Hypoglycaemia is an ongoing concern in patients with type 2 diabetes treated with insulin and can have serious acute and long-term impacts.1 To better understand the impact of hypoglycaemia on insulin optimisation, the limbic spoke with Dr Ted Wu, Director of the Diabetes Centre, Royal Prince Alfred Hospital in Sydney.
“A lot of hypoglycaemia in type 2 diabetes is unrecognised, it is asymptomatic, and the problem with that is that it can lead to a propensity for major hypoglycaemia later on.2 As a result, anything we can do to minimise the risk of hypoglycaemia in our patients with type 2 diabetes is a positive thing,” explains Dr Wu.
Fear of hypoglycaemia in patients taking insulin
While insulin remains a critical tool in the management of type 2 diabetes, some patients will experience hypoglycaemia2. This can result in a range of behaviours that have the potential to create barriers to effective glycaemic control.
Dr Wu explains, “A lot of clinicians think that patients do not want to start insulin because they are afraid of needles, but in fact a lot of our patients are actually concerned about hypoglycaemia. Patients often know relatives or friends who have been treated with the older insulins or sulphonylureas (SUs) and experienced hypoglycaemia, and they are really quite afraid of that. It is certainly very reasonable that patients fear hypoglycaemia, but I think that we as clinicians sometimes underestimate this fear in our patients.”
In some cases, a patient’s response to this fear of hypoglycaemia will negatively impact their disease management. “This is a really major issue”, explains Dr Wu. “As soon as a patient experiences hypoglycaemia with insulin, one of two things often happen.
The first is that they will decrease their dose or, worse still, they might even omit insulin doses altogether. This has the consequence of higher blood sugars, but also very unpredictable blood sugars, because sometimes they will take a larger dose of insulin and sometimes a smaller dose, or none at all, in order to try to avoid the hypoglycaemia.
Secondly, a patient might start eating defensively. This of course leads to weight gain and again higher blood glucose levels. In the long-term, higher weight will lead to the requirement for greater insulin doses, which will then potentially feed into the problem creating a vicious cycle.”
Hypoglycaemia and cardiovascular outcomes
The acute effects of hypoglycaemia extend beyond QT prolongation and include abnormalities in atrioventricular conduction and ventricular repolarisation as well as catecholamine release and increased risk of cardiac arrhythmia.3 There is also evidence of long-term effects of hypoglycaemia from multiple large cardiovascular (CV) outcome trials, which demonstrate an association between severe hypoglycaemia and increased rates of major adverse cardiovascular events (MACE) and all-cause mortality.4-9
Dr Wu explains that, “While this evidence of an association does not prove causation, a link between hypoglycaemia and risk of CV events is biologically plausible.”
Indeed, there is a wide range of mechanisms in type 2 diabetes that are thought to increase risk of CV disease including effects on coagulation, inflammation, endothelial dysfunction, and cell adhesion.10
“We know that hyperglycaemia impacts on all of these systems, but what is slightly less appreciated is that hypoglycaemia does almost exactly the same things. So these pathways that are negatively stimulated by hyperglycaemia, are also negatively stimulated by hypoglycaemia. And as a result, hypoglycaemia not only has an acute effect on the patient, but can have a prolonged negative effect on the patient’s CV system”, says Dr Wu.
Strategies for reducing the risk of hypoglycaemia
Dr Wu explains, “There are several strategies to reduce hypoglycaemia in clinical practice. Firstly, we need to set realistic HbA1c targets. In someone who is at risk of hypoglycaemia, a higher HbA1c target would be appropriate.
It is also important to select the right treatment – so not just the right class, but the right treatment within that class. Fortunately, we have new insulin analogues that have been shown to reduce the risk of hypoglycaemia… so clinicians need to be aware of some of the newer options that are available.
Finally, we need to be aware that our patients may not volunteer their experiences of hypoglycaemia. We need to ask all of our patients taking insulin, at every visit, whether they are having hypoglycaemic events. And not just asking about symptoms, but about what their lowest blood sugar levels are.”
The benefits of Toujeo beyond HbA1c control
Toujeo® (insulin glargine 300 units/mL) is a basal insulin analogue development that offers reduced variability and a greater duration of action than Lantus® (insulin glargine 100 units/mL), and has also been shown to be associated with a lower risk of hypoglycaemia in type 2 diabetes.11,12
“I think this is certainly something that we should offer our patients who are getting hypoglycaemia on insulin or to those who are more vulnerable to hypoglycaemia, such as our older patients,” explains Dr Wu.
Dr Wu continues, “Hypoglycaemia is one of the main reasons that people are hospitalised for diabetes 13. This costs the healthcare system a lot of money as well as causing a lot of inconvenience and hassle for our patients. So we really do need ways of reducing this burden, not just on individuals, but on the healthcare system as a whole.”
This article was sponsored by sanofi aventis. The content is based on published studies and experts’ opinions, the views expressed are not necessarily those of sanofi aventis.
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- Bonds et al. BMJ 2010;340:b4909
- Mellbin et al. Eur Heart J 2013;34:3137–44.
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- Meneghini L et al. Hypoglycemia risk associated with basal insulin use in type 2 diabetes (T2DM): The Lightning study. Presented at the 11th Annual Conference on Advanced Technologies and Treatments for Diabetes (ATTD), February 14–17, 2018, Vienna, Austria. Abstract ATTD8-0420.
- Piya, M et al. Diabetes 2018;