Hypoglycaemia in Clinical Diabetes

52 FREQUENCY, CAUSES AND RISK FACTORSquality of glycaemic control (The Diabetes Control and Complications Trial Research Group,1997) and the presence of impaired awareness of hypoglycaemia (Gold et al., 1997) havea major influence on the frequency of hypoglycaemia. Participants in clinical interventionalstudies are often not representative of the wider body of people with type 1 diabetes. Forexample, in the DCCT (The Diabetes Control and Complications Trial Research Group,1993), the subjects were young, motivated and received substantial professional support(particularly those in the intensive group). They were pre-selected depending on their historyof hypoglycaemia. Thus, individuals were excluded if, in the previous two years, theyhad experienced more than one episode of severe hypoglycaemia causing neurologicalimpairment, without experiencing warning symptoms, or more than two episodes of seizureor coma, regardless of attributed cause. Such exclusions will have inevitably influenced thebaseline frequency of severe hypoglycaemia in the study groups.Small studies estimating the frequency of hypoglycaemia are likely to be biased becausechance variations in the prevalence of risk factors for hypoglycaemia can magnify (ordiminish) the frequency of hypoglycaemic events to a much greater extent than would beobserved in larger investigations. There is also likely to be a major period effect in studiesof the prevalence of hypoglycaemia. In the post-DCCT era, it might be anticipated thatthe incidence of hypoglycaemia would rise as patients and diabetes healthcare professionalssought to tighten glycaemic control (Johnson et al., 2002). This trend may be counterbalancedby the increased use of home blood glucose monitoring, improved educational programmesand the greater use of insulin analogues and continuous subcutaneous insulin infusion therapy(Chase et al., 2001).Thus, estimates of the frequency of hypoglycaemia must be considered in relation to thedefinitions employed and the characteristics of the patients studied. Comparisons betweenpresent-day and historical studies must be made in the knowledge that treatment targets,methods of monitoring blood glucose and insulin therapy have changed greatly in recentyears.Frequency of Mild, Symptomatic HypoglycaemiaThe features of several studies that have examined the frequency of mild hypoglycaemia,either prospectively or retrospectively, in adults with type 1 diabetes are shown in Table 3.1.Rates of mild hypoglycaemia vary substantially, ranging from 8 to 160 episodes per patientper year. However, it is extremely difficult to make direct comparisons between individualstudies because of differences in methodology and patient characteristics.Retrospective studiesTwo retrospective studies by a Danish group (Pedersen-Bjergaard et al., 2001; Pedersen-Bjergaard et al., 2004) were very similar in their patient characteristics, most of whom wereadministering four or more injections of insulin per day and had moderate glycaemic control.On being asked to recall the number of episodes of mild, symptomatic hypoglycaemiaexperienced in the preceding week, the subjects reported a frequency of two episodes perpatient per week. The strength of these studies lies in the large numbers of patients examinedand the short period of recall. This should have minimised inaccuracy, but may have beenan unrepresentative time frame.