Hypoglycaemia in Clinical Diabetes

68 FREQUENCY, CAUSES AND RISK FACTORSstatistical adjustment for HbA 1c concentration. Indeed, in the intensive group, only about 5%of the variation in frequency of severe hypoglycaemia could be explained by the glycatedhaemoglobin concentration (The Diabetes Control and Complications Trial Research Group,1997).Other studies have reported variable relationships between glycaemic control andfrequency of severe hypoglycaemia. In the study by Bott et al., (1997) a lower mean HbA 1cwas associated with severe hypoglycaemia, but there was no linear or quadratic relationshipbetween HbA 1c and severe hypoglycaemia. In the EURODIAB IDDM ComplicationsStudy, severe hypoglycaemia (defined as episodes requiring third party assistance) occurredin 32% of individuals over 12 months. A clear relationship to glycated haemoglobin wasevident, in that 40% of individuals with an HbA 1c < 54% were affected compared with24% of individuals with a HbA 1c > 78% (The EURODIAB IDDM Complications StudyGroup, 1994). In the study of workplace hypoglycaemia, recurrent severe hypoglycaemiawas associated with strict glycaemic control, but no link was found in individuals who hadexperienced only one episode (Leckie et al., 2005). In several other studies, no relationshipwas observed between severe hypoglycaemia and glycated haemoglobin (Muhlhauseret al., 1985; Muhlhauser et al., 1987; MacLeod et al., 1993; Gold et al., 1997; Muhlhauseret al., 1998; ter Braak et al., 2000; Pedersen-Bjergaard et al., 2001; Leese et al., 2003;Pedersen-Bjergaard et al., 2003a; Pedersen-Bjergaard et al., 2004) after adjustment for otherrisk factors.Glycated haemoglobin does not, of course, provide the entire picture about an individual’sglycaemic control and although HbA 1c may not predict risk of hypoglycaemia, low meanhome blood glucose concentrations and excessive variability in blood glucose can identifyindividuals more prone to hypoglycaemia (Cox et al., 1994; Janssen et al., 2000).Thus, a straightforward relationship does not exist between severe hypoglycaemia andglycaemic control. For an episode of mild hypoglycaemia to progress to one that causessignificant neuroglycopenia and impairs consciousness, other factors must operate, whichnegate the normal symptomatic and hormonal responses to hypoglycaemia.Acquired Hypoglycaemia SyndromesWithin each treatment group of the DCCT, the number of previous episodes of severehypoglycaemia was the strongest predictor of risk of future episodes (The Diabetes Controland Complications Trial Research Group, 1997). Moreover, approximately 30% of patientsin each group experienced a second episode of severe hypoglycaemia within four monthsfollowing an initial episode. The importance of a previous history of severe hypoglycaemiain predicting future risk has been replicated in several other studies (MacLeod et al., 1993;Bott et al., 1997; Gold et al., 1997; Muhlhauser et al., 1998). Moreover, as demonstrated inTable 3.3, many studies have also linked increased duration of diabetes with an increasedrisk of severe hypoglycaemia.Cryer has suggested that the integrity of the glucose counterregulatory system may be apivotal factor in determining whether the relative or absolute hyperinsulinism that frequentlyoccurs in insulin-treated diabetes ultimately results in the development of hypoglycaemia(Cryer, 1994; Cryer et al., 2003). Three acquired hypoglycaemia syndromes are associatedwith an increased risk of severe hypoglycaemia in people with type 1 diabetes. These areconsidered in greater detail in Chapters 6 and 7.