BackgroundThe threshold-suspend feature of sensor-augmented insulin pumps is designed to minimize the risk of hypoglycemia by interrupting insulin delivery at a preset sensor glucose value. We evaluated sensor-augmented insulin-pump therapy with and without the threshold-suspend feature in patients with nocturnal hypoglycemia. MethodsWe randomly assigned patients with type 1 diabetes and documented nocturnal hypoglycemia to receive sensor-augmented insulin-pump therapy with or without the threshold-suspend feature for 3 months. The primary safety outcome was the change in the glycated hemoglobin level. The primary efficacy outcome was the area under the curve (AUC) for nocturnal hypoglycemic events. Two-hour threshold-suspend events were analyzed with respect to subsequent sensor glucose values. ResultsA total of 247 patients were randomly assigned to receive sensor-augmented insulin-pump therapy with the threshold-suspend feature (threshold-suspend group, 121 patients) or standard sensor-augmented insuli...

https://www.nejm.org/doi/pdf/10.1056/NEJMoa1303576

Threshold-based insulin-pump interruption for reduction of hypoglycemia

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 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.auIdentifier:ACTRN12610000024044

https://jamanetwork.com/journals/jama/articlepdf/1741822/joi130060.pdf

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.

Objective To evaluate the efficacy and safety of artificial pancreas treatment in non-pregnant outpatients with type 1 diabetes. Design Systematic review and meta-analysis of randomised controlled trials. Data sources Medline, Embase, Cochrane Library, and grey literature up to 2 February 2018. Eligibility criteria for selecting studies Randomised controlled trials in non-pregnant outpatients with type 1 diabetes that compared the use of any artificial pancreas system with any type of insulin based treatment. Primary outcome was proportion (%) of time that sensor glucose level was within the near normoglycaemic range (3.9-10 mmol/L). Secondary outcomes included proportion (%) of time that sensor glucose level was above 10 mmol/L or below 3.9 mmol/L, low blood glucose index overnight, mean sensor glucose level, total daily insulin needs, and glycated haemoglobin. The Cochrane Collaboration risk of bias tool was used to assess study quality. Results 40 studies (1027 participants with data for 44 comparisons) were included in the meta-analysis. 35 comparisons assessed a single hormone artificial pancreas system, whereas nine comparisons assessed a dual hormone system. Only nine studies were at low risk of bias. Proportion of time in the near normoglycaemic range (3.9-10.0 mmol/L) was significantly higher with artificial pancreas use, both overnight (weighted mean difference 15.15%, 95% confidence interval 12.21% to 18.09%) and over a 24 hour period (9.62%, 7.54% to 11.7%). Artificial pancreas systems had a favourable effect on the proportion of time with sensor glucose level above 10 mmol/L (−8.52%, −11.14% to −5.9%) or below 3.9 mmol/L (−1.49%, −1.86% to −1.11%) over 24 hours, compared with control treatment. Robustness of findings for the primary outcome was verified in sensitivity analyses, by including only trials at low risk of bias (11.64%, 9.1% to 14.18%) or trials under unsupervised, normal living conditions (10.42%, 8.63% to 12.2%). Results were consistent in a subgroup analysis both for single hormone and dual hormone artificial pancreas systems. Conclusions Artificial pancreas systems are an efficacious and safe approach for treating outpatients with type 1 diabetes. The main limitations of current research evidence on artificial pancreas systems are related to inconsistency in outcome reporting, small sample size, and short follow-up duration of individual trials.

https://www.bmj.com/content/bmj/361/bmj.k1310.full.pdf

Artificial pancreas treatment for outpatients with type 1 diabetes: systematic review and meta-analysis

Supplementary Table S1 Continuous Glucose Monitoring (CGM) has been demonstrated to be clinically valuable, reducing risks of hypoglycemia and hyperglycemia, glycemic variability (GV), and improving patient quality of life for a wide range of patient populations and clinical indications. Use of CGM can help reduce HbA1c and mean glucose. One CGM device, with accuracy (%MARD) of approximately 10%, has recently been approved for self-adjustment of insulin dosages (nonadjuvant use) and approved for reimbursement for therapeutic use in the United States. CGM had previously been used off-label for that purpose. CGM has been demonstrated to be clinically useful in both type 1 and type 2 diabetes for patients receiving a wide variety of treatment regimens. CGM is beneficial for people using either multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII). CGM is used both in retrospective (professional, masked) and real-time (personal, unmasked) modes: both approaches can be ben...

/pdf/continuous-glucose-monitoring-a-review-of-recent-studies-1zao7olrs2.pdf

Continuous Glucose Monitoring: A Review of Recent Studies Demonstrating Improved Glycemic Outcomes

By providing blood glucose (BG) concentration measurements in an almost continuous-time fashion for several consecutive days, wearable minimally-invasive continuous glucose monitoring (CGM) sensors are revolutionizing diabetes management, and are becoming an increasingly adopted technology especially for diabetic individuals requiring insulin administrations. Indeed, by providing glucose real-time insights of BG dynamics and trend, and being equipped with visual and acoustic alarms for hypo- and hyperglycemia, CGM devices have been proved to improve safety and effectiveness of diabetes therapy, reduce hypoglycemia incidence and duration, and decrease glycemic variability. Furthermore, the real-time availability of BG values has been stimulating the realization of new tools to provide patients with decision support to improve insulin dosage tuning and infusion. The aim of this paper is to offer an overview of current literature and future possible developments regarding CGM technologies and applications. In particular, first, we outline the technological evolution of CGM devices through the last 20 years. Then, we discuss about the current use of CGM sensors from patients affected by diabetes, and, we report some works proving the beneficial impact provided by the adoption of CGM. Finally, we review some recent advanced applications for diabetes treatment based on CGM sensors.

/pdf/continuous-glucose-monitoring-sensors-for-diabetes-3r27ztv2ba.pdf

Continuous Glucose Monitoring Sensors for Diabetes Management: A Review of Technologies and Applications

In this paper, we report Q-factor over 1 million on both n = 2 wineglass modes, and high-frequency symmetry (Af/f ) of 132 ppm on wafer-level microglassblown 3-D fused silica wineglass resonators at a compact size of 7-mm diameter and center frequency of 105 kHz. In addition, we demonstrate for the first time, out-of-plane capacitive transduction on microelectromechanical systems wineglass resonators. High Q-factor is enabled by a high aspect ratio, self-aligned glassblown stem structure, careful surface treatment of the perimeter area, and low internal loss fused silica material. Electrostatic transduction is enabled by detecting the spatial deformation of the 3-D wineglass structure using a new out-of-plane electrode architecture. Out-of-plane electrode architecture enables the use of sacrificial layers to define the capacitive gaps and 10 μm capacitive gaps have been demonstrated on a 7-mm shell, resulting in over 9 pF of active capacitance within the device. Microglassblowing may enable batch-fabrication of high-performance fused silica wineglass gyroscopes at a significantly lower cost than their precision-machined macroscale counterparts.

Demonstration of 1 million Q -factor on microglassblown wineglass resonators with out-of-plane electrostatic transduction

Background: Sensor-augmented insulin pumps may be programmed to suspend insulin delivery in response to hypoglycemia. The Medtronic Paradigm ® Veo™ pump with automatic low glucose suspend (LGS) was released in 2009. Data from 7 months of real-world use of the system were analyzed to assess usage patterns and effectiveness of LGS. Method: Data from 935 patients totaling 49,867 patient days were collected; the LGS feature was on for 82% of these days. A subset of 278 subjects who used the pump for ≥3 months was analyzed separately; these subjects provided 28,401 patient days of data, with LGS used for 92% of the time. Results:

https://journals.sagepub.com/doi/pdf/10.1177/193229681100500514

Usage and Effectiveness of the Low Glucose Suspend Feature of the Medtronic Paradigm Veo Insulin Pump

This paper reports a new type of degenerate mode gyroscope with measured Q-factor of > 100,000 on both modes at a compact size of 1760 μm diameter. The toroidal ring gyroscope consists of an outer anchor ring, concentric rings nested inside the anchor ring and an electrode assembly at the inner core. Current implementation uses n = 3 wineglass mode, which is inherently robust to fabrication asymmetries. Devices were fabricated using high-temperature, ultra-clean epitaxial silicon encapsulation (EpiSeal) process. Over the 4 devices tested, lowest as fabricated frequency split was found to be 8.5 Hz (122 ppm) with a mean of 21 Hz (Δf/f = 300 ppm). Further electrostatic tuning brought the frequency split below 100 mHz (<; 2 ppm). Whole angle mechanization and pattern angle was demonstrated using a high speed DSP control system. Characterization of the gyro performance using force-rebalance mechanization revealed ARW of 0.047°/√hr and an in-run bias stability of 0.65 deg/hr. Due to the high Q-factor and robust support structure, the device can potentially be instrumented in whole angle mechanization for applications which require high rate sensitivity and robustness to g-forces.

100K Q-factor toroidal ring gyroscope implemented in wafer-level epitaxial silicon encapsulation process

We present a study on the effect of mounting position of IMU to a foot on the navigation accuracy of ZUPT-aided pedestrian inertial navigation. In this study, we compared two IMU mounting positions, forefoot and heel, in terms of the length of the stance phase, velocity uncertainty, and the shock level during the stance phase. Circular Error Probable (CEP) of localization was experimentally demonstrated to be reduced by about 50%, when mounting the IMU on the forefoot rather than behind the heel. The conclusion was demonstrated by investigating different walking paces, types of floors (hard floor, grass lawn, and sand), trajectories (upstairs and downstairs), and gait patterns produced by different persons. To the best of our knowledge, this study is the first attempt to investigate the velocity uncertainty during the stance phase in pedestrian navigation, a critical characteristic of ZUPT-aided algorithms.

Study on Mounting Position of IMU for Better Accuracy of ZUPT-Aided Pedestrian Inertial Navigation

Micro resonators and vibratory gyroscopes could reach their fundamental thermo-elastic damping (TED) limit in an ultravacuum condition where the viscous damping is eliminated. This article presents a reliable and repeatable high vacuum sealing process as a standalone approach for performance evaluation of dynamic micro devices. We demonstrated a micro-Torr vacuum level in a ceramic leadless chip carrier package and achieved the Q-factor over 2million on a quad mass gyroscope, approaching the TED limit of the device by effectively eliminating the viscous damping. The long-term vacuum stability was characterized over 1 year and demonstrated that the Q-factor does not degrade over time and even continues improving. The long-term ultrahigh vacuum condition is enabled by surface desorption prior to sealing, pumping of residual gases by passive getters, and defect-free solder reflow in the sealing area. The experimental results confirmed the reliability and repeatability of the proposed sealing procedure, which can be adapted for other Micro Electro-Mechanical Systems (MEMS) with ultrahigh vacuum requirements.

/pdf/an-ultrahigh-vacuum-packaging-process-demonstrating-over-2-5x8p2lp9ta.pdf

Sina Askari

Papers

Demonstration of 1 million Q -factor on microglassblown wineglass resonators with out-of-plane electrostatic transduction

Usage and Effectiveness of the Low Glucose Suspend Feature of the Medtronic Paradigm Veo Insulin Pump

100K Q-factor toroidal ring gyroscope implemented in wafer-level epitaxial silicon encapsulation process

Study on Mounting Position of IMU for Better Accuracy of ZUPT-Aided Pedestrian Inertial Navigation

An Ultrahigh Vacuum Packaging Process Demonstrating Over 2 Million Q-Factor in MEMS Vibratory Gyroscopes