Interview with Prof John Wilding - Obesity & Diabetes | World Obesity Federation

Interview with Prof John Wilding - Obesity & Diabetes

NewsInterview with Prof John Wilding - Obesity & Diabetes

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How common and prevalent is obesity in patients living with type 2 diabetes?

Type 2 diabetes is perhaps one of the diseases that is most clearly associated with obesity. If we look at the epidemiological data, what we see is that the majority of people with type 2 diabetes are living with overweight or obesity. If we look at clinic populations, we will find that the prevalence of obesity in people with type 2 diabetes is a lot higher than it is in the general population.

There are a couple of important points to make about these associations. Obesity as a disease is defined not just by body mass index (BMI), but also by its ability to cause poor health, and diabetes is a classic example of that. As BMI rises, the risk of developing diabetes increases in an almost exponential fashion. There are still some people even with very severe obesity that will never develop diabetes, and there are some people with very minor degrees of overweight as measured by BMI, particularly people from some ethnic backgrounds, such as people from South Asia, who can develop diabetes at a relatively low BMI, maybe even 23, or 24.

So BMI in the context of diabetes is not a very good way or metric to be used when defining obesity and what we do know from research is that as body weight increases, that would determine your risk of developing diabetes.

People who tend to, for probably genetic reasons, have fat deposits in places like the liver and the pancreas, are much more likely to develop diabetes. So, when we start looking at strategies for prevention and treatment of diabetes, we know any degree of weight loss is likely to be helpful across the whole spectrum of BMI; even people that have quite low BMI will benefit from weight loss in terms of reducing their risk of developing diabetes or have diabetes progressing, once they've developed it.

What are the strategies for treatment and prevention in adults living with obesity and type 2 diabetes?

In some ways, it makes sense to think about both prevention and treatment together, because the strategies are the same. But we do know from quite a few large clinical trials, that in people who have not yet developed diabetes, who have prediabetes, even very modest weight loss can reduce their risk of progressing to developing diabetes. That can be achieved through lifestyle intervention, and more effective interventions like bariatric surgery, that are also very useful in terms of people who have developed type 2 diabetes.

There is some very good evidence now from multiple trials that shows that weight loss can in some ways reverse a lot of the pathophysiology of diabetes. So, as I have mentioned before, we know that obesity is associated with the risk of developing diabetes, and that different individuals, depending on their genetic makeup, may develop diabetes at different levels of BMI. Also, everybody almost has their personal level of BMI of which they will develop diabetes. What we do know is that if people are able to restrict energy intake and maintain that restriction of energy intake, the pathophysiological processes that lead to development of diabetes, insulin resistance and a failure to produce sufficient insulin in the pancreas can be quite dramatically reversed, at least during the early course of the disease.

For example, from the DIRECT study, which used liquid meal replacements as a strategy for reducing energy intake, participants got their energy intake down to about 800 calories a day for eight to twelve weeks. A very high proportion of those individuals with reasonably recent onset of diabetes, who were treated with either diet alone or one or two tablets, were able to go into remission from their diabetes. We have learned very recently that this intervention also works for people with a healthy BMI with type 2 diabetes as well. 

Over time, as we follow these people for two or three years after this initial 12-weeks intervention, if we gradually introduced normal food, they do tend to regain some of that body weight, and in some of them, diabetes will return, but for those people who are able to maintain most all of that weight loss, the diabetes is likely to remain in remission for quite a long period of time. So, this is a very effective intervention.

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I do think that we need to think more about obesity when we are helping to treat people with diabetes, because in the past, many of the medications that we have used commonly tended to cause weight gain. Whereas some of the newer medications that were used to treat diabetes, and some of the older ones like metformin, tend to cause weight loss. So, when we're choosing medications for people with diabetes, we really should be trying to choose, in my view, medications that make it a little bit easier for people to lose weight. That would include medications like metformin, the sodium glucose co-transporter-2 (SGLT2) inhibitors, and medicines like GLP-1 receptor agonists, that stimulate insulin secretion, but also through brain mechanisms help people lose weight. 

Perhaps the most dramatic effects that we see of weight loss are in people who have severe obesity with type 2 diabetes who are treated with bariatric surgery, where we can see a really effective reduction in the blood glucose that can be sustained often for many, many years after, with only a substantial weight loss.

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What are the biggest challenges that physicians face when treating patients living with obesity and type 2 diabetes?

There are a number of different challenges that we have to consider. The first point is the fact that clinicians don't always recognise obesity as an underlying cause, and the patient may also not know this. That means we need to think about how to raise the issue of obesity with patients in a sensitive way and then try and target the therapies; whether they can be diet-approaches, physical activity interventions, medical interventions, or even surgical interventions in a way that supports weight loss. These interventions are targeting obesity as the underlying cause of the disease, rather than just reaching for medicines that may actually be quite effective for lowering the blood glucose but may not necessarily be treating the underlying disease process. These patients may develop one of the metabolic complications if not treated, which is type 2 diabetes, and is effectively reversible, at least in the early stages, with weight loss, so I think that's really important.

There are a number of other specific challenges for people with diabetes that physicians need to remember, and the first fact is that obesity is not the individual’s fault or choice.

It's very easy for people to blame the individual for their obesity, whereas we know from all the studies that have been done over the last few years that that is not the case. Obesity develops in genetically susceptible individuals in the context of an abnormal environment, which is largely outside that individual's control. So, blaming the person for their diabetes can be very counterproductive and it is something we need to remember and think about.

The other challenge is to deal with their condition, and it's important to do this in a sensitive way. People with diabetes are often worried about not just the complications of the diabetes. Many of them will experience other complications from obesity, as well as the diabetes, but they may be specifically worried about some of the complications of diabetes.

We know that diabetes is a leading cause of blindness, and one of the leading causes of kidney failure. Also, it is a leading cause of heart disease, and amputations and all these complications are psychologically affecting people living with diabetes and they tend to worry about them. We can give people support to lose weight and show them that it is possible to control diabetes, as well as control obesity through effective weight loss interventions, then that can translate in the future into a lower risk of developing these important complications of both conditions.

What are the most effective interventions in patients living with obesity and type 2 diabetes?

I will start talking about nutritional-based interventions first. We do know that weight loss is beneficial in people with diabetes and a number of different trials have looked at that. The DIRECT trial, as I have discussed before, used liquid meal replacements at just above 800 calories a day. They are not actually officially very low energy diets, as that would be below 800 calories a day. This is a short-term intervention that is followed on by a gradual transition and ongoing support with normal food. This can result in remission of diabetes in significant proportion of people with type 2 diabetes that can be maintained for up to at least three years from the current data.

We also know that other lifestyle interventions can be effective and dietary changes that can result in weight loss can be beneficial. The Look Ahead study did this over 10 years and showed improvement such as blood pressure and lipids in people with obesity and type 2 diabetes with a comprehensive lifestyle intervention programme. We also know that those individuals in the trial who were most successful in losing weight did seem to have lower rates of cardiovascular events. I think there are good reasons to encourage these approaches in everyone with type 2 diabetes and potentially this can lead some people into remission.

In terms of pharmacotherapy, I think it's important to remember that for most people with type 2 diabetes, increased weight is an important factor for the cause of their diabetes, and therefore, to use pharmacotherapies that are not going to cause weight gain is important. Drugs that can cause substantial weight loss should be a real priority in the treatment of people with diabetes. That doesn't mean to say that we should never use drugs that can cause weight gain.

The drugs that can cause weight gain include sulfonylureas, thiazolidinediones and insulin.There are some situations where these are very useful medications; I still prescribe them, and certainly some people with diabetes, particularly as the disease advances, absolutely need insulin therapy. We shouldn't deny those individuals that need insulin therapy even though it may cause it more difficult for those people to lose weight. We can then still use other medications that might reduce the weight gain with insulin such as the SGLT-2 inhibitors in the GLP-1 receptor agonists to modify that that effect.

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In conclusion, some of the most dramatic effects that we see come with bariatric surgery, which in people with severe obesity can be a very effective way of treating diabetes. Again, it's more effective if it's used early in the course of the disease. So, we know that people who have bariatric surgery within a few years of diagnosis of diabetes are much more likely to maintain long-term remission of their diabetes than someone who's had diabetes for more than 10 years and is perhaps already on insulin therapy. In that case, they might still have diabetes, even after they've lost 30% of their weight from bariatric surgery.

We often find is that the disease is somewhat easier to treat in those situations, for example with lower insulin doses. It is not that it is ineffective in those individuals. It's just that once the diseases become very advanced, the weight loss interventions are perhaps less effective at helping people achieve complete remission.

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When should you recommend pharmacotherapy to individuals living with overweight or obesity and type 2 diabetes, and is there any threshold to consider?

It depends which medicines we're talking about. If we're talking about medicines that are being prescribed for the treatment of diabetes, then the evidence suggests that these medications that cause weight loss are probably effective for nearly everybody with diabetes, if it really is type 2 diabetes. There are some specific clinical situations where we must really check that the person really has type 2 diabetes and has not actually got type 1 diabetes or late onset autoimmune diabetes where the correct treatment is insulin.

So, that's a relatively small proportion, but an important group that we must think about, in terms of the thresholds for use of medicines that are specifically being prescribed for weight loss, as opposed to diabetes.

We're talking about mostly the GLP-1 receptor agonist, but also other obesity medications like orlistat or in the United States, there is also this phentermine/topiramate combination, which we don't have in the UK. Those medications can only be used in people with a BMI over 30. However, in people living with diabetes, the threshold can be considered usually in individual with a BMI of 27, because they would count as an overweight with a comorbidity or complication of the of the overweight, such as diabetes. And then people from some ethnic backgrounds, you might even take that threshold down to a BMI of 23 or 25 because that would be considered overweight in that population.

What are your top tips for healthcare professionals to help patients?

I would give three important tips here. The first thing is, when people are diagnosed with diabetes, or when you're treating a person with diabetes, and you recognize, as is often the case, that the obesity or increased weight is an important part of the cause of that person's diabetes and should be addressed, is to raise it with that person in a sensitive way, and not imply to the person that they're the reason why they've got diabetes, because we know obesity is not their fault, and therefore the diabetes is not their fault. That should help get the person on board, which is a really important part of the therapeutic process of treating the underlying cause of the diabetes - which is the obesity.

Secondly, it is really helpful for physicians or other healthcare professionals treating people with diabetes to understand and recognise how powerful weight loss can be as an intervention to treat diabetes, and to get that across to people with diabetes, because that can help them start to take those steps that can lead to effective treatment.

Finally, it's for clinicians to acknowledge themselves that that obesity is a major cause of diabetes, and therefore focus their therapy more on the obesity than perhaps they have done in the past. I think if we take that weight-centric approach to managing diabetes, we have a good chance of getting a lot more people into remission or having good control of their diabetes in the long term, which will ultimately prevent them from getting complications.

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Why do you think obesity and diabetes training & education are important?

There's been a perhaps a reluctance to consider the importance of management of obesity as an integral part of treatment of people with type 2 diabetes, and a certain amount of nihilism amongst clinicians that has meant that it has tended not to be prioritized. The situation has changed a lot now, because we now have a good evidence base for interventions that restrict energy, such as the information from the DIRECT trial with low energy, liquid meal diets, and we have evidence from drugs that are effective at causing weight loss and treating diabetes. We also have the option of bariatric surgery, which in many international guidelines now can be considered in people with type 2 diabetes and obesity, because the evidence base is very strong that at least early during diabetes, this is a very effective treatment.

So, for all those reasons, it's going to be very important to make sure that clinicians across the world that are treating people with type 2 diabetes, are aware of this information, understand this very strong relationships between these two diseases, and can offer effective intervention to much more people than at present.

I think the key points that I would take to summarise are to recognise the importance of obesity as a cause of type 2 diabetes, and the fact that BMI is a very poor marker for obesity in this context. Hence, it's really important to think about obesity as a disease that is causing ill health, particularly in people type 2 diabetes, where there is an excess accumulation of fat,  often in the wrong part of the body, particularly in the liver and the pancreas, which is causing insulin resistance and beta cell failure.

So, it's about understanding that and then, as soon as you get that, you can move that on and say: “If we treat the underlying cause, then we will make a big difference to people living with diabetes.”

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