This study shows for the first time that the short-term availability of continuous glucose readings, together with a low glucose alarm set to 80 mg/dl and specific instructions for responding to low alarms, significantly reduces the incidence and duration of hypoglycemia by 44 and 64%, respectively, without having any effect on average BG levels. The inability of the CGMSs tested here to prevent all hypoglycemia is most likely due to its ~15-mg/dl overestimation of BG level in the hypoglycemic range.
Our findings support those of others who have shown that use of a low glucose alarm reduces time spent below hypoglycemic thresholds, but differ from previous studies in that our protocol results in a marked reduction in the incidence of hypoglycemia. As mentioned previously, use of an alarm has been reported by others to reduce the average duration of hypoglycemic episodes by between only 21 and 47%,4,9,10,38,39
with no other study reporting a fall in the incidence of hypoglycemia. The findings of these studies are consistent with those of McGarraugh and Bergenstal,40
who reported that many hypoglycemic events detected by a CGMS and verified with BG tests are not treated adequately, leading to an extended episode of hypoglycemia. Also, it was noted that most studies assessing the capabilities of a CGMS with RT glucose information and glucose alarms do not specify what the patient should do with the information made available to them.32
In our study, patients were given specific instructions favoring immediate action in response to low glucose alarms, which may explain why the relative fall in the duration of hypoglycemia was so pronounced and why the incidence of hypoglycemia was reduced markedly with the alarm treatment. It is important to stress, however, that the effect of providing instructions per se on the incidence and duration of hypoglycemia was not examined here and remains to be determined. Finally, the fact that the lesser incidence and the duration of hypoglycemia in the alarm treatment were not accompanied by an increase in average BG level is not surprising given that less than 3.5% of the time was spent below the hypoglycemic threshold.
Our results showing that the use of a CGMS for 3 days can reduce the incidence and duration of hypoglycemic episodes in diabetic individuals is clinically highly relevant, as most individuals with T1DM are more likely to use a CGMS occasionally over successive days when at a high risk of hypoglycemia rather than continuously over weeks and months due to the high cost associated with using these devices. Also, triggering of the low BG level alarm informing the diabetes patient that an episode of hypoglycemia is imminent is particularly important during the day because BG can fall rapidly to reach severe hypoglycemic levels, whereas during the night nocturnal seizures can occur after several hours of low BG levels.41
Despite the potential benefits associated with the protocol described here, the extent to which the broader population of individuals with T1DM would benefit from using CGMSs in this way remains to be determined, as success of the measures adopted in this study to prevent hypoglycemia depends on some members of the population accepting and actually adhering to a few rather stringent guidelines. Also, the extent to which other devices from Medtronic and other manufacturers would perform compared to the Guardian RT CGMS tested in this study remains to be determined. Nevertheless, what this study suggests is that the risk of hypoglycemia should fall significantly if the principles adopted here were to be implemented irrespective of the CGMS tested.
The observation that use of the low glucose alarm, together with some simple instructions, did not decrease the incidence of symptomatic hypoglycemia despite reducing the risk of hypoglycemia determined from a BG level assay, was expected to some extent, due to the inaccuracies of the CGMS at low BG levels. If no mismatches existed between CGMS readings and BG levels, the incidence of symptomatic hypoglycemia and hypoglycemia determined based on BG readings would be expected to be lower for the alarm treatment. However, because CGMS readings in the low glucose range in this study overestimated BG levels by an average of 14.8 mg/dl, it follows that a CGMS alarm triggered at 80 mg/dl would, on average, correspond to a BG level of 65 mg/dl, which, as stated earlier, is within the BG range that would normally elicit a mild symptomatic response to hypoglycemia in hypoglycemia-aware individuals.42
As a result and as observed in our study, the incidence of symptomatic hypoglycemia would be expected to be comparable for both treatments. Also, it must be stressed that the highly subjective nature of the participants’ records of their symptomatic hypoglycemia further increases the difficulty of detecting significant effects of the alarm treatment.
Importantly, the mismatch between the CGMS reading and the BG level also implies that this and other studies9,10,39
underestimate the true frequency and durationof hypoglycemic events, thus overestimating the performance of a CGMS. However, it is important to mention that McGowan and colleagues12
reported thata CGMS may also overestimate
the frequency and durationof hypoglycemia. Indeed, in their study, the CGMS underestimated BG in the low BG range, as determined using reference BG values, suggesting that asymptomatic hypoglycemic events detected by a CGMS may not have been true hypoglycemia.12
Irrespective of whether CGMSoverestimates or underestimates BG levels in the hypo-glycemic range, the susceptibility of a CGMS to error in the low BG range, as well as the considerable variation in the definition and assessment of hypoglycemia, suggests that studies showing that CGMSs are useful for detecting hypoglycemia2,7,43–48
should be interpreted cautiously.
One way to prevent hypoglycemia despite the CGMS overestimation of BG level observed in this study may be simply to increase the low glucose alarm. However, we show in agreement with others that increasing the alarm level results in a favorable increase in the sensitivity of the CGMS to detect hypoglycemia, but at the cost of an undesirable increase in already elevated false alarm rates.9
Because a high rate of false alarms is likely to reduce the compliance of the user,49
this would be considered unacceptable in a free-living setting. However, the improved sensitivity to detect hypoglycemia with an alarm set at levels above 80 mg/dl may be appropriate at times of increased hypoglycemic risk, such as following exercise or in cases of hypoglycemia unawareness.