Acceptability of Implantable Continuous Glucose Monitoring Sensor.

BACKGROUND: Real-time continuous glucose monitoring is associated with significant benefits for diabetes management. Implantable sensors could overcome some challenges reportedly associated with device visibility, psychosocial functioning and sensor durability. METHODS: A psychosocial assessment was conducted to determine acceptability and impact of an implantable continuous glucose monitoring (CGM) sensor as part of the PRECISE trial. Questionnaires were administered to participants comprising the Diabetes Distress Scale, the CGM impact scale, and bespoke device satisfaction. RESULTS: Fifty-one participants across the United Kingdom (n = 10) and Germany (n = 41) completed the questionnaires. Of these, 90% had T1D, 50% followed an insulin pump therapy regimen, and 45% of the participants were previous CGM users. CGM Impact Scale results show 86% (n = 44) of participants reported feeling better (14% neutral) about their diabetes control with 90% CGM naïve participants and 81% previous CGM users reporting increased confidence about their diabetes management. Furthermore, 73% (n = 37) felt more safe (27% neutral) while sleeping and 78% (n = 39) more confident (22% neutral) about avoiding serious hypoglycemia. Responses correspond with an average improvement in HbA1c from 7.51 to 7.05 ( P < .0001) over the 90 days use of the CGM. Overall, the system was rated highly on ease of use, convenience and comfort. 84% would choose to be inserted again with 93% of CGM naïve participants (86% previous CGM users) reporting minimized burden of diabetes. CONCLUSIONS: Implantable CGM devices are acceptable to users and are evaluated favorably. The considerable majority of participants (93% of first time users and 77% previous CGM users) would like to continue using the system to help manage their diabetes more effectively.

Venous, Arterialized-Venous, or Capillary Glucose Reference Measurements for the Accuracy Assessment of a Continuous Glucose Monitoring System.

BACKGROUND: Different reference methods are used for the accuracy assessment of continuous glucose monitoring (CGM) systems. The effect of using venous, arterialized-venous, or capillary reference measurements on CGM accuracy is unclear. METHODS: We evaluated 21 individuals with type 1 diabetes using a capillary calibrated CGM system. Venous or arterialized-venous reference glucose samples were taken every 15 min at two separate visits and assessed per YSI 2300 STAT Plus. Arterialization was achieved by heated-hand technique. Capillary samples were collected hourly during the venous reference visit. The investigation sequence (venous or arterialized-venous) was randomized. Effectiveness of arterialization was measured by comparing free venous oxygen pressure (PO2) of both visit days. Primary endpoint was the median absolute relative difference (ARD). RESULTS: Median ARD using arterialized-venous reference samples was not different from venous samples (point estimated difference 0.52%, P = 0.181). When comparing the three reference methods, median ARD was also not different over the full glycemic range (venous 9.0% [n = 681], arterialized-venous 8.3% [n = 684], and capillary 8.1% [n = 205], P = 0.216), nor over the separate glucose ranges. Arterialization was successful (PO2 venous 5.4 kPa vs. arterialized-venous 8.9 kPa, P < 0.001). Arterialized-venous glucose was significantly higher than venous glucose and numerically higher than capillary glucose (arterialized-venous 142 mg/dL vs. venous 129 mg/dL [P < 0.001] and vs. capillary 134 mg/dL [P = 0.231]). Inconvenience related to arterialization included transient mild edema and redness of the hand in 4 out of 21 (19%) patients. CONCLUSIONS: The use of venous, arterialized-venous, or capillary reference measurements did not significantly impact CGM accuracy. Venous reference seems preferable due to its ease of operation.

Accuracy and Longevity of an Implantable Continuous Glucose Sensor in the PRECISE Study: A 180-Day, Prospective, Multicenter, Pivotal Trial.

OBJECTIVE: It is known that continuous glucose monitoring (CGM) systems can lower mean glucose compared with episodic self-monitoring of blood glucose. Implantable CGM systems may provide additional benefits. RESEARCH DESIGN AND METHODS: We studied the Eversense (Senseonics Inc.) implantable CGM sensor in 71 participants aged 18 years and older with type 1 and type 2 diabetes in a 180-day multinational, multicenter pivotal trial. Participants used the CGM system at home and in the clinic. CGM accuracy was assessed during eight in-clinic visits with the mean absolute relative difference (MARD) for venous reference glucose values >4.2 mmol/L as the primary end point. Secondary end points included Clarke Error Grid Analysis and alarm performance. The primary safety outcome was device-related serious adverse events. This trial is registered with ClinicalTrials.gov, number NCT02154126. RESULTS: The MARD value against reference glucose values >4.2 mmol/L was 11.1% (95% CI 10.5, 11.7). Clarke Error Grid Analysis showed 99.2% of samples in the clinically acceptable error zones A and B. Eighty-one percent of hypoglycemic events were detected by the CGM system within 30 min. No device-related serious adverse events occurred during the study. CONCLUSIONS: Our results indicate the safety and accuracy of this new type of implantable CGM system and support it as an alternative for transcutaneous CGM.

Day-and-Night Closed-Loop Glucose Control in Patients With Type 1 Diabetes Under Free-Living Conditions: Results of a Single-Arm 1-Month Experience Compared With a Previously Reported Feasibility Study of Evening and Night at Home.

OBJECTIVE: After testing of a wearable artificial pancreas (AP) during evening and night (E/N-AP) under free-living conditions in patients with type 1 diabetes (T1D), we investigated AP during day and night (D/N-AP) for 1 month. RESEARCH DESIGN AND METHODS: Twenty adult patients with T1D who completed a previous randomized crossover study comparing 2-month E/N-AP versus 2-month sensor augmented pump (SAP) volunteered for 1-month D/N-AP nonrandomized extension. AP was executed by a model predictive control algorithm run by a modified smartphone wirelessly connected to a continuous glucose monitor (CGM) and insulin pump. CGM data were analyzed by intention-to-treat with percentage time-in-target (3.9-10 mmol/L) over 24 h as the primary end point. RESULTS: Time-in-target (mean ± SD, %) was similar over 24 h with D/N-AP versus E/N-AP: 64.7 ± 7.6 vs. 63.6 ± 9.9 (P = 0.79), and both were higher than with SAP: 59.7 ± 9.6 (P = 0.01 and P = 0.06, respectively). Time below 3.9 mmol/L was similarly and significantly reduced by D/N-AP and E/N-AP versus SAP (both P < 0.001). SD of blood glucose concentration (mmol/L) was lower with D/N-AP versus E/N-AP during whole daytime: 3.2 ± 0.6 vs. 3.4 ± 0.7 (P = 0.003), morning: 2.7 ± 0.5 vs. 3.1 ± 0.5 (P = 0.02), and afternoon: 3.3 ± 0.6 vs. 3.5 ± 0.8 (P = 0.07), and was lower with D/N-AP versus SAP over 24 h: 3.1 ± 0.5 vs. 3.3 ± 0.6 (P = 0.049). Insulin delivery (IU) over 24 h was higher with D/N-AP and SAP than with E/N-AP: 40.6 ± 15.5 and 42.3 ± 15.5 vs. 36.6 ± 11.6 (P = 0.03 and P = 0.0004, respectively). CONCLUSIONS: D/N-AP and E/N-AP both achieved better glucose control than SAP under free-living conditions. Although time in the different glycemic ranges was similar between D/N-AP and E/N-AP, D/N-AP further reduces glucose variability.

Assessing the Accuracy of Continuous Glucose Monitoring (CGM) Calibrated With Capillary Values Using Capillary or Venous Glucose Levels as a Reference.

BACKGROUND: Using the standard venous reference for the evaluation of continuous glucose monitoring (CGM) systems could possibly negatively affect measured CGM accuracy since CGM are generally calibrated with capillary glucose and venous and capillary glucose concentrations differ. We therefore aimed to quantify the effect of using capillary versus venous glucose reference samples on estimated accuracy in capillary calibrated CGM. METHODS: We evaluated 41 individuals with type 1 diabetes mellitus (T1DM) using the Dexcom G4 CGM system over 6 days. Patients calibrated their CGM devices with capillary glucose by means of the HemoCue system. During 2 visits, capillary and venous samples were simultaneously measured by HemoCue and compared to concomitantly obtained CGM readings. The mean absolute relative difference (MARD) was calculated using capillary and venous reference samples. RESULTS: Venous glucose values were 0.83 mmol/L (15.0 mg/dl) lower than capillary values over all glycemic ranges, P < .0001. Below 4 mmol/l (72 mg/dl), the difference was 1.25 mmol/l (22.5 mg/dl), P = .0001, at 4-10 mmol/l (72-180 mg/dl), 0.67 mmol/l (12.0 mg/dl), P < .0001 and above 10 mmol/l (180 mg/dl), 0.95 mmol/l (17.1 mg/dl), P < .0001. MARD was 11.7% using capillary values as reference compared to 13.7% using venous samples, P = .037. Below 4 mmol/l (72 mg/dl) MARD was 16.6% and 31.8%, P = .048, at 4-10 mmol/l (72-180 mg/dl) 12.1% and 12.6%, P = .32, above 10 mmol/l (180 mg/dl) 8.7% and 9.2%, P = .82. CONCLUSION: Using capillary glucose concentrations as reference to evaluate the accuracy of CGM calibrated with capillary samples is associated with a lower MARD than using venous glucose as the reference. Capillary glucose concentrations were significantly higher than venous in all glycemic ranges.

Continuous Glucose Monitoring, Future Products, and Update on Worldwide Artificial Pancreas Projects.

The development of accurate and easy-to-use continuous glucose monitoring (CGM) improved diabetes treatment by providing additional temporal information on glycemia and glucose trends to patient and physician. Although CGM enables users to lower their average glucose level without an increased incidence of hypoglycemia, this comes at the price of additional patient effort. Automation of insulin administration, also known as closed-loop (CL) or artificial pancreas treatment, has the promise to reduce patient effort and improve glycemic control. CGM data serve as the conditional input for insulin automation devices. The first commercial product for partial automation of insulin administration used insulin delivery shutoff at a predefined glucose level. These systems showed a reduction in hypoglycemia. Insulin-only CL devices show increased time spent in euglycemia and a reduction of hypo- and hyperglycemia. Improved glycemic control, coinciding with a minor decrease in hemoglobin A1c level, was confirmed in recent long-term home studies investigating these devices, paving the way for pivotal studies for commercialization of the artificial pancreas. Although the first results from dual-hormone CL systems are promising, because of increased cost of consumables of these systems, long-term head-to-head studies will have to prove superiority over insulin-only approaches. Now CL glucose control for daily use might finally become reality. Improved continuous glucose sensing technology, miniaturization of electrical devices, and development of algorithms were key in making this possible. Clinical adoption challenges, including device usability and reimbursement, need to be addressed. Time will tell for which patient groups CL systems will be reimbursed and whether these devices can deliver the promise that they hold.

2 month evening and night closed-loop glucose control in patients with type 1 diabetes under free-living conditions: a randomised crossover trial.

BACKGROUND: An artificial pancreas (AP) that can be worn at home from dinner to waking up in the morning might be safe and efficient for first routine use in patients with type 1 diabetes. We assessed the effect on glucose control with use of an AP during the evening and night plus patient-managed sensor-augmented pump therapy (SAP) during the day, versus 24 h use of patient-managed SAP only, in free-living conditions. METHODS: In a crossover study done in medical centres in France, Italy, and the Netherlands, patients aged 18-69 years with type 1 diabetes who used insulin pumps for continuous subcutaneous insulin infusion were randomly assigned to 2 months of AP use from dinner to waking up plus SAP use during the day versus 2 months of SAP use only under free-living conditions. Randomisation was achieved with a computer-generated allocation sequence with random block sizes of two, four, or six, masked to the investigator. Patients and investigators were not masked to the type of intervention. The AP consisted of a continuous glucose monitor (CGM) and insulin pump connected to a modified smartphone with a model predictive control algorithm. The primary endpoint was the percentage of time spent in the target glucose concentration range (3·9-10·0 mmol/L) from 2000 to 0800 h. CGM data for weeks 3-8 of the interventions were analysed on a modified intention-to-treat basis including patients who completed at least 6 weeks of each intervention period. The 2 month study period also allowed us to asses HbA1c as one of the secondary outcomes. This trial is registered with ClinicalTrials.gov, number NCT02153190. FINDINGS: During 2000-0800 h, the mean time spent in the target range was higher with AP than with SAP use: 66·7% versus 58·1% (paired difference 8·6% [95% CI 5·8 to 11·4], p<0·0001), through a reduction in both mean time spent in hyperglycaemia (glucose concentration >10·0 mmol/L; 31·6% vs 38·5%; -6·9% [-9·8% to -3·9], p<0·0001) and in hypoglycaemia (glucose concentration <3·9 mmol/L; 1·7% vs 3·0%; -1·6% [-2·3 to -1·0], p<0·0001). Decrease in mean HbA1c during the AP period was significantly greater than during the control period (-0·3% vs -0·2%; paired difference -0·2 [95% CI -0·4 to -0·0], p=0·047), taking a period effect into account (p=0·0034). No serious adverse events occurred during this study, and none of the mild-to-moderate adverse events was related to the study intervention. INTERPRETATION: Our results support the use of AP at home as a safe and beneficial option for patients with type 1 diabetes. The HbA1c results are encouraging but preliminary. FUNDING: European Commission.