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Diabesity and the food-brain relationship

Scientists from Imperial College London have enhanced our understanding of the food-brain relationship by discovering a brain mechanism that drives our appetite for foods rich in glucose, which could lead to treatments for diabesity.

Obesity, insulin resistance, metabolic syndrome and type-2 diabetes have reached epidemic proportions, yet few people understand how closely they're related, and what causes them. Diabesity is a metabolic dysfunction that ranges from mild blood glucose imbalance to fully-fledged type-2 diabetes.


Intimate food-brain relationship

Diabesity accounts for between 65 and 85% of new cases of type-2 diabetes, and affects more than one billion people worldwide; including 60 million Europeans, and 100 million Americans.

For most people, neither dieting nor current pharmacological interventions are effective in achieving long-term weight reduction. Therefore, to prevent and treat diabesity we must develop approaches to modulate the ways in which the brain controls body weight.

"This is the first time anyone has discovered a system in the brain that responds to a specific nutrient, rather than energy intake in general, and it raises the potential that diabesity could be reduced and prevented by medication acting on the part of the brain that craves glucose," says Dr James Gardiner who led the study.

Our brain rules our belly
Researchers identified a mechanism, which senses how much glucose is reaching our brain, and if our brain detects a shortfall, it makes prompts to seek more glucose. This mechanism is more active in people who are obese-prone, suggesting that the brain can promote obesity.

The Imperial College study is published in The Journal of Clinical Investigation . According to its lead author, Dr Syed Sufyan Hussain, 'Glucose is a component of carbohydrates, and the main energy source used by brain cells. This study demonstrates that the brain plays a significant role in driving our preference for sweet and starchy foods. Prior to industrialisation, such glucose rich foods were not easily available, but today they're everywhere.'

Addicted to food?
Dr Mohammed Hankir, a neuroscientist at the University of Leipzig, Germany, says, 'It's becoming increasingly clear that when we consume certain types of food, particularly those high in fat and sugar, the same brain circuits are engaged as when taking drugs of abuse. We may therefore have little choice about overeating and becoming obese.'

If the diabesity epidemic is the result of our brains being hard-wired to consume energy rich food, can we cure diabesity with pharmacological manipulation of these brain pathways?

Bowels control the brain
Professor Sir Stephen Bloom, Head of Division for Diabetes, Endocrinology and Metabolism, Imperial College London, thinks we can, and says, 'Gut hormones are chemical messengers secreted by the digestive system that affect our brain and control appetite. Hijacking this natural messenger system is an attractive and likely option for treating diabesity'. The GLP-1 hormone is widely used for the treatment of diabetes. It also leads to weight loss. There are other such gut hormones that need further evaluation because they could provide attractive solutions for obesity. 
 
Takeaways
The food-gut-brain relationship promises a much-needed solution for the diabesity epidemic. Whilst the search continues, we must act now to prevent this. Most healthcare systems are organized to treat the acute symptoms of diabesity, and manage the condition once it's been diagnosed. Healthcare systems are less adept at prevention, and early detection. This requires effective education, which is currently not available. 

 

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In October 2014 Harvard professor Douglas Melton announced a breakthrough in the treatment of type-1 diabetes by creating stem cells that produce insulin.

Melton demonstrated that mice treated with transplanted pancreatic cells are still producing insulin months after being injected. Testing in primates is now underway at the University of Chicago, and clinical studies in humans should begin in just a few years.

"Most patients are sick of hearing that something's just around the corner," says Melton, but he's convinced that his research represents a significant turning point in the fight against diabetes.

Type-1
Type-1 diabetes, which usually occurs in children, is an autoimmune disease in which the body attacks its own beta cells of the pancreas and destroys their ability to make insulin. It's a devastating lifelong chronic condition, which affects some three million Americans and 400,000 English people. Treatment is daily insulin doses, a healthy diet and regular physical activity.
 
Increasing incidence
For reasons not completely understood, the incidence of type-1 diabetes has been increasing throughout the world at about three to five per cent a year, and is most prevalent in Europe. This is troubling, because type-1 diabetes has the potential to disable or kill people early in their lives.

The search to discover why type-1 diabetes is increasing resembles the penultimate chapter of an Agatha Christie mystery, where there are many suspects, but no prime candidate. The last chapter to explain the increasing incidence of type-1 diabetes is yet to be written.  
 
Parents unaware of symptoms
A 2012 UK report suggests that parents are unaware of the warning signs of type-1 diabetes: thirstiness, tiredness, weight loss and frequently passing urine. As a consequence 25% of children with the condition are diagnosed once they are already seriously ill with diabetic ketoacidosis (DKA). DKA occurs because a severe lack of insulin upsets the body's normal chemical balance, and leads to the production of poisonous chemicals called ketones. This build-up can be life threatening, and needs immediate specialist treatment in hospital.
The challenge of cell production
Making industrial quantities of the insulin-producing cells of the pancreas has been a Holy Grail of diabetes research. All previous attempts have failed to achieve scalable quantities of the mature beta cells that could be of practical benefit to people living with diabetes.

Just over 20 years ago when Professor Melton's son Sam was diagnosed with type-1 diabetes Melton promised that he would find a cure. He was further inspired when his daughter at 14 was also diagnosed with type-1 diabetes.

According to Melton, it should be possible to produce 'scalable' quantities of beta pancreatic cells from stem cells in industrial-sized bioreactors, and then transplant them into a patient to protect them from immune attack. This would result in an effective cure.

"The biggest hurdle has been to get glucose-sensing, insulin-secreting beta cells, and that's what our group has done," says Melton.

In addition to offering a new form of treatment, and possibly a 'cure' for type-1 diabetes, Melton believes his discovery could also offer hope for the 10% of people living with type-2 diabetes who have to rely on regular insulin injections.

Takeaway
If Professor Melton is successful, not only will his discovery honour a promise to his children, but also it'll be a medical game-changer on a par with antibiotics and bacterial infections.
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