A predictive detection system helps to reduce risk of low blood glucose.
Continuous glucose monitoring (CGM) systems and insulin pumps have been used more recently to help better improve clinical outcomes in type 1 diabetes (T1D). These designs contain a monitoring algorithm known as the “Low glucose suspend” algorithm. It detects hypoglycemia and responds by shutting off basal insulin delivery. To improve the design of CGMs, detection of hypoglycemia before it occurs is imperative. This detection is done by a system known as the predictive low-glucose management (PLGM) system. The PLGM system has shown to reduce hypoglycemia in short-term outpatient observational studies and in a 2-week randomized controlled trial. These studies lack findings of poor glycemic control. Also, the effects of behavioral changes have not been addressed in previous trials. Lastly, these studies have not measured the longevity and efficacy of PLGM systems. Based on the lack of evidence mentioned, a 6-month study was conducted to evaluate the overall efficacy of PLGM systems. The MiniMed 640G pump, equipped with the PLGM technology, a special sensor and transmitter works by suspending insulin infusions before glycemic levels become too low. Recent surveys show that adolescents are at a higher risk for hypoglycemia and have higher HbA1c. To best evaluate the safety and efficacy of this technology, adolescents with T1D were tested in real-life conditions.
A phase-3 multicenter, unblinded, parallel, randomized control trial was conducted in Australia. Inclusion criteria were as follows: 8-20 years of age, at least one year of T1D diagnosis, HbA1c <10%, and the use of insulin pump therapy for >6 months. Randomization was done for 169 patients into one of two groups: sensor-augmented pump therapy (SAPT) alone or the intervention group with SAPT+PLGM. SAPT works by suspending insulin when hypoglycemia is detected. The “low-limit” was set at 3.4mmol/L. PLGM was programmed to detect levels at £7.3mmol/L, with the expectation of dropping to £4.5mmol/L within 30mins of detection. If PLGM suspends insulin infusion, the pump will automatically reset within two hours, if all parameters are met. Patients had control over most alert settings, other than the default low-limit alarm. A 2-week run-in period was used to establish proficiency in SAPT and SAPT+PLGM. HbA1c levels, hypoglycemia awareness questionnaires, and CGM satisfaction questionnaires were all used to determine the safety and efficacy of SAPT+PLGM. Study outcomes were based on data collected at 3- and 6-month follow-ups. The primary outcome was the average percentage of time spent in hypoglycemia in each study group. Secondary outcomes were events of hypoglycemia and what time of day they occurred. Safety was also evaluated through the number of ketosis events (blood ketones >0.6mmol/L) and glycemic control at 6 months. Quality of life (QoL) with the system was also assessed.
Results were based on 74 participants in the control group (SAPT alone), and 80 participants in the intervention group (SAPT+PLGM). The mean serum glucose (SG) was (SAPT alone: 9.8mmol/L [9.5-10] vs. SAPT+PLGM: 9.3mmol/L [9.1-9.5]; P< 0.005). There was a statistically significant reduction in the average percentage of time spent in hypoglycemia for the SAPT+PLGM group (2.8%à1.4%, P<0.0001) in comparison to the SAPT group alone (3%à2.6%, P=0.03). The SAPT+PLGM group spent only 20 mins/day with SG <3.5mmol/L, while the SAPT group alone spent 37.7mins/day. SAPT+PLGM resulted in hypoglycemia reduction both during the day (-1.09 [1.33-0.85]; P<0.001) and night (-1.96 [-2.37-1.54]; P<0.0001). At the end of the 6-month study, the SAPT+PLGM group (139 [134-143]; P<0.001) had fewer hypoglycemic events in comparison to the SAPT alone group (227 [217-234]). There were no differences between HbA1c levels from baseline, ketosis events, and quality of life between the two groups.
In conclusion, the use of a PLGM system resulted in a nearly two-fold reduction of hypoglycemia risk. PLGM system proved to be safe and effective without compromising glycemic control and the quality of life for young patients. This 6-month, long-term trial validated the findings of the short-term observational studies. A reduction in hypoglycemia did not have correlation to hyperglycemia. There were some reported adverse events, which led to attrition: installment difficulties, pain or bleeding at sensor site. Some strengths of this study included study duration and the ability to give clinical insight about real-life conditions. A limitation of this study was the small sample size used.
- Preventing hypoglycemia is a goal in patients on insulin and oral antidiabetic therapy.
- The sensor-augmented pump therapy (SAPT) paired with the predictive low-glucose management (PLGM) system allowed a greater reduction in hypoglycemia in T1D adolescents.
- Although patients have control over alarms and alerts, leaving the “Suspend before low” alert on helped to reduce the risk of hypoglycemic events day and night.
Abraham, Mary B., et al. “Reduction in Hypoglycemia with the Predictive Low-Glucose Management System: A Long-Term Randomized Controlled Trial in Adolescents With Type 1 Diabetes.” Diabetes Care, 30 Nov. 2017, p. dc171604., doi:10.2337/dc17-1604.
Adrianna Jackson, Doctor of Pharmacy Candidate: Class of 2018; LECOM College of Pharmacy