x Abu Dhabi, UAEMonday 24 July 2017

Are insulin surges the trigger for cancer?

New research has shown a connection between obesity, insulin and the prevalance of cancer, and new insights suggest a diabetic treatment will not only reduce insulin levels but take the fight to the 'Big C'.

Scientists are unravelling the mysteries of the link between obesity, diabetes and cancer, which offers hope that new treatments will be developed.
Scientists are unravelling the mysteries of the link between obesity, diabetes and cancer, which offers hope that new treatments will be developed.

Are you struggling to find motivation for your new year diet? Look no further than a list of the ills linked to obesity: everything from back pain and cellulitis to heart attacks and stroke. But there is one threat that is enough to get anyone back to nibbling on celery - cancer.

Evidence linking obesity with the "Big C" has been accumulating since the 1980s, and is now a major source of concern in many developed nations. It suggests that obesity accounts for up to half of some of the most notorious forms of the disease, such as breast, pancreatic and oesophageal cancer.

Just last month, researchers at Tawam Hospital in Al Ain expressed concern over the deaths of young women from endometrial cancer linked to obesity and diabetes. And with more than a third of the UAE's adult population classified as obese, such findings are clearly of prime concern to the future health of the nation.

But behind the statistics lies a major scientific riddle: what is it about being overweight that increases the risk of cancer?

One obvious idea is that obese people consume more of the cancer-causing substances lurking in food. But, according to Gary Taubes, a US-based nutrition expert and author of the acclaimed study The Diet Delusion, research is increasingly pointing to something much more specific.

Writing in the journal Science this month, Mr Taubes reported that the prime suspect was the hormone insulin. But there was good news too - as this could mean the cancer risk from obesity may be reduced relatively easily.

Produced by the pancreas, insulin is released whenever we consume carbohydrates, keeping blood glucose at a safe level. Through their unhealthy diets, obese people typically have relatively high levels of insulin - which notoriously can trigger diabetes, in which insulin struggles to maintain safe glucose limits.

But cancer researchers have long known of another use for insulin: promoting the growth of tumour cells. In the lab, such cells are routinely cultured using a mix that includes insulin. Unlike normal cells, they appear to thrive when given the hormone - and shrivel and die without it. Indeed, so keen are cancer cells to acquire the stuff that they develop insulin "receptors" on their surface, which is missing on healthy cells.

Further hints of a link between insulin and cancer come from the fact that patients with certain types of diabetes treated using extra insulin face a higher risk of developing cancer than those treated without the hormone.

So why the fondness of cancer cells for insulin? The consensus, Mr Taubes says, is that they use it to get the energy-rich glucose they need to construct copies of themselves, create proteins for growth and spread around the body.

And in obese people, there is no shortage of glucose - which would explain why they are at more risk from cancer. Put simply, it is not what they are ingesting that is the problem; it is the resulting insulin surges. Any cancer cells present in their bodies find themselves flooded with copious amounts of what they need to thrive.

But where do the cancer cells come from in the first place? While levels of insulin and a related protein called IGF play a role, exactly how they turn healthy cells cancerous is still controversial.

According to Mr Taubes, one theory is that high levels of insulin and IGF can corrupt healthy cells, leading them to acquire features found in bacteria - including massively increased use of glucose.

That, in turn, produces higher levels of "free radicals", extremely reactive fragments of molecules that can do serious damage to the cell's DNA. The resulting mutations can then undermine the cell's own anti-cancer mechanisms, leading to untrammelled growth - the very definition of cancer.

Other experts think the key lies in insulin's effect on the natural ability of cells to commit suicide. Known as apoptosis, this process is kept in check for healthy cells by insulin and IGF. But if there is too much of either, it can be switched off completely - allowing cells to proliferate.

But while scientists are trying to pin down the precise mechanism, doctors are already planning to use the new insights to reduce the cancer risk among those most vulnerable. And this may be relatively simple, as it just needs some way of reducing insulin levels - and drugs that do this have long been used for treating so-called type 2 diabetes.

Indeed, the anti-cancer benefits of such compounds have already been seen with a compound called metformin, first used to treat diabetics in the 1950s.

Like insulin, metformin reduces the amount of glucose in the blood stream - and as a side effect reduces the level of insulin. If the insulin-cancer link is correct, this suggests metformin should also reduce cancer risk.

Sure enough, several recent studies have shown diabetics treated with metformin have up to 40 per cent less cancer than those treated with insulin-boosting therapies.

Experiments with mice have found that metformin may combat lung cancer, and a team at the US National Cancer Institute is now planning clinical trials to see if the compound has a similar effect with human patients.

Another team, which is based in Canada, has already begun a study of 3,500 breast cancer patients to see if those given metformin alongside standard therapy do better than those given the usual medication.

It will be at least five years before the results become clear, and the history of cancer therapy is littered with "breakthroughs" that turn out to be damp squibs. In particular, the cancer cells in patients may have acquired so many insulin-boosting mutations that they are unstoppable.

Even so, it is hard not to see the science of insulin-induced cancer as a ray of hope in the long war against this most feared of diseases.

 

Robert Matthews is visiting reader in science at Aston University, Birmingham, England