Spotlight on…diabetes

Hannah Blake interviews Professor Carel le Roux

Conway Institute, University College Dublin

Following our “spotlight on…” series, this month’s article is about diabetes. We speak to Professor Carel le Roux about the early symptoms of diabetes, the current treatments available to patients and the aim of Diabetes UK awareness week.

Did you know that by the year 2025, an estimated four million people in the UK will have diabetes1? Our latest “Spotlight on…” article focuses on Type 1 and Type 2 diabetes, in line with Diabetes UK awareness week 2012, from the 10th-16th June.

We interview Prof Carel le Roux, recognised globally as a world-leader in metabolism and weight-loss surgery, to find out how common diabetes really is, what the typical symptoms to look out for are and what treatments, both surgical and non-surgical, are available for patients.

HB: Hi Carel, thanks for speaking to me today. Would you mind telling me a bit about your background and how you got into your current role please?

CLR: I’m a consultant in metabolic medicine. My position is to try and work out how we can make people healthier, from a metabolic point of view. I’ve undergone specialist training in both internal medicine as well as chemical pathology to allow us to understand metabolism. My focus is on patients with type 2 diabetes and obesity.

HB: What is diabetes?

CLR: Diabetes is a condition where the blood sugar levels while patients are fasting rise above a limit that we have set at 7 millimoles per litre. The reasons why patients have a rise in blood sugar vary between patients. Some patient’s bodies don’t produce enough insulin, and therefore they can’t get the glucose from the bloodstream into the cells, because it needs insulin to bring glucose into the cell.

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“Diabetes is a condition where the blood sugar levels while patients are fasting rise above a limit that we have set at 7 millimoles per litre.”

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Other patients have type 2 diabetes because their body is resistant to insulin, so despite them producing vast amounts of insulin, there’s a blockage at the level of the cell in the muscle or in the liver so the glucose can’t come into the cell. Therefore diabetes is either a problem of not enough insulin or a lot of resistance. Of course some people have a combination of the two, where the resistance becomes higher and the body doesn’t produce enough insulin anymore.

HB: What are the initial symptoms to look out for?

CLR: Typically people feel very thirsty, and pass a lot of urine. The reason for this is if your blood sugar goes above a level of 10 millimoles per litre, it actually spills out into the urine. Whenever there is sugar in urine it tries to pull more water along with it, therefore the body is losing water and dehydrating.

Another symptom could be weight loss, because you’re losing a lot of calories and losing a lot of water.

HB: What treatment is available for diabetes?

CLR: There are two major forms of diabetes. The first: type 1 diabetes is typically what young people get when the pancreas stops working. At that point you urgently need insulin to stay alive, and if you don’t get insulin then you become very sick.

The other form of diabetes is type 2 diabetes, where you have a resistance to insulin, and over a period of time the pancreas begins to fail. We approach these problems very differently. Type 2 diabetes is the most common form of diabetes, and is the form that most adults get. We first of all address type 2 diabetes with lifestyle changes. If you are able to lose approximately three to five kilograms of body weight, you immediately reduce the resistance to insulin, and therefore the whole body works much better. We can also change the type of food that we give patients, so we give them low glycaemic index food, these are foods that do not require a lot of insulin to be pushed over the cell wall, so we can deal with it over a longer period of time. Low glycaemic index foods include brightly coloured vegetables such as red, green, yellow, orange or purple.

If that’s not enough for type 2 diabetes, we normally add metformin which has been around for a very long time. It actually makes people not only healthier, but may also make them live a little bit longer. Metformin allows the body to accept the insulin, and therefore reduces the insulin resistance. After that we have to use medication that actually drives insulin secretion, making you produce more insulin, or make the insulin that you have work a little bit better. This treatment that we’re using is called sulfonylureas, which is a very old medication, and is associated with complications such as weight gain.

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“We first of all address type 2 diabetes with lifestyle changes.”

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Newer medications on the market include glucagon-like peptide-1 analogues, GLP-1 analogues. These are typically injections patients give themselves once or twice a day, which make the body produce more natural insulin. Another newer medication is DPP-4 inhibitors, which are drugs to block the enzyme that break down GLP-1.

HB: In your opinion are there any treatments that should be available or perhaps aren’t available widely enough?

CLR: The treatments that are being considered at the moment to be breakthroughs are actually interventions on the gut. If we can change the way the gut sends a signal to the pancreas or the gut sends a signal to the liver, we can actually affect long-term benefit. At the moment, patients are having operations to change the plumbing of the gut, and if we change it in a certain format, called a gastric bypass operation, what happens is that patients lose weight and more importantly, the diabetes gets better immediately. Because we change those two main problems, we reduce inflammatory resistance immediately, and we also increase insulin secretion. So the two main problems of diabetes are immediately addressed.

However 90% of patients with diabetes do not want to have an operation, so there are also now medical devices available. One of these is called EndoBarrier, which is a 60 centimetre long liner that is placed inside a section of the patient’s intestine endoscopically. There is a hole at the bottom, so you eat normal food, which goes into your stomach through the sleeve and comes out at the bottom. As the liner is only 60cm there is no blocking the absorption of nutrients. What it does do is sends a very strong signal from the gut to the liver, which changes insulin resistance within days. The EndoBarrier device acts as a physical barrier between food and that part of the intestinal wall where the device is present, mimicking the effects of a gastric bypass, with reduced risks. So a lot of people who may not be interested or not eligible for surgery may be prepared to undergo one of these devices to improve their diabetes.

HB: I understand that you’re involved in Diabetes UK week – what is the aim of this awareness week, and what is hoped to be achieved?

CLR: The most important thing we hope to achieve in Diabetes Week is to make patients aware that they may have diabetes and for them to actually get tested. Although we describe the typical symptoms of diabetes as feeling very thirsty and passing a lot of urine, there’s still a lot of patients who are in a stage just before they develop diabetes, or they may have had the diabetes for a few months already, but they don’t know about it because they don’t have these severe symptoms. Therefore we would like for patients to think about these symptoms and go to their doctor and say, “Do I have diabetes?” if they are unsure. Especially patients who are getting a bit heavier, and if their waist circumference is increasing. The doctor can do a simple blood test, when the patient is in a fasting state, to work out if they have diabetes or not. If they don’t have diabetes they can be reassured, and we can talk to them about how to prevent developing diabetes. However if they do have diabetes, we can start to act quickly, as addressing the problem early can prevent the complications of diabetes in the long term. These complications can really harm or kill them, and that’s what we want to prevent. The sooner we can start the better.

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“…a lot of people who may not be interested in surgery may be prepared to undergo one of these devices that can improve their diabetes as well.”

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HB: In your opinion, what does the future for diabetes patients look like?

CLR: What we see on the population basis is that many more patients will develop diabetes in the next couple of years. At the moment between 6% or 8% of the population have diabetes, but if you go to countries like the Middle East, 25% to 35% of patients have diabetes in those countries. This tells us where we are going in the next couple of year if we don’t address the problems right now.

What’s happening today is that patients are developing diabetes at an earlier age, and because of this, there is a much higher risk of developing complications when they are 50 or 60 years old. From that perspective, the future for diabetes is bleak, because more people will have it, people will have it earlier, and people will develop complications earlier. However there is also a flipside as we are starting to understand the disease. Research funding from Diabetes UK and others enables us to understand better how we can improve diabetes awareness, which is very important and has yielded lots of benefit. Now we understand that if we start treating patients earlier, and we treat them well with the current medication that we have, we can have a real impact in stopping them developing complications or dying because of the diabetes.

We also know now that if we can understand how the gut sends signals to the liver, and the gut sends signals to the pancreas, this will help future treatments being developed. So from that perspective, we are now making great advances into the treatment of diabetes, which is a very positive outlook. On balance, there are a lot of risks but there’s also a lot of potential in addressing this disease in the long term.

HB: Thank you for speaking to me today Carel.

CLR: Thank you. At the end of the day, it’s just about making people healthier, making them more functional, with better, improved treatments.

References

1. http://www.diabetes.org.uk/Documents/Reports/Diabetes_in_the_UK_2010.pdf

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About the interviewee:

Prof Carel le Roux, M.D., Ph.D is head of Experimental Pathology at University College Dublin. Previously he led the clinical obesity program at the Imperial Weight Centre at Imperial College London.

Prof le Roux graduated from medical school in Pretoria, South Africa, and completed his medical education in the UK. He was previously a Wellcome Clinical Research Fellow and National Institute of Health Research Clinician Scientist.

He is recognised as a world-leader in metabolism and weight-loss surgery. He has studied hormones produced in the stomach (ghrelin), pancreas, (pancreatic polypeptide – PP) and distal small bowel (peptide YY, oxyntomodulin, glucagon-like-peptide 1) to establish their roles and mechanism of action in appetite control in obesity, under-nutrition and after weight loss achieved with bariatric surgery.

How can we raise awareness of diabetes?