Page 262 - Glucose Monitoring Devices

Future direction 269

main issue with the Medtronic LGS system was sensor inaccuracy that resulted in
the activation of LGS due to sensor reading a low value when blood glucose was
not in the hypoglycemic range or even was elevated. From many clinical trials
and real-life studies, it is evident that the mean LGS suspension period was less
than 30 min, mainly during the day, suggesting that often patients would terminate
LGS events either due to sensor glucose errors or because they acted by consuming
carbohydrates before checking capillary blood glucose. Another limitation of LGS
systems is the inability to prevent hypoglycemia. In the LGS pump, the suspension is
triggered by the absolute prevailing glucose level, but there may be advantages to
suspending insulin infusion based on predicted hypoglycemia. Studies under
short-term hospital conditions have already shown that algorithms that activate
insulin suspend when hypoglycemia is predicted (predicted low glucose suspend
system, PLGS) can significantly reduce both daytime and nocturnal hypoglycemic
events. The details on the safety and effectiveness of PLGS are discussed in the
following chapter of this book. The efficacy of the LGS system should also be
considered in the context of currently available insulin pharmacokinetics. It takes
at least 30 min after suspension of basal insulin delivery before plasma insulin levels
will decline enough to allow blood glucose to increase, suggesting that although the
suspension of basal insulin alone will often not be enough to prevent hypoglycemia
from occurring, it will usually be sufficient to reduce the duration and depth of
hypoglycemia. If hypoglycemia is caused by an excess of bolus insulin, suspending
the basal insulin will be less effective, which may explain why there is less of a
reduction in day-time hypoglycemia when the LGS feature is used. The LGS
systems (Medtronic 530G and Paradigm Veo) suspend insulin delivery for 2 h
once the LGS is activated and patients can choose not to override. Therefore, 2 h
of insulin interruption may result in hyperglycemia especially when LGS activation
may have happened while actual capillary glucose may not be low enough. However,
a small interventional study described earlier was reassuring that 2 h of insulin inter-
ruption, even with normal glucose levels, does not result in clinically significant
ketonemia [33e35].
In summary, marketed LGS systems helped patients with T1D reduce the
severity and duration of hypoglycemia, and this result was confirmed in both ran-
domized controlled clinical trials and real-life studies.

Future direction
As discussed earlier, the LGS system does not completely prevent hypoglycemia as
it suspends insulin delivery only when sensor glucose reaches a predetermined
glucose threshold. The next development toward closing the loop was suspending
insulin based on PLGS. Studies have shown that the PLGS system significantly
reduced the hypoglycemic episodes compared to the LGS system in patients with
T1D [56e59]. The PLGS system led to the development of the hybrid closed-
loop system (670G System) where the insulin pump adjusts basal insulin delivery