The Latest on Hypoglycaemia Risks From ADA

Prof Simon Heller, BA, MB, Bchir, DM, FRCP


June 13, 2019

This transcript has been edited for clarity.

Hello, my name is Simon Heller. I am Professor of Clinical Diabetes at the University of Sheffield in the North of England, and I'm a practising physician at the associated teaching hospital, Sheffield Hospitals Foundation Trust.

I've been asked to talk about some of the highlights at the American Diabetes Association professional meeting, and I'm going to be concentrating on hypoglycaemia because that is my interest.

Hypoglycaemia and Heart Risks

On the first day of the meeting we had a debate in which two individuals debated whether hypoglycaemia was a cause of cardiovascular events, or merely a risk marker.

David Matthews gave a very good presentation when he showed some quite convincing evidence that hypoglycaemia is indeed causal in causing cardiovascular disease and probable cardiovascular mortality.

He showed statistical evidence and clinical trials, which certainly suggested that hypoglycaemia contributed. There was a contrary opinion, which was presented by Professor Thomas Pieber from Austria. And he showed data which didn't always support that argument, and suggested that, at least in part, there was confounding evidence. And by that, I mean, hypoglycaemia may merely be indicating people who have comorbidities and are frail. And so hypoglycaemia may well occur in those patients when they're treated with insulin, or possibly a sulfonylurea, but they then die of associated co-morbidities.

So there was a robust discussion, and time for just a very few questions.

So what are we to conclude from this debate? I think we can conclude that there's almost certainly a multifactorial issue going on here. I think there is almost certainly some causal effects. There are certainly plausible mechanisms, whereby hypoglycaemia might lead to increased cardiovascular disease. But I think we should also acknowledge that it's also important that hypoglycaemia is identified in patients who may not only experience severe episodes, but are more likely to die.

But I think the important conclusion perhaps overall is that because hypoglycaemia causes these unfortunate effects, we should avoid it whenever possible.

Impaired Hypoglycaemia Awareness

I now want to talk about some of the oral presentations. And actually just to single out one single one which looks at treatment of impaired awareness of hypoglycaemia, which can affect nearly 25% of patients with type 1 diabetes.

So these investigators, led by Rory McCrimmon from Dundee in Scotland, began to theorise that it may be that reduced awareness of hypoglycaemia is due to repeated stress of hypoglycaemic events. And so they wondered whether this habituation, as they describe it, might lead to a reversal of unawareness. And by this habituation, they hypothesised that maybe extreme exercise might reverse some of these effects.

Now, they showed that in an animal model, but this is a proof of concept trial, in which they took 12 individuals with impaired awareness of hypoglycaemia, and subjected them to high intensity exercise on a bicycle over a very short period. And on the following day, tested their responses to experimental hypoglycaemia, lowering the glucose to around 2.5 mmol/L, 45 mg/dL.

And interestingly, they showed that following this exercise, the amount of adrenaline, a key counter regulator of hormones, increased, and symptoms increased as well.

Now, these are small numbers, showing interesting changes. But I think this is really important work.

We really don't have any good treatments to prevent or treat hypoglycaemia unawareness. And it would be great if a simple intervention like this could work.

So I think what this calls for is a much larger and longer duration trial, which the investigators are indeed planning.

Hypoglycaemia in Type 2 Diabetes

The last area of hypoglycaemia, which I think is worth commenting on, is hypoglycaemia in type 2 diabetes. And many primary care physicians don't recognise this as a problem, and indeed that is also true for general internists, and some specialists.

But we had data presented at this meeting showing that hypoglycaemia in type 2 diabetes is indeed a problem. And I just want to single out two studies, one, which showed that patients with type 2 diabetes on insulin who had impaired unawareness had a much increased chance of having severe events.

And another study, which was based on the LEADER trial, and they looked at the type 2 population, which involved over 9000 patients, they categorised patients into those who had no non-severe events, episodes of hypoglycaemia symptoms, and a glucose over 3.1 mmol/L, 55 md/dL.

And they showed conclusively that if there were no events, then there was no increased risk of a severe episode, but those who are having frequent events, over one episode per month over a calendar period of 1 year, were at increased risk not only of severe hypoglycaemia, but also classical MACE - major adverse cardiovascular events, such as myocardial infarction, cardiovascular mortality, and stroke.

Now we know that non-severe hypoglycaemia predicts severe hypoglycaemia in type 1, but we have very few data in type 2 diabetes.

So I think to sum up, these studies show that hypoglycaemia is a matter of concern in type 2 diabetes, indeed, in numerical terms, it probably causes more morbidity and mortality than in type 1 diabetes. So, it's more important you could argue numerically in type 2 diabetes, and it's important that clinicians take this into account when choosing therapy for their patients.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as: