Hypoglycaemia in Clinical Diabetes

CONCLUSIONS 95glycaemic control (Heller et al., 1999; Heller et al., 2004), and although this has generallybeen demonstrated for symptomatic episodes, these data might reflect a lower frequency ofsevere hypoglycaemia (Holleman et al., 1997).The long-acting analogues – insulins glargine and detemir – which provide basal insulinreplacement, also appear to lower the risk of nocturnal hypoglycaemia. They have a longerduration of action when compared to isophane (NPH) insulin, together with less of a peakin their time-action profile and a more consistent duration of action (Barnett, 2003). Bothof these properties probably contribute to the lower rates of nocturnal hypoglycaemia thathave been observed during clinical trials. Relative risk reductions of around 30% have beenreported for long-acting preparations in trials involving patients with type 1 (De Leeuw et al.,2005; Pieber et al., 2000) and with type 2 diabetes (Hermansen et al., 2006; Yki-Jarvinenet al., 2000).The combination of both rapid and long-acting insulin analogues might be expected to havea particularly powerful effect in lowering the risk of nocturnal hypoglycaemia. In the fewstudies comparing combinations of insulin analogues to conventional insulins this appears tobe the case. Hermansen et al. (2004) reported a 55% lower rate of symptomatic nocturnalhypoglycaemia when using an insulin detemir/aspart combination as basal-bolus therapy inpatients with type 1 diabetes, which was accompanied by a modest but significant fall in HbA 1cof 0.2%. Ashwell et al. (2006) observed a fall in HbA 1c of 0.5% using insulin glargine andlispro in a basal-bolus regimen in patients with type 1 diabetes, while nocturnal hypoglycaemiawas 44% lower in frequency. However, nocturnal hypoglycaemia was not eradicated,leading to the conclusion that although insulin analogues may help to reduce the side-effectsof insulin therapy, they do not approach the requirements of therapeutic insulin delivery.Continuous Subcutaneous Insulin Infusion (CSII)Since nocturnal hypoglycaemia is largely the result of inadequate basal insulin replacement,one would expect that the most effective method of basal insulin delivery currently available,CSII, could limit the frequency of nocturnal hypoglycaemia (Pickup and Keen, 2002).However, early studies reported surprisingly little effect on hypoglycaemia, perhaps becauseof a failure to train patients in the essential related skills of carbohydrate and insulindose adjustment. More recent work has indicated that CSII can reduce overall rates ofhypoglycaemia (Bode et al., 1996; Boland et al., 1999; Kanc et al., 1998), but specificreporting on rates of nocturnal episodes is unusual. Furthermore, few trials have used arandomised design, suggesting that a lower risk might relate to other characteristics ofthose who use CSII rather than to the technology itself. Thus the amount to which modernpump therapy lowers the risk of nocturnal hypoglycaemia has still be to be established.Nevertheless, in those who have experienced recurrent nocturnal episodes and who have notimproved after a trial of insulin analogues, it seems worthwhile undertaking a trial of CSII.CONCLUSIONS• Nocturnal hypoglycaemia remains an unresolved clinical side-effect of insulin therapypreventing the attainment of strict glycaemic control for many people. It contributes tomorbidity, and perhaps mortality, in patients with type 1 diabetes.