Impaired Awareness Of Hypoglycaemia Definition

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No satisfactory or comprehensive definition of impaired hypoglycaemia awareness has been suggested to date. Many laboratory-based studies of experimental hypoglycaemia have used arbitrary definitions based on witnessed observations of subjects who fail to develop classical features of hypoglycaemia, or the failure of physiological or hormonal responses to exceed twice the standard deviation from mean basal levels. These are statistical devices, which take no account of subjective reality, require the application of sophisticated and unphysiological glucose clamp procedures, and have little direct application to clinical management.

Asymptomatic biochemical hypoglycaemia occurs more frequently during routine blood glucose monitoring in diabetic patients who report impaired awareness of hypoglycaemia (Gold et al., 1994; Clarke et al., 1995) and such a record may alert the clinician to the possibility that an individual is developing this problem. A much higher rate of undetected hypoglycaemia in people with impaired awareness has been demonstrated during waking hours using continuous blood glucose monitoring (Kubiak et al., 2004). However, in clinical practice a careful history is essential in determining whether reduced warning symptoms of hypoglycaemia are a significant problem, and if this is occurring consistently. Patients who assert that they have a problem with perceiving the onset of symptoms of hypoglycaemia are generally correct in this belief (Clarke et al., 1995), so that the identification of impaired awareness of hypoglycaemia should be based principally on clinical history. Validated scoring systems to assess awareness of hypoglycaemia have been described by Gold et al. (1994) and Clarke et al. (1995), and supportive information can be derived from simultaneous inspection of the individual's blood glucose results. Detailed questioning of a patient about his or her ability to detect the onset of hypoglycaemic symptoms may need to be supplemented by questioning close relatives, who often report a much higher rate of severe hypoglycaemia

(Heller et al., 1995; Jorgensen et al., 2003). This will provide a witnessed description of how hypoglycaemia develops in a patient, with information on its true frequency and severity. Patients often underestimate the frequency of severe hypoglycaemia, partly because of post-hypoglycaemia amnesia.


In one study, Hepburn et al. (1990) subdivided hypoglycaemia awareness into three categories: normal, partial and absent awareness. These were defined as follows:

• Normal awareness: the individual is always aware of the onset of hypoglycaemia.

• Partial awareness: the symptom profile has changed with a reduction either in the intensity or in the number of symptoms and, in addition, the individual may be aware of some episodes of some episodes of hypoglycaemia but not of others.

• Absent awareness: the individual is no longer aware of any episode of hypoglycaemia.

Although the subdivision into partial and absent awareness is artificial, it reflects the natural history of this clinical problem, illustrating the gradual progression of this disability, and emphasising that in some patients the abnormality is severe (absent awareness) although total absence of clinical manifestations of hypoglycaemia (particularly the neuroglycopenic features) is exceptionally rare (Gold et al., 1994, Clarke et al., 1995). The problem may not be simply an absence of symptoms, but rather that the time during which warning symptoms can be detected is extremely short, allowing the affected individual a very limited opportunity to take avoiding action. Some patients describe how the onset of hypoglycaemia appears to have become much more rapid compared with their previous experience and progresses quickly to severe neuroglycopenia. However, impaired awareness may not necessarily evolve into total unawareness of hypoglycaemia, and may vary over time, presumably because of major influences of environmental factors on the generation and perception of symptoms.

The above classification of awareness of hypoglycaemia is far from comprehensive. In addition, the state of hypoglycaemia awareness can be ascertained only when the individual is in a physical state in which recognition of the onset of hypoglycaemia is possible. Therefore, if the person is asleep, intoxicated, inebriated, anaesthetised or sedated, so that their conscious level is reduced, they are not able to perceive (as subjective symptoms) the normal physiological manifestations of hypoglycaemia. An individual's awareness of hypoglycaemia can be evaluated only if hypoglycaemia occurs while the individual is awake.

A further prerequisite is that the person must have had previous experience of hypo-glycaemia at some time during treatment with insulin. In assessing the present state of hypoglycaemia awareness, it is desirable that the patient should have experienced one or more episodes of hypoglycaemia (confirmed biochemically) within a recent time interval such as the preceding year, so that a comparison of the symptoms can be made with earlier episodes of hypoglycaemia. A diagnosis of impaired hypoglycaemia awareness cannot be entertained or surmised if a patient has either never been exposed previously to acute hypo-glycaemia or has only started to experience hypoglycaemic events very recently. Because hypoglycaemia awareness and its impairment is a continuum ranging from normality to complete inability to detect the onset of hypoglycaemia, a classification of this condition will need to consider alterations in symptom intensity as well as detection of hypoglycaemia by any means and the ability of the patient to self-treat low blood glucose.

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