Classification of hypoglycemia awareness in people with type 1 diabetes in clinical practice
Introduction
A reduced ability to perceive the onset of hypoglycemia — impaired hypoglycemia awareness — is the major known risk indicator for severe hypoglycemia in patients with Type 1 diabetes (Bragd et al., 2003, Clarke et al., 1995, Gold et al., 1994, Hepburn et al., 1994, MacLeod et al., 1993, Mühlhauser et al., 1998, Pedersen-Bjergaard et al., 2003, Pedersen-Bjergaard et al., 2004, ter Braak et al., 2000) and insulin-treated Type 2 diabetes (Akram et al., 2006, Henderson et al., 2003). In most instances, awareness is gradually impaired along the course of diabetes simultaneously with the occurrence of hypoglycemia-associated autonomic failure (Cryer, 2005). The most severe cases of impaired awareness are termed hypoglycemia unawareness. Presence of impaired hypoglycemia awareness is associated with 3- to 10-fold increased risk of severe hypoglycemia in both types of diabetes (Akram et al., 2006, Bragd et al., 2003, Clarke et al., 1995, Gold et al., 1994, Henderson et al., 2003, Hepburn et al., 1994, MacLeod et al., 1993, Mühlhauser et al., 1998, Pedersen-Bjergaard et al., 2003, Pedersen-Bjergaard et al., 2004, ter Braak et al., 2000). It is important to identify patients with impaired hypoglycemia awareness in order to prevent severe hypoglycemic episodes and — equally important — to identify patients with normal hypoglycemia awareness and low risk of severe hypoglycemia because these patients may benefit from stricter glycemic control.
Methods of assessing hypoglycemia awareness for clinical use should ideally provide maximal information about the risk of severe hypoglycemia in the most simple and reliable way. Furthermore, they should reflect the fact that impairment covers a wide spectrum of abnormality, meaning that awareness is not an all-or-none phenomenon. Due to the complexity of hypoglycemia awareness, there is, at present, no general agreement on a classification.
Only three studies validating prospective recording of severe hypoglycemic episodes against self-estimated state of awareness at entry into the study have been published (Clarke et al., 1995, Gold et al., 1994, Pedersen-Bjergaard et al., 2003). Two of the methods divide hypoglycemia awareness into two classes (Clarke et al., 1995, Gold et al., 1994), while the third method includes three classes of hypoglycemia awareness (Pedersen-Bjergaard, Pramming et al., 2003).
We conducted a cross-sectional questionnaire survey comparing the usefulness of these three methods for assessment of self-estimated hypoglycemia awareness in a clinical setting (Clarke et al., 1995, Gold et al., 1994, Pedersen-Bjergaard et al., 2003) in a large cohort of patients with Type 1 diabetes.
Section snippets
Methods
In May 2006, a questionnaire comprising a random combination of all questions from all three methods for classification of hypoglycemia awareness (Clarke et al., 1995, Gold et al., 1994, Pedersen-Bjergaard et al., 2003) was mailed to all patients with Type 1 diabetes in our outpatient diabetes clinic together with a return envelope. Questions were explained in paragraphs so that misunderstandings could be avoided. The patients were requested to contact the clinic in case of doubt of how to fill
Results
A total of 470 patients were invited to participate and 385 patients (82%) returned the questionnaire. Thirteen patients had to be excluded because of missing or incomplete answers, leaving 372 patients (79%) for evaluation. Participants were older and had lower HbA1c levels than nonparticipants but did not otherwise differ (Table 1).
Discussion
The clinical assessment of awareness can be based on four different types of data: (a) subjects' own estimation of their state of awareness, (b) self-monitored glucose data or continuous glucose monitoring data with scoring of symptoms in case of hypoglycemia, (c) an objective measure in terms of the response to a provoked hypoglycemic challenge, (d) an evaluation of the clinical consequence of impaired awareness: occurrence of severe hypoglycemia, or a combination of these methods. A simple
Acknowledgments
The authors thank research nurses Pernille Banck-Petersen and Tove Larsen for skilful data collection.
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