Page 323 - Glucose Monitoring Devices

330 CHAPTER 16 The dawn of automated insulin delivery

than the prospect of increasing insulin delivery if sensor glucose levels are above a
target range [16,17]. This document harmonized the goals for academic researchers,
industry sponsors, and regulators and provided patients’ perspectives on the process.

Making the dive less deep and shorter: low glucose suspend
systems
Interrupting preset basal insulin delivery when the sensor glucose reached a prede-
fined low threshold was the first step toward closing the loop. As the fear of
hypoglycemia is a well-known barrier to achieving glycemic targets, this step was
critical in motivating patients, their families, and healthcare providers to attain
targeted glycemia [12]. Interestingly, early data from feasibility studies of closed-
loop systems provided some justification for threshold suspend systems [18,19].
Low glucose suspend (LGS) systems stop insulin delivery at a preset glucose
threshold between 60 and 90 mg/dL (3.3e5 mmol/L) for 2 h unless the patient
intervenes by resuming insulin delivery. Regardless of sensor glucose levels 2 h
following the suspension, insulin delivery resumes. The Automation to Simulate
Pancreatic Insulin Response (ASPIRE) In-Clinic study examined how the LGS
feature worked if hypoglycemia was induced through exercise and demonstrated
that duration and severity of hypoglycemia are reduced when the feature is
activated [20].
Regulatory approval of LGS systems occurred in Europe in 2009 with the com-
mercial availability of the Medtronic Paradigm Veo with LGS. Using real-world data
extracted from insulin pump uploads, Agrawal and colleagues were able to assess
nearly 50,000 patient-days of system use [21]. Although LGS events were not
uncommon, occurring on 50% of days studied, the median duration of these events
was w10 min with only 11% lasting >115 min [21]. A subanalysis of 278 partici-
pants with at least 3 months of LGS use demonstrated that the feature was able to
reduce hypoglycemic (<50 mg/dL) and hyperglycemic (>300 mg/dL) episodes [21].
Building on the In-Clinic ASPIRE study assessment, the ASPIRE In-Home study
sought to assess the use of the LGS feature in a cohort of individuals with T1D with
documented nocturnal hypoglycemia [22]. In this study, 247 participants were ran-
domized to either sensor-augmented pump (SAP) therapy or SAP with the LGS
feature for 3 months’ time [22]. Nocturnal hypoglycemia was significantly reduced
in the LGS group compared to the SAP control group without causing an increase in
HbA1c [22]. Furthermore, a randomized controlled trial of participants with T1D
and impaired hypoglycemia awareness demonstrated a reduction in severe (e.g.,
seizure or coma) and moderate hypoglycemic events in the LGS group. Furthermore,
this group had less biochemical hypoglycemia based on sensor glucose readings,
especially in the overnight period [23]. In September 2013, the first LGS system,
the MiniMed 530G with Enlite, was approved by the FDA for persons with diabetes
16 years of age and older.