Enlite Sensor Research Articles

#3637 ROLE OF CONTINUOUS GLUCOSE MONITORING OF BLOOD GLUCOSE CONTROL IN PATIENTS WITH DIABETES UNDERGOING HEMODIALYSIS: A PILOT STUDY

Abstract Background and Aims End-stage kidney disease (ESKD) is a global health problem, with a steep increase in its prevalence. Diabetes is a major cause and common comorbidity in patients with ESKD. As already known, glycemic control is an important factor in preventing micro- and macrovascular complications in diabetes. Besides, glycemic variability has recently been considered an important factor in the treatment of diabetes. However, both hypoglycemia and hyperglycemia can frequently occur in patients with diabetes undergoing hemodialysis. This study aimed to determine the role of continuous glucose monitoring (CGM) for glycemic control and glycemic variability stabilization in patients with diabetes undergoing hemodialysis. Method Eighteen patients aged ≥18 years with type 1 or 2 diabetes and ≥3 months on hemodialysis at the Eulji Medical Center, Daejeon, Republic of Korea between November 2021 and May 2022 were included. Patients underwent 7-day CGM twice: the baseline study period (T0) and the follow-up study period (T1), at a 12-week interval. Physicians modified the treatment strategy according to the T0 results, and then patients conducted T1. iPro2 CGM (MMT-7745) and Enlite glucose sensors MMT-7008A (Medtronic Minimed, Northridge, CA, USA) were used to assess glycemic control. As indicators of glycemic control, the mean glucose levels and glycated hemoglobin A1c (HbA1c) were measured. As indicators of glycemic variability, standard deviation (SD) and %coefficient variation (%CV) were measured. Results Data from 18 patients were analyzed. The mean age was 62.0±11.2 years, male/female ratio was 13 (72.2%)/5 (27.8%). The mean dialysis duration was 5.2±3.5 years. Among the 18 patients, only one had type 1 diabetes, and the mean diabetes duration was 22.9±7.0 years. The mean glucose levels decreased from 179.1±42.3 mg/dL during T0 to 153.2±25.6 mg/dL during T1 (P = 0.001). HbA1c decreased from 7.4±1.3% during T0 to 6.9±1.2% during T1 (P = 0.023). SD improved from 55.7±19.8 mg/dL during T0 to 42.6±15.3 mg/dL during T1 (P = 0.001). %CV improved from 30.5±7.3% during T0 to 25.5±5.5% during T1 (P < 0.001). During T0, the mean glucose level was significantly lower on a day with hemodialysis than on a day without (P≪0.05), and SD and %CV were significantly higher on a day with hemodialysis than on a day without (P≪0.05). After the physicians modified the treatment according to the T0 results, the mean blood glucose levels decreased on both the hemodialysis-on and hemodialysis-off days, as compared to those values during T0 (from 174.7±46.5 to 154.6±29.7 mg/dL, and from 184.7±50.5 to 156.3±28.7 mg/dL, respectively), and consequently there were no statistically significant differences between the hemodialysis-on and hemodialysis-off days during T1 (P = 0.638). SD improved on both the hemodialysis-on and hemodialysis-off days compared to those values during T0 (from 46.9±21.5 to 33.2±14.6, and from 39.5±20.6 to 32.3±13.3, respectively), and consequently, there were no statistically significant differences between the hemodialysis-on and hemodialysis-off days during T1 (P = 0.384). %CV improved from 27.8±10.9 on the hemodialysis-on day during T0 to 21.4±9.2 on that during T1, and there was no statistically significant difference between the hemodialysis-on and hemodialysis-off days during T1 (P = 0.166). Conclusion CGM could be a promising tool for individualizing treatment strategies in patients with diabetes undergoing hemodialysis.

A head-to-head comparison between Guardian Connect and FreeStyle Libre systems and an evaluation of user acceptability of sensors in patients with type 1 diabetes.

A user-calibrated real-time continuous glucose monitoring (rt-CGM) system is compared to a factory-calibrated flash glucose monitoring (FGM) system and assessed in terms of accuracy and acceptability in patients with type 1 diabetes (T1D). Ten participants with T1D were enroled from a specialist diabetes centre in Singapore and provided with the Guardian Connect with Enlite Sensor (Medtronic, Northridge, CA, USA) and first-generation Freestyle Libre System (Abbott Diabetes Care, Witney, UK), worn simultaneously. Participants had to check capillary blood glucose four times per day. At the end of week 1 and week 2, participants returned for data download and were given a user evaluation survey. Accuracy evaluation between Guardian Connect and Freestyle Libre includes the overall mean absolute relative difference value (9.7±11.0% vs. 17.5±10.9%), Clarke Error Grid zones A+B (98.6% vs. 98.1%), sensitivity (78.9% vs. 63.4%), and specificity (93.4% vs. 81.0%). Notably, time below range (<3.9mmol/L) was 10.5% for FGM versus 2% for rt-CGM. From the evaluation survey, 90% of participants perceived rt-CGM to be accurate versus 40% for FGM, although the majority found both devices to be easy to use, educational, and useful in improving glycaemic control. However, due to the cost of sensors, only 30% were keen to use either device for continuous monitoring. Although rt-CGM was superior to FGM in terms of accuracy, the value of glucose trends in both devices is still useful in diabetes self-management. Patients and clinicians may consider either technology depending on their requirements.

The Impact of Removal of Exercise for 3 Days on Glycemic Control in Older Active Adults

Postprandial glycemia (PPG) predicts cardiovascular disease, and 3 days of physical inactivity impairs PPG in young, active adults. Whether this occurs in older, active adults who may be more prone to bouts of inactivity is unknown. This study determined if PPG was impaired in active older adults (old) following a 3 day removal of exercise compared to active young adults. In this randomized, crossover study, 10 older (73.0 ± 1.9 yrs) and 9 young (32.8 ± 1.8 yrs) habitually active (≥90 min/week of exercise) adults completed a 3 day period of exercise removal (NOEX) and a 3 day period of normal exercise maintenance (EX), separated by ≥ 1 week. Diet was standardized across phases. Glycemic control (GC) (2 hour PPG, peak glucose values, and standard deviation (STDEV) of blood glucose values) was assessed via continuous glucose monitoring (IPro2, Enlite Sensors, Medtronic Inc., Northridge, CA) during both phases. No differences in body mass index (Old: 26.5 ± 1.3, Young: 24.8 ± 1.0 kg/m2, p&gt;0.05) existed between groups. Both groups had a similar reduction in activity during NOEX (Old: ‐64.6% ± 6.2, Young: ‐55.7% ± 4.9, p&gt;0.05). There were significant main effects (p&lt;0.05) in PPG of age (Old: 116±1.2 mg/dL, Young: 106 ± 1.3 mg/dL), phase (Inactive: 113 ± 1.3 mg/dL, Active: 109 ± 1.2 mg/dL), and time (0 min: 99 ± 2.0, 30 min: 118 ± 2.0, 60 min: 117 ± 2.0, 90 min: 112 ± 2.0, 120 min: 108 ± 2.0 mg/dL), but no interaction (p&gt;0.05). Further, a trend (p=0.06) for significant main effect of age (Old: 149±5.6, Young: 133±5.9 mg/dL) and phase (p&lt;0.05; Inactive: 145±4.4, Active: 136±4.4 mg/dL) were found for peak glucose values. Significant main effects (p&lt;0.05) exist for age (Old: 15.3±1.2, Young: 11.3±1.2) and phase (Inactive: 14.4±0.97, Active: 12.2±0.97) for blood glucose STDEV. These results indicate that older adults have impaired GC compared to young adults and that removal of exercise impairs GC. Yet, the impairment in GC with exercise removal is not different between old and young adults when the decrease in daily physical activity is similar.

Continuous Glucose Monitoring Metrics in the Assessment of Glycemia in Moderate-to-Advanced CKD in Diabetes

IntroductionGlycated hemoglobin A1c (HbA1c) has reduced reliability in advanced chronic kidney disease (CKD) owing to factors influencing red cell turnover. Recent guidelines support the use of continuous glucose monitoring (CGM) in glycemic assessment in these patients. We evaluated relationships between HbA1c and CGM metrics of average glycemia and glucose variability (GV) in moderate-to-advanced CKD.MethodsThere were a total of 90 patients with diabetes in CKD stages G3b (n = 33), G4 (n = 43), and G5 (nondialysis) (n = 14) (age [mean ± SD] 65.4 ± 9.0 years, estimated glomerular filtration rate [eGFR] 26.1 ± 9.6 ml/min per 1.73 m2, and HbA1c 7.4 ± 0.8%). CGM metrics were estimated from blinded CGM (Medtronic Ipro2 with Enlite sensor) and compared with HbA1c in the same week.ResultsCorrelations between glucose management indicator (GMI) and HbA1c attenuated with advancing CKD (G3b [r = 0.68, P < 0.0001], G4 [r = 0.52, P < 0.001], G5 [r = 0.22, P = 0.44], P = 0.01 for CKD stage). In G3b and G4, HbA1c correlated significantly with time-in-range (TIR) (3.9–10.0 mmol/l) (r = −0.55 and r = −0.54, respectively) and % time > 13.9 mmol/l (r = 0.53 and r = 0.44, respectively), but not in G5. HbA1c showed no correlation with % time <3.0 mmol/l (r = −0.045, P = 0.67) or % coefficient of variation (CV) (r = −0.05, P = 0.64) in any CKD stage. Only eGFR was a significant determinant of bias for the difference between GMI and HbA1c (difference −0.28%, 95% CI [−0.52 to −0.03] per 15 ml/min per 1.73 m2 decrement, P = 0.03).ConclusionCGM-derived indices might serve as an adjunct to HbA1c monitoring to guide glycemic management, especially in those with eGFR <30 ml/min per 1.73 m2. Time in hypoglycemia and glycemic variability are relevant glycemic targets for optimization not reflected by HbA1c.

Study of blood glucose and insulin infusion rate in real-time in diabetic rats using an artificial pancreas system.

Artificial pancreas system (APS) is an emerging new treatment for type 1 diabetes mellitus. The aim of this study was to develop a rat APS as a research tool and demonstrate its application. We established a rat APS using Medtronic Minimed Pump 722, Medtronic Enlite sensor, and the open artificial pancreas system as a controller. We tested different dilutions of Humalog (100 units/ml) in saline ranged from 1:3 to 1:20 and determined that 1:7 dilution works well for rats with ~500g bodyweight. Blood glucose levels (BGL) of diabetic rats fed with chow diet (58% carbohydrate) whose BGL was managed by the closed-loop APS for the total duration of 207h were in euglycemic range (70-180 mg/dl) for 94.5% of the time with 2.1% and 3.4% for hyperglycemia (>180mg/dl) and hypoglycemia (<70 mg/dl), respectively. Diabetic rats fed with Sucrose pellets (94.8% carbohydrate) for the experimental duration of 175h were in euglycemic range for 61% of the time with 35% and 4% for hyperglycemia and hypoglycemia, respectively. Heathy rats fed with chow diet showed almost a straight line of BGL ~ 95 mg/dl (average 94.8 mg/dl) during the entire experimental period (281h), which was minimally altered by food intake. In the healthy rats, feeding sucrose pellets caused greater range of BGL in high and low levels but still within euglycemic range (99.9%). Next, to study how healthy and diabetic rats handle supra-physiological concentrations of glucose, we intraperitoneally injected various amounts of 50% dextrose (2, 3, 4g/kg) and monitored BGL. Duration of hyperglycemia after injection of 50% dextrose at all three different concentrations was significantly greater for healthy rats than diabetic rats, suggesting that insulin infusion by APS was superior in reducing BGL as compared to natural insulin released from pancreatic β-cells. Ex vivo studies showed that islets isolated from diabetic rats were almost completely devoid of pancreatic β-cells but with intact α-cells as expected. Lipid droplet deposition in the liver of diabetic rats was significantly lower with higher levels of triacylglyceride in the blood as compared to those of healthy rats, suggesting lipid metabolism was altered in diabetic rats. However, glycogen storage in the liver determined by Periodic acid-Schiff staining was not altered in diabetic rats as compared to healthy rats. A rat APS may be used as a powerful tool not only to study alterations of glucose and insulin homeostasis in real-time caused by diet, exercise, hormones, or antidiabetic agents, but also to test mathematical and engineering models of blood glucose prediction or new algorithms for closed-loop APS.

Motivational Stage at Continuous Glucose Monitoring (CGM) Initiation in Pediatric Type 1 Diabetes Is Associated With Current Glycemic Control but Does Not Predict Future CGM Adherence or Glycemic Control

ObjectivesThe Timing of Initiation of Continuous Glucose Monitoring in Established Pediatric Diabetes (CGM TIME) Trial is a multicenter, randomized controlled trial in children with type 1 diabetes, comparing simultaneous pump and CGM with CGM initiation 6 months later (Paradigm, Veo, Enlite Sensor, Medtronic Canada). This study addresses the ability of SOCRATES (Stages Of Change Readiness And Treatment Eagerness Scale) to classify children and parents into distinct motivational stages and identify the stages’ association with glycated hemoglobin (A1C) at trial entry and outcomes 6 months after CGM initiation. MethodsNinety-eight of 99 eligible children 10 to 18 years of age and 137 of 141 eligible parents completed SOCRATES at trial entry and 6 months later. Parent-child agreement for motivational stage was determined by weighted kappa. Linear regression was used to examine association between motivational stage and i) A1C at trial entry and ii) change in A1C and CGM adherence 6 months after CGM initiation. ResultsMore than 87% of children and 88% of parents were classified into distinct motivational stages, with weak parent-child agreement. At trial entry, motivational stage was associated with A1C, which was 1.02% higher for children in the Action stage than in the Precontemplation stage (p<0.0001). When compared with children of parents in Precontemplation, A1C for children of parents in the Maintenance and Action stages were 0.83% (p=0.02) and 0.36% (p=0.048) higher, respectively. Precontemplation was associated with shorter diabetes duration. Motivational stage at CGM initiation did not predict change in A1C or CGM adherence 6 months later. ConclusionsSOCRATES can categorize children with type 1 diabetes and their parents into motivational stages. Although motivational stage was associated with glycemic control at trial entry, it did not predict future diabetes-related behaviour or A1C.

Real-time CGM Is Superior to Flash Glucose Monitoring for Glucose Control in Type 1 Diabetes: The CORRIDA Randomized Controlled Trial.

OBJECTIVEThe aim of this trial was to compare the efficacy of real-time and intermittently scanned continuous glucose monitoring (rtCGM and isCGM, respectively) in maintaining optimal glycemic control.RESEARCH DESIGN AND METHODSIn this randomized study, adults with type 1 diabetes (T1D) and normal hypoglycemia awareness (Gold score <4) used rtCGM (Guardian Connect Mobile) or isCGM (FreeStyle Libre) during 4 days of physical activity (exercise phase) and in the subsequent 4 weeks at home (home phase). Primary end points were time in hypoglycemia (<3.9 mmol/L [<70 mg/dL]) and time in range (3.9–10.0 mmol/L [70–180 mg/dL]). The isCGM group wore an additional masked Enlite sensor (iPro2) for 6 days to check for bias between the different sensors used by the rtCGM and isCGM systems.RESULTSSixty adults with T1D (mean age 38 ± 13 years; A1C 62 ± 12 mmol/mol [7.8 ± 1.1%]) were randomized to rtCGM (n = 30) or isCGM (n = 30). All participants completed the study. Percentage of time in hypoglycemia (<3.9 mmol/L [<70 mg/dL]) was lower among rtCGM versus isCGM participants in the exercise phase (6.8 ± 5.5% vs. 11.4 ± 8.6%, respectively; P = 0.018) and during the home phase (5.3 ± 2.5% vs. 7.3 ± 4.4%, respectively; P = 0.035). Hypoglycemia differences were significant and most notable during the night. rtCGM participants spent more time in range (3.9–10 mmol/L [70–180 mg/dL]) than isCGM participants throughout both the exercise (78.5 ± 10.2% vs. 69.7 ± 16%, respectively; P = 0.0149) and home (75.6 ± 9.7% vs. 67.4 ± 17.8%, respectively; P = 0.0339) phases. The results were robust to the insignificant bias between rtCGM and isCGM sensors that masked CGM found in the isCGM arm.CONCLUSIONSrtCGM was superior to isCGM in reducing hypoglycemia and improving time in range in adults with T1D with normal hypoglycemia awareness, demonstrating the value of rtCGM alarms during exercise and in daily diabetes self-management.

Coronavirus lockdown effect on type 1 diabetes management οn children wearing insulin pump equipped with continuous glucose monitoring system

AimsOn the 10th of March, Greece imposed the closure of schools and universities and a full lockdown a few days later in order to counter the spread of the coronavirus outbreak. Our aim was to monitor the effect of the coronavirus lockdown in diabetes management in children with Type 1 Diabetes Mellitus (T1DM) wearing insulin pump equipped with continuous glucose monitoring system. MethodsIn 34 children with T1DM on Medtronic 640G insulin pump equipped with the Enlite Sensor uploaded CareLink data were categorized in 2 three-week periods before and after the 10th of March. ResultsMean time in range (TIR) did not significantly differ between the two periods. However, a significantly higher Coefficient of Variation (CV) indicating an increased glucose variability in the pre-lockdown period was observed (39.52% versus 37.40%, p = 0.011). Blood glucose readings were significantly fewer during the lockdown period (7.91 versus 7.41, p = 0.001). No significant difference was recorded regarding the total daily dose of insulin and the reported carbohydrates consumed. However, the meal schedule has changed dramatically as the percentage of breakfast consumed before 10.00 a.m. has fallen from 80.67% to 41.46% (p < 0.001) during the lockdown. Correspondingly, the percentage of dinner consumption before 10.00 p.m. significantly fell during the lockdown period (60.22% versus 53.78%, p = 0.019). ConclusionsGlycemic control during the coronavirus lockdown can be adequately achieved and be comparable to the pre-lockdown period in children with type 1 diabetes mellitus wearing insulin pump equipped with sensor.

876-P: Accuracy of Continuous Glucose Monitoring Compared with Capillary Blood and Venous Plasma Glucose Measurements in Medical Intensive Care Unit Patients

Objective: To assess the accuracy of the subcutaneous continuous glucose monitoring (CGM) sensor by comparing to the capillary blood glucose (CBG) and venous plasma glucose (VPG) measurements in the medical intensive care unit (MICU) patients. Subjects and Methods: In a prospective study in patients in the MICUs, Medtronic Enlite sensor was inserted in the abdominal area. Paired sensor glucose readings with reference glucose values (CBG and VPG) were collected from MICU patients receiving intravenous insulin infusion therapy. The accuracy was assessed using the mean absolute relative difference (MARD), surveillance error grid (SEG) analysis and modified Bland-Altman plot. Results: Twelve patients completed the study (age 69.3 ± 11.6 years; BMI 21.6 ± 2.9 kg/m2; APACHE II score 21.8 ± 6.3 and duration of CGM use 108.7 ± 41.1 hours). A total of 353 paired CGM and CBG glucose readings and 125 paired CGM and VPG readings were included in the analysis. Using CBG as the reference, MARD was 7.2%. The modified Bland-Altman plot showed 95% of the limit of agreement (LoA) was -18.4% to 19.2%. The SEG analysis showed that 100% of paired glucose values were within zones A or B. No clinically significant difference in the accuracy was seen between subgroups of vasopressor use (MARD 6.1% in the vasopressor group vs. 6.8% in the non-vasopressor group, p = NS). Using VPG as the reference, the MARD was 8.8%. The modified Bland-Altman plot showed 95% LoA of - 22.6% to 28.2%. The SEG analysis showed 95.2% of glucose readings were within zones A or B. Conclusion: The accuracy of the subcutaneous CGM sensor in MICU patients was comparable to that observed in non-critical care settings, with no device-related adverse events. The sensor accuracy remained within the similar range when using VPG as the references compared to using CBG as the references. No differences in terms of accuracy between the vasopressor and non-vasopressor groups were found in this study. Disclosure N. Laichuthai: None. P. Buranasupkajorn: None. W. Khovidhunkit: Speaker’s Bureau; Self; Amgen, AstraZeneca. Funding Quality Improvement Fund; King Chulalongkorn Memorial Hospital; Thai Red Cross Society (1-62-30101-A-11)

Allergic contact dermatitis caused by isobornyl acrylate in the Enlite glucose sensor and the Paradigm MiniMed Quick‐set insulin infusion set

The FreeStyle Libre glucose sensor has caused many cases of allergic contact dermatitis, and isobornyl acrylate (IBOA) in this sensor has been identified as one of the culprit allergens. To report on the presence of IBOA in devices produced by Medtronic, namely, the Enlite sensor and the insulin infusion set Paradigm MiniMed Quick-set. Five patients reacting to the glucose sensor Enlite and/or the insulin infusion set Paradigm MiniMed Quick-set observed in three clinics (two Belgian and one Swedish) were patch tested with the baseline and other series, as well as with IBOA; four of them also with pieces of adhesive patches from the devices, and two with a thin layer chromatogram of Enlite glucose sensor extracts. Gas chromatography-mass spectrometry (GC-MS) analyses were performed. Four patients reacted to IBOA and one to colophonium, a known allergen in Enlite, and three to the adhesive part of the sensor or the insulin infusion set. IBOA was identified in the sensor by GC-MS, and its presence was indicated in the infusion set. IBOA is a contact allergen in Enlite glucose sensor, and likely also in the infusion set. Therefore, these devices are not suitable alternatives for patients sensitized to the FreeStyle Libre sensor.

Evaluation of Isobornyl Acrylate Content in Medical Devices for Diabetes Treatment.

Background: Along with increased usage of continuous glucose monitors, flash glucose monitors, and patch pumps by patients with diabetes, the frequency of skin reactions has also increased. Skin irritation and itching can be annoying to users. However, more serious contact allergies to one or more components of the adhesives or plastic material of the housing of the devices can become lifelong. Redness and itchiness are so strong that patients can no longer use a particular system. In August 2017, a major culprit allergen, isobornyl acrylate (IBOA), was identified for these more serious reactions. Objectives: Our objective was to evaluate IBOA content in different medical products. Methods: The plastic material used for the housing of the Freestyle Libre (n = 3), Dexcom G6 (n = 3), and Enlite (n = 4) was analyzed for IBOA content by gas chromatography-mass spectrometry. Adhesives of the different systems were also analyzed. Results: IBOA was found in the housings of Freestyle Libre and Enlite sensor, but not in the Dexcom G6. Conclusions: Patients with an IBOA allergy should consider switching to a medical product without IBOA. Furthermore, removal of IBOA from devices that contact the skin is encouraged.

Use of continuous glucose monitoring for sport in type 1 diabetes

BackgroundThe benefits of exercise for patients with type 1 diabetes (T1D) are difficult to balance with associated glycaemic excursions. The aim of this cohort study was to show that continuous...

Continuous glucose monitoring (CGM) in very low birth weight newborns needing parenteral nutrition: validation and glycemic percentiles.

BackgroundContinuous glucose monitoring using subcutaneous sensors is useful in the management of glucose control in neonatal intensive care. We evaluated feasibility and reliability of a continuous glucose monitoring system in a population of very low birth weight neonates needing parenteral nutrition. Moreover, we presented percentiles of glycemia of the studied population.MethodsVery low birth weight neonates were enrolled within 24 h from birth. An ENLITE sensor connected to a continuous glucose monitoring system was inserted and maintained for at least 72 h. Data obtained with the continuous glucose monitoring system and with a glucometer were compared. Calibration was performed every 12 h.ResultsTwenty-three patients (9 males) were included. Median gestational age was 28 weeks (range 23–30) and median birth weight was 860 g (range 500–1092). A total of 299 paired glucose values were obtained. Modified Clarke Error Grid criteria for clinical significance were met. 74 and 33 episodes of hypoglycemia and hyperglycemia were detected, respectively. 31,329 values of glycemia were analyzed and the percentiles calculated.ConclusionsThis continuous glucose monitoring system is safe and accurate. It allows increasing the detection of hypo- and hyper-glycaemia episodes and it could be routinely used in the management of glucose infusion in very low birth weight neonates under total parenteral nutrition.

The risk for hypoglycemia during Ramadan fasting in patients with adrenal insufficiency.

The risk for hypoglycemia during Ramadan fasting in patients with adrenal insufficiency (AI) is not fully known. The aims of this study were to evaluate this risk objectively and to determine the associated factors. This prospective case-crossover study included 25 women and 5 men with known and treated AI and a median age of 38.5y. Patients underwent clinical examination and a fasting blood sample was collected to measure glucose, urea, creatinine, sodium, potassium, cortisol, growth hormone and free thyroxine. A 24-h continuous glucose monitoring system (CGMS) using iPro2 (Medtronic, Parsippany, NJ, USA) with Enlite sensor (Medtronic) was performed for each patient during a Ramadan fasting day then again during a nonfasting day. Interstitial glucose levels during the 24-h period, the fasting period, and the fasting period after exclusion of the 5 postprandial hours were significantly lower during the fasting day than on the nonfasting day. Hypoglycemia occurred in three patients (10%) during the fasting day but not during the nonfasting day (P=0.23). Hypoglycemia was asymptomatic in two cases. Male sex was significantly associated with the occurrence of hypoglycemia. Interstitial glucose levels were lower during fasting in patients with AI. However, the risk for hypoglycemia was not increased.

Modeling the Error of the Medtronic Paradigm Veo Enlite Glucose Sensor.

Continuous glucose monitors (CGMs) are prone to inaccuracy due to time lags, sensor drift, calibration errors, and measurement noise. The aim of this study is to derive the model of the error of the second generation Medtronic Paradigm Veo Enlite (ENL) sensor and compare it with the Dexcom SEVEN PLUS (7P), G4 PLATINUM (G4P), and advanced G4 for Artificial Pancreas studies (G4AP) systems. An enhanced methodology to a previously employed technique was utilized to dissect the sensor error into several components. The dataset used included 37 inpatient sessions in 10 subjects with type 1 diabetes (T1D), in which CGMs were worn in parallel and blood glucose (BG) samples were analyzed every 15 ± 5 min Calibration error and sensor drift of the ENL sensor was best described by a linear relationship related to the gain and offset. The mean time lag estimated by the model is 9.4 ± 6.5 min. The overall average mean absolute relative difference (MARD) of the ENL sensor was 11.68 ± 5.07% Calibration error had the highest contribution to total error in the ENL sensor. This was also reported in the 7P, G4P, and G4AP. The model of the ENL sensor error will be useful to test the in silico performance of CGM-based applications, i.e., the artificial pancreas, employing this kind of sensor.

Continuous glucose monitoring for patients with type 1 diabetes and impaired awareness of hypoglycaemia (IN CONTROL): a randomised, open-label, crossover trial

Patients with type 1 diabetes who have impaired awareness of hypoglycaemia have a three to six times increased risk of severe hypoglycaemia. We aimed to assess whether continuous glucose monitoring (CGM) improves glycaemia and prevents severe hypoglycaemia compared with self-monitoring of blood glucose (SMBG) in this high-risk population. We did a randomised, open-label, crossover trial (IN CONTROL) at two medical centres in the Netherlands. Eligible participants were patients diagnosed with type 1 diabetes according to American Diabetes Association criteria, aged 18-75 years, with impaired awareness of hypoglycaemia as confirmed by a Gold score of at least 4, and treated with either continuous subcutaneous insulin infusion or multiple daily insulin injections and doing at least three SMBG measurements per day. After screening, re-education about diabetes management, and a 6-week run-in phase (to obtain baseline CGM data), we randomly assigned patients (1:1) with a computer-generated allocation sequence (block size of four) to either 16 weeks of CGM followed by 12 weeks of washout and 16 weeks of SMBG, or 16 weeks of SMBG followed by 12 weeks of washout and 16 weeks of CGM (where the SMBG phase was the control). During the CGM phase, patients used a real-time CGM system consisting of a Paradigm Veo system with a MiniLink transmitter and an Enlite glucose sensor (Medtronic, CA, USA). During the SMBG phase, patients were equipped with a masked CGM device, consisting of an iPro 2 continuous glucose monitor and an Enlite glucose sensor, which does not display real-time glucose values. The number of SMBG measurements per day and SMBG systems were not standardised between patients, to mimic real-life conditions. During both intervention periods, patients attended follow-up visits at the centres each month and had telephone consultations 2 weeks after each visit inquiring about adverse events, episodes of hypoglycaemia, etc. The primary endpoint was the mean difference in percentage of time spent in normoglycaemia (4-10 mmol/L) over the total intervention periods, analysed on an intention-to-treat basis. Severe hypoglycaemia (requiring third party assistance) was a secondary endpoint. This trial is registered with ClinicalTrials.gov, number NCT01787903. Between March 4, 2013, and Feb 9, 2015, we recruited and randomly assigned 52 patients to either the CGM-SMBG sequence (n=26) or the SMBG-CGM sequence (n=26). The last patient visit was on March 21, 2016. Time spent in normoglycaemia was higher during CGM than during SMBG: 65·0% (95% CI 62·8-67·3) versus 55·4% (53·1-57·7; mean difference 9·6%, 95% CI 8·0-11·2; p<0·0001), with reductions in both time spent in hypoglycaemia (ie, blood glucose ≤3·9 mmol/L [6·8% vs 11·4%, mean difference 4·7%, 3·4-5·9; p<0·0001]) and time spent in hyperglycaemia (ie, blood glucose >10 mmol/L [28·2% vs 33·2%, mean difference 5·0%, 3·1-6·9; p<0·0001]). During CGM, the number of severe hypoglycaemic events was lower (14 events vs 34 events, p=0·033). Five serious adverse events other than severe hypoglycaemia occurred during the trial, but all were deemed unrelated to the trial intervention. Additionally, no mild to moderate adverse events were related to the trial intervention. CGM increased time spent in normoglycaemia and reduced severe hypoglycaemia in patients with type 1 diabetes and impaired awareness of hypoglycaemia, compared with SMBG. Our results support the concept of using CGM in this high-risk population. Eli Lilly and Sanofi.

Intraperitoneal Glucose Sensing is Sometimes Surprisingly Rapid

Rapid, accurate and robust glucose measurements are needed to make a safe articial pancreas for the treatment of diabetes mellitus type 1 and 2. The present gold standard of continuous glucose sensing, subcutaneous (SC) glucose sensing, has been claimed to have slow response and poor robustness towards local tissue changes such as mechanical pressure, temperature changes, etc. The present study aimed at quantifying glucose dynamics from central circulation to intraperitoneal (IP) sensor sites, as an alternative to the SC location. Intraarterial (IA) and IP sensors were tested in three anaesthetized non-diabetic pigs during experiments with intravenous infusion of glucose boluses, enforcing rapid glucose level excursions in the range 70{360 mg/dL (approximately 3.8{20 mmol/L). Optical interferometric sensors were used for IA and IP measurements. A rst-order dynamic model with time delay was tted to the data after compensating for sensor dynamics. Additionally, o-the-shelf Medtronic Enlite sensors were used for illustration of SC glucose sensing. The time delay in glucose excursions from central circulation (IA) to IP sensor location was found to be in the range 0{26 s (median: 8.5 s, mean: 9.7 s, SD 9.5 s), and the time constant was found to be 0.5{10.2 min (median: 4.8 min, mean: 4.7 min, SD 2.9 min). IP glucose sensing sites have a substantially faster and more distinctive response than SC sites when sensor dynamics is ignored, and the peritoneal uid reacts even faster to changes in intravascular glucose levels than reported in previous animal studies. This study may provide a benchmark for future, rapid IP glucose sensors.

Performance of a predictive algorithm in sensor-augmented pump therapy in the prevention of hypoglycaemia

The Predictive Low Glucose Management (PLGM) system consists of a Medtronic Veo pump, Enlite sensor, MiniLink REAL-Time transmitter, Bluetooth-RF translator and a predictive algorithm operating from a Blackberry smartphone. The system suspended insulin delivery when the pre-set hypoglycaemic threshold of 4.4mmol/L was predicted to be reached in 30 minutes. The aim of this study was to determine the plasma glucose profile with the PLGM system when hypoglycaemia was induced by (a) moderate-intensity exercise, (b) subcutaneous insulin bolus and (c) increasing the overnight basal infusion rate in individuals with type 1 diabetes. The primary outcome was the plasma glucose nadir following each hypoglycaemic stimulus with and without PLGM. Participants performed 30-60 minutes of moderate-intensity exercise or were administered a subcutaneous insulin bolus following a glucose stabilisation period on basal continuous subcutaneous insulin infusion. In participants studied with increased overnight basal rates, hypoglycaemia was induced by increasing basal rates by 180%. They were randomised and studied on 2 separate days; with PLGM off and with PLGM on. On both days, participants were observed until plasma glucose dropped to 2.8mmol/L or were symptomatic.

Diabetes technology and the human factor.

The impressive progress achieved in recent years in diabetes technologies has made diabetes technological devices such as continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring (CGM) a significant part of diabetes treatment. Many studies conducted in recent years emphasized the advantages of using these technologies. The concept of the “human factor” in diabetes technologies as discussed in this chapter has several different aspects. First, it can refer to the way patients are satisfied with the use of the device and whether it is perceived convenient or inconvenient. For example, is the device perceived as “user friendly” (easy to learn and to operate, comfortable, does not cause many hassles). Second, there is the issue of effectiveness of the technology as it relates to their day-to-day diabetes management. For example, there is an improvement in glycemic control when one diabetes treatment regimen is compared to another (i.e., CSII vs. multiple daily injections (MDI)). Those two fundamental aspects may have different meanings for different groups. For example, different age groups (toddlers, children, adolescents, young adults, adults, and older people) can see different advantages and disadvantages in technological devices. The feasibility and utility of technological devices also need to fit the environments in which they will be used, such as school, the work place, and/or home. Specific subgroups such as diabetic youth with eating disorders can have unique interactions with diabetes technologies. In addition, diabetes technologies can be used as a measurement device, providing more rich and accurate data about patients' self-care that can contribute to our understanding of concepts such as adherence and satisfaction, and they can provide measurement tools to assess how glycemic control can effect cognition and intelligence. The present chapter will review articles published in the last year that have studied some of these issues.

Experience with the Enlite sensor in a multicenter pediatric study.

The purpose of this article is to outline the experience of certified diabetes educators (CDEs) using the Enlite continuous glucose monitoring sensor system in a pediatric multicenter randomized controlled trial. Continuous glucose monitoring (CGM) is becoming popular as a tool for educators and families to improve glycemic control. CGM can be a valuable educational tool to demonstrate to the user the impact of insulin dosing and effects of physical activity, food intake, and other life events such as work, illness, and stress on their glycemic control. The authors will share education tips and practical applications for diabetes educators to facilitate education and sustained use of Enlite glucose sensors in children and adolescents using insulin pump therapy. The Enlite glucose sensor is a comfortable and user-friendly device. Improvements to both the insertion device and the Enlite glucose sensor have resulted in improved level of comfort on insertion and with ongoing wear, which may translate into greater adherence and effectiveness.