Hypoglycaemia in Clinical Diabetes

PATHOPHYSIOLOGY OF HYPOGLYCAEMIA 241Arterialised bloodglucose (mmol/l)4.03.5SYMPTOMSYounger men(3.6 mmol/l)3.0SYMPTOMSREACTION TIMEOlder men (3.0 mmol/l)2.5FOUR CHOICEREACTION TIMEYounger men(2.6 mmol/l)2.0Figure 11.1 Glycaemic thresholds for subjective symptomatic awareness of hypoglycaemia and forthe onset of cognitive dysfunction in young and elderly non-diabetic males. Figure based on dataderived from Matyka et al. (1997) and reproduced from McAulay and Frier (2001), with permissionfrom John Wiley and Sons, LtdCounterregulationEarly studies examining counterregulatory responses in elderly non-diabetic adults yieldedconflicting results, partly because interpretation of the data was confounded by the presenceof co-morbidities in many of the participants. However, subsequent studies suggest that theremay be age-related alterations in counterregulation. One study used an intravenous infusionof insulin to compare the counterregulatory responses to hypoglycaemia in non-diabeticelderly and young adults (Marker et al., 1992). This study suggested that with advancingage the secretion of growth hormone and cortisol is diminished, with modest attenuation ofblood glucose recovery in older non-diabetic adults, in whom the rise in plasma epinephrineis slower than in younger subjects (Marker et al., 1992). The secretion of glucagon and therate of insulin clearance were also lower. A reduced rate of clearance of insulin has beennoted in several studies (Minaker et al., 1982; Reaven et al., 1982; Fink et al., 1985). Thechanges observed by Marker and colleagues were unaffected by preceding physical training,suggesting that they are not simply a consequence of a more sedentary lifestyle associatedwith ageing (Marker et al., 1992). The glycaemic thresholds for the secretion of glucagonand epinephrine in response to hypoglycaemia also occur at a lower blood glucose level thanin younger subjects. In young non-diabetic adults, these hormones are released at a bloodglucose level of 3.3 mmol/l, compared to approximately 2.8 mmol/l in older adults (Meneillyet al., 1994a).With increasing age, the intensity of the hypoglycaemic stimulus (as demonstrated byblood glucose nadir) appears to influence the magnitude of the counterregulatory response.