Adam Retterath

Effect of sensor-augmented insulin pump therapy and automated insulin suspension vs standard insulin pump therapy on hypoglycemia in patients with type 1 diabetes: a randomized clinical trial.

IMPORTANCE Hypoglycemia is a critical obstacle to the care of patients with type 1 diabetes. Sensor-augmented insulin pump with automated low-glucose insulin suspension has the potential to reduce the incidence of major hypoglycemic events. OBJECTIVE To determine the incidence of severe and moderate hypoglycemia with sensor-augmented pump with low-glucose suspension compared with standard insulin pump therapy. DESIGN, SETTING, AND PARTICIPANTS A randomized clinical trial involving 95 patients with type 1 diabetes, recruited from December 2009 to January 2012 in Australia. INTERVENTIONS Patients were randomized to insulin pump only or automated insulin suspension for 6 months. MAIN OUTCOMES AND MEASURES The primary outcome was the combined incidence of severe (hypoglycemic seizure or coma) and moderate hypoglycemia (an event requiring assistance for treatment). In a subgroup, counterregulatory hormone responses to hypoglycemia were assessed using the hypoglycemic clamp technique. RESULTS Of the 95 patients randomized, 49 were assigned to the standard-pump (pump-only) therapy and 46 to the low-glucose suspension group. The mean (SD) age was 18.6 (11.8) years; duration of diabetes, 11.0 (8.9) years; and duration of pump therapy, 4.1 (3.4) years. The baseline rate of severe and moderate hypoglycemic events in the pump-only group was 20.7 vs 129.6 events per 100 patient months in the low-glucose suspension group. After 6 months of treatment, the event rates decreased from 28 to 16 in the pump-only group vs 175 to 35 in the low-glucose suspension group. The adjusted incidence rate per 100 patient-months was 34.2 (95% CI, 22.0-53.3) for the pump-only group vs 9.5 (95% CI, 5.2-17.4) for the low-glucose suspension group. The incidence rate ratio was 3.6 (95% CI, 1.7-7.5; P <.001). There was no change in glycated hemoglobin in either group: mean, 7.4 (95% CI, 7.2-7.6) to 7.4 (95% CI, 7.2-7.7) in the pump-only group vs mean, 7.6 (95%, CI, 7.4-7.9) to 7.5 (95% CI, 7.3-7.7) in the low-glucose suspension group. Counterregulatory hormone responses to hypoglycemia were not changed. There were no episodes of diabetic ketoacidosis or hyperglycemia with ketosis. CONCLUSIONS AND RELEVANCE Sensor-augmented pump therapy with automated insulin suspension reduced the combined rate of severe and moderate hypoglycemia in patients with type 1 diabetes. TRIAL REGISTRATION anzctr.org.au Identifier: ACTRN12610000024044.

The Use of an Automated, Portable Glucose Control System for Overnight Glucose Control in Adolescents and Young Adults With Type 1 Diabetes

OBJECTIVE A key milestone in progress towards providing an efficacious and safe closed-loop artificial pancreas system for outpatient use is the development of fully automated, portable devices with fault detection capabilities to ensure patient safety. The ability to remotely monitor the operation of the closed-loop system would facilitate future physician-supervised home studies. RESEARCH DESIGN AND METHODS This study was designed to investigate the efficacy and safety of a fully automated, portable, closed-loop system. The Medtronic Portable Glucose Control System (PGCS) consists of two subcutaneous glucose sensors, a control algorithm based on proportional-integral-derivative with insulin feedback operating from a BlackBerry Storm smartphone platform, Bluetooth radiofrequency translator, and an off-the-shelf Medtronic Paradigm Veo insulin pump. Participants with type 1 diabetes using insulin pump therapy underwent two consecutive nights of in-clinic, overnight, closed-loop control after a baseline open-loop assessment. RESULTS Eight participants attended for 16 overnight studies. The PGCS maintained mean overnight plasma glucose levels of 6.4 ± 1.7 mmol/L (115 ± 31 mg/dL). The proportion of time with venous plasma glucose <3.9, between 3.9 and 8 (70 and 144 mg/dL), and >8 mmol/L was 7, 78, and 15%, respectively. The proportion of time the sensor glucose values were maintained between 3.9 and 8 mmol/L was greater for closed-loop than open-loop (84.5 vs. 46.7%; P < 0.0001), and time spent <3.3 mmol/L was also reduced (0.9 vs. 3%; P < 0.0001). CONCLUSIONS These results suggest that the PGCS, an automated closed-loop device, is safe and effective in achieving overnight glucose control in patients with type 1 diabetes.

Analysis of Glucose Responses to Automated Insulin Suspension With Sensor-Augmented Pump Therapy

OBJECTIVE The advent of sensor-augmented pump therapy with a low-glucose suspend (LGS) function (Medtronic Paradigm Veo System), allowing insulin to be automatically suspended for up to 2 h when sensor glucose falls below a preset threshold, has the potential to reduce the duration of hypoglycemia. In this article, we analyzed blood glucose profiles following a full 2-h insulin suspension activated by the LGS function, as well as examined different patterns of use among patients. RESEARCH DESIGN AND METHODS Data from a cohort of participants using the Veo System for up to 6 months were analyzed to determine the time and duration of insulin suspension activated by the LGS function. We further evaluated overnight suspend events with no patient response occurring prior to 3:00 a.m., which allowed us to determine the pattern of sensor glucose values with no patient intervention during and after the period of insulin suspension. RESULTS There were 3,128 LGS events during the 2,493 days evaluated. The median duration was 11.2 min, and 36% of events occurred overnight. There were 126 full 2-h suspend events that occurred overnight with no patient response, occurring before 3:00 a.m. For these events, the mean sensor glucose at the end of the 2-h suspend period was 99 ± 6 mg/dL ([means ± SE] 5.5 ± 0.3 mmol/L). The mean sensor glucose 2 h after insulin delivery resumed was 155 ± 10 mg/dL (8.6 ± 0.6 mmol/L). There were no episodes of severe hypoglycemia or diabetic ketoacidosis. CONCLUSIONS Analyses of sensor glucose patterns following insulin suspension activated by LGS suggest that this technology is safe and unlikely to be associated with adverse outcomes.

Feasibility of Outpatient 24-Hour Closed-Loop Insulin Delivery

Studies using outpatient closed-loop insulin delivery for type 1 diabetes have recently been published (1–5). We conducted a 5-day outpatient feasibility study comparing hybrid closed-loop (HCL) to sensor-augmented pump therapy with low-glucose suspend (SAPT + LGS) in eight patients with type 1 diabetes using an open-label randomized crossover trial design (ACTRN12614001005640). We used the Medtronic HCL system: MiniMed insulin pump, MiniMed Enlite II glucose sensor, MiniMed MiniLink REAL-time sensor, MiniMed Translator, and an Android mobile device with the algorithm (proportional integrative derivate with insulin feedback and additional safety parameters—primarily being an upper limit of allowable insulin delivery). Multiple algorithm parameters were individualized according to total daily insulin requirements in the preceding 48 h. Meals were announced by entering a capillary glucose value and meal carbohydrate content, for which bolus insulin was delivered according to the patient’s unique carbohydrate ratio. The Android mobile device sent data via the Internet, …

Exploration of the Performance of a Hybrid Closed Loop Insulin Delivery Algorithm That Includes Insulin Delivery Limits Designed to Protect Against Hypoglycemia

Background: Hypoglycemia remains a risk for closed loop insulin delivery particularly following exercise or if the glucose sensor is inaccurate. The aim of this study was to test whether an algorithm that includes a limit to insulin delivery is effective at protecting against hypoglycemia under those circumstances. Methods: An observational study on 8 participants with type 1 diabetes was conducted, where a hybrid closed loop system (HCL) (Medtronic™ 670G) was challenged with hypoglycemic stimuli: exercise and an overreading glucose sensor. Results: There was no overnight or exercise-induced hypoglycemia during HCL insulin delivery. All daytime hypoglycemia was attributable to postmeal bolused insulin in those participants with a more aggressive carbohydrate factor. Conclusion: HCL systems rely on accurate carbohydrate ratios and carbohydrate counting to avoid hypoglycemia. The algorithm that was tested against moderate exercise and an overreading glucose sensor performed well in terms of hypoglycemia avoidance. Algorithm refinement continues in preparation for long-term outpatient trials.

Continuous Glucose Monitoring Adherence: Lessons From a Clinical Trial to Predict Outpatient Behavior

Aims: This study reports continuous glucose monitoring (CGM) adherence patterns and contributing factors in patients who were part of a 6-month clinical trial using sensor augmented pump therapy with low glucose insulin suspension. Methods: CGM data from 38 patients using sensor augmented pump therapy for 6 months were analyzed. CGM adherence was defined by having a working sensor available and determined by the time it was switched on as a proportion of available time for the 6 month study period with allowance for practical CGM use. Age, gender, HbA1c, duration of diagnosis, capillary blood glucose testing frequency, sensor accuracy, and insulin pump alarm frequency were characterized and examined for an association with CGM adherence. Results: Overall CGM adherence was 75% (range: 35% to 96%), CGM adherence was demonstrated to fall after 9 to 11 weeks before reaching a steady rate. CGM adherence patterns showed substantial variation. Mean adherence differed (P < .01) between age groups 72% (<12 years), 69% (12-18 years), and 88% (≥18 years). Sensor accuracy predicted adherence, where every 1% decline in mean absolute difference in a given week was associated with a 0.5% decline in sensor adherence (P < .01). Gender, HbA1c, duration of diagnosis, capillary blood glucose testing frequency, and insulin pump alarm frequency were not associated with CGM adherence. Conclusions: CGM adherence and patterns of use are individualized. However, a predictable fall in adherence at 9 to 11 weeks may present an opportunity for timed interventions to increase CGM use. Adolescent age and sensor accuracy predict CGM adherence.

The time lag prior to the rise in glucose requirements to maintain stable glycaemia during moderate exercise in a fasted insulinaemic state is of short duration and unaffected by the level at which glycaemia is maintained in Type 1 diabetes

To determine the duration of the low hypoglycaemia risk period after the start of moderate‐intensity exercise performed under basal insulinaemic conditions and whether this period is affected by the level at which glycaemia is maintained under these conditions.

7.5 Reduction of Severe Hypoglycemia with Sensor-Augmented Insulin Pump Therapy and Automated Insulin Suspension in Patients with Type 1 Diabetes (228-OR)

SamenvattingProlonged, severe hypoglycemia is a critical obstacle in the care of patients with T1DM. Sensor-augmented insulin pump therapy with automated low glucose insulin suspension has potential to reduce the incidence of severe hypoglycemia.