Microarrow sensor array with enhanced skin adhesion for transdermal continuous monitoring of glucose and reactive oxygen species

Conventional blood sampling for glucose detection is prone to cause pain and fails to continuously record glucose fluctuations in vivo.Continuous glucose monitoring based on implantable electrodes could induce pain and potential tissue inflammation,and the presence of reactive oxygen species(ROS)due to inflammationmay affect glucose detection.Microneedle technology is less invasive,yet microneedle adhesion with skin tissue is limited.In this work,we developed a microarrow sensor array(MASA),which provided enhanced skin surface adhesion and enabled simultaneous detection of glucose and H_(2)O_(2)(representative of ROS)in interstitial fluid in vivo.The microarrows fabricated via laser micromachining were modified with functional coating and integrated into a patch of a three-dimensional(3D)microneedle array.Due to the arrow tip mechanically interlocking with the tissue,the microarrow array could better adhere to the skin surface after penetration into skin.The MASA was demonstrated to provide continuous in vivo monitoring of glucose and H_(2)O_(2) concentrations,with the detection of H_(2)O_(2) providing a valuable reference for assessing the inflammation state.Finally,the MASA was integrated into a monitoring system using custom circuitry.This work provides a promising tool for the stable and reliable monitoring of blood glucose in diabetic patients.

Application and management of continuous glucose monitoring in diabetic kidney disease

Diabetic kidney disease(DKD)is a common complication of diabetes mellitus that contributes to the risk of end-stage kidney disease(ESKD).Wide glycemic var-iations,such as hypoglycemia and hyperglycemia,are broadly found in diabetic patients with DKD and especially ESKD,as a result of impaired renal metabolism.It is essential to monitor glycemia for effective management of DKD.Hemoglobin A1c(HbA1c)has long been considered as the gold standard for monitoring glycemia for>3 months.However,assessment of HbA1c has some bias as it is susceptible to factors such as anemia and liver or kidney dysfunction.Continuous glucose monitoring(CGM)has provided new insights on glycemic assessment and management.CGM directly measures glucose level in interstitial fluid,reports real-time or retrospective glucose concentration,and provides multiple glycemic metrics.It avoids the pitfalls of HbA1c in some contexts,and may serve as a precise alternative to estimation of mean glucose and glycemic variability.Emerging studies have demonstrated the merits of CGM for precise monitoring,which allows fine-tuning of glycemic management in diabetic patients.Therefore,CGM technology has the potential for better glycemic monitoring in DKD patients.More research is needed to explore its application and management in different stages of DKD,including hemodialysis,peritoneal dialysis and kidney transplantation.

Continuous glucose monitoring metrics in pregnancy with type 1 diabetes mellitus

Managing diabetes during pregnancy is challenging,given the significant risk it poses for both maternal and foetal health outcomes.While traditional methods involve capillary self-monitoring of blood glucose level monitoring and periodic HbA1c tests,the advent of continuous glucose monitoring(CGM)systems has revolutionized the approach.These devices offer a safe and reliable means of tracking glucose levels in real-time,benefiting both women with diabetes during pregnancy and the healthcare providers.Moreover,CGM systems have shown a low rate of side effects and high feasibility when used in pregnancies complicated by diabetes,especially when paired with continuous subcutaneous insulin infusion pump as hybrid closed loop device.Such a combined approach has been demonstrated to improve overall blood sugar control,lessen the occurrence of preeclampsia and neonatal hypoglycaemia,and minimize the duration of neonatal intensive care unit stays.This paper aims to offer a comprehensive evaluation of CGM metrics specifically tailored for pregnancies impacted by type 1 diabetes mellitus.

Accuracy of FreeStyle Libre flash glucose monitoring in patients with type 2 diabetes who migrated from highlands to plains

BACKGROUND The FreeStyle Libre flash glucose monitoring(FGM)system entered the Chinese market in 2017 to complement the self-monitoring of blood glucose.Due to its increased usage in clinics,the number of studies investigating its accuracy has increased.However,its accuracy has not been investigated in highland populations in China.AIM To evaluate measurements recorded using the FreeStyle Libre FGM system compared with capillary blood glucose measured using the enzyme electrode method in patients with type 2 diabetes(T2D)who had migrated within 3 mo from highlands to plains.METHODS Overall,68 patients with T2D,selected from those who had recently migrated from highlands to plains(within 3 mo),were hospitalized at the Department of Endocrinology from August to October 2017 and underwent continuous glucose monitoring(CGM)with the FreeStyle Libre FGM system for 14 d.Throughout the study period,fingertip capillary blood glucose was measured daily using the enzyme electrode method(Super GL,China),and blood glucose levels were read from the scanning probe during fasting and 2 h after all three meals.Moreover,the time interval between reading the data from the scanning probe and collecting fingertip capillary blood was controlled to<5 min.The accuracy of the FGM system was evaluated according to the CGM guidelines.Subsequently,the factors influencing the mean absolute relative difference(MARD)of this system were analyzed by a multiple linear regression method.RESULTS Pearson’s correlation analysis showed that the fingertip and scanned glucose levels were positively correlated(R=0.86,P=0.00).The aggregated MARD of scanned glucose was 14.28±13.40%.Parker's error analysis showed that 99.30%of the data pairs were located in areas A and B.According to the probe wear time of the FreeStyle Libre FGM system,MARD_(1 d) and MARD_(2-14 d) were 16.55%and 14.35%,respectively(t=1.23,P=0.22).Multiple stepwise regression analysis showed that MARD did not correlate with blood glucose when the largest amplitude of glycemic excursion(LAGE)was<5.80 mmol/L but negatively correlated with blood glucose when the LAGE was≥5.80 mmol/L.CONCLUSION The FreeStyle Libre FGM system has good accuracy in patients with T2D who had recently migrated from highlands to plains.This system might be ideal for avoiding the effects of high hematocrit on blood glucose monitoring in populations that recently migrated to plains.MARD is mainly influenced by glucose levels and fluctuations,and the accuracy of the system is higher when the blood glucose fluctuation is small.In case of higher blood glucose level fluctuations,deviation in the scanned glucose levels is the highest at extremely low blood glucose levels.

A Review: Biosensor Progression in Glucose Monitoring for Patients with Diabetes

Diabetes is a condition that can come to the surface at any point throughout a person’s life. Although Type 1 and Type 2 Diabetes have different triggers that cause them to arise, a person can experience similar complications from either if not monitored and treated accordingly. Through the Diabetes Control and Complications Trial, it was found that a significant way to monitor diabetes is through glucose levels in a person’s body. The research surrounding glucose monitoring dates to the mid-1800s, with the first successful reagent for glucose testing being developed in 1908. Since then, glucose sensing has become one of the most rapidly growing areas of research and development in biosensor technology, creating a competitive market for more advanced, accurate, and convenient glucose monitoring. This article reviews the history of biosensors used for glucose monitoring, and major advancements in biosensor technology to enhance performance and improve quality of life for patients with diabetes.

Pros and cons of continuous glucose monitoring in the intensive care unit

Diabetes mellitus affects people worldwide,and management of its acute complications or treatment-related adverse events is particularly important in critically ill patients.Previous reports have confirmed that hyperglycemia can increase the risk of mortality in patients cared in the intensive care unit(ICU).In addition,severe and multiple hypoglycemia increases the risk of mortality when using insulin or intensive antidiabetic therapy.The innovation of continuous glucose monitoring(CGM)may help to alert medical caregivers with regard to the development of hyperglycemia and hypoglycemia,which may decrease the potential complications in patients in the ICU.The major limitation of CGM is the measurement of interstitial glucose levels rather than real-time blood glucose levels;thus,there will be a delay in the treatment of hyperglycemia and hypoglycemia in patients.Recently,the European Union approved a state-of-art artificial intelligence directed loop system coordinated by CGM and a continuous insulin pump for diabetes control,which may provide a practical way to prevent acute adverse glycemic events related to antidiabetic therapy in critically ill patients.In this mini-review paper,we describe the application of CGM to patients in the ICU and summarize the pros and cons of CGM.

Continuous glucose monitoring defined time-in-range is associated with sudomotor dysfunction in type 2 diabetes

BACKGROUND Time in range(TIR),as a novel metric for glycemic control,has robust relevance with diabetic complications.Diabetic peripheral neuropathy(DPN)is characterized by sudomotor dysfunction.AIM To explore the relationship between TIR obtained from continuous glucose monitoring(CGM)and sudomotor function detected by SUDOSCAN in subjects with type 2 diabetes.METHODS The research enrolled 466 inpatients with type 2 diabetes.All subjects underwent 3-d CGM and SUDOSCAN.SUDOSCAN was assessed with electrochemical skin conductance in hands(HESC)and feet(FESC).Average feet ESC<60μS was defined as sudomotor dysfunction(+),otherwise it was sudomotor dysfunction(-).TIR refers to the percentage of time when blood glucose is between 3.9-10 mmol/L during 1 d period.RESULTS Among the enrolled subjects,135(28.97%)presented with sudomotor dysfunction.Patients with sudomotor dysfunction(+)showed a decreased level of TIR(P<0.001).Compared to the lowest tertile of TIR,the middle and the highest tertiles of TIR was associated with an obviously lower prevalence of sudomotor dysfunction(20.51%and 21.94%vs 44.52%)(P<0.001).In addition,with the increase of TIR,HESC and FESC increased(P<0.001).Regression analysis demonstrated that TIR was inversely and independently linked with the prevalence of sudomotor dysfunction after adjusting for confounding values(odds ratio=0.979,95%CI:0.971-0.987,P<0.001).CONCLUSION The tight glycemic control assessed by TIR is of vitally protective value for sudomotor dysfunction in type 2 diabetes mellitus.

Review of minimally invasive continuous glucose monitoring technology & instruments

Continuous blood glucose monitoring is important for the diagnosis,treatment,and study of diabetes. many organizations have been working on this subject in recent two decades. Glucose concentration in interstitial fluid is closely related to the blood glucose levels. Minimally invasive continuous blood glucose monitoring technology based on the glucose detection in interstitial fluid develops rapidly and gets more and more attentions from the patients and the doctors,due to its instantaneous real-time display of glucose level,"24/7"coverage,and the ability to characterize glycemic variability. According to the different detection methods,most of the continuous glucose monitoring technology could be divided into two kinds: subcutaneous implantation method and transdermal extraction method. This paper review s the recent development of minimally invasive blood glucose monitoring technology and instruments. The mainly remained challenges and related research directions are presented as well.

Preliminary prospective study of real-time post-gastrectomy glycemic fluctuations during dumping symptoms using continuous glucose monitoring

BACKGROUND Although dumping symptoms constitute the most common post-gastrectomy syndromes impairing patient quality of life,the causes,including blood sugar fluctuations,are difficult to elucidate due to limitations in examining dumping symptoms as they occur.AIM To investigate relationships between glucose fluctuations and the occurrence of dumping symptoms in patients undergoing gastrectomy for gastric cancer.METHODS Patients receiving distal gastrectomy with Billroth-I(DG-BI)or Roux-en-Y reconstruction(DG-RY)and total gastrectomy with RY(TG-RY)for gastric cancer(March 2018-January 2020)were prospectively enrolled.Interstitial tissue glycemic profiles were measured every 15 min,up to 14 d,by continuous glucose monitoring.Dumping episodes were recorded on 5 patient-selected days by diary.Within 3 h postprandially,dumping-associated glycemic changes were defined as a dumping profile,those without symptoms as a control profile.These profiles were compared.RESULTS Thirty patients were enrolled(10 DG-BI,10 DG-RY,10 TG-RY).The 47 early dumping profiles of DG-BI showed immediately sharp rises after a meal,which 47 control profiles did not(P<0.05).Curves of the 15 late dumping profiles of DG-BI were similar to those of early dumping profiles,with lower glycemic levels.DGRY and TG-RY late dumping profiles(7 and 13,respectively)showed rapid glycemic decreases from a high glycemic state postprandially to hypoglycemia,with a steeper drop in TG-RY than in DG-RY.CONCLUSION Postprandial glycemic changes suggest dumping symptoms after standard gastrectomy for gastric cancer.Furthermore,glycemic profiles during dumping may differ depending on reconstruction methods after gastrectomy.

Development of Wearable Semi-invasive Blood Sampling Devices for Continuous Glucose Monitoring: A Survey

Semi-invasive blood sampling devices mimic the way female mosquitoes extract blood from a host. They generally consist of a microneedle, a microactuator for needle insertion, a blood extraction mechanism and a blood glucose sensor. These devices have great potential to overcome the major disadvantages of several current blood glucose monitoring methods. Over last two decades, extensive research has been made in all of these related fields. More recently, several wearable devices for semi-invasive blood sampling have been developed. This review aims at summarizing the current state-of-the-art development and utilization of such wearable devices for continuous monitoring of blood glucose levels, with a special attention on design considerations, fabrication technologies and testing methods.

Characteristics of glucose change in diabetes mellitus generalized through continuous wavelet transform processing:A preliminary study

BACKGROUND The continuous glucose monitoring(CGM)system has become a popular evaluation tool for glucose fluctuation,providing a detailed description of glucose change patterns.We hypothesized that glucose fluctuations may contain specific information on differences in glucose change between type 1 diabetes mellitus(T1DM)and type 2 diabetes mellitus(T2DM),despite similarities in change patterns,because of different etiologies.Unlike Fourier transform,continuous wavelet transform(CWT)is able to simultaneously analyze the time and frequency domains of oscillating data.AIM To investigate whether CWT can detect glucose fluctuations in T1DM.METHODS The 60-d and 296-d glucose fluctuation data of patients with T1DM(n=5)and T2DM(n=25)were evaluated respectively.Glucose data obtained every 15 min for 356 d were analyzed.Data were assessed by CWT with Morlet form(n=7)as the mother wavelet.This methodology was employed to search for limited frequency glucose fluctuation in the daily glucose change.The frequency and enclosed area(0.02625 scalogram value)of 18 emerged signals were compared.The specificity for T1DM was evaluated through multiple regression analysis using items that demonstrated significant differences between them as explanatory variables.RESULTS The high frequency at midnight(median:75 Hz,cycle time:19 min)and middle frequency at noon(median:45.5 Hz,cycle time:32 min)were higher in T1DM vs T2DM(median:73 and 44 Hz;P=0.006 and 0.005,respectively).The area of the>100 Hz zone at midnight to forenoon was more frequent and larger in T1DM vs T2DM.In a day,the lower frequency zone(15-35 Hz)was more frequent and the area was larger in T2DM than in T1DM.The threedimensional scatter diagrams,which consist of the time of day,frequency,and area of each signal after CWT,revealed that high frequency signals belonging to T1DM at midnight had a loose distribution of wave cycles that were 17-24 min.Multivariate analysis revealed that the high frequency signal at midnight could characterize T1DM(odds ratio:1.33,95%confidence interval:1.08-1.62;P=0.006).CONCLUSION CWT might be a novel tool for differentiate glucose fluctuation of each type of diabetes mellitus using CGM data.

What,why and how to monitor blood glucose in critically ill patients

Critically ill patients are prone to high glycemic variations irrespective of their diabetes status.This mandates frequent blood glucose(BG)monitoring and regulation of insulin therapy.Even though the most commonly employed capillary BG monitoring is convenient and rapid,it is inaccurate and prone to high bias,overestimating BG levels in critically ill patients.The targets for BG levels have also varied in the past few years ranging from tight glucose control to a more liberal approach.Each of these has its own fallacies,while tight control increases risk of hypoglycemia,liberal BG targets make the patients prone to hyperglycemia.Moreover,the recent evidence suggests that BG indices,such as glycemic variability and time in target range,may also affect patient outcomes.In this review,we highlight the nuances associated with BG monitoring,including the various indices required to be monitored,BG targets and recent advances in BG monitoring in critically ill patients.

Factors influencing the effectiveness of using flash glucose monitoring on glycemic control for type 1 diabetes in Saudi Arabia

BACKGROUND In 2017,35000 Saudi children and adolescents were living with a type 1 diabetes(T1D)diagnosis.Diabetic complications are minimized upon strengthened glycemic regulation.The annual cost of treating diabetic patients with complications was four-fold higher than for patients without complications.The use of flash glucose monitoring(FGM)enables better diabetes treatment and thereby improves glycemic control.Understanding the factors that affect effectiveness of FGM will help enhance the device’s use and management of hospital resources,resulting in improved outcomes.AIM To investigate factors that affect effectiveness of the FGM system for glycated hemoglobin(HbA1c)levels/glycemic control among T1D patients.METHODS A retrospective empirical analysis of T1D patient records from King Abdul-Aziz University Hospital and Prince Sultan Military Medical City was performed.T1D patients who began FGM between 2017 and 2019 were included.RESULTS The data included 195 T1D patients(70 males and 125 females)with a mean age of 23.6±8.1 years.Among them,152 patients used multiple daily injection and 43 used an insulin pump.The difference in HbA1c level from baseline and after using FGM was-0.60±2.10,with a maximum of 4.70 and a minimum of-6.30.There was a statistically significant negative correlation between the independent variables(age,duration of diabetes,level of engagement)and HbA1c.The group with the highest HbA1c mean(9.85)was 18-years-old,while the group with the lowest HbA1c mean(7.87)was 45-years-old.Patients with a low level of engagement(less than six scans per day)had the highest HbA1c mean(9.84),whereas those with a high level of engagement(more than eight scans per day)had the lowest HbA1c mean(8.33).CONCLUSION With proper education,FGM can help people with uncontrolled T1D over the age of 18 years to control their glucose level.

Decreasing complexity of glucose time series derived from continuous glucose monitoring is correlated with deteriorating glucose regulation

Most information used to evaluate diabetic statuses is collected at a special time-point,such as taking fasting plasma glucose test and providing a limited view of individual’s health and disease risk.As a new parameter for continuously evaluating personal clinical statuses,the newly developed technique“continuous glucose monitoring”(CGM)can characterize glucose dynamics.By calculating the complexity of glucose time series index(CGI)with refined composite multi-scale entropy analysis of the CGM data,the study showed for the first time that the complexity of glucose time series in subjects decreased gradually from normal glucose tolerance to impaired glucose regulation and then to type 2 diabetes(P for trend<0.01).Furthermore,CGI was significantly associated with various parameters such as insulin sensitivity/secretion(all P<0.01),and multiple linear stepwise regression showed that the disposition index,which reflectsβ-cell function after adjusting for insulin sensitivity,was the only independent factor correlated with CGI(P<0.01).Our findings indicate that the CGI derived from the CGM data may serve as a novel marker to evaluate glucose homeostasis.

Artificial intelligence biosensors for continuous glucose monitoring

Artificial intelligence(AI)algorithms in combination with continuous monitoring technologies have the potential to revolutionize chronic disease management.The recent innovations in both continuous glucose monitoring(CGM)and the closed-loop highlight the far-reaching potential of AI biosensors for individual healthcare.This review summarizes some of the most advanced progress made in CGM biosensing.We will focus on three main applications of AI algorithms in diabetes management:closed-loop control algorithms,glucose predictions,and calibrations.The challenges and opportunities of AI technologies for CGM in individualized and proactive medicine will also be discussed.

Anti-biofouling strategies for implantable biosensors of continuous glucose monitoring systems

Continuous glucose monitoring(CGM)systems play an increasingly vital role in the glycemic control of patients with diabetes mellitus.However,the immune responses triggered by the implantation of poorly biocompatible sensors have a significant impact on the accuracy and lifetime of CGM systems.In this review,research efforts over the past few years to mitigate the immune responses by enhancing the anti-biofouling ability of sensors are summarized.This review divided these works into active immune engaging strategy and passive immune escape strategy based on their respective mechanisms.In each strategy,the various biocompatible layers on the biosensor surface,such as drug-releasing membranes,hydrogels,hydrophilic membranes,anti-biofouling membranes based on zwitterionic polymers,and bio-mimicking membranes,are described in detail.This review,therefore,provides researchers working on implantable biosensors for CGM systems with vital information,which is likely to aid in the research and development of novel CGM systems with profound anti-biofouling properties.

CGM技术监测2型糖尿病患者血糖波动幅度与SMBG血糖波动指标的相关性研究

目的:研究2型糖尿病患者持续葡萄糖监测(CGM)技术监测血糖波动幅度与自我血糖监测(SMBG)血糖波动指标的相关性。方法:选取我院2022年6月至2023年6月收治的82例2型糖尿病患者进行研究。所有患者均接受7个时间点(三餐前、餐后2 h以及睡前)的SMBG和48~72 h的CGM,同时根据7个时间点SMBG数据计算血糖变异系数(CV)、最大血糖波动幅度(LAGE)、平均血糖波动幅度(MAGE1,SMBG计算得出)、血糖水平的标准差(SDBG)、餐后血糖波动幅度(PPGE)等血糖波动指标,采用简单线性回归分析法、Spearman秩相关分析法、多元逐步回归分析法,分析通过CGM获得的MAGE与通过SMBG计算得出的CV、LAGE、MAGE1、SDBG、PPGE之间的相关性。结果:以通过CGM获得的MAGE为因变量,以通过SMBG计算得出的CV、LAGE、MAGE1、SDBG、PPGE为自变量进行多元逐步回归分析,结果显示,通过CGM获得的MAGE与通过SMBG计算得出的CV、LAGE、MAGE1、SDBG、PPGE有关(P<0.05)。Spearman秩相关分析结果显示,通过CGM获得的MAGE与通过SMBG计算得出的CV、LAGE、MAGE1、SDBG、PPGE之间呈正相关(P<0.05)。结论:2型糖尿病患者CGM技术监测得出的MAGE与SMBG计算得出的CV、LAGE、MAGE1、SDBG、PPGE等血糖波动指标具有一定相关性,因此可通过SMBG计算得出的血糖波动指标反映2型糖尿病患者日内血糖波动情况。

CGMS联合胰岛素强化治疗ICU高血糖危重患者的临床效果研究

目的:观察动态血糖监测(CGMS)联合胰岛素强化治疗重症监护室(ICU)高血糖危重患者的临床效果。方法:选择我院重症监护室收治的高血糖危重患者135例,随机分为对照组(n=67)和观察组(n=68)。对照组行指尖血糖监测联合胰岛素常规治疗;观察组行CGMS联合胰岛素强化治疗。观察2组患者在不同时段的FBG值、ICU住院时间、平均机械通气时间、病死率、低血糖发生情况。结果:观察组的FBG值在治疗第3、5、7天均比对照组低,差异有统计学意义(P<0.05);观察组的ICU住院时间、平均机械通气时间均比对照组短,病死率也比对照组低,但差异无统计学意义(P>0.05);观察组的低血糖发生次数及发生率均比对照组低,差异有统计学意义(P<0.05)。结论:CGMS联合胰岛素强化治疗有助于更精准地掌握高血糖危重患者的血糖变化情况,进而更科学地制定胰岛素的使用量,快速降低患者的血糖并减少低血糖的发生率,具有很好的临床疗效,值得加以推广。

基于MATLAB的CGMS数据整合分析软件的开发和在糖尿病合并低血糖时血糖波动特点研究上的使用

目的:观察低血糖血糖波动趋势,探究低血糖发生的特点。方法:通过矩阵实验室(Matrix Laboratory,MATLAB)编程设计了与MiniMed解决方案(MiniMed Solutions CGMS Sensor,MSCS)的接口,利用MATLAB分析能力,实现大样本量的CGMS数据整合分析。结果:对829例CGMS数据进行筛选,符合研究条件405例,其中出现低血糖患者204例占50.62%。CGMS血糖监测系统与指测血糖在不同血糖范围均有较高一致性(P<0.01)。低血糖患者整体血糖低于非低血糖患者,低血糖发生时间尤以半夜及午餐前居多。低血糖聚集发生时间平均在1点09分,标准差时间为5小时31分。不同年龄段低血糖患者比较,低血糖发生时间随年龄增长而提前(P<0.01)。结论:MATLAB在大量CGMS监测数据处理具有速度快、设计灵活、使用方便等优点。低血糖的发生具有规律性,我们今后的研究方向是和低血糖发生可能相关的方向调节激素,神经内分泌的调节和脑生物钟的变化。

CGMS与CSⅡ泵联合治疗初诊老年2型糖尿病疗效观察

目的旨在观察分析动态血糖监测系统（CGMS）与CSⅡ泵联合治疗初诊老年2型糖尿病患者相关临床疗效。方法采用自身前、后对照，对90例初诊老年2型糖尿病予以胰岛素泵输注法控制血糖，同时使用CGMS评估。结果与治疗前相比其基线血糖水平均明显降低（P〈0．05）；基线血糖漂移幅度均明显下降（P〈0．05）。结论CGMS与CSⅡ联合应用能更有效地控制初诊老年2型糖尿病患者血糖水平。