Unawareness of Hypoglycaemia in Insulin‐treated Diabetic Patients: Prevalence and Relationship to Autonomic Neuropathy

Hepburn, David; Patrick, A. W.; Eadington, D. W.; Ewing, D J; Frier, Brian M.

doi:10.1111/j.1464-5491.1990.tb01475.x

Cited by 181 publications

(105 citation statements)

References 35 publications

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“…Classic autonomic neuropathy does not segregate with loss of symptomatic responses to hypoglycaemia [14], perhaps because the body becomes more sensitive to the diminished counterregulatory hormone responses it is able to mount [15]. Although loss of subjective awareness of hypoglycaemia is undoubtedly more common with increasing disease duration [16], it can occur early in the course of diabetes [17] and may be reversible in all cases [18].…”

Section: Defects In Counterregulation In Diabetesmentioning

confidence: 99%

Hypoglycaemia in diabetes mellitus - protecting the brain

Amiel

1997

Diabetologia

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The principal danger of hypoglycaemia is the associated loss of brain function. Under normal circumstances, the brain is almost exclusively dependent on glucose to fuel its metabolism and function and, since its glucose stores are negligible, normal brain function relies upon an adequate supply of glucose from its blood supply.In animal models, prolonged very profound hypoglycaemia eventually results in neurone death (compared with ischaemia, which results in non-selective loss of all brain cell types) [1]. In clinical practice, apparent full recovery is the rule even from severe episodes of hypoglycaemia. Permanent impairment of brain function is seen only after the most severe episodes, usually associated with massive insulin overdose, often either deliberate or malicious [2]. In general, the loss of brain function due to hypoglycaemia presents in any degree from mild confusion or disinhibition to coma and full recovery apparently occurs within an hour of restoration of normoglycaemia [3]. There are concerns that recurrent episodes of hypoglycaemia-associated coma may result in permanent damage to cortical (intellectual) function although in adults the data are inconclusive, with some studies suggesting an acceleration of the age-related decline in performance on IQ testing [4], while others relate this to associated diabetic neuropathy [5]. Prospective studies of people who have been at particular risk for recurrent severe hypoglycaemia show no effect on long-term cognitive function [6,7]. There is evidence of permanent impairment of IQ after recurrent hypoglycaemic episodes occurring before the age of 5 years (i. e. affecting the developing brain) [8]. (For a review of the possible long-term effects of recurrent hypoglycaemia, see [9]). Protective mechanisms against severe hypoglycaemiaIn health, severe hypoglycaemia (now defined as the state in which the patient is unable to self-treat because of impaired function and has to be treated by someone else [10]), does not occur because of the efficient systems the body has to detect and deal with

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Section: Defects In Counterregulation In Diabetesmentioning

confidence: 99%

Hypoglycaemia in diabetes mellitus - protecting the brain

Amiel

1997

Diabetologia

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“…Their main defence against progressive hypoglycaemia is subjective recognition of symptoms such as sweating, tremor and hunger that prompts eating [5]. However, a significant number of patients lose their ability to generate or recognise the symptoms of developing hypoglycaemia [6,7], developing a syndrome of hypoglycaemia unawareness in which there are no warning symptoms of hypoglycaemia prior to cognitive dysfunction [1], but rapid progression to severe hypoglycaemia with confusion, coma and increased risk of further severe hypoglycaemia [8]. Fear of severe hypoglycaemia limits patients' enthusiasm for the tight glycaemic goals known to protect against diabetic complications and is a limiting factor in achieving good diabetes control [9].…”

Section: Introductionmentioning

confidence: 99%

Differential changes in brain glucose metabolism during hypoglycaemia accompany loss of hypoglycaemia awareness in men with type 1 diabetes mellitus. An [11C]-3-O-methyl-d-glucose PET study

et al. 2005

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Differential changes in brain glucose metabolism during hypoglycaemia accompany loss of hypoglycaemia awareness in men with type 1 diabetes mellitus. An Abstract Aims/hypothesis: Hypoglycaemia unawareness in type 1 diabetes increases the risk of severe hypoglycaemia and impairs quality of life for people with diabetes. To explore the central mechanisms of hypoglycaemia awareness, we used [ 11 C]-3-O-methyl-D-glucose (CMG) positron emission tomography (PET) to measure changes in global and regional brain glucose metabolism between euglycaemia and hypoglycaemia in aware and unaware diabetic subjects. Materials and methods: Twelve men with type 1 diabetes, of whom six were characterised as aware and six as unaware of hypoglycaemia, underwent two CMG-PET brain scans while plasma glucose was controlled by insulin and glucose infusion either at euglycaemia (5 mmol/l) or at hypoglycaemia (2.6 mmol/l) in random order. Results: With hypoglycaemia, symptoms and sweating occurred only in the aware group. Brain glucose content fell in both groups (p=0.0002; aware, 1.18± 0.45 to 0.02±0.2 mmol/l; unaware, 1.07±0.46 to 0.19±0.23 mmol/l), with a relative increase in tracer uptake in prefrontal cortical regions, including the anterior cingulate. No detectable differences were found between groups in global brain glucose transport parameters (K 1 , k 2 ). The cerebral metabolic rate for glucose (CMRglc) showed a relative rise in the aware subjects (11.839±2.432 to 13.958± 2.372) and a fall in the unaware subjects (from 12.457± 1.938 to 10.16±0.801 μmol 100 g −1 min −1 , p=0.043). Conclusions/interpretation: Hypoglycaemia is associated with reduced brain glucose content in aware and unaware subjects, with a relative preservation of metabolism in areas associated with sympathetic activation. The relative rise in global glucose metabolic rate seen in aware subjects during hypoglycaemia contrasted with the relative fall in the unaware subjects and suggests that cortical neuronal activation is a necessary correlate of the state of hypoglycaemia awareness.

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“…Unawareness, in some degree, is estimated to affect up to 25% of all patients with Type 1 diabetes, with the proportion increasing to 50% in patients who have had diabetes for over 20 y. 7,8 Those with hypoglycaemic unawareness are more prone to suffer severe hypoglycaemia, particularly if they maintain strict glycaemic control. Estimates suggest that patients with partial or complete unawareness are seven times more likely to experience severe episodes than those who retain their awareness.…”

Section: Hypoglycaemic Unawarenessmentioning

confidence: 99%

Reducing hypoglycaemia with insulin analogues

Heller

2002

Int J Obes

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Numerous studies have demonstrated that tight glycaemic control reduces long-term complications in both Type 1 and Type 2 diabetes. However, current intensive insulin regimens increase the risk of hypoglycaemia, dissuading many attempting this approach. Normal physiological insulin profiles consist of a stable, basal component and meal-related surges in secretion. Conventional insulin regimens cannot mimic this profile accurately due to pharmacokinetic limitations. Human insulin has a slow onset of action, thus patients are advised to inject about 30 min before a meal, ensuring peak insulin concentrations coincide with postprandial glucose excursions. This is clearly impractical for many and can lead to pre-meal hypoglycaemia if the meal is delayed. Furthermore, it only partially overcomes the unphysiological insulin profile and patients experience postprandial hyperglycaemia and are vulnerable to postabsorptive hypoglycaemia. Insulin aspart and insulin lispro are rapid-acting analogues that allow a more physiological replacement of mealtime insulin secretion. They reduce postprandial glucose and usefully reduce the incidence of hypoglycaemia when used in a basal-bolus regimen in tightly controlled patients. Pre-mixed insulins, containing a combination of rapid-acting and intermediate-acting insulin, are widely used, particularly in Type 2 diabetes. They have limitations achieving tight glucose targets but early data suggest that the combination of 30% insulin aspart and 70% protaminated insulin aspart may also reduce severe hypoglycaemia. On-going clinical trials will establish whether they can be used to achieve better glycaemic control with less hypoglycaemia.

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Unawareness of Hypoglycaemia in Insulin‐treated Diabetic Patients: Prevalence and Relationship to Autonomic Neuropathy

Cited by 181 publications

References 35 publications

Hypoglycaemia in diabetes mellitus - protecting the brain

Hypoglycaemia in diabetes mellitus - protecting the brain

Differential changes in brain glucose metabolism during hypoglycaemia accompany loss of hypoglycaemia awareness in men with type 1 diabetes mellitus. An [11C]-3-O-methyl-d-glucose PET study

Reducing hypoglycaemia with insulin analogues

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