Page 253 - Glucose Monitoring Devices

260 CHAPTER 13 Low glucose suspend systems

replicated by other researchers demonstrating the safety of insulin interruptions for
at least 2 h without increasing significantly hyperglycemia or ketone levels [31,32].
Moreover, studies have reported that metabolic abnormalities due to insulin delivery
interruptions can be easily corrected by resuming insulin delivery [32]. These early
studies on insulin delivery interruptions used human regular insulin, which has a
longer duration of action compared to rapid-acting insulin analogs. It is also impor-
tant to note that these early studies did not assess the role of insulin suspension in the
presence of hypoglycemia or impending hypoglycemia, where longer duration of in-
sulin delivery may not be associated with significant hyperglycemia or ketoacidosis.
With the availability of rapid-acting insulin analogs such as insulin lispro in
August of 1996, which has a faster onset and shorter duration of action compared
to human regular insulin, it became necessary to replicate the earliest experiment
to document the safe duration of insulin interruptions. To compare the safety
between human regular insulin and insulin lispro after insulin pump interruption,
insulin delivery was stopped at night (3:00 a.m.) for up to 6 h in 18 patients with
T1D [33]. The investigators also evaluated the differences in the time required by
the two insulins to correct metabolic abnormalities after insulin pump resumption
in the second phase of the same experiment [33]. They found no significant differ-
ences between the human regular insulin group and the insulin lispro group in the
reduction in plasma insulin levels or rise in the concentrations of plasma glucose
and 3-hydroxybutyrate. However, in those treated with lispro compared to regular
human insulin, the increase in insulin levels and decrease in plasma glucose were
more rapid [33]. This study reassured the safety of insulin lispro interruption for
at least 2 h, but it also provided evidence that insulin lispro in pumps had better out-
comes when correcting metabolic abnormalities compared to human regular insulin
for insulin-requiring patients with diabetes. Similar results were reported by other
investigators, suggesting that the use of rapid-acting insulin analogs might be a
better option in treating mildly decompensated patients with T1D [34]. These
studies paved the way toward the development of the LGS system for the prevention
of severity of hypoglycemia through insulin delivery interruptions in patients with
T1D using insulin pumps.

Clinical studies with LGS system
The first LGS system, the Paradigm Veo Insulin Pump, was developed by Medtronic
(Northridge, CA) and became commercially available in Europe in June 2009. The
Paradigm Veo can automatically suspend basal insulin delivery for up to 2 h when
the sensor glucose value is at the predetermined threshold. The threshold for insulin
pump suspension in the Paradigm Veo can be set anywhere between 40 and 90 mg/
dL depending on patient and provider preference. Clinical studies with LGS system
has been summarized in Table 13.1 and detailed here in this chapter.
The safety and efficacy of the Paradigm Veo were assessed in 31 patients with
T1D from six centers in the United Kingdom [35]. During the first 2 weeks of the