Hypoglycaemia in Clinical Diabetes

164 IMPAIRED AWARENESS OF HYPOGLYCAEMIAFigure 7.9 Augmentation of the normal secretory response of epinephrine (adrenaline) to, andawareness of, acute hypoglycaemia (blood glucose 2.8 mmol/l) by the prior ingestion of caffeine ininsulin-treated diabetic patients. Derived from data in Debrah et al. (1996)achieve as it is extremely time-consuming and labour-intensive both for patients and healthprofessionals. The use of continuous subcutaneous insulin infusion overnight instead ofisophane (NPH) insulin at bedtime has been shown to be beneficial in diabetic patientswith impaired awareness of hypoglycaemia, improving warning symptoms and counterregulatoryresponses to hypoglycaemia, presumably by reducing the frequency of nocturnalhypoglycaemia (Kanc et al., 1998).The ingestion of caffeine uncouples the relationship between cerebral blood flow andglucose utilisation via antagonism of adenosine receptors, causing relative neuroglycopeniaand earlier release of counterregulatory hormones during moderate hypoglycaemia. Theprior consumption of caffeine augments the symptomatic and counterregulatory hormonalresponses to a modest reduction of blood glucose in non-diabetic subjects (Kerr et al., 1993),and a similar phenomenon occurs in people with type 1 diabetes following the ingestion of adose of caffeine equivalent to two or three cups of coffee (Debrah et al., 1996). The reductionin cerebral blood flow is sustained, the counterregulatory response is augmented (Figure 7.9)and greater awareness of hypoglycaemia occurs (see Chapter 5). This raises the prospectof identifying some form of therapeutic intervention, which utilises a similar mechanism toheighten the residual symptomatic response in people with type 1 diabetes who have impairedawareness of hypoglycaemia. The adenosine-receptor antagonist, theophylline, stimulatesthe secretion of catecholamines and reduces cerebral blood flow, and a single intravenousdose has been shown to enhance counterregulatory hormone responses to hypoglycaemiaand partially restore perception of hypoglycaemic symptoms in patients with type 1 diabeteswith impaired awareness of hypoglycaemia (de Galan et al., 2002). Glycaemic thresholdsfor haemodynamic and symptomatic responses were restored to normal. It is not knownwhether oral theophylline would be as effective, and whether the effects can be sustained,as the development of tolerance to these drugs is common.It is clearly desirable to avoid severe hypoglycaemia at all costs, and treatment strategiesshould be adopted to achieve this aim (Box 7.5). Frequent blood glucose monitoring isessential in affected patients, and may require occasional nocturnal measurements to detect