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Focus on hypoglycaemia

26th January 2022

Episodes of hypoglycaemia – especially severe hypoglycaemia – are an ongoing concern in diabetes, so an update given at the 19th World Congress on Insulin Resistance, Diabetes and Cardiovascular Disease recently was especially welcome. Dr Susan Aldridge reports.

Guillermo Umpierrez, Professor of Medicine at Emory University School of Medicine and also President Elect of the American Diabetes Association (ADA), pointed out the scale of hypoglycaemia in the USA, where it results in more than 100,000 visits to the emergency room every year. Two-thirds of these visits involve patients treated with insulin and one third of them need to be admitted. The other third involved those treated with an insulin secretagogue, of whom one quarter had to be admitted. “Hypoglycaemia is the most common complication of diabetes,” Professor Umpierrez said. “While mild hypoglycaemia is frequent and does not lead to complications, severe hypoglycaemia is a marker of poor health and is associated with cardiovascular complications and mortality.”

Hypoglycaemia often goes unrecognised. A study of 70 patients with type 1 diabetes on continuous glucose monitoring (CGM) reveals that 63% of them were having hypos, of which 83% occurred at night. “It may be that hormone responses to a hypo are impaired at night,” Professor Umpierrez said. “Studies show a lowered secretion of catecholamines in patients with and without diabetes during the night.”

Consequences of hypoglycaemia

The consequences of hypoglycaemia are well known, including fear of having an episode, its impact on employment, seizures, cognitive dysfunction and cardiovascular risk, of which the last is the most important, according to Professor Umpierrez. “And in addition to cardiovascular complications there are cognitive impairments involving decision-making, memory and attention. Full recovery requires 45 minutes after glucose has recovered and this affects things like driving.”

Hypoglycaemia also reduces quality of life and several studies have shown that it affects sleep, household chores, sport and emotional wellbeing, especially in people with type 1 diabetes. ‘’Our patients with type 1 diabetes don’t get involved in sport for this reason. And it also affects insulin dosing, with some patients willing to accept suboptimal glycaemic control in order to avoid hypoglycaemia.”

There are also a large number of people with impaired awareness of hypoglycaemia. This affects 25 to 40% of those with type 1 diabetes and 6 to 17% of those with type 2. Impaired awareness increases the risk of severe hypoglycaemia six-fold in type 1 diabetes and 17-fold in type 2. It occurs because recurrent hypoglycaemia reduces the counter-regulatory response that is required to restore euglycaemia. “Several studies show differences in cerebral blood flow in response to hypoglycaemia in those who have impaired awareness. The expected redistribution of blood flow to the thalamus is not seen,” said Professor Umpierrez.    

Medication and hypoglycaemia

When it comes to medication, there are now 12 different groups of diabetes drugs. But only two of these cause hypoglycaemia – the insulin secretagogues, like the sulphonylureas and glinides, and insulin. ADA/EASD consensus guidelines do not recommend either as first-line treatment for type 2 diabetes where hypoglycaemia is a concern.

“There’s a very nice publication in the New England Journal of Medicine showing trends of diabetes treatment in the USA,” Professor Umpierrez observed. “Insulin and sulphonylureas – the two medications that produce hypos – are currently used in 54% of people with diabetes in this country. So, there’s no question that hypoglycaemia will continue to be a problem.” Might this explain why the number of hospital admissions is so high?

When it comes to treating an episode of hypoglycaemia, the 15/15 rule still holds. Take 15 g of carbohydrate and allow it 15 minutes to get into the blood. There are various new rapid-acting glucagon formulations now available, including a nasal or ‘epipen’ version.

Finally, Professor Umpierrez highlighted the growing prevalence of post-bariatric surgery hypoglycaemia (PBH). Characterised by frequent symptomatic hypoglycaemia, it affects 29-39% of patients after Roux-en-Y bypass and 10-23% after vertical sleeve gastrectomy. Symptoms may include seizures, loss of consciousness, cognitive dysfunction and altered mental status, with a severe impact on quality of life. It is hard to treat BPH, but a recent clinical trial showed promise for avexitide, a GLP-1 receptor antagonist. This is a peptide fragment of exenatide, which competes for the GLP-1 receptor, thereby countering excessive levels of GLP-1 secretion. Avexitide has limited approval in the USA and the EU for indications that would include BPH. 

For more on hypoglycaemia, why not enrol on our course ‘Hypoglycaemia’. The course contains two modules that have now been accredited for continuing professional development by the UK’s Royal College of General Practitioners (RCGP).

For more from Professor Umpierrez, see his Insulin@100 presentation ‘Inpatient insulin protocols’ and his contribution to ‘The long and the short of it’, ‘HHS: past, present and future’.

For more on cognitive function and diabetes, see Professors Stephanie Amiel and Rory McCrimmon’s discussion of hypolgycaemia’s acute and long-term effects ‘Cognitive function and hypoglycaemia’.

Any opinions expressed in this article are the responsibility of the EASD e-Learning Programme Director, Dr Eleanor D Kennedy.