Epidemiology of hypoglycaemia
It is difficult to ascertain the true incidence of hypoglycaemia. A uniform definition of mild hypoglycaemia is lacking and the literature relies to a large extent on self-reported data. While severe hypoglycaemia does have a more consistent definition, most of the data are derived from (pharmaceutical) studies which may not be representative of real-life settings. However, some estimates can be made.
Several factors hamper the proper estimation of hypoglycaemia incidence.
- Firstly, the symptoms of hypoglycaemia are diverse and most are unspecific, i.e. they may occur for other reasons as well. Therefore a finger stick is necessary to confirm the state of hypoglycaemia. This is not always practicable. Particularly with severe hypoglycemic events, people will often treat before measuring glucose.
Figure 1. Relation between glucose level used for the definition of hypoglycaemia and the percentage of patients with type 2 diabetes identified as having hypoglycaemia. The higher cut-off level of 3.9 mmol/l more than doubles the percentage of patients affected.
- This leads to another problem: which glucose-cut-off level should be used? Specialists have not yet agreed on a common definition of mild hypoglycaemia, with glucose cut-off levels varying between 2.8 mmol/L and 3.9 mmol/L. Altering the glucose cut-off level has a profound influence on the frequency of hypoglycaemia, with higher cut-off levels increasing the counted frequency of hypoglycaemia up to four-fold compared to lower cut-off levels (Figure 1) .
- Hypoglycaemia may be asymptomatic. When symptoms of hypoglycaemia are absent, for instance when the subject suffers from hypoglycaemia unawareness, the hypoglycaemic episode might be missed.
- Retrospective recall of episodes of mild hypoglycaemia is not reliable over a period of more than 1 week. When investigating the frequency of mild hypoglycaemia it is therefore advised to invite the patient to perform capillary blood tests at multiple (4-8 time daily) pre-set time points and document the measurements in a logbook.
- There are also several factors hampering the estimation of the frequency of severe hypoglycaemia. At first, the definition of severe hypoglycaemia differs between studies, hindering comparison. However, the most common definitions of severe hypoglycaemia are: 1) treatment by a third party is required to recover from hypoglycaemia or 2) medical assistance is required to recover from hypoglycemia. The diagnosis of hypoglycaemia is hard to make retrospectively, since the blood glucose may have returned to normal by the time the patient receives medical attention, and can't be made reliably following death. Furthermore, the distribution of episodes of severe hypoglycaemia is much skewed, i.e. the majority of patients do not have any episode of severe hypoglycaemia, while others have recurrent episodes. Retrospective recall of episodes of severe hypoglycaemia is considered robust.
- An extra problem that occurs in patients with type 2 diabetes treated with oral agents, basal insulin or premixed insulin, is that most patients do not possess a home blood glucose monitoring device and do not test their blood glucose on a regular basis. Thus, the confirmation of episodes of hypoglycaemia and estimating the frequency of mild hypoglycaemia is a challenge in this group of patients.
^ Swinnen SG et al.: Changing the glucose cut-off values that define hypoglycaemia has a major effect on reported frequencies of hypoglycaemia. Diabetologia 38-41, 2009
^ Janssen MM et al.: Biological and behavioural determinants of the frequency of mild, biochemical hypoglycaemia in patients with Type 1 diabetes on multiple insulin injection therapy. Diabetes Metab Res Rev 2000; 157–163.
^ Akram K et al.: Prospective and retrospective recording of severe hypoglycaemia, and assessment of hypoglycaemia awareness in insulin-treated Type 2 diabetes. Diabet Med 1306-1308, 2009
^ Pedersen-Bjergaard U et al.: Recall of severe hypoglycaemia and self-estimated awareness in type 1 diabetes. Diabet Metab Res Rev 2003; 232–240.