Hypoglycaemia in Clinical Diabetes

110 MODERATORS, MONITORING AND MANAGEMENTMinutes of interstitial hypoglycaemia20016012080400DayplaceboDaycaffeineNightplaceboNightcaffeineFigure 5.8 Diurnal variation in time spent in hypoglycaemic range (interstitial glucose < 35 mmol/l)comparing caffeine and placebo. Error bars indicate the confidence intervals of the meansPrevious studies have shown that ingestion of moderate amounts of caffeine may be usefulby augmenting the symptomatic and hormonal responses to mild hypoglycaemia. Caffeine(3–4 cups of drip-brewed coffee each day) enhances the symptomatic and sympathoadrenalresponses to hypoglycaemia in healthy non-diabetic volunteers and in patients with type 1diabetes (Kerr et al., 1993; Debrah et al., 1996). This may enhance the ability of individualsto perceive the onset of symptoms and take appropriate action by ingesting carbohydratebefore neuroglycopenia develops. The beneficial effect of caffeine on hypoglycaemia risk isindependent of a change in glycaemic control (Watson et al., 2000). Putative mechanismshave included an increase in counterregulatory hormones, including epinephrine, growthhormone and cortisol, but not norepinephrine (Debrah et al., 1996).More recently the influence of caffeine on frequency of hypoglycaemia in patients withlong-standing type 1 diabetes has been studied using CGMS. By using continuous monitoring,caffeine appears to reduce the duration of nocturnal hypoglycaemia in subjects with type 1diabetes by almost 50% (Richardson et al., 2005a) (Figure 5.8). It has been suggested thata beneficial effect of the caffeine-associated reduction in nocturnal hypoglycaemia may beto reduce the risk of developing impaired awareness of hypoglycaemia on the next day. Thecaffeine-associated reduction in ‘antecedent’ nocturnal hypoglycaemia seen in these studiesmay explain the augmentation in the symptomatic and hormonal responses to mild daytimehypoglycaemia described previously (Debrah et al., 1996).The relationship between autonomic dysfunction and the development of impaired awarenessof hypoglycaemia was unclear for many years (see Chapter 7). Most studies havesuggested that peripheral autonomic neuropathy is not associated with an increased riskof severe hypoglycaemia (Polinsky et al., 1980; Bjork et al., 1990; Ryder et al., 1990;The DCCT Research Group, 1991) although central autonomic dysfunction may be important(Evans et al., 2003). Although caffeine improves parasympathetic autonomic function(Richardson et al., 2004), no correlation was found with the observed reduction in nocturnalhypoglycaemia associated with caffeine. As mentioned earlier, it is possible that caffeineuncouples cerebral blood flow and glucose utilisation via antagonism of adenosine receptors(Laurienti et al., 2003), attenuating the glucose supply to the brain (reduced cerebral blood