Diabetic Neuropathy: An interview with Dr Brian Callaghan

Please can you tell us a little bit about diabetic neuropathy?

Diabetes is the number 1 cause of neuropathy, which is a very common condition in itself.

In fact, up to half of all neuropathy is caused by diabetes, although other people can get the condition as well.

Diabetic neuropathy is a neuropathy that starts in the feet and spreads up the legs and into the fingertips.

It usually presents with numbness, tingling, pain or weakness in those areas.

Do people with diabetes type 1 and type 2 develop diabetic neuropathy? Which type is more prone to it?

People with both types of diabetes get diabetic neuropathy and the neuropathy that they experience is very similar.

There aren’t any good studies comparing the susceptibility of people with type 1 and type 2 diabetes to neuropathy.

In general, patients with type 1 diabetes tend to have had the condition longer before developing neuropathy than those with type 2 diabetes.

Thus, patients with type 2 diabetes and neuropathy tend to be older than those with type 1 diabetes.

Can you tell us a little bit about the different ways in which diabetic neuropathy can be prevented?

There aren’t a lot of ways to prevent diabetic neuropathy other than with glucose control.

The purpose of the recent review was to see how this number one treatment stacks up.

Lots of other potential treatments have been tried and have failed in clinical trials.

Currently, if you can’t treat the glucose level, the only other option we have is to treat the pain.

Essentially, you have two options, either to treat the root of the cause, or to treat the symptoms themselves.

At the moment, all we have to treat the root of the cause is to control the sugar levels in some way.

Are there different methods to prevent diabetic neuropathy in type 1 and type 2 diabetes?

No, we have similar ways to control sugars: insulin or other medicines that control sugar.

The difference is that with type 1 diabetes the patients are insulin-dependent by definition; whereas patients with type 2 diabetes can use insulin, other medicines, or diet and exercise.

What factors, besides high glucose levels, may be responsible for causing nerve damage in type 2 diabetes patients?

This is something that we are learning more and more about and it is something that is going to be very different between type 1 and type 2 diabetes.

This is probably why we see such differences in the recent review.

In type 2 diabetes you often have coexistent dyslipidemia (high blood cholesterol levels, high triglycerides), obesity and other factors that go along with the high sugars.

In type 2 diabetes, there is insulin resistance; whereas in type 1 diabetes there is no insulin signalling. So they have different pathophysiology.

Ultimately, we do not yet know whether other factors such as obesity are responsible for causing nerve damage in type 2 neuropathy. This is a hot area of study at the moment.

What side effects can arise as a result of the treatment for diabetic neuropathy?

The two most common side effects are weight gain and severe hypoglycaemia, which is where the sugars go too low.

In the ACCORD study,(1) they tried to make the sugar controls even stricter than any previous study, and they had an increase in mortality in that population.

There’s always a side effect to every treatment, but right now we don’t really know what the optimal target should be.

How do the benefits of the treatment compare to the potential side effects?

That’s a hard question, as few of the studies report side effects with the same rigour that they report the primary outcome that they’re looking at, which is neuropathy or something else.

So it is hard to compare them.

Nowadays people are focussing more and more on the importance of side effects.

So hopefully future studies will be able to get at what is that appropriate balance.

You have to remember that when you are treating someone with diabetes you are not just trying to prevent neuropathy, but also retinopathy, nephropathy, strokes and heart attacks.

So it is within that context that you have to weigh how aggressive to be with sugar control.

Do you think the level of sugar control in preventing diabetic neuropathy will vary depending on the person?

I think the optimum level of sugar control will vary from person to person. It is always easier to say one size fits all, but it probably makes sense to do this in a more individualized way.

It is not as simple as the more aggressive the sugar control regimen, the better it is for the patient.

Every patient is different. One person might need more aggressive control than another.

There are lots of things we still need to learn about personalizing the way we treat diabetic neuropathy.

How does this relate to treating type 1 and type 2 diabetes?

Often type 1 and type 2 diabetes are lumped together because they cause such a similar neuropathy. However, other than the neuropathy, the diseases are very different, so it makes sense that you probably would have to treat them very differently.

I think that the recent study highlights the need to learn more about the mechanisms in the two diseases.

There is a big need to come up with medicines that target, not just the sugar control but, all the other things that go on to cause nerve injury. These are probably going to be very different in the two types of diabetes.

Overall, I think the recent research highlights the need for new therapies, particularly for type 2 diabetes.

This is because there seems to be more potentially modifiable treatments outside sugar control for type 2 diabetes.

Also, the treatment of more aggressive sugar control in type 2 diabetes has a much smaller effect on preventing neuropathy than type 1. Thus, there is more room for improvement.

Where can people go to find out more information?

They can read the review in the Cochrane Library: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD007543.pub2/abstract

We have also recently had published a review in the Lancet of Neurology that describes the mechanisms behind the two types of diabetes: http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(12)70065-0/fulltext

References

(1) Ismail-Beigi, Craven et al. “Effect of intensive treatment of hyperglycaemia on microvascular outcomes in type 2 diabetes: an analysis of the ACCORD randomised trial.” Lancet 2010; 376: 419-30

About Dr Brian Callaghan

Dr. Callaghan completed his medical degree and neurology residency at the University of Pennsylvania. He completed a fellowship in neuromuscular disease at the University of Michigan. He has a Master's degree in clinical research design and statistical analysis from the University of Michigan School of Public Health. Dr. Callaghan’s clinical and research interests focus on peripheral neuropathy and amyotrophic lateral sclerosis (ALS).