Hypoglycaemia in Clinical Diabetes

142 IMPAIRED AWARENESS OF HYPOGLYCAEMIAArterialised venous blood glucose concentration (mmol/L)5.04.03.02.01.04.6 mmol/LInhibition of endogenousinsulin secretion3.8 mmol/LCounterregulatoryhormone release• Glucagon• Epinephrine3.2–2.8 mmol/LOnset of symptoms• Autonomic• Neuroglycopenic3.0–2.4 mmol/LNeurophysiologicaldysfunction• Evoked responses3.0 mmol/LWidespreadEEG changes2.8 mmol/LCognitivedysfunction• Inability toperform complextasks< 1.5 mmol/LSevereneuroglycopenia• Reducedconscious level• Convulsions• Coma0Figure 7.1 Hierarchy of endocrine, symptomatic and neurological responses to acute hypoglycaemiain non-diabetic subjects. Glycaemic thresholds are based on glucose concentrations in arterialisedvenous blood. Modified from Textbook of Diabetes, 2nd edition (1997) (eds J. Pickup and G. Williams),by permission of Blackwell Science LtdDepriving the brain of glucose causes it to malfunction, and cognitive impairment quicklybecomes evident as an overt manifestation of neuroglycopenia. Some of these features arerelatively subtle, and may not be detected immediately by the patient. A fall in blood glucosetriggers activation of the peripheral autonomic nervous system via central hypothalamic autonomiccentres within the brain, and stimulates the sympathoadrenal system. This promotestypical physiological responses including sweating, an increase in rate and contractility of theheart (sensed as a pounding heart), and tremor, these being some of the classical features ofthe autonomic reaction (Figure 7.2). Epinephrine (adrenaline) is secreted in large quantitiesfrom the adrenal medullae and contributes to some of the symptoms mainly by heighteningthe magnitude of the response. The early literature on hypoglycaemia and diabetes providesaccurate descriptions of the autonomic features of acute hypoglycaemia, and patients andphysicians alike commonly discussed hypoglycaemic ‘reactions’, a term that regrettably isnow seldom used. It emphatically describes the sudden, and often florid, onset of the autonomicfeatures of hypoglycaemia, which drive the individual to seek assistance or obtain asupply of glucose to relieve these unpleasant symptoms.‘Awareness’ of HypoglycaemiaThe generation of typical physiological responses to hypoglycaemia is perceived throughsensory feedback to the brain, and after central processing, an appropriate motor responseis made. Much has been made by some commentators of the predominant importanceof autonomic symptoms in the detection of the onset of hypoglycaemia. This premise is