Outside the Lab Metabolism & Diabetes, Clinical trials, Public health

Trimming the Fat

At a Glance

  • Diabetes has long been regarded as a lifelong progressive condition – and often, medication and intervention must increase over time
  • A recent study has found that significant weight loss could put diabetic patients into remission, removing the need for other treatments
  • The next challenge is to help patients lose weight in a primary care setting – and to maintain a lighter weight over time
  • If weight loss proves to be a successful strategy in the long term, it could potentially replace medication as the first option for patients

Type II diabetes is a big contributor to disease and disability around the world, and can result in a range of side effects, from loss of limbs, to coma and death. Medicine can be prescribed to manage it, but should drugs be the first port of call?

A recent UK study has found that weight management – already recommended for those with diabetes – could have an even bigger effect than previously thought, even years after disease onset. In the trial, participants went on a meal replacement formula diet of 825–853 calories per day for several months, followed by gradual reintroduction of food. Over half of the 306 people who took part achieved remission from their diabetes (1). We spoke to Roy Taylor, Professor of Medicine and Metabolism at Newcastle University, to find out more.

How did you get involved in this research?

I have been looking after people with diabetes since 1976, and since 1981 have been researching the causes of type II diabetes, which has always been regarded as a lifelong and inevitably progressive disease. More and more tablets are required, and eventually insulin injections. This appears to be caused by the insulin producing cells of the pancreas slowly dying over time.

But in 2006, blood sugar levels in people with type 2 diabetes were shown to fall to normal within seven days after bariatric surgery (2). And because research at that time was revealing the link between excess fat in the liver and the failure of insulin effects on the liver, the explanation for the normalized sugar after bariatric surgery seemed obvious. The people undergoing surgery would suddenly have to stop eating – nil by mouth. That would rapidly deplete liver fat. Then the liver would respond properly to insulin, and stop pumping sugar into the blood.

But could this also explain the problem with the pancreas? Excess fat in the liver causes excess fat in the blood, and excess fat delivered to the pancreas. Some early studies had shown that this long term exposure to fat would cause the insulin producing cells to stop working.

I published these ideas as the Twin Cycle Hypothesis (3) (one vicious cycle in the liver interacting with a second vicious cycle in the pancreas). And now we had a hypothesis to test.

My first test of the Twin Cycle Hypothesis was published in 2011. It showed that a 700 calorie diet (achieving 15 kg weight loss in eight weeks) would return blood sugar to normal within seven days because of a fall in liver fat; we also showed that over eight weeks the level of fat in the pancreas gradually fell, and the insulin producing cells steadily returned to normal function. The outcomes were all the more remarkable as the tablets used to control blood sugar had been stopped on day one of the diet.

Next, we set about testing whether the reversal would last after returning to normal eating. It did!

And whilst that study was underway (and once we had already seen that the effect was long term, provided weight was not regained), we asked our next question: Could a simple but effective weight loss program be delivered in primary care? And the DiRECT study was born, funded by Diabetes UK.

Did you expect weight loss to have such a dramatic impact?

In short, yes! In view of our work on small groups over the last decade, we expected a dramatic impact – but only if the practice nurses involved could effectively deliver the program. By using the low calorie diet, people feel better very rapidly. Within a couple of weeks they are delighted by their weight loss, running upstairs and getting up without a struggle. The commonest comment is “I feel 10 years younger!” – which is a great incentive for people to continue with the program.

What are the challenges when working with patients to achieve and maintain weight loss?

It is really important to emphasize that substantial weight loss can only be achieved by decreasing food intake, and that additional exercise should actually be avoided during weight loss – which may seem counterintuitive. Misinterpretation of epidemiological data has led to widespread advice to take up exercise and eat less if you want to lose weight, and that is a recipe for failure because of compensatory eating (partly conscious, and partly unconscious). The impressive weight loss in all of our studies is achieved solely by cutting down food intake. However, it is also important to add that for long term avoidance of weight regain, daily increased physical activity as part of everyday life is very useful, along with modest food limitation.

But what support is most effective in helping people avoid regaining the weight they’ve lost? That’s the really important question. Somehow, we must find a way to work with and regulate food companies, who spend huge sums persuading the population to eat between meals, to eat unsatisfying prepared portions, and who are offering unreasonable portions sizes at bargain prices. In a democracy, it’s a tough challenge.

From a research perspective, we also we need to know much more about the insulin producing cells (beta cells) and their de-differentiation.

What’s next?

We are at a watershed moment for type II diabetes understanding and management. We have shown that this disease can be reversed to normal by substantial weight loss, and we describe a practical way to achieve that weight loss. The first step in managing type II diabetes on diagnosis must now be to explain to the individual that they have a choice – a lifetime with diabetes, tablets and complications – or substantial weight loss and long-term avoidance of weight regain. Drugs should no longer be the first line.

Ongoing research will answer the questions of whether diabetes stays away long term, and a formal health economic analysis will determine the cost savings. As prescription of tablets to control blood sugar cost over £1 billion annually in the UK alone, and as the number of blood pressure tablets required is halved for patients on this program, the potential savings are huge. But the greatest savings will come in the form of better health outcomes for patients: less blindness, less amputation and less kidney failure.

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  1. ME lean et al., “Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial”, Lancet, [Epub ahead of print] (2017). PMID: 29221645.
  2. GH Ballantyne et al., “Short-term changes in insulin resistance following weight loss surgery for morbid obesity: laparoscopic adjustable gastric banding versus laparoscopic Roux-en-Y gastric bypass”, Obes Surg, 1189–1197 (2006). PMID: 16989703.
  3. R Taylor, AC Barnes, “Translating aetiological insight into sustainable management of type 2 diabetes”, Diabetologia, [Epub ahead of print] (2017). PMID: 29143063.
About the Author
Roisin McGuigan

I have an extensive academic background in the life sciences, having studied forensic biology and human medical genetics in my time at Strathclyde and Glasgow Universities. My research, data presentation and bioinformatics skills plus my ‘wet lab’ experience have been a superb grounding for my role as a deputy editor at Texere Publishing. The job allows me to utilize my hard-learned academic skills and experience in my current position within an exciting and contemporary publishing company.

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