, raising hopes that the effect could be greater if combined with lifestyle changes. In a similar way, a newer family of drugs, known as glitazones, is also showing promise as a preventive medication rather than simply a treatment for active diabetes.

Chisholm believes these avenues offer hope of a lessening, as opposed to an eradication, of type 2 within the coming decade. "I don't think we will find a way of preventing it altogether for a long time because I don't think it's a single condition," he explained. "It will probably turn out to be 10 different conditions, all of which have different mechanisms."

In the field of improved type 2 drug compounds, Cardia Technologies and Metabolic Pharmaceutical are major local players. In May, Cardia announced it would spend up to $1.3 million to develop a compound identified 30 years ago in human urine by current Monash University Professor of Diabetes and director of the International Diabetes Institute, Paul Zimmet.

The compound, known only as ISF402, has been found to reduce insulin resistance and increase blood sugar levels. Cardia's money is already enabling the scientist to synthesise large amounts of the material in preparation for testing. Metabolic is following a path based on the work of another Monash scientist, Assoc Prof Frank Ng, who identified a class of compounds called Advanced Diabetes Drug (ADD) that is hoped to alleviate diabetic conditions by providing insulin sensitisation.

In its May investor update, the company reported that its two lead compounds, codenamed ADD9918 and ADD9922, were currently proceeding through animal efficacy tests. Eiffel Technologies, on the other hand, is using its Supercritical Fluid platform technology to reformulate existing insulins, already achieving some success at a research level by micronising drug molecules so they could be inhaled rather than injected.

Yet another area of research creating some debate is in the identification of genes related to diabetes. While a number of academic institutes are engaged in such work, the only commercial group within Australia is believed to be Melbourne-based Autogen. In its most recent announcement, the company revealed it had identified a genetic link between diabetes and heart disease, offering a potential new target for drug therapies.

The company, which through its access to the genes of communities in the Pacific, Tasmania and Mauritius, uses functional genomics to identify potential drug target in a range of diseases, has previously discovered that a receptor called Tanis was abnormally regulated in animal models of type 2. CEO Greg Collier said Tanis had now been linked to heart disease via an inflammatory response protein called serum amyloid A (SAA), helping scientists better understand why diabetics have a high risk of heart disease.

Assoc Prof Stephen Colagiuri of the Australian Centre for Diabetes Strategies said that, without wanting to play down the work of groups like Autogen, he did not believe Australian research was any closer to curing type 2. "We don't know enough about the genetics and the mechanisms by which it occurs," Colagiuri said.

"There's research into understanding of type 2 that may translate into better care of people with diabetes, but I don't think Australia is doing a lot in trying to solve the problem of why it develops and therefore trying to cure it." He said genomics work was also hindered by focusing on small, isolated populations, such as Pacific Islanders.

"You need big populations to have a look at the genetics and I think there's a long way to go," he said. "(A result) is more likely to come from bigger populations of the US or pooled European data, but it is a needle in a haystack situation." It was a sentiment vehemently opposed by Zimmet, who also sits on Autogen's scientific advisory board. Zimmet said that the company's work drew from a range of ethnicities within its research populations, boosting its potential for real-world applications.

But Chisholm also doubted genomics would lead to a cure, saying tailored treatments based on the genetic differences between individuals with the disease were more likely. "There are genes being identified that may contribute to the development of diabetes that may lead to a cure, but to be honest I do see as a very likely event that they will lead to better therapies," he said. "One could argue that if you have the blood sugar levels under control that is a cure, but I think that if you are on life-long therapy it is simply a better treatment."

Diabetes facts and figures

Type 1 What is it? The disease is characterised by a complete deficiency of insulin, the hormone that metabolises glucose, requiring sufferers to use insulin therapy to control their blood glucose levels.

How many people have it? About 100,000 Australians are diagnosed with type 1 diabetes.

What's being done about it? Research groups are trying to prevent the onset of the illness through immunotherapy techniques to stop the patient's body destroying insulin-producing cells. Others are looking at disease trigger factors in the hope of vaccinating against diabetes. Stem cell scientists are also examining the possibility of engineering insulin producing cells from the patient's own tissue.

Type 2 What is it? Most commonly afflicting people aged over 40, the late-onset condition is characterised by insulin insufficiency or resistance to its action. While it is thought to be largely genetic, risk factors contributing to its development include overweight, inactivity, high blood pressure and poor diet.

How many people have it? It is estimated that about 800,000 Australians have type 2 diabetes, but that only half are aware of it.

What's being done about it? A lot of work in the area of lifestyle education is aiming to reduce the incidence of risk factors for the disease. A new group of drugs called glitazones is in clinical use for treatment of existing cases, and are also being studied for their potential in preventing the disease in high-risk populations. Researchers are also identifying genes involved in the disease, with the aim of developing improved or tailored treatments and potential cures.

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