Hypoglycaemia in diabetes mellitus: epidemiology and clinical implications

Key Points

  • Hypoglycaemia, a common adverse effect of treatment of diabetes mellitus with insulin and sulphonylureas, is associated with impairment of cognitive function, which can have important consequences on everyday behaviour

  • Adults with type 1 diabetes mellitus have 2 episodes of mild hypoglycaemia per week; the annual prevalence of severe hypoglycaemia is 30%, with several factors, such as long disease duration, increasing its incidence

  • Adults with insulin-treated type 2 diabetes mellitus experience a lower frequency of mild and severe hypoglycaemia episodes than those with type 1 diabetes mellitus, but frequency rises progressively with increasing duration of insulin therapy

  • Sympathoadrenal activation in response to hypoglycaemia has haemodynamic, haemostatic, haemorrheological and electrophysiological effects, all of which can affect cardiovascular function and potentially lead to myocardial ischaemia, cardiac arrhythmias or sudden death

  • Hypoglycaemia provokes neurophysiological, electrical activity and regional vascular flow changes in the brain, which can lead to coma, seizures, vascular events such as hemiplegia, and cognitive dysfunction in young children and elderly people

  • Prevention of hypoglycaemia depends on effective patient education, diet, exercise, frequent glucose monitoring and appropriate adjustment of therapies; new technologies, such as real-time continuous glucose monitoring and insulin pumps, might also help

Abstract

Hypoglycaemia is a frequent adverse effect of treatment of diabetes mellitus with insulin and sulphonylureas. Fear of hypoglycaemia alters self-management of diabetes mellitus and prevents optimal glycaemic control. Mild (self-treated) and severe (requiring help) hypoglycaemia episodes are more common in type 1 diabetes mellitus but people with insulin-treated type 2 diabetes mellitus are also exposed to frequent hypoglycaemic events, many of which occur during sleep. Hypoglycaemia can disrupt many everyday activities such as driving, work performance and leisure pursuits. In addition to accidents and physical injury, the morbidity of hypoglycaemia involves the cardiovascular and central nervous systems. Whereas coma and seizures are well-recognized neurological sequelae of hypoglycaemia, much interest is currently focused on the potential for hypoglycaemia to cause dangerous and life-threatening cardiac complications, such as arrhythmias and myocardial ischaemia, and whether recurrent severe hypoglycaemia can cause permanent cognitive impairment or promote cognitive decline and accelerate the onset of dementia in middle-aged and elderly people with diabetes mellitus. Prevention of hypoglycaemia is an important part of diabetes mellitus management and strategies include patient education, glucose monitoring, appropriate adjustment of diet and medications in relation to everyday circumstances including physical exercise, and the application of new technologies such as real-time continuous glucose monitoring, modified insulin pumps and the artificial pancreas.

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Figure 1: Proportion of each group experiencing at least one severe self-reported hypoglycaemia episode during 9–12 months of follow-up.
Figure 2: Proposed mechanisms linking hypoglycaemia and arrhythmias in patients with type 2 diabetes mellitus during the day and during the night.

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Correspondence to Brian M. Frier.

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The author has received honoraria for giving lectures at scientific meetings arranged by Boehringer Ingelheim, Eli Lilly, Janssen, MSD, Novo Nordisk and Sanofi, and as a member of scientific advisory boards for the same pharmaceutical companies.

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Frier, B. Hypoglycaemia in diabetes mellitus: epidemiology and clinical implications. Nat Rev Endocrinol 10, 711–722 (2014). https://doi.org/10.1038/nrendo.2014.170

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