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Why more caution is needed in administering QT prolonging drugs to type 1 diabetic patients.

3rd March 2021

400,000 people are currently living with type 1 diabetes in the UK, one of the highest rates in the world. 

Sadly, cardiovascular disease is the leading cause of premature death in these patients and studies have shown that they are also at a higher risk of sudden cardiac death (SCD).
But why?

Why QT intervals matter

QT prolongation (when the heart takes longer than it should do to electrically recharge between beats) could be an important risk factor.

In diabetic patients, hyperglycaemia -which often happens in diabetic patients and for extended periods -has been reported to prolong these QT intervals 

Cardiac ion channel blockers

Cardiac ion channel blocking drugs, interfere with QT intervals by blocking both the rapidly (IKr) and slowly (IKs) activating delayed rectifier potassium channels in the heart, and cause adverse cardiac effects for some patients with type 1 diabetes. Leading to increased risk of cardiac arrythmia and potentially SCD.

Alarmingly, there are currently no safety warnings to caution prescribers administering QT prolonging drugs to type 1 diabetic patients. 

The study 

To assess the impact of hyperglycaemia converging with QT prolonging medication (in this study: moxifloxacin), the Richmond Research Institute study team, alongside researchers from St George’s University London, Cardiovascular and Cell Sciences Research Institute and Richmond Pharmacology, London; assessed 22 type 1 diabetic patients (10 males, 12 females) over three days. 

  • They first examined the effects of hyperglycaemia on QTcF* in type 1 diabetic patients.
  • Then investigated the combined impact of a QT prolonging medicine and the hyperglycaemic state on QTcF intervals, and the level of blood potassium.

Key findings

This phase I study revealed that:

  • A hyperglycaemic state prolonged the QTcF interval by a mean of 17 ms.
  • Co-administration of moxifloxacin prolonged the QTcF interval by a further 10 ms - raising the mean QTc prolongations up to 27 ms
    (with QTc prolongations of up to 40 ms observed in individual patients).
  • They found a positive association between blood potassium concentration and QTcF interval prolongation.
  • An increase in blood potassium levels also correlated with QTcF prolongation. 

View the full results here.

The gender divide 

There were interesting findings when comparing results in our male and female participants.

  • Hyperglycaemia caused a 10 ms greater QT prolonging effect in female patients (21 ms) than males (11 ms), in the time course analysis.
  • Potassium, glucose and QTcF prolongation correlation also differed in men and women: during hyperglycaemia no correlation between potassium and QTcF could be seen in men.

Next steps 

Given the increase of QT interval prolongation with the administering of Moxifloxacin, especially the extended prolongation evidenced in female patients, current guidance urgently needs to be revised. This will ensure the safe administering of QT prolonging drugs for type 1 diabetic patients and further reduce their cardiac risk. We are now interested in exploring these effects in type 2 diabetic patients.

You can explore more detailed information about this study here

[1] https://jdrf.org.uk/information-support/about-type-1-diabetes/facts-and-figures/
[2] https://www.diabetes.org.uk/about_us/news/premature-deaths-diabetes
*QTcF = QT interval corrected for heart rate using Fridericia’s correction formula

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