Sample records for continuous glucose monitoring
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Continuous Monitoring of Glucose for Type 1 Diabetes: A Health Technology Assessment.
2018-01-01
Type 1 diabetes is a condition in which the pancreas produces little or no insulin. People with type 1 diabetes must manage their blood glucose levels by monitoring the amount of glucose in their blood and administering appropriate amounts of insulin via injection or an insulin pump. Continuous glucose monitoring may be beneficial compared to self-monitoring of blood glucose using a blood glucose meter. It provides insight into a person's blood glucose levels on a continuous basis, and can identify whether blood glucose levels are trending up or down. We conducted a health technology assessment, which included an evaluation of clinical benefit, value for money, and patient preferences related to continuous glucose monitoring. We compared continuous glucose monitoring with self-monitoring of blood glucose using a finger-prick and a blood glucose meter. We performed a systematic literature search for studies published since January 1, 2010. We created a Markov model projecting the lifetime horizon of adults with type 1 diabetes, and performed a budget impact analysis from the perspective of the health care payer. We also conducted interviews and focus group discussions with people who self-manage their type 1 diabetes or support the management of a child with type 1 diabetes. Twenty studies were included in the clinical evidence review. Compared with self-monitoring of blood glucose, continuous glucose monitoring improved the percentage of time patients spent in the target glycemic range by 9.6% (95% confidence interval 8.0-11.2) to 10.0% (95% confidence interval 6.75-13.25) and decreased the number of severe hypoglycemic events.Continuous glucose monitoring was associated with higher costs and small increases in health benefits (quality-adjusted life-years). Incremental cost-effectiveness ratios (ICERs) ranged from $592,206 to $1,108,812 per quality-adjusted life-year gained in analyses comparing four continuous glucose monitoring interventions to usual care. However, the uncertainty around the ICERs was large. The net budget impact of publicly funding continuous glucose monitoring assuming a 20% annual increase in adoption of continuous glucose monitoring would range from $8.5 million in year 1 to $16.2 million in year 5.Patient engagement surrounding the topic of continuous glucose monitoring was robust. Patients perceived that these devices provided important social, emotional, and medical and safety benefits in managing type 1 diabetes, especially in children. Continuous glucose monitoring was more effective than self-monitoring of blood glucose in managing type 1 diabetes for some outcomes, such as time spent in the target glucose range and time spent outside the target glucose range (moderate certainty in this evidence). We were less certain that continuous glucose monitoring would reduce the number of severe hypoglycemic events. Compared with self-monitoring of blood glucose, the costs of continuous glucose monitoring were higher, with only small increases in health benefits. Publicly funding continuous glucose monitoring for the type 1 diabetes population in Ontario would result in additional costs to the health system over the next 5 years. Adult patients and parents of children with type 1 diabetes reported very positive experiences with continuous glucose monitoring. The high ongoing cost of continuous glucose monitoring devices was seen as the greatest barrier to their widespread use.
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Continuous Monitoring of Glucose for Type 1 Diabetes: A Health Technology Assessment
Vandersluis, Stacey; Kabali, Conrad; Djalalov, Sandjar; Gajic-Veljanoski, Olga; Wells, David; Holubowich, Corinne
2018-01-01
Background Type 1 diabetes is a condition in which the pancreas produces little or no insulin. People with type 1 diabetes must manage their blood glucose levels by monitoring the amount of glucose in their blood and administering appropriate amounts of insulin via injection or an insulin pump. Continuous glucose monitoring may be beneficial compared to self-monitoring of blood glucose using a blood glucose meter. It provides insight into a person's blood glucose levels on a continuous basis, and can identify whether blood glucose levels are trending up or down. Methods We conducted a health technology assessment, which included an evaluation of clinical benefit, value for money, and patient preferences related to continuous glucose monitoring. We compared continuous glucose monitoring with self-monitoring of blood glucose using a finger-prick and a blood glucose meter. We performed a systematic literature search for studies published since January 1, 2010. We created a Markov model projecting the lifetime horizon of adults with type 1 diabetes, and performed a budget impact analysis from the perspective of the health care payer. We also conducted interviews and focus group discussions with people who self-manage their type 1 diabetes or support the management of a child with type 1 diabetes. Results Twenty studies were included in the clinical evidence review. Compared with self-monitoring of blood glucose, continuous glucose monitoring improved the percentage of time patients spent in the target glycemic range by 9.6% (95% confidence interval 8.0–11.2) to 10.0% (95% confidence interval 6.75–13.25) and decreased the number of severe hypoglycemic events. Continuous glucose monitoring was associated with higher costs and small increases in health benefits (quality-adjusted life-years). Incremental cost-effectiveness ratios (ICERs) ranged from $592,206 to $1,108,812 per quality-adjusted life-year gained in analyses comparing four continuous glucose monitoring interventions to usual care. However, the uncertainty around the ICERs was large. The net budget impact of publicly funding continuous glucose monitoring assuming a 20% annual increase in adoption of continuous glucose monitoring would range from $8.5 million in year 1 to $16.2 million in year 5. Patient engagement surrounding the topic of continuous glucose monitoring was robust. Patients perceived that these devices provided important social, emotional, and medical and safety benefits in managing type 1 diabetes, especially in children. Conclusions Continuous glucose monitoring was more effective than self-monitoring of blood glucose in managing type 1 diabetes for some outcomes, such as time spent in the target glucose range and time spent outside the target glucose range (moderate certainty in this evidence). We were less certain that continuous glucose monitoring would reduce the number of severe hypoglycemic events. Compared with self-monitoring of blood glucose, the costs of continuous glucose monitoring were higher, with only small increases in health benefits. Publicly funding continuous glucose monitoring for the type 1 diabetes population in Ontario would result in additional costs to the health system over the next 5 years. Adult patients and parents of children with type 1 diabetes reported very positive experiences with continuous glucose monitoring. The high ongoing cost of continuous glucose monitoring devices was seen as the greatest barrier to their widespread use. PMID:29541282
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Hirsch, Irl B; Verderese, Carol A
2017-11-01
Recent consensus statements strongly advocate downloading and interpreting continuous glucose data for diabetes management in patients with type 1 or 2 diabetes. Supplementing periodic glycated hemoglobin (A1C) testing with intermittent continuous glucose monitoring (CGM) using a standardized report form known as the ambulatory glucose profile (AGP) is an evolving standard of care. The rationale for this approach and its implementation with a recently approved novel monitoring technology are explored. Search of the medical literature, professional guidelines, and real-world evidence guided this introduction of an integrative practice framework that uses AGP in conjunction with intermittent flash continuous glucose monitoring (FCGM) as a supplement to A1C testing. The combination of intermittent continuous glucose pattern analysis, standardized glucose metrics, and a readily interpretable data report has the potential to practically extend the recognized benefits of CGM to more patients and clarify the relationship between A1C and average glucose levels in individual cases. Novel FCGM technologies portend greater use of continuous forms of glucose monitoring and wider adoption of AGP report analysis. Additional formal and empirical evidence is needed to more fully characterize best practice. A1C = glycated hemoglobin; AGP = ambulatory glucose profile; CGM = continuous glucose monitoring; FCGM = flash continuous glucose monitoring; IQR = interquartile range; SMBG = self-monitoring of blood glucose.
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Current concepts in blood glucose monitoring
Khadilkar, Kranti Shreesh; Bandgar, Tushar; Shivane, Vyankatesh; Lila, Anurag; Shah, Nalini
2013-01-01
Blood glucose monitoring has evolved over the last century. The concept of adequate glycemic control and minimum glycemic variability requires an ideal, accurate and reliable glucose monitoring system. The search for an ideal blood glucose monitoring system still continues. This review explains the various blood glucose monitoring systems with special focus on the monitoring systems like self- monitored blood glucose (SMBG) and continuous glucose monitoring system (CGMS). It also focuses on the newer concepts of blood glucose monitoring and their incorporation in routine clinical management of diabetes mellitus. PMID:24910827
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Noninvasive Continuous Monitoring of Tear Glucose Using Glucose-Sensing Contact Lenses.
Ascaso, Francisco J; Huerva, Valentín
2016-04-01
: The incidence of diabetes mellitus is dramatically increasing in the developed countries. Tight control of blood glucose concentration is crucial to diabetic patients to prevent microvascular complications. Self-monitoring of blood glucose is widely used for controlling blood glucose levels and usually performed by an invasive test using a portable glucometer. Many technologies have been developed over the past decades with the purpose of obtaining a continuous physiological glycemic monitoring. A contact lens is the ideal vehicle for continuous tear glucose monitoring of glucose concentration in tear film. There are several research groups that are working in the development of contact lenses with embedded biosensors for continuously and noninvasively monitoring tear glucose levels. Although numerous aspects must be improved, contact lens technology is one step closer to helping diabetic subjects better manage their condition, and these contact lenses will be able to measure the level of glucose in the wearer's tears and communicate the information to a mobile phone or computer. This article reviews studies on ocular glucose and its monitoring methods as well as the attempts to continuously monitor the concentration of tear glucose by using contact lens-based sensors.
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Glucose Biosensors: An Overview of Use in Clinical Practice
Yoo, Eun-Hyung; Lee, Soo-Youn
2010-01-01
Blood glucose monitoring has been established as a valuable tool in the management of diabetes. Since maintaining normal blood glucose levels is recommended, a series of suitable glucose biosensors have been developed. During the last 50 years, glucose biosensor technology including point-of-care devices, continuous glucose monitoring systems and noninvasive glucose monitoring systems has been significantly improved. However, there continues to be several challenges related to the achievement of accurate and reliable glucose monitoring. Further technical improvements in glucose biosensors, standardization of the analytical goals for their performance, and continuously assessing and training lay users are required. This article reviews the brief history, basic principles, analytical performance, and the present status of glucose biosensors in the clinical practice. PMID:22399892
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Continuous Glucose Monitoring: Impact on Hypoglycemia.
van Beers, Cornelis A J; DeVries, J Hans
2016-11-01
The necessity of strict glycemic control is unquestionable. However, hypoglycemia remains a major limiting factor in achieving satisfactory glucose control, and evidence is mounting to show that hypoglycemia is not benign. Over the past decade, evidence has consistently shown that real-time continuous glucose monitoring improves glycemic control in terms of lowering glycated hemoglobin levels. However, real-time continuous glucose monitoring has not met the expectations of the diabetes community with regard to hypoglycemia prevention. The earlier trials did not demonstrate any effect on either mild or severe hypoglycemia and the effect of real-time continuous glucose monitoring on nocturnal hypoglycemia was often not reported. However, trials specifically designed to reduce hypoglycemia in patients with a high hypoglycemia risk have demonstrated a reduction in hypoglycemia, suggesting that real-time continuous glucose monitoring can prevent hypoglycemia when it is specifically used for that purpose. Moreover, the newest generation of diabetes technology currently available commercially, namely sensor-augmented pump therapy with a (predictive) low glucose suspend feature, has provided more convincing evidence for hypoglycemia prevention. This article provides an overview of the hypoglycemia outcomes of randomized controlled trials that investigate the effect of real-time continuous glucose monitoring alone or sensor-augmented pump therapy with a (predictive) low glucose suspend feature. Furthermore, several possible explanations are provided why trials have not shown a reduction in severe hypoglycemia. In addition, existing evidence is presented of real-time continuous glucose monitoring in patients with impaired awareness of hypoglycemia who have the highest risk of severe hypoglycemia. © 2016 Diabetes Technology Society.
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van Beers, Cornelis A. J.; DeVries, J. Hans
2016-01-01
The necessity of strict glycemic control is unquestionable. However, hypoglycemia remains a major limiting factor in achieving satisfactory glucose control, and evidence is mounting to show that hypoglycemia is not benign. Over the past decade, evidence has consistently shown that real-time continuous glucose monitoring improves glycemic control in terms of lowering glycated hemoglobin levels. However, real-time continuous glucose monitoring has not met the expectations of the diabetes community with regard to hypoglycemia prevention. The earlier trials did not demonstrate any effect on either mild or severe hypoglycemia and the effect of real-time continuous glucose monitoring on nocturnal hypoglycemia was often not reported. However, trials specifically designed to reduce hypoglycemia in patients with a high hypoglycemia risk have demonstrated a reduction in hypoglycemia, suggesting that real-time continuous glucose monitoring can prevent hypoglycemia when it is specifically used for that purpose. Moreover, the newest generation of diabetes technology currently available commercially, namely sensor-augmented pump therapy with a (predictive) low glucose suspend feature, has provided more convincing evidence for hypoglycemia prevention. This article provides an overview of the hypoglycemia outcomes of randomized controlled trials that investigate the effect of real-time continuous glucose monitoring alone or sensor-augmented pump therapy with a (predictive) low glucose suspend feature. Furthermore, several possible explanations are provided why trials have not shown a reduction in severe hypoglycemia. In addition, existing evidence is presented of real-time continuous glucose monitoring in patients with impaired awareness of hypoglycemia who have the highest risk of severe hypoglycemia. PMID:27257169
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[Design and implementation of real-time continuous glucose monitoring instrument].
Huang, Yonghong; Liu, Hongying; Tian, Senfu; Jia, Ziru; Wang, Zi; Pi, Xitian
2017-12-01
Real-time continuous glucose monitoring can help diabetics to control blood sugar levels within the normal range. However, in the process of practical monitoring, the output of real-time continuous glucose monitoring system is susceptible to glucose sensor and environment noise, which will influence the measurement accuracy of the system. Aiming at this problem, a dual-calibration algorithm for the moving-window double-layer filtering algorithm combined with real-time self-compensation calibration algorithm is proposed in this paper, which can realize the signal drift compensation for current data. And a real-time continuous glucose monitoring instrument based on this study was designed. This real-time continuous glucose monitoring instrument consisted of an adjustable excitation voltage module, a current-voltage converter module, a microprocessor and a wireless transceiver module. For portability, the size of the device was only 40 mm × 30 mm × 5 mm and its weight was only 30 g. In addition, a communication command code algorithm was designed to ensure the security and integrity of data transmission in this study. Results of experiments in vitro showed that current detection of the device worked effectively. A 5-hour monitoring of blood glucose level in vivo showed that the device could continuously monitor blood glucose in real time. The relative error of monitoring results of the designed device ranged from 2.22% to 7.17% when comparing to a portable blood meter.
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Hanaire, Hélène; Dubet, Audrey; Chauveau, Marie-Emilie; Anduze, Yves; Fernandes, Martine; Melki, Vincent; Ritz, Patrick
2010-01-01
Hypoglycemia is rare after a gastric bypass and can be taken for a dumping syndrome. There is no report in the literature of the contribution of continuous glucose monitoring to the diagnosis of hypoglycemia in these circumstances. The present case report shows that continuous glucose monitoring can be a useful tool for the diagnosis and the management of such episodes. Continuous glucose monitoring revealed hypoglycemic episodes in free living circumstances that were not present during 72-h fasting. These episodes followed wide hyperglycemic swings. No such episode resumed over 8 months after specific dietary advices and treatment by 50 mg TID of acarbose. Because hypoglycemia can be difficult to diagnose from dumping syndrome, continuous glucose monitoring is a very useful tool revealing the episodes in free living circumstances and can be used to monitor the treatment success.
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Allen, Nancy; Whittemore, Robin; Melkus, Gail
2011-11-01
Diabetes technology has the potential to provide useful data for theory-based behavioral counseling. The aims of this study are to evaluate the feasibility, acceptability, and preliminary efficacy of a continuous glucose monitoring and problem-solving counseling intervention to change physical activity (PA) behavior in women with type 2 diabetes. Women (n=29) with type 2 diabetes were randomly assigned to one of two treatment conditions: continuous glucose counseling and problem-solving skills or continuous glucose monitoring counseling and general diabetes education. Feasibility data were obtained on intervention dose, implementation, and satisfaction. Preliminary efficacy data were collected at baseline and 12 weeks on the following measures: PA amount and intensity, diet, problem-solving skills, self-efficacy for PA, depression, hemogoloin A1c, weight, and blood pressure. Demographic and implementation variables were described using frequency distributions and summary statistics. Satisfaction data were analyzed using Wilcoxon rank. Differences between groups were analyzed using linear mixed-modeling. Women were mostly white/non-Latina with a mean age of 53 years, a 6.5-year history of diabetes, and suboptimal glycemic control. Continuous glucose monitoring plus problem-solving group participants had significantly greater problem-solving skills and had greater, although not statistically significant, dietary adherence, moderate activity minutes, weight loss, and higher intervention satisfaction pre- to post-intervention than did participants in the continuous glucose monitoring plus education group. A continuous glucose monitoring plus problem-solving intervention was feasible and acceptable, and participants had greater problem-solving skills than continuous glucose monitoring plus education group participants.
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Wearable Contact Lens Biosensors for Continuous Glucose Monitoring Using Smartphones.
Elsherif, Mohamed; Hassan, Mohammed Umair; Yetisen, Ali K; Butt, Haider
2018-05-17
Low-cost, robust, and reusable continuous glucose monitoring systems that can provide quantitative measurements at point-of-care settings is an unmet medical need. Optical glucose sensors require complex and time-consuming fabrication processes, and their readouts are not practical for quantitative analyses. Here, a wearable contact lens optical sensor was created for the continuous quantification of glucose at physiological conditions, simplifying the fabrication process and facilitating smartphone readouts. A photonic microstructure having a periodicity of 1.6 μm was printed on a glucose-selective hydrogel film functionalized with phenylboronic acid. Upon binding with glucose, the microstructure volume swelled, which modulated the periodicity constant. The resulting change in the Bragg diffraction modulated the space between zero- and first-order spots. A correlation was established between the periodicity constant and glucose concentration within 0-50 mM. The sensitivity of the sensor was 12 nm mM -1 , and the saturation response time was less than 30 min. The sensor was integrated with commercial contact lenses and utilized for continuous glucose monitoring using smartphone camera readouts. The reflected power of the first-order diffraction was measured via a smartphone application and correlated to the glucose concentrations. A short response time of 3 s and a saturation time of 4 min was achieved in the continuous monitoring mode. Glucose-sensitive photonic microstructures may have applications in point-of-care continuous monitoring devices and diagnostics at home settings.
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De Block, Christophe; Manuel-y-Keenoy, Begoña; Rogiers, Peter; Jorens, Philippe; Van Gaal, Luc
2008-08-01
Stress hyperglycemia recently became a major therapeutic target in the Intensive Care Unit (ICU) since it occurs in most critically ill patients and is associated with adverse outcome, including increased mortality. Intensive insulin therapy to achieve normoglycemia may reduce mortality, morbidity and the length of ICU and in-hospital stay. However, obtaining normoglycemia requires extensive efforts from the medical staff, including frequent glucose monitoring and adjustment of insulin dose. Current insulin titration is based upon discrete glucose measurements, which may miss fast changes in glycemia and which does not give a full picture of overall glycemic control. Recent evidence suggests that continuous monitoring of glucose levels may help to signal glycemic excursions and eventually to optimize insulin titration in the ICU. In this review we will summarise monitoring and treatment strategies to achieve normoglycemia in the ICU, with special emphasis on the possible advantages of continuous glucose monitoring.
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Optical biosensor optimized for continuous in-line glucose monitoring in animal cell culture.
Tric, Mircea; Lederle, Mario; Neuner, Lisa; Dolgowjasow, Igor; Wiedemann, Philipp; Wölfl, Stefan; Werner, Tobias
2017-09-01
Biosensors for continuous glucose monitoring in bioreactors could provide a valuable tool for optimizing culture conditions in biotechnological applications. We have developed an optical biosensor for long-term continuous glucose monitoring and demonstrated a tight glucose level control during cell culture in disposable bioreactors. The in-line sensor is based on a commercially available oxygen sensor that is coated with cross-linked glucose oxidase (GOD). The dynamic range of the sensor was tuned by a hydrophilic perforated diffusion membrane with an optimized permeability for glucose and oxygen. The biosensor was thoroughly characterized by experimental data and numerical simulations, which enabled insights into the internal concentration profile of the deactivating by-product hydrogen peroxide. The simulations were carried out with a one-dimensional biosensor model and revealed that, in addition to the internal hydrogen peroxide concentration, the turnover rate of the enzyme GOD plays a crucial role for biosensor stability. In the light of this finding, the glucose sensor was optimized to reach a long functional stability (>52 days) under continuous glucose monitoring conditions with a dynamic range of 0-20 mM and a response time of t 90 ≤ 10 min. In addition, we demonstrated that the sensor was sterilizable with beta and UV irradiation and only subjected to minor cross sensitivity to oxygen, when an oxygen reference sensor was applied. Graphical abstract Measuring setup of a glucose biosensor in a shake flask for continuous glucose monitoring in mammalian cell culture.
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Glucose Sensing for Diabetes Monitoring: Recent Developments
Bruen, Danielle; Delaney, Colm; Florea, Larisa
2017-01-01
This review highlights recent advances towards non-invasive and continuous glucose monitoring devices, with a particular focus placed on monitoring glucose concentrations in alternative physiological fluids to blood. PMID:28805693
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Ricci, Francesco; Caprio, Felice; Poscia, Alessandro; Valgimigli, Francesco; Messeri, Dimitri; Lepori, Elena; Dall'Oglio, Giorgio; Palleschi, Giuseppe; Moscone, Danila
2007-04-15
Glucose biosensors based on the use of planar screen-printed electrodes modified with an electrochemical mediator and with glucose oxidase have been optimised for their application in the continuous glucose monitoring in diabetic patients. A full study of their operative stability and temperature dependence has been accomplished, thus giving useful information for in vivo applications. The effect of dissolved oxygen concentration in the working solution was also studied in order to evaluate its effect on the linearity of the sensors. Glucose monitoring performed with serum samples was performed to evaluate the effect of matrix components on operative stability and demonstrated an efficient behaviour for 72 h of continuous monitoring. Finally, these studies led to a sensor capable of detecting glucose at concentrations as low as 0.04 mM and with a good linearity up to 2.0 mM (at 37 degrees C) with an operative stability of ca. 72 h, thus demonstrating the possible application of these sensors for continuous glucose monitoring in conjunction with a microdialysis probe. Moreover, preliminary in vivo experiments for ca. 20 h have demonstrated the feasibility of this system.
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Mangrola, Devna; Cox, Christine; Furman, Arianne S; Krishnan, Sridevi; Karakas, Sidika E
2018-01-01
When glucose records from self blood glucose monitoring (SBGM) do not reflect estimated average glucose from glycosylated hemoglobin (HgBA1) or when patients' clinical symptoms are not explained by their SBGM records, clinical management of diabetes becomes a challenge. Our objective was to determine the magnitude of differences in glucose values reported by SBGM versus those documented by continuous glucose monitoring (CGM). The CGM was conducted by a clinical diabetes educator (CDE)/registered nurse by the clinic protocol, using the Medtronic iPRO2 ™ system. Patients continued SBGM and managed their diabetes without any change. Data from 4 full days were obtained, and relevant clinical information was recorded. De-identified data sets were provided to the investigators. Data from 61 patients, 27 with type 1 diabetes (T1DM) and 34 with T2DM were analyzed. The lowest, highest, and average glucose recorded by SBGM were compared to the corresponding values from CGM. The lowest glucose values reported by SBGM were approximately 25 mg/dL higher in both T1DM ( P = .0232) and T2DM ( P = .0003). The highest glucose values by SBGM were approximately 30 mg/dL lower in T1DM ( P = .0005) and 55 mg/dL lower in T2DM ( P<.0001). HgBA1c correlated with the highest and average glucose by SBGM and CGM. The lowest glucose values were seen most frequently during sleep and before breakfast; the highest were seen during the evening and postprandially. SBGM accurately estimates the average glucose but underestimates glucose excursions. CGM uncovers glucose patterns that common SBGM patterns cannot. CDE = certified diabetes educator; CGM = continuous glucose monitoring; HgBA1c = glycosylated hemoglobin; MAD = mean absolute difference; SBGM = self blood glucose monitoring; T1DM = type 1 diabetes; T2DM = type 2 diabetes.
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Continuous glucose monitoring: quality of hypoglycaemia detection.
Zijlstra, E; Heise, T; Nosek, L; Heinemann, L; Heckermann, S
2013-02-01
To evaluate the accuracy of a (widely used) continuous glucose monitoring (CGM)-system and its ability to detect hypoglycaemic events. A total of 18 patients with type 1 diabetes mellitus used continuous glucose monitoring (Guardian REAL-Time CGMS) during two 9-day in-house periods. A hypoglycaemic threshold alarm alerted patients to sensor readings <70 mg/dl. Continuous glucose monitoring sensor readings were compared to laboratory reference measurements taken every 4 h and in case of a hypoglycaemic alarm. A total of 2317 paired data points were evaluated. Overall, the mean absolute relative difference (MARD) was 16.7%. The percentage of data points in the clinically accurate or acceptable Clarke Error Grid zones A + B was 94.6%. In the hypoglycaemic range, accuracy worsened (MARD 38.8%) leading to a failure to detect more than half of the true hypoglycaemic events (sensitivity 37.5%). Furthermore, more than half of the alarms that warn patients for hypoglycaemia were false (false alert rate 53.3%). Above the low alert threshold, the sensor confirmed 2077 of 2182 reference values (specificity 95.2%). Patients using continuous glucose monitoring should be aware of its limitation to accurately detect hypoglycaemia. © 2012 Blackwell Publishing Ltd.
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Clinical Use of Continuous Glucose Monitoring in Adults with Type 1 Diabetes.
Slattery, David; Choudhary, Pratik
2017-05-01
With the emphasis on intensive management of type 1 diabetes, data from studies support frequent monitoring of glucose levels to improve glycemic control and reduce glucose variability, which can be related to an increase in macro and microvascular complications. However, few perform capillary blood glucose that frequently. There are currently two available alternatives that this review will discuss, continuous glucose monitoring (CGM) and flash glucose monitoring. CGM has become an important diagnostic and therapeutic option in optimizing diabetes management. CGM systems are now more accurate, smaller, and easier to use compared to original models. Randomized controlled trials (RCTs) have demonstrated that CGM can improve Hemoglobin A1c (HbA1C) and reduce glucose variability in both continuous subcutaneous insulin infusion and multiple daily injection users. When used in an automated "insulin-suspend" system, reduced frequency of hypoglycemia and shorter time spent in hypoglycemic range have been demonstrated. Despite the potential benefits CGM has to offer in clinical practice, concerns exist on the accuracy of these devices and patient compliance with therapy, which may prevent the true clinical benefit of CGM being achieved, as observed in RCTs. Flash glucose monitoring systems FreeStyle ® Libre™ (Abbott Diabetes Care, Alameda, CA) are as accurate as many CGM systems available and have the added benefit of being factory calibrated. Studies have shown that flash glucose monitoring systems are very well tolerated by patients and effectively reduce glucose variability, increasing time in range.
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Continuous non-invasive blood glucose monitoring by spectral image differencing method
NASA Astrophysics Data System (ADS)
Huang, Hao; Liao, Ningfang; Cheng, Haobo; Liang, Jing
2018-01-01
Currently, the use of implantable enzyme electrode sensor is the main method for continuous blood glucose monitoring. But the effect of electrochemical reactions and the significant drift caused by bioelectricity in body will reduce the accuracy of the glucose measurements. So the enzyme-based glucose sensors need to be calibrated several times each day by the finger-prick blood corrections. This increases the patient's pain. In this paper, we proposed a method for continuous Non-invasive blood glucose monitoring by spectral image differencing method in the near infrared band. The method uses a high-precision CCD detector to switch the filter in a very short period of time, obtains the spectral images. And then by using the morphological method to obtain the spectral image differences, the dynamic change of blood sugar is reflected in the image difference data. Through the experiment proved that this method can be used to monitor blood glucose dynamically to a certain extent.
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[CGM-continuous glucose monitoring - statement of the Austrian Diabetes Association].
Schütz-Fuhrmann, Ingrid; Schober, Edith; Rami, Birgit; Stadler, Marietta; Bischof, Martin; Fortunat, Sandra; Laimer, Markus; Weitgasser, Raimund; Prager, Rudolf
2012-12-01
This position statement represents the recommendations of the Austrian Diabetes Association regarding the clinical diagnostic and therapeutic application, safety and benefits of continuous subcutaneous glucose monitoring systems in patients with diabetes mellitus, based on current evidence.
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[CGM-Continuous Glucose Monitoring--Statement of the Austrian Diabetes Association].
Schütz-Fuhrmann, Ingrid; Rami-Merhar, Birgit; Hofer, Sabine; Stadler, Marietta; Bischof, Martin; Zlamal-Fortunat, Sandra; Laimer, Markus; Weitgasser, Raimund; Prager, Rudolf
2016-04-01
This position statement represents the recommendations of the Austrian Diabetes Association regarding the clinical diagnostic and therapeutic application, safety and benefits of continuous subcutaneous glucose monitoring systems in patients with diabetes mellitus, based on current evidence.
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Validation of the continuous glucose monitoring sensor in preterm infants.
Beardsall, K; Vanhaesebrouck, S; Ogilvy-Stuart, A L; Vanhole, C; VanWeissenbruch, M; Midgley, P; Thio, M; Cornette, L; Ossuetta, I; Palmer, C R; Iglesias, I; de Jong, M; Gill, B; de Zegher, F; Dunger, D B
2013-03-01
Recent studies have highlighted the need for improved methods of monitoring glucose control in intensive care to reduce hyperglycaemia, without increasing the risk of hypoglycaemia. Continuous glucose monitoring is increasingly used in children with diabetes, but there are little data regarding its use in the preterm infant, particularly at extremes of glucose levels and over prolonged periods. This study aimed to assess the accuracy of the continuous glucose monitoring sensor (CGMS) across the glucose profile, and to determine whether there was any deterioration over a 7 day period. Prospectively collected CGMS data from the NIRTURE Trial was compared with the data obtained simultaneously using point of care glucose monitors. An international multicentre randomised controlled trial. One hundred and eighty-eight very low birth weight control infants. Optimal accuracy, performance goals (American Diabetes Association consensus), Bland Altman, Error Grid analyses and accuracy. The mean (SD) duration of CGMS recordings was 156.18 (29) h (6.5 days), with a total of 5207 paired glucose levels. CGMS data correlated well with point of care devices (r=0.94), with minimal bias. It met the Clarke Error Grid and Consensus Grid criteria for clinical significance. Accuracy of single readings to detect set thresholds of hypoglycaemia, or hyperglycaemia was poor. There was no deterioration over time from insertion. CGMS can provide information on trends in glucose control, and guidance on the need for blood glucose assessment. This highlights the potential use of CGMS in optimising glucose control in preterm infants.
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Gómez, Ana M; Marín Sánchez, Alejandro; Muñoz, Oscar M; Colón Peña, Christian Alejandro
2015-12-01
Insulin pump therapy associated with continuous glucose monitoring has shown a positive clinical impact on diabetes control and reduction of hypoglycemia episodes. There are descriptions of the performance of this device in other populations, but its precision and accuracy in Colombia and Latin America are unknown, especially in the routine outpatient setting. Data from 33 type 1 and type 2 diabetes patients with sensor-augmented pump therapy with threshold suspend automation, MiniMed Paradigm® Veo™ (Medtronic, Northridge, California), managed at Hospital Universitario San Ignacio (Bogotá, Colombia) and receiving outpatient treatment, were analyzed. Simultaneous data from continuous glucose monitoring and capillary blood glucose were compared, and their precision and accuracy were calculating with different methods, including Clarke error grid. Analyses included 2,262 continuous glucose monitoring -reference paired glucose values. A mean absolute relative difference of 20.1% was found for all measurements, with a value higher than 23% for glucose levels ≤75mg/dL. Global compliance with the ISO criteria was 64.9%. It was higher for values >75mg/dl (68.3%, 1,308 of 1,916 readings), than for those ≤ 75mg/dl (49.4%, 171 of 346 readings). Clinical accuracy, as assessed by the Clarke error grid, showed that 91.77% of data were within the A and B zones (75.6% in hypoglycemia). A good numerical accuracy was found for continuous glucose monitoring in normo and hyperglycemia situations, with low precision in hypoglycemia. The clinical accuracy of the device was adequate, with no significant safety concerns for patients. Copyright © 2015 SEEN. Published by Elsevier España, S.L.U. All rights reserved.
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Torres Lacruz, M; Barrio Castellanos, R; García Cuartero, B; Gómez Gila, A; González Casado, I; Hermoso López, F; Luzuriaga Tomás, C; Oyarzabal Irigoyen, M; Rica Etxebarria, I; Rodríguez Rigual, M
2011-08-01
Glucose monitoring methods have made great advances in the last decade with the appearance of the continuous glucose monitoring systems (CGMS) that measure the glucose levels in the interstitial liquid, providing information about glucose patterns and trends, but do not replace the self-monitoring of capillary glucose. Improvement in diabetes control using the CGMS depends on the motivation and training received by the patient and family and on the continuity in its use. Due to the development and widespread use of these systems in clinical practice, the diabetes group of the Sociedad Española de Endocrinología Pediátrica has drafted a document of consensus for their indication and use in children and adolescents. Only a limited number of trials have been performed in children and adolescent populations. More data are needed on the use of this technology in order to define the impact on metabolic control. Copyright © 2010 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.
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Szymońska, Izabela; Jagła, Mateusz; Starzec, Katarzyna; Hrnciar, Katarzyna; Kwinta, Przemko
2015-01-01
To determine the incidence of hyperglycaemia in very low birth weight preterm newborns. To assess risk factors in hyperglycemia and outcome in groups of children with and without clinically significant hyperglycaemia. The prospective study included newborns with very low birth weight in whom the continuous glucose monitoring system was used for glucose measurements. A standardized hyperglycaemia treatment schedule was implemented and a uniform nutrition strategy introduced. The patients were divided into groups: group A--patients with under 5% of the readings over 150 mg/dL of glucose (control group), group B--patients with more than 5% of the readings over 150 mg/dL of glucose and under 5% of the readings over 180 mg/dL of glucose (mild hyperglycaemia), and group C--patients with over 5% of the readings > 180 mg/dL or on insulin treatment (moderate or severe hyperglycaemia). 63 patients were included in the study. Their mean gestational age was 27.7 weeks (SD:2.4), the mean birth weight was 1059g (SD: 262 g). Hyperglycaemia was detected in 27 (42.9%), including mild hyperglycaemia in 19 (30.2%), and moderate or severe hyperglycaemia in 8 (12.7%) neonates. Lower gestational age (p = 0.02) and higher CRIB IIscore (p < 0.01) were positively associated with hyperglycaemia. Early-onset sepsis (p < 0.01) was associated with higher glucose levels as well. A significantly higher mortality rate on the 28th day of life (p = 0.02), depending on the severity of hyperglycemia, was noted. No adverse effects related to the continuous glucose monitoring system were observed. The study confirmed the usefulness and safety of the continuous glucose monitoring system in VLBW neonates. A continuous glucose monitoring system should be used in neonatal intensive care units as a standard method.
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Korstanje, Ron; Ryan, Jennifer L; Savage, Holly S; Lyons, Bonnie L; Kane, Kevin G; Sukoff Rizzo, Stacey J
2017-09-01
Previous studies with continuous glucose monitoring in mice have been limited to several days or weeks, with the mouse's physical attachment to the equipment affecting behavior and measurements. In the current study, we measured blood glucose and body temperature at 10-second intervals for 12 weeks in a cohort of NOD/ShiLtJ female mice using wireless telemetry. This allowed us to obtain a high-resolution profile of the circadian rhythm of these two parameters and the onset of hyperglycemic development in real time. The most striking observations were the elevated nocturnal concentrations of glucose into the diabetic range days before elevations in diurnal glucose (when glucose concentrations are historically measured) and the strong, negative correlation between elevated blood glucose concentrations and body temperature with a steady decline of the body temperature with diabetes development. Taken together, this technological advancement provides improved resolution in the study of the disease trajectory of diabetes in mouse models, including relevant translatability to the current technologies of continuous glucose monitoring now regularly used in patients. Copyright © 2017 Endocrine Society.
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NASA Astrophysics Data System (ADS)
Heise, H. Michael; Damm, Uwe; Kondepati, Venkata R.
2006-02-01
For clinical research, in-vivo blood glucose monitoring is an ongoing important topic to improve glycemic control in patients with non-adequate blood glucose regulation. Critically ill patients received much interest, since the intensive insulin therapy treatment, as established for diabetics, reduces mortality significantly. Despite the existence of commercially available, mainly amperometric biosensors, continued interest is in infrared spectroscopic techniques for reagent-free glucose monitoring. For stable long-term operation, avoiding also sensor recalibration, a bed-side device coupled to a micro-dialysis probe was developed for quasi-continuous glucose monitoring. Multivariate calibration is required for glucose concentration prediction due to the complex composition of dialysates from interstitial body fluid. Measurements were carried out with different test persons, each experiment lasting for more than 8 hours. Owing to low dialysis recovery rates, glucose concentrations in the dialysates were between 0.83 and 4.44 mM. Standard errors of prediction (SEP) obtained with Partial Least Squares (PLS) calibration and different cross-validation strategies were mainly between 0.13 and 0.18 mM based on either full interval data or specially selected spectral variables.
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Seo, Dongmin; Paek, Sung-Ho; Oh, Sangwoo; Seo, Sungkyu; Paek, Se-Hwan
2016-09-24
The incidence of diabetes is continually increasing, and by 2030, it is expected to have increased by 69% and 20% in underdeveloped and developed countries, respectively. Therefore, glucose sensors are likely to remain in high demand in medical device markets. For the current study, we developed a needle-type bio-layer interference (BLI) sensor that can continuously monitor glucose levels. Using dialysis procedures, we were able to obtain hypoglycemic samples from commercial human serum. These dialysis-derived samples, alongside samples of normal human serum were used to evaluate the utility of the sensor for the detection of the clinical interest range of glucose concentrations (70-200 mg/dL), revealing high system performance for a wide glycemic state range (45-500 mg/dL). Reversibility and reproducibility were also tested over a range of time spans. Combined with existing BLI system technology, this sensor holds great promise for use as a wearable online continuous glucose monitoring system for patients in a hospital setting.
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Mori, Akihiro; Kurishima, Miyuki; Oda, Hitomi; Saeki, Kaori; Arai, Toshiro; Sako, Toshinori
2013-01-31
Monitoring of blood glucose concentration is important to evaluate the diabetic status of dogs. Continuous glucose monitoring systems (CGMS) have been applied in veterinary medicine for glucose monitoring in diabetic dogs. The purpose of the study was to evaluate the daily glycemic profiles obtained with CGMS and compare glucose fluctuations between day- and night-time in diabetic dogs. Five diabetic dogs were used in this study and were treated with either NPH insulin or insulin detemir. For data analyses, day-time was defined as 9:00 am-9:00 pm and night-time as 9:00 pm-9:00 am. Using glucose profiles, we determined the mean glucose concentrations (1- and 12-hr intervals), and times spent in hyperglycemia >200 mg/dl or hypoglycemia <60 mg/dl. None of the parameters differed significantly between day-time and night-time in dogs treated with NPH insulin or insulin detemir. In conclusion, this study confirmed, using CGMS, that there are no differences in glucose fluctuations between day- and night-time, in diabetic dogs on a similar feeding regimen and insulin administration.
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Yum, Kyungsuk; McNicholas, Thomas P.; Mu, Bin; Strano, Michael S.
2013-01-01
This article reviews research efforts on developing single-walled carbon nanotube (SWNT)-based near-infrared (NIR) optical glucose sensors toward long-term in vivo continuous glucose monitoring (CGM). We first discuss the unique optical properties of SWNTs and compare SWNTs with traditional organic and nanoparticle fluorophores regarding in vivo glucose-sensing applications. We then present our development of SWNT-based glucose sensors that use glucose-binding proteins and boronic acids as a high-affinity molecular receptor for glucose and transduce binding events on the receptors to modulate SWNT fluorescence. Finally, we discuss opportunities and challenges in translating the emerging technology of SWNT-based NIR optical glucose sensors into in vivo CGM for practical clinical use. PMID:23439162
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Lind, Marcus; Polonsky, William; Hirsch, Irl B; Heise, Tim; Bolinder, Jan; Dahlqvist, Sofia; Schwarz, Erik; Ólafsdóttir, Arndís Finna; Frid, Anders; Wedel, Hans; Ahlén, Elsa; Nyström, Thomas; Hellman, Jarl
2017-01-24
The majority of individuals with type 1 diabetes do not meet recommended glycemic targets. To evaluate the effects of continuous glucose monitoring in adults with type 1 diabetes treated with multiple daily insulin injections. Open-label crossover randomized clinical trial conducted in 15 diabetes outpatient clinics in Sweden between February 24, 2014, and June 1, 2016 that included 161 individuals with type 1 diabetes and hemoglobin A1c (HbA1c) of at least 7.5% (58 mmol/mol) treated with multiple daily insulin injections. Participants were randomized to receive treatment using a continuous glucose monitoring system or conventional treatment for 26 weeks, separated by a washout period of 17 weeks. Difference in HbA1c between weeks 26 and 69 for the 2 treatments. Adverse events including severe hypoglycemia were also studied. Among 161 randomized participants, mean age was 43.7 years, 45.3% were women, and mean HbA1c was 8.6% (70 mmol/mol). A total of 142 participants had follow-up data in both treatment periods. Mean HbA1c was 7.92% (63 mmol/mol) during continuous glucose monitoring use and 8.35% (68 mmol/mol) during conventional treatment (mean difference, -0.43% [95% CI, -0.57% to -0.29%] or -4.7 [-6.3 to -3.1 mmol/mol]; P < .001). Of 19 secondary end points comprising psychosocial and various glycemic measures, 6 met the hierarchical testing criteria of statistical significance, favoring continuous glucose monitoring compared with conventional treatment. Five patients in the conventional treatment group and 1 patient in the continuous glucose monitoring group had severe hypoglycemia. During washout when patients used conventional therapy, 7 patients had severe hypoglycemia. Among patients with inadequately controlled type 1 diabetes treated with multiple daily insulin injections, the use of continuous glucose monitoring compared with conventional treatment for 26 weeks resulted in lower HbA1c. Further research is needed to assess clinical outcomes and longer-term adverse effects. clinicaltrials.gov Identifier: NCT02092051.
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Augusto, Gustavo A; Sousa, André G P; Perazo, Marcela N A; Correa-Giannella, Maria L C; Nery, Marcia; Melo, Karla F S de
2009-06-01
Continuous glucose monitoring system is a valuable instrument to measure glycemic control, which uses a retrospective calibration based upon 3 to 4 capillary glucose meter values inserted by the patient each day. We evaluated the interference of calibration during the dawn period in the system accuracy. The monitoring data were retrospectively divided into two groups: with (Group A) or without (Group B) the dawn period calibration (between 1:00 and 5:00 AM). Accuracy of the method was expressed by relative absolute difference. Thirty-four continuous glucose monitoring data were evaluated comprising a total of 112 nights. A total of 289 paired readings were analyzed - 195 in Group A and 94 in Group B. We did not find a difference in relative absolute difference (RAD%) in any analyzed period of day by adding dawn calibration. These data suggest that dawn calibration does not alter accuracy of method.
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Continuous glucose monitoring in acute coronary syndrome.
Rodríguez-Quintanilla, Karina Alejandra; Lavalle-González, Fernando Javier; Mancillas-Adame, Leonardo Guadalupe; Zapata-Garrido, Alfonso Javier; Villarreal-Pérez, Jesús Zacarías; Tamez-Pérez, Héctor Eloy
2013-01-01
Diabetes mellitus is an independent risk factor for cardiovascular disease. To compare the efficacy of devices for continuous glucose monitoring and capillary glucose monitoring in hospitalized patients with acute coronary syndrome using the following parameters: time to achieve normoglycemia, period of time in normoglycemia, and episodes of hypoglycemia. We performed a pilot, non-randomized, unblinded clinical trial that included 16 patients with acute coronary artery syndrome, a capillary or venous blood glucose ≥ 140 mg/dl, and treatment with a continuous infusion of fast acting human insulin. These patients were randomized into 2 groups: a conventional group, in which capillary measurement and recording as well as insulin adjustment were made every 4h, and an intervention group, in which measurement and recording as well as insulin adjustment were made every hour with a subcutaneous continuous monitoring system. Student's t-test was applied for mean differences and the X(2) test for qualitative variables. We observed a statistically significant difference in the mean time for achieving normoglycemia, favoring the conventional group with a P = 0.02. Continuous monitoring systems are as useful as capillary monitoring for achieving normoglycemia. Copyright © 2012 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.
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Analysis: Continuous Glucose Monitoring in the Intensive Care Unit
Kenneth Ward, W.
2012-01-01
Control of glycemia in hospitalized patients is important; hypoglycemia is associated with increased mortality, and hyperglycemia is associated with adverse outcomes. For these reasons, though no such device is currently available, continuous glucose monitoring (CGM) is an attractive option, especially in the critical care setting. Schierenbeck and coauthors, in this issue of Journal of Diabetes Science and Technology, report on the use of a specialized central catheter designed to monitor glucose continuously in post cardiac surgery patients. This catheter, which was indwelled within the great veins, was specially designed with a separate lumen and membrane that allowed continuous glucose microdialysis. Accuracy was quite good, better than has been reported with the use of commercially-available CGM devices. Ideally, further development of this quite promising catheter-based device would allow it to be used also to deliver fluids and drugs, thus avoiding the need for a second catheter elsewhere. PMID:23294782
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Assessment of hypoglycaemia awareness using continuous glucose monitoring.
Kubiak, T; Hermanns, N; Schreckling, H J; Kulzer, B; Haak, T
2004-05-01
To investigate the possibility of assessing hypoglycaemia awareness in patients with Type 1 diabetes using continuous glucose monitoring. Twenty patients with Type 1 diabetes were investigated. Ten patients with Type 1 diabetes and strongly impaired hypoglycaemia awareness were compared with 10 patients with intact hypoglycaemia awareness regarding quality of hypoglycaemia perception (number of undetected hypoglycaemic episodes per 24 h, glucose level < 3.3 mmol/l). Hypoglycaemia detection was assessed using the event function of the Continuous Glucose Monitoring System (CGMS; Medtronic MiniMed, Northridge, CA, USA). Patients were instructed to enter an event upon suspecting being hypoglycaemic. Satisfactory CGMS performance could be achieved [mean r = 0.893 between calibration measurements and CGMS data, mean absolute difference (MAD) = 20.6%], although artefacts were observable and had to be controlled. Hypoglycaemia unaware patients showed a significantly higher total number of hypoglycaemic episodes (P < 0.05), number of undetected hypoglycaemic episodes (P < 0.01), and mean glucose levels (P < 0.05). Even in aware patients, undetected hypoglycaemia was observable. No significant differences regarding occurrence of nocturnal hypoglycaemia were observable. The possibility of direct assessment of hypoglycaemia awareness using continuous glucose monitoring was demonstrated. Its application in clinical practice could be of use for assessing hypoglycaemia perception and evaluating the impact of treatment changes on hypoglycaemia awareness.
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Harris, Deborah L; Battin, Malcolm R; Williams, Chris E; Weston, Philip J; Harding, Jane E
2009-01-01
The optimal approach to detection and management of neonatal hypoglycaemia remains unclear. We sought to demonstrate whether electro-encephalography (EEG) changes could be detected on the amplitude-integrated EEG monitor during induced hypoglycaemia in newborn lambs, and also to determine the accuracy of continuously measured interstitial glucose in this situation. Needle electrodes were placed in the P3-P4, O1-O2 montages. The interstitial glucose sensor was placed subcutaneously. After 30 min baseline recordings, hypoglycaemia was induced by insulin infusion and blood glucose levels were monitored every 5 min. The infusion was adjusted to reduce blood glucose levels by 0.5 mmol/l every 15 min and then maintain a blood glucose level <1.0 mmol/l for 4 h. EEG parameters analysed included amplitude, continuity and spectral edge frequency. The interstitial and blood glucose levels were compared. All lambs (n = 15, aged 3-11 days) became hypoglycaemic, with median blood glucose levels falling from 6.5 to 1.0 mmol/l, p < 0.0001. There were no detectable changes in any of the measured EEG parameters related to hypoglycaemia, although seizures occurred in 2 lambs. There was moderate agreement between the intermittent blood glucose and continuous interstitial glucose measurements in the baseline, decline, and hypoglycaemia periods (mean difference -0.7 mmol/l, 95% confidence interval, CI, -2.8 to 1.4 mmol/l). However, agreement was poor during reversal of hypoglycaemia (mean difference 4.5 mmol/l, 95% CI -1.1 to 10.7 mmol/l). The cot-side EEG may not be a useful clinical tool in the detection of neurological changes induced by hypoglycaemia. However, continuous interstitial glucose monitoring may be useful in the management of babies at risk of hypoglycaemia. (c) 2008 S. Karger AG, Basel.
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Development of a nanowire based titanium needle probe sensor for glucose monitoring
NASA Astrophysics Data System (ADS)
Deshpande, Devesh C.
The need for continuous monitoring of various physiological functions such as blood glucose levels, neural functions and cholesterol levels has fostered the research and development of various schemes of biosensors to sense and help control the respective function. The needs of patients for sensors with minimal discomfort, longer life and better performance have necessitated the development towards smaller and more efficient sensors. In addition, the need for higher functionality from smaller sensors has led to the development of sensors with multiple electrodes, each electrode capable of sensing a different body function. Such multi-electrode sensors need to be fabricated using micro-fabrication processes in order to achieve precise control over the size, shape and placement of the electrodes. Multielectrode sensors fabricated using silicon and polymers have been demonstrated. One physiological function that attracts widespread interest is continuous glucose monitoring in our blood, since Diabetes affects millions of people all over the world. Significant deviations of blood glucose levels from the normal levels of 4-8 mM can cause fainting, coma and damage to the eyes, kidneys, nerves and blood vessels. For chronic patients, continuous monitoring of glucose levels is essential for accurate and timely treatment. A few continuous monitoring sensors are available in the market, but they have problems and cannot replace the strip type one-time glucose monitoring systems as yet. To address this need, large scale research efforts have been targeted towards continuous monitoring. The demand for higher accuracy and sensitivity has motivated researchers to evaluate the use of nanostructures in sensing. The large surface area-to-volume ratio of such structures could enable further miniaturization and push the detection limits, potentially enabling even single molecule detection. This research involved the development of a biocompatible titanium needle probe sensor for glucose monitoring. The working electrode of the sensor comprised of vertically aligned, free standing Au nanowires to utilize the advantages of nanostructures. The sensor was fabricated on biocompatible titanium substrate using Micro/Nano fabrication processes such as Plasma Enhanced Chemical Vapor Deposition (PECVD), Electron Beam Evaporation, Lithography, aligned nanowire growth and wet and plasma etching. Arrays of free-standing nanowires were grown at room temperature and pressure using a novel template based growth process. After fabrication of the sensor, immobilization of an enzyme was carried out on the sensing electrode to ensure selectivity of the sensor to glucose. This was achieved by using self-assembled thiol monolayers and entrapment in a conducting polymer matrix. Glucose oxidase was used for this purpose, which catalyzed the conversion of glucose to gluconic acid, producing hydrogen peroxide in the process. Amperometry was used for glucose detection, in which a constant voltage was applied to the sensor. This potential oxidized the hydrogen peroxide and produced changes in the current which were correlated to the glucose concentration. This dissertation will address the importance of continuous glucose monitoring, current technology and problems faced, the design and fabrication of the sensor and electrochemical sensing to detect glucose levels in solution. Finally, the problems encountered during the process will be discussed and the future work will be detailed.
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Joseph, Jeffrey I; Torjman, Marc C; Strasma, Paul J
2015-07-01
Hyperglycemia, hypoglycemia, and glycemic variability have been associated with increased morbidity, mortality, length of stay, and cost in a variety of critical care and non-critical care patient populations in the hospital. The results from prospective randomized clinical trials designed to determine the risks and benefits of intensive insulin therapy and tight glycemic control have been confusing; and at times conflicting. The limitations of point-of-care blood glucose (BG) monitoring in the hospital highlight the great clinical need for an automated real-time continuous glucose monitoring system (CGMS) that can accurately measure the concentration of glucose every few minutes. Automation and standardization of the glucose measurement process have the potential to significantly improve BG control, clinical outcome, safety and cost. © 2015 Diabetes Technology Society.
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Powers, Margaret A; Cuddihy, Robert M; Wesley, David; Morgan, Blaine
2010-12-01
This single-center, meal-intervention, crossover study was conducted to determine the glycemic response to fixed meals with varying carbohydrate content. Continuous glucose monitoring was used to document the glycemic response. Participants were 14 people with type 2 diabetes on metformin only. On 4 consecutive days in March or July 2008, study participants consumed a fixed breakfast and one of two test meals (lunch) provided in random order. The two lunch types varied only in carbohydrate content; the protein, fat, fiber, and glycemic index were similar. They consumed no caloric food or beverages for 4 hours after each meal. Consuming double the carbohydrate content did not double the glycemic response variables, yet most were substantially different in glucose value (mg/dL) or minutes. General linear model analyses revealed substantial differences for peak glucose, change from baseline glucose to peak, time to return to preprandial glucose, 4-hour glucose area under the curve, and 4-hour mean glucose. Continuous glucose monitoring data provided a robust description of the glycemic response to the two meals. Such data can help improve postprandial glucose levels through more informed nutrition recommendations and synchronization of food intake, diabetes medication, and/or physical activity. Copyright © 2010 American Dietetic Association. Published by Elsevier Inc. All rights reserved.
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Design, development, and evaluation of a novel microneedle array-based continuous glucose monitor.
Jina, Arvind; Tierney, Michael J; Tamada, Janet A; McGill, Scott; Desai, Shashi; Chua, Beelee; Chang, Anna; Christiansen, Mark
2014-05-01
The development of accurate, minimally invasive continuous glucose monitoring (CGM) devices has been the subject of much work by several groups, as it is believed that a less invasive and more user-friendly device will result in greater adoption of CGM by persons with insulin-dependent diabetes. This article presents the results of preliminary clinical studies in subjects with diabetes of a novel prototype microneedle-based continuous glucose monitor. In this device, an array of tiny hollow microneedles is applied into the epidermis from where glucose in interstitial fluid (ISF) is transported via passive diffusion to an amperometric glucose sensor external to the body. Comparison of 1396 paired device glucose measurements and fingerstick blood glucose readings for up to 72-hour wear in 10 diabetic subjects shows the device to be accurate and well tolerated by the subjects. Overall mean absolute relative difference (MARD) is 15% with 98.4% of paired points in the A+B region of the Clarke error grid. The prototype device has demonstrated clinically accurate glucose readings over 72 hours, the first time a microneedle-based device has achieved such performance. © 2014 Diabetes Technology Society.
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Fault Detection and Safety in Closed-Loop Artificial Pancreas Systems
2014-01-01
Continuous subcutaneous insulin infusion pumps and continuous glucose monitors enable individuals with type 1 diabetes to achieve tighter blood glucose control and are critical components in a closed-loop artificial pancreas. Insulin infusion sets can fail and continuous glucose monitor sensor signals can suffer from a variety of anomalies, including signal dropout and pressure-induced sensor attenuations. In addition to hardware-based failures, software and human-induced errors can cause safety-related problems. Techniques for fault detection, safety analyses, and remote monitoring techniques that have been applied in other industries and applications, such as chemical process plants and commercial aircraft, are discussed and placed in the context of a closed-loop artificial pancreas. PMID:25049365
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Heinemann, Lutz
2018-04-01
At the 2017 10th annual International Conference on Advanced Technologies and Treatments for Diabetes (ATTD) in Paris, France, four speakers presented their perspectives on the roles of continuous glucose monitoring (CGM) and of blood glucose monitoring (BGM) in patient management within one symposium. These presentations included discussions of the differences in the accuracy of CGM and BGM, a clinical perspective on the physiological reasons behind differences in CGM and BGM values, and an overview of the impact of variations in device accuracy on patients with diabetes. Subsequently a short summary of these presentations is given, highlighting the value of good accuracy of BGM or CGM systems and the ongoing need for standardization. The important role of both BGM and CGM in patient management was a theme across all presentations.
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Ito, N; Saito, A; Kayashima, S; Kimura, J; Kuriyama, T; Nagata, N; Arai, T; Kikuchi, M
1995-01-01
A transcutaneous blood glucose monitoring system consists of an ion-sensitive field-effect transistor (ISFET) glucose sensor unit and a suction effusion fluid (SEF) collecting unit. The SEF is directly collected by a weak suction (400 mmHg absolute pressure) through the skin from which the corneum layer of the epidermis has been previously removed. An ISFET glucose sensor unit is able to measure glucose concentrations in a microliter order sampling volume. The system was applied to three diabetic patients during a 75 g oral glucose tolerance test for monitoring blood glucose levels. During the experiments, glucose changes in the SEF followed actual blood glucose levels with 10 min delays. Results suggest the feasibility of utilizing quasi-continuous, transcutaneous blood glucose monitoring for individual patients with various diabetic histories or diabetic complications.
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Seo, Dongmin; Paek, Sung-Ho; Oh, Sangwoo; Seo, Sungkyu; Paek, Se-Hwan
2016-01-01
The incidence of diabetes is continually increasing, and by 2030, it is expected to have increased by 69% and 20% in underdeveloped and developed countries, respectively. Therefore, glucose sensors are likely to remain in high demand in medical device markets. For the current study, we developed a needle-type bio-layer interference (BLI) sensor that can continuously monitor glucose levels. Using dialysis procedures, we were able to obtain hypoglycemic samples from commercial human serum. These dialysis-derived samples, alongside samples of normal human serum were used to evaluate the utility of the sensor for the detection of the clinical interest range of glucose concentrations (70–200 mg/dL), revealing high system performance for a wide glycemic state range (45–500 mg/dL). Reversibility and reproducibility were also tested over a range of time spans. Combined with existing BLI system technology, this sensor holds great promise for use as a wearable online continuous glucose monitoring system for patients in a hospital setting. PMID:27669267
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Zanderigo, Francesca; Sparacino, Giovanni; Kovatchev, Boris; Cobelli, Claudio
2007-09-01
The aim of this article was to use continuous glucose error-grid analysis (CG-EGA) to assess the accuracy of two time-series modeling methodologies recently developed to predict glucose levels ahead of time using continuous glucose monitoring (CGM) data. We considered subcutaneous time series of glucose concentration monitored every 3 minutes for 48 hours by the minimally invasive CGM sensor Glucoday® (Menarini Diagnostics, Florence, Italy) in 28 type 1 diabetic volunteers. Two prediction algorithms, based on first-order polynomial and autoregressive (AR) models, respectively, were considered with prediction horizons of 30 and 45 minutes and forgetting factors (ff) of 0.2, 0.5, and 0.8. CG-EGA was used on the predicted profiles to assess their point and dynamic accuracies using original CGM profiles as reference. Continuous glucose error-grid analysis showed that the accuracy of both prediction algorithms is overall very good and that their performance is similar from a clinical point of view. However, the AR model seems preferable for hypoglycemia prevention. CG-EGA also suggests that, irrespective of the time-series model, the use of ff = 0.8 yields the highest accurate readings in all glucose ranges. For the first time, CG-EGA is proposed as a tool to assess clinically relevant performance of a prediction method separately at hypoglycemia, euglycemia, and hyperglycemia. In particular, we have shown that CG-EGA can be helpful in comparing different prediction algorithms, as well as in optimizing their parameters.
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Blood Glucose Monitoring Devices
... of interferences ability to transmit data to a computer cost of the meter cost of the test ... Performance FDA expands indication for continuous glucose monitoring system, first to replace fingerstick testing for diabetes treatment ...
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Modeling and Measurement of Correlation between Blood and Interstitial Glucose Changes
Shi, Ting; Li, Dachao; Li, Guoqing; Zhang, Yiming; Xu, Kexin; Lu, Luo
2016-01-01
One of the most effective methods for continuous blood glucose monitoring is to continuously measure glucose in the interstitial fluid (ISF). However, multiple physiological factors can modulate glucose concentrations and affect the lag phase between blood and ISF glucose changes. This study aims to develop a compensatory tool for measuring the delay in ISF glucose variations in reference to blood glucose changes. A theoretical model was developed based on biophysics and physiology of glucose transport in the microcirculation system. Blood and interstitial fluid glucose changes were measured in mice and rats by fluorescent and isotope methods, respectively. Computer simulation mimicked curves were fitted with data resulting from fluorescent measurements of mice and isotope measurements of rats, indicating that there were lag times for ISF glucose changes. It also showed that there was a required diffusion distance for glucose to travel from center of capillaries to interstitial space in both mouse and rat models. We conclude that it is feasible with the developed model to continuously monitor dynamic changes of blood glucose concentration through measuring glucose changes in ISF with high accuracy, which requires correct parameters for determining and compensating for the delay time of glucose changes in ISF. PMID:27239479
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Takeishi, Soichi; Tsuboi, Hiroki; Takekoshi, Shodo
2017-10-28
To investigate whether sodium glucose co-transporter 2 inhibitors (SGLT2i), tofogliflozin or ipragliflozin, achieve optimal glycemic variability, when used together with insulin glargine 300 U/mL (Glargine 300). Thirty patients with type 2 diabetes were randomly allocated to 2 groups. For the first group: After admission, tofogliflozin 20 mg was administered; Fasting plasma glucose (FPG) levels were titrated using an algorithm and stabilized at 80 mg/dL level with Glargine 300 for 5 days; Next, glucose levels were continuously monitored for 2 days using continuous glucose monitoring (CGM); Tofogliflozin was then washed out over 5 days; Subsequently, ipragliflozin 50 mg was administered; FPG levels were titrated using the same algorithm and stabilized at 80 mg/dL level with Glargine 300 for 5 days; Next, glucose levels were continuously monitored for 2 days using CGM. For the second group, ipragliflozin was administered prior to tofogliflozin, and the same regimen was maintained. Glargine 300 and SGLT2i were administered at 8:00 AM. Data collected on the second day of measurement (mean amplitude of glycemic excursion [MAGE], average daily risk range [ADRR]; on all days of measurement) were analyzed. Area over the glucose curve (<70 mg/dL; 0:00 to 6:00, 24-h), M value, standard deviation, MAGE, ADRR, and mean glucose levels (24-h, 8:00 to 24:00) were significantly lower in patients on tofogliflozin than in those on ipragliflozin. Tofogliflozin, which reduces glycemic variability by preventing nocturnal hypoglycemia and decreasing postprandial glucose levels, is an ideal SGLT2i when used together with Glargine 300 during basal insulin therapy.
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Flash Glucose Monitoring: Differences Between Intermittently Scanned and Continuously Stored Data.
Pleus, Stefan; Kamecke, Ulrike; Link, Manuela; Haug, Cornelia; Freckmann, Guido
2018-03-01
The flash glucose monitoring system FreeStyle Libre (Abbott Diabetes Care Ltd., Witney, UK) measures interstitial glucose concentrations and continuously stores measurement values every 15 minutes. To obtain a current glucose reading, users have to scan the sensor with the reader. In a clinical trial, 5% of the scanned data showed relative differences of more than ±10% compared with continuously stored data points (median -0.5%). Such differences might impact results of studies using this system. It should be indicated whether scanned or continuously stored data were used for analyses. Health care professionals might have to differentiate between data reports from clinical software and the scanned data their patients are provided with. Additional information on these differences and their potential impact on therapeutic decisions would be helpful.
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Rossetti, Paolo; Bondia, Jorge; Vehí, Josep; Fanelli, Carmine G.
2010-01-01
Evaluation of metabolic control of diabetic people has been classically performed measuring glucose concentrations in blood samples. Due to the potential improvement it offers in diabetes care, continuous glucose monitoring (CGM) in the subcutaneous tissue is gaining popularity among both patients and physicians. However, devices for CGM measure glucose concentration in compartments other than blood, usually the interstitial space. This means that CGM need calibration against blood glucose values, and the accuracy of the estimation of blood glucose will also depend on the calibration algorithm. The complexity of the relationship between glucose dynamics in blood and the interstitial space, contrasts with the simplistic approach of calibration algorithms currently implemented in commercial CGM devices, translating in suboptimal accuracy. The present review will analyze the issue of calibration algorithms for CGM, focusing exclusively on the commercially available glucose sensors. PMID:22163505
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Chen, Yin-Chun; Huang, Yu-Yao; Li, Hung-Yuan; Liu, Shih-Wei; Hsieh, Sheng-Hwu; Lin, Chia-Hung
2015-01-01
The identification of type 1 diabetes in diabetic subjects receiving insulin therapy is sometimes difficult. The purpose of this study is to evaluate whether results of professional continuous glucose monitoring can improve the identification of type 1 diabetes.From 2007 to 2012, 119 adults receiving at least twice-daily insulin therapy and professional continuous glucose monitoring were recruited. Type 1 diabetes was diagnosed by endocrinologists according to American Diabetes Association standards, including a very low C-peptide level (<0.35 pg/mL) or the presence of diabetic ketoacidosis. Continuous glucose monitoring was applied for 3 days.Among 119 subjects, 86 were diagnosed with type 1 diabetes. Subjects with type 1 diabetes were younger (33.8 vs 52.3 years old, P < 0.001), had lower body mass index (BMI, 21.95 vs 24.42, P = 0.003), lower serum creatinine (61.77 vs 84.65 μmol/L, P = 0.001), and higher estimated glomerular filtration rate (108.71 vs 76.48 mg/mL/min/1.73m2, P < 0.001) than subjects with type 2 diabetes. Predictive scores for identification of type 1 diabetes were constructed, including age, BMI, average mean amplitude of glucose excursion in days 2 and 3, and the area under the curve of nocturnal hyperglycemic and hypoglycemic states. The area under the receiver operating characteristic curve was 0.90. With the cutoff of 0.58, the sensitivity was 86.7% and the specificity was 80.8%. The good performance was validated by the leave-one-out method (sensitivity 83.3%, specificity 73.1%).Professional continuous glucose monitoring is a useful tool that improves identification of type 1 diabetes among diabetic patients receiving insulin therapy.
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Strauss, A; Tiurbe, C; Chodnevskaja, I; Thiede, A; Timm, S; Ulrichs, K; Moskalenko, V
2008-03-01
Adult pig islet isolation has greatly improved in the past few years. Islet grafts may now be tested in large animals. Continuous Glucose Monitoring System (CGMS) was applied to diabetic Goettingen Minipigs (GMP) to improve the management of hyperglycemia and hypoglycemia and their welfare before transplantation. GMP (25-35 kg) received a minipig diet once daily. Diabetes was induced by streptozotocin (STZ; 150 mg/kg intravenous [IV]; n = 5) or by surgical pancreatectomy (PGMP; n = 3). Interstitial glucose concentration (IGC) was monitored continuously with an implanted sensor; CGMS was calibrated using conventional blood glucose tests 3-4 times per day; CGMS data were fed into the monitor memory and analyzed using CGMS software. Glucose sensors were handled accurately. Diabetes occurred 2-3 days after STZ or immediately after pancreatectomy with basal C-peptide secretion of <0.4 ng/mL (measured using intravenous glucose tolerance test) and prompt loss of body weight. Insulin substitution was necessary to keep the GMP in good condition for up to 5-6 months, with stable body weight and normal behavior. Some GMP became hypoglycemic, which was only documented by CGMS, but not by conventional glucose assays. Tight glucose control and substitution of exocrine enzymes (Creon 25,000 E/d) reduced morbidity of the PGMP, which was then comparable with that of STZ-GMP. The CGMS, developed for humans, is equally suitable for the 2 GMP diabetes models. Close-meshed glucose monitoring and insulin treatment improved the general condition of the diabetic GMP, ie, the islet graft recipients, and will thus greatly add to posttransplantation success.
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McGarraugh, Geoffrey; Bergenstal, Richard
2009-03-01
The objective of the analysis was to compare detection of hypoglycemic episodes (glucose <70 mg/dL lasting >15 min) with the FreeStyle Navigator Continuous Glucose Monitoring System (FSN-CGM) (Abbott Diabetes Care, Alameda, CA) alarms to detection with traditional finger stick testing at an average frequency of eight tests per day. The performance of FSN-CGM alarms was evaluated in a clinic setting using 58 subjects with type 1 diabetes mellitus (T1DM) monitoring interstitial glucose concentration over a 5-day period compared to reference YSI measurements (instrument manufactured by YSI, Yellow Springs, OH) at 15-min intervals. Finger stick glucose testing was evaluated in the home environment with 91 subjects with TIDM monitoring with the blood glucose meter integrated into the FreeStyle Navigator (FSN-BG) over a 20-day period. The reference was FSN-CGM with results masked from the subjects. Blood glucose values <=85 mg/dL were considered the optimal treatment level to avoid or reverse hypoglycemia. With a threshold alarm setting of 85 mg/dL, 90.6% of hypoglycemic episodes were detected within +/- 30 min by FSN-CGM in the clinic study. When the alarm was activated, YSI glucose was <= 85 mg/dL 77.2% of the time. In the home environment, the average FSN-BG testing frequency was 7.9 tests per day. Hypoglycemia was verified within +/- 30 min by FSN-BG measurements <= 85 mg/dL at a rate of 27.5%. Even with a high rate of FSN-BG testing, hypoglycemia detected by FSN-CGM was verified by patients with T1DM very infrequently. A high rate of hypoglycemia detection with a moderate rate of unnecessary alarms can be attained using FSN-CGM.
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Uzal, Natalia E; Chavez, Benjamin; Kosirog, Emily R; Billups, Sarah J; Saseen, Joseph J
2018-02-01
In 2004, a consensus statement outlining recommended metabolic monitoring for patients prescribed second-generation antipsychotics (SGAs) was published. More than a decade later, suboptimal adherence rates to these recommendations continue to be reported, which could lead to long-term and costly complications. To define the prevalence of appropriately monitored Medicaid patients receiving care at federally qualified health centers (FQHCs) prescribed SGAs. This was a retrospective study examining electronic health record and Medicaid claims data to assess the rates of glucose and lipid monitoring for patients prescribed SGAs from January 2014 to August 2016 in a FQHC. Prescription and laboratory claims for patients receiving care at 4 FQHCs were reviewed. Descriptive statistics were used to evaluate the primary outcome. A total of 235 patients were included in the analysis. Patients initiated on SGA therapy (n = 92) had baseline glucose and lipid monitoring rates of 50% and 23%, respectively. The 3-month monitoring rates were 37% for glucose and 26% for lipids, whereas annual rates were 71% and 40%, respectively. Patients continuing SGA therapy (n = 143) had annual glucose and lipid monitoring rates of 67% and 44%. Medicaid patients at FQHCs initially prescribed SGAs have low baseline and 3-month metabolic monitoring, whereas annual monitoring was comparable to previously published studies. Adults receiving chronic care at a FQHC were more likely to receive glucose monitoring. Those with type 2 diabetes mellitus and/or hyperlipidemia were more likely to receive glucose and lipid monitoring.
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A history of continuous glucose monitors (CGMs) in self-monitoring of diabetes mellitus.
Olczuk, David; Priefer, Ronny
Self-monitoring of glucose for individuals afflicted with diabetes mellitus has allowed patients to take control of their disease and thus directly affect the outcomes related to it. It has been almost a century since the first test to monitor one's sugar was developed; that being a urine test. The most well-known and prominent medical device for monitor blood glucose for individuals with diabetes are the finger-prick devices. This itself is an approximately 50year old technology. More recently has been the introduction of continuous glucose monitors (CGMs) which entered the market place in the last year of the 20th century. As this technology has been further refined and improved, limitations associated with it have decreased. The scope of this review is to present a brief history of CGMs, both with the development of these medical devices and the challenges/limitations that they have shown. Copyright © 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.
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Use of continuous glucose monitoring in patients with type 1 diabetes.
Ellis, Samuel L; Naik, Ramachandra G; Gemperline, Kate; Garg, Satish K
2008-08-01
The prevalence of type 1 diabetes continues to increase worldwide at a rate higher than previously projected, while the number of patients achieving American Diabetes Association (ADA) glycated hemoglobin (A1c) goals remains suboptimal. There are numerous barriers to patients achieving A1c targets including increased frequency of severe hypoglycemia associated with lowering plasma glucose as measured by lower A1c values. Continuous glucose monitoring (CGM) was first approved for retrospective analysis and now has advanced to the next step in diabetes management with the approval of real-time glucose sensing. Real-time CGM, in short term studies, has been shown to decrease A1c values, improve glucose variability (GV), and minimize the time and number of hypoglycemic events in patients with type 1 diabetes. These products are approved for adjunctive use to self-monitoring of blood glucose (SMBG), but future long-term studies are needed to document their safety, efficacy, ability to replace SMBG as a tool of monitoring, and ultimately utility into closed-loop insulin delivery systems. New algorithms will need to be developed that account for rapid changes in the glucose values, so that accuracy of the sensor data can be maintained. In addition, for better clinical care and usage, algorithms also need to be developed for both patients and the providers to guide them for their ongoing diabetes care.
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NASA Astrophysics Data System (ADS)
Vahlsing, Thorsten; Delbeck, Sven; Budde, Janpeter; Ihrig, Dieter; Leonhardt, Steffen; Heise, H. Michael
2017-02-01
Blood glucose monitoring has been realised by biosensors in combination with micro-dialysis, using either subcutaneously or intravascularly implanted catheters. Another alternative is ex-vivo micro-dialysis of continuously sampled heparinized whole blood available from the patient even under critical care conditions. However, most devices suffer from inaccuracies due to variable recovery rates. Infrared spectrometry has been suggested for analyte quantification, since besides glucose other clinically relevant analytes can be simultaneously determined that are, e.g., important for intensive care patients. Perfusates with acetate and mannitol have been investigated as recovery markers (internal standards). In contrast to the previously used acetate, an almost linear dependency between mannitol loss and glucose recovery was observed for micro-dialysis of glucose spiked aqueous albumin solutions or porcine heparinized whole blood when testing flat membranes within a custom-made micro-dialysator. By this, a straightforward compensation of any dialysis recovery rate variation during patient monitoring is possible. The combination of microdialysis with infrared spectrometry provides a calibration-free assay for accurate continuous glucose monitoring, as reference spectra of dialysate components can be a-priori allocated.
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Hoss, Udo; Jeddi, Iman; Schulz, Mark; Budiman, Erwin; Bhogal, Claire; McGarraugh, Geoffrey
2010-08-01
Commercial continuous subcutaneous glucose monitors require in vivo calibration using capillary blood glucose tests. Feasibility of factory calibration, i.e., sensor batch characterization in vitro with no further need for in vivo calibration, requires a predictable and stable in vivo sensor sensitivity and limited inter- and intra-subject variation of the ratio of interstitial to blood glucose concentration. Twelve volunteers wore two FreeStyle Navigator (Abbott Diabetes Care, Alameda, CA) continuous glucose monitoring systems for 5 days in parallel for two consecutive sensor wears (four sensors per subject, 48 sensors total). Sensors from a prototype sensor lot with a low variability in glucose sensitivity were used for the study. Median sensor sensitivity values based on capillary blood glucose were calculated per sensor and compared for inter- and intra-subject variation. Mean absolute relative difference (MARD) calculation and error grid analysis were performed using a single calibration factor for all sensors to simulate factory calibration and compared to standard fingerstick calibration. Sensor sensitivity variation in vitro was 4.6%, which increased to 8.3% in vivo (P < 0.0001). Analysis of variance revealed no significant inter-subject differences in sensor sensitivity (P = 0.134). Applying a single universal calibration factor retrospectively to all sensors resulted in a MARD of 10.4% and 88.1% of values in Clarke Error Grid Zone A, compared to a MARD of 10.9% and 86% of values in Error Grid Zone A for fingerstick calibration. Factory calibration of sensors for continuous subcutaneous glucose monitoring is feasible with similar accuracy to standard fingerstick calibration. Additional data are required to confirm this result in subjects with diabetes.
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Romey, Matthew; Jovanovič, Lois; Bevier, Wendy; Markova, Kateryna; Strasma, Paul; Zisser, Howard
2012-11-01
Stress hyperglycemia in the critically ill is associated with increased morbidity and mortality. Continuous glucose monitoring offers a solution to the difficulties of dosing intravenous insulin properly to maintain glycemic control. The purpose of this study was to evaluate an intravascular continuous glucose monitoring (IV-CGM) system with a sensing element based on the concept of quenched fluorescence. A second-generation intravascular continuous glucose sensor was evaluated in 13 volunteer subjects with type 1 diabetes mellitus. There were 21 study sessions of up to 24 h in duration. Sensors were inserted into peripheral veins of the upper extremity, up to two sensors per subject per study session. Sensor output was compared with temporally correlated reference measurements obtained from venous samples on a laboratory glucose analyzer. Data were obtained from 23 sensors in 13 study sessions with 942 paired reference values. Fourteen out of 23 sensors (60.9%) had a mean absolute relative difference ≤ 10%. Eighty-nine percent of paired points were in the clinically accurate A zone of the Clarke error grid and met ISO 15197 performance criteria. Adequate venous blood flow was identified as a necessary condition for accuracy when local sensor readings are compared with venous blood glucose. The IV-CGM system was capable of achieving a high level of glucose measurement accuracy. However, superficial peripheral veins may not provide adequate blood flow for reliable indwelling blood glucose monitoring. © 2012 Diabetes Technology Society.
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Romey, Matthew; Jovanovič, Lois; Bevier, Wendy; Markova, Kateryna; Strasma, Paul; Zisser, Howard
2012-01-01
Background Stress hyperglycemia in the critically ill is associated with increased morbidity and mortality. Continuous glucose monitoring offers a solution to the difficulties of dosing intravenous insulin properly to maintain glycemic control. The purpose of this study was to evaluate an intravascular continuous glucose monitoring (IV-CGM) system with a sensing element based on the concept of quenched fluorescence. Method A second-generation intravascular continuous glucose sensor was evaluated in 13 volunteer subjects with type 1 diabetes mellitus. There were 21 study sessions of up to 24 h in duration. Sensors were inserted into peripheral veins of the upper extremity, up to two sensors per subject per study session. Sensor output was compared with temporally correlated reference measurements obtained from venous samples on a laboratory glucose analyzer. Results Data were obtained from 23 sensors in 13 study sessions with 942 paired reference values. Fourteen out of 23 sensors (60.9%) had a mean absolute relative difference ≤ 10%. Eighty-nine percent of paired points were in the clinically accurate A zone of the Clarke error grid and met ISO 15197 performance criteria. Adequate venous blood flow was identified as a necessary condition for accuracy when local sensor readings are compared with venous blood glucose. Conclusions The IV-CGM system was capable of achieving a high level of glucose measurement accuracy. However, superficial peripheral veins may not provide adequate blood flow for reliable indwelling blood glucose monitoring. PMID:23294770
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Morrow, Linda; Hompesch, Marcus; Tideman, Ann M; Matson, Jennifer; Dunne, Nancy; Pardo, Scott; Parkes, Joan L; Schachner, Holly C; Simmons, David A
2011-07-01
This glucose clamp study assessed the performance of an electrochemical continuous glucose monitoring (CGM) system for monitoring levels of interstitial glucose. This novel system does not require use of a trocar or needle for sensor insertion. Continuous glucose monitoring sensors were inserted subcutaneously into the abdominal tissue of 14 adults with type 1 or type 2 diabetes. Subjects underwent an automated glucose clamp procedure with four consecutive post-steady-state glucose plateau periods (40 min each): (a) hypoglycemic (50 mg/dl), (b) hyperglycemic (250 mg/dl), (c) second hypoglycemic (50 mg/dl), and (d) euglycemic (90 mg/dl). Plasma glucose results obtained with YSI glucose analyzers were used for sensor calibration. Accuracy was assessed retrospectively for plateau periods and transition states, when glucose levels were changing rapidly (approximately 2 mg/dl/min). Mean absolute percent difference (APD) was lowest during hypoglycemic plateaus (11.68%, 14.15%) and the euglycemic-to-hypoglycemic transition (14.21%). Mean APD during the hyperglycemic plateau was 17.11%; mean APDs were 18.12% and 19.25% during the hypoglycemic-to-hyperglycemic and hyperglycemic-to-hypoglycemic transitions, respectively. Parkes (consensus) error grid analysis (EGA) and rate EGA of the plateaus and transition periods, respectively, yielded 86.8% and 68.6% accurate results (zone A) and 12.1% and 20.0% benign errors (zone B). Continuous EGA yielded 88.5%, 75.4%, and 79.3% accurate results and 8.3%, 14.3%, and 2.4% benign errors for the euglycemic, hyperglycemic, and hypoglycemic transition periods, respectively. Adverse events were mild and unlikely to be device related. This novel CGM system was safe and accurate across the clinically relevant glucose range. © 2011 Diabetes Technology Society.
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Morrow, Linda; Hompesch, Marcus; Tideman, Ann M; Matson, Jennifer; Dunne, Nancy; Pardo, Scott; Parkes, Joan L; Schachner, Holly C; Simmons, David A
2011-01-01
Background This glucose clamp study assessed the performance of an electrochemical continuous glucose monitoring (CGM) system for monitoring levels of interstitial glucose. This novel system does not require use of a trocar or needle for sensor insertion. Method Continuous glucose monitoring sensors were inserted subcutaneously into the abdominal tissue of 14 adults with type 1 or type 2 diabetes. Subjects underwent an automated glucose clamp procedure with four consecutive post-steady-state glucose plateau periods (40 min each): (a) hypoglycemic (50 mg/dl), (b) hyperglycemic (250 mg/dl), (c) second hypoglycemic (50 mg/dl), and (d) euglycemic (90 mg/dl). Plasma glucose results obtained with YSI glucose analyzers were used for sensor calibration. Accuracy was assessed retrospectively for plateau periods and transition states, when glucose levels were changing rapidly (approximately 2 mg/dl/min). Results Mean absolute percent difference (APD) was lowest during hypoglycemic plateaus (11.68%, 14.15%) and the euglycemic-to-hypoglycemic transition (14.21%). Mean APD during the hyperglycemic plateau was 17.11%; mean APDs were 18.12% and 19.25% during the hypoglycemic-to-hyperglycemic and hyperglycemic-to-hypoglycemic transitions, respectively. Parkes (consensus) error grid analysis (EGA) and rate EGA of the plateaus and transition periods, respectively, yielded 86.8% and 68.6% accurate results (zone A) and 12.1% and 20.0% benign errors (zone B). Continuous EGA yielded 88.5%, 75.4%, and 79.3% accurate results and 8.3%, 14.3%, and 2.4% benign errors for the euglycemic, hyperglycemic, and hypoglycemic transition periods, respectively. Adverse events were mild and unlikely to be device related. Conclusion This novel CGM system was safe and accurate across the clinically relevant glucose range. PMID:21880226
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Evaluation of a minimally invasive glucose biosensor for continuous tissue monitoring.
Sharma, Sanjiv; Huang, Zhenyi; Rogers, Michelle; Boutelle, Martyn; Cass, Anthony E G
2016-11-01
We describe here a minimally invasive glucose biosensor based on a microneedle array electrode fabricated from an epoxy-based negative photoresist (SU8 50) and designed for continuous measurement in the dermal compartment with minimal pain. These minimally invasive, continuous monitoring sensor devices (MICoMS) were produced by casting the structures in SU8 50, crosslinking and then metallising them with platinum or silver to obtain the working and reference electrodes, respectively. The metallised microneedle array electrodes were subsequently functionalised by entrapping glucose oxidase in electropolymerised polyphenol (PP) film. Sensor performance in vitro showed that glucose concentrations down to 0.5 mM could be measured with a response times (T 90 ) of 15 s. The effect of sterilisation by Co60 irradiation was evaluated. In preparation for further clinical studies, these sensors were tested in vivo in a healthy volunteer for a period of 3-6 h. The sensor currents were compared against point measurements obtained with a commercial capillary blood glucometer. The epoxy MICoMS devices showed currents values that could be correlated with these. Graphical Abstract Microneedle arrays for continuous glucose monitoring in dermal interstitial fluid.
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Skin-like biosensor system via electrochemical channels for noninvasive blood glucose monitoring.
Chen, Yihao; Lu, Siyuan; Zhang, Shasha; Li, Yan; Qu, Zhe; Chen, Ying; Lu, Bingwei; Wang, Xinyan; Feng, Xue
2017-12-01
Currently, noninvasive glucose monitoring is not widely appreciated because of its uncertain measurement accuracy, weak blood glucose correlation, and inability to detect hyperglycemia/hypoglycemia during sleep. We present a strategy to design and fabricate a skin-like biosensor system for noninvasive, in situ, and highly accurate intravascular blood glucose monitoring. The system integrates an ultrathin skin-like biosensor with paper battery-powered electrochemical twin channels (ETCs). The designed subcutaneous ETCs drive intravascular blood glucose out of the vessel and transport it to the skin surface. The ultrathin (~3 μm) nanostructured biosensor, with high sensitivity (130.4 μA/mM), fully absorbs and measures the glucose, owing to its extreme conformability. We conducted in vivo human clinical trials. The noninvasive measurement results for intravascular blood glucose showed a high correlation (>0.9) with clinically measured blood glucose levels. The system opens up new prospects for clinical-grade noninvasive continuous glucose monitoring.
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Skin-like biosensor system via electrochemical channels for noninvasive blood glucose monitoring
Chen, Yihao; Lu, Siyuan; Zhang, Shasha; Li, Yan; Qu, Zhe; Chen, Ying; Lu, Bingwei; Wang, Xinyan; Feng, Xue
2017-01-01
Currently, noninvasive glucose monitoring is not widely appreciated because of its uncertain measurement accuracy, weak blood glucose correlation, and inability to detect hyperglycemia/hypoglycemia during sleep. We present a strategy to design and fabricate a skin-like biosensor system for noninvasive, in situ, and highly accurate intravascular blood glucose monitoring. The system integrates an ultrathin skin-like biosensor with paper battery–powered electrochemical twin channels (ETCs). The designed subcutaneous ETCs drive intravascular blood glucose out of the vessel and transport it to the skin surface. The ultrathin (~3 μm) nanostructured biosensor, with high sensitivity (130.4 μA/mM), fully absorbs and measures the glucose, owing to its extreme conformability. We conducted in vivo human clinical trials. The noninvasive measurement results for intravascular blood glucose showed a high correlation (>0.9) with clinically measured blood glucose levels. The system opens up new prospects for clinical-grade noninvasive continuous glucose monitoring. PMID:29279864
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Grunberger, George; Handelsman, Yehuda; Bloomgarden, Zachary T; Fonseca, Vivian A; Garber, Alan J; Haas, Richard A; Roberts, Victor L; Umpierrez, Guillermo E
2018-03-01
This document represents the official position of the American Association of Clinical Endocrinologists and American College of Endocrinology. Where there are no randomized controlled trials or specific U.S. FDA labeling for issues in clinical practice, the participating clinical experts utilized their judgment and experience. Every effort was made to achieve consensus among the committee members. Position statements are meant to provide guidance, but they are not to be considered prescriptive for any individual patient and cannot replace the judgment of a clinician. AACE/ACE Task Force on Integration of Insulin Pumps and Continuous Glucose Monitoring in the Management of Patients With Diabetes Mellitus Chair George Grunberger, MD, FACP, FACE Task Force Members Yehuda Handelsman, MD, FACP, FNLA, MACE Zachary T. Bloomgarden, MD, MACE Vivian A. Fonseca, MD, FACE Alan J. Garber, MD, PhD, FACE Richard A. Haas, MD, FACE Victor L. Roberts, MD, MBA, FACP, FACE Guillermo E. Umpierrez, MD, CDE, FACP, FACE Abbreviations: AACE = American Association of Clinical Endocrinologists ACE = American College of Endocrinology A1C = glycated hemoglobin BGM = blood glucose monitoring CGM = continuous glucose monitoring CSII = continuous subcutaneous insulin infusion DM = diabetes mellitus FDA = Food & Drug Administration MDI = multiple daily injections T1DM = type 1 diabetes mellitus T2DM = type 2 diabetes mellitus SAP = sensor-augmented pump SMBG = self-monitoring of blood glucose STAR 3 = Sensor-Augmented Pump Therapy for A1C Reduction phase 3 trial.
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Yamada, Eijiro; Okada, Shuichi; Nakajima, Yasuyo; Bastie, Claire C; Vatish, Manu; Tagaya, Yuko; Osaki, Aya; Shimoda, Yoko; Shibusawa, Ryo; Saito, Tsugumichi; Okamura, Takashi; Ozawa, Atsushi; Yamada, Masanobu
2017-01-01
Optimum therapy for patients with diabetes depends on both acute and long-term changes in plasma glucose, generally assessed by glycated hemoglobin (HbA1c) levels. However, the correlation between HbA1c and circulating glucose has not been fully determined. Therefore, we carefully examined this correlation when glucose levels were assessed by continuous glucose monitoring (CGM). Fifty-one patients (70% female, 30% male) were examined; among them were 28 with type 1 diabetes and 23 with type 2 diabetes. Clinically determined HbA1c levels were compared with blood glucose determined by CGM during a short time period. Changes in HbA1c levels up to 8.0% showed a clear and statistically strong correlation (R = 0.6713; P<.0001) with mean blood glucose levels measured by CGM, similar to that observed in the A1c-derived Average Glucose study in which patients were monitored for a longer period. However, we found no statistical correlation (R = 0.0498; P = .83) between HbA1c and CGM-assessed glucose levels in our patient population when HbA1c was >8.0%. Short-term CGM appears to be a good clinical indicator of long-term glucose control (HbA1c levels); however, cautions should be taken while interpreting CGM data from patients with HbA1c levels >8.0%. Over- or underestimation of the actual mean glucose from CGM data could potentially increase the risks of inappropriate treatment. As such, our results indicate that a more accurate analysis of CGM data might be useful to adequately tailor clinical treatments. ADAG = A1c-Derived Average Glucose CGM = continuous glucose monitoring %CV = percent coefficient of variation HbA1c = glycated hemoglobin.
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Weisman, Itamar; Romano, Jacob; Ivics, Zoltán; Izsvák, Zsuzsanna; Barkai, Uriel
2017-01-01
Diabetes is a chronic disease characterized by high levels of blood glucose. Diabetic patients should normalize these levels in order to avoid short and long term clinical complications. Presently, blood glucose monitoring is dependent on frequent finger pricking and enzyme based systems that analyze the drawn blood. Continuous blood glucose monitors are already on market but suffer from technical problems, inaccuracy and short operation time. A novel approach for continuous glucose monitoring is the development of implantable cell-based biosensors that emit light signals corresponding to glucose concentrations. Such devices use genetically modified cells expressing chimeric genes with glucose binding properties. MSCs are good candidates as carrier cells, as they can be genetically engineered and expanded into large numbers. They also possess immunomodulatory properties that, by reducing local inflammation, may assist long operation time. Here, we generated a novel immortalized human MSC line co-expressing hTERT and a secreted glucose biosensor transgene using the Sleeping Beauty transposon technology. Genetically modified hMSCs retained their mesenchymal characteristics. Stable transgene expression was validated biochemically. Increased activity of hTERT was accompanied by elevated and constant level of stem cell pluripotency markers and subsequently, by MSC immortalization. Furthermore, these cells efficiently suppressed PBMC proliferation in MLR transwell assays, indicating that they possess immunomodulatory properties. Finally, biosensor protein produced by MSCs was used to quantify glucose in cell-free assays. Our results indicate that our immortalized MSCs are suitable for measuring glucose concentrations in a physiological range. Thus, they are appropriate for incorporation into a cell-based, immune-privileged, glucose-monitoring medical device. PMID:28949988
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McGarraugh, Geoffrey
2010-01-01
Continuous glucose monitoring (CGM) devices available in the United States are approved for use as adjuncts to self-monitoring of blood glucose (SMBG); all CGM alarms require SMBG confirmation before treatment. In this report, an analysis method is proposed to determine the CGM threshold alarm accuracy required to eliminate SMBG confirmation. The proposed method builds on the Clinical and Laboratory Standards Institute (CLSI) guideline for evaluating CGM threshold alarms using data from an in-clinic study of subjects with type 1 diabetes. The CLSI method proposes a maximum time limit of +/-30 minutes for the detection of hypo- and hyperglycemic events but does not include limits for glucose measurement accuracy. The International Standards Organization (ISO) standard for SMBG glucose measurement accuracy (ISO 15197) is +/-15 mg/dl for glucose <75 mg/dl and +/-20% for glucose > or = 75 mg/dl. This standard was combined with the CLSI method to more completely characterize the accuracy of CGM alarms. Incorporating the ISO 15197 accuracy margins, FreeStyle Navigator CGM system alarms detected 70 mg/dl hypoglycemia within 30 minutes at a rate of 70.3%, with a false alarm rate of 11.4%. The device detected high glucose in the range of 140-300 mg/dl within 30 minutes at an average rate of 99.2%, with a false alarm rate of 2.1%. Self-monitoring of blood glucose confirmation is necessary for detecting and treating hypoglycemia with the FreeStyle Navigator CGM system, but at high glucose levels, SMBG confirmation adds little incremental value to CGM alarms. 2010 Diabetes Technology Society.
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Maegawa, Hiroshi; Morino, Katsutaro; Nishio, Yoshihiko; Sato, Toshiyuki; Okada, Seiki; Kikkawa, Yasuo; Watanabe, Toshihiro; Nakajima, Hiromu; Kashiwagi, Atsunori
2016-01-01
Background Management of postprandial hyperglycemia is a key aspect in diabetes treatment. We developed a novel system to measure glucose area under the curve (AUC) using minimally invasive interstitial fluid extraction technology (MIET) for simple monitoring of postprandial glucose excursions. In this study, we evaluated the relationship between our system and continuous glucose monitoring (CGM) by comparing glucose AUC obtained using MIET with that obtained using CGM for a long duration. Methods Twenty diabetic inpatients wearing a CGM system were enrolled. For MIET measurement, a plastic microneedle array was applied to the skin as pretreatment, and hydrogels were placed on the pretreated area to collect interstitial fluid. Hydrogels were replaced every 2 or 4 hours and AUC was predicted on the basis of glucose and sodium ion levels. Results AUC predicted by MIET correlated well with that measured by CGM (r=0.93). Good performances of both consecutive 2- and 4-hour measurements were observed (measurement error: 11.7%±10.2% for 2 hours and 11.1%±7.9% for 4 hours), indicating the possibility of repetitive measurements up to 8 hours. The influence of neither glucose fluctuation nor average glucose level over the measurement accuracy was observed through 8 hours. Conclusion Our system showed good relationship with AUC values from CGM up to 8 hours, indicating that single pretreatment can cover a large portion of glucose excursion in a day. These results indicated possibility of our system to contribute to convenient monitoring of glucose excursions for a long duration. PMID:27535643
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Ugi, Satoshi; Maegawa, Hiroshi; Morino, Katsutaro; Nishio, Yoshihiko; Sato, Toshiyuki; Okada, Seiki; Kikkawa, Yasuo; Watanabe, Toshihiro; Nakajima, Hiromu; Kashiwagi, Atsunori
2016-08-01
Management of postprandial hyperglycemia is a key aspect in diabetes treatment. We developed a novel system to measure glucose area under the curve (AUC) using minimally invasive interstitial fluid extraction technology (MIET) for simple monitoring of postprandial glucose excursions. In this study, we evaluated the relationship between our system and continuous glucose monitoring (CGM) by comparing glucose AUC obtained using MIET with that obtained using CGM for a long duration. Twenty diabetic inpatients wearing a CGM system were enrolled. For MIET measurement, a plastic microneedle array was applied to the skin as pretreatment, and hydrogels were placed on the pretreated area to collect interstitial fluid. Hydrogels were replaced every 2 or 4 hours and AUC was predicted on the basis of glucose and sodium ion levels. AUC predicted by MIET correlated well with that measured by CGM (r=0.93). Good performances of both consecutive 2- and 4-hour measurements were observed (measurement error: 11.7%±10.2% for 2 hours and 11.1%±7.9% for 4 hours), indicating the possibility of repetitive measurements up to 8 hours. The influence of neither glucose fluctuation nor average glucose level over the measurement accuracy was observed through 8 hours. Our system showed good relationship with AUC values from CGM up to 8 hours, indicating that single pretreatment can cover a large portion of glucose excursion in a day. These results indicated possibility of our system to contribute to convenient monitoring of glucose excursions for a long duration.
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Siska, Evangelia K; Weisman, Itamar; Romano, Jacob; Ivics, Zoltán; Izsvák, Zsuzsanna; Barkai, Uriel; Petrakis, Spyros; Koliakos, George
2017-01-01
Diabetes is a chronic disease characterized by high levels of blood glucose. Diabetic patients should normalize these levels in order to avoid short and long term clinical complications. Presently, blood glucose monitoring is dependent on frequent finger pricking and enzyme based systems that analyze the drawn blood. Continuous blood glucose monitors are already on market but suffer from technical problems, inaccuracy and short operation time. A novel approach for continuous glucose monitoring is the development of implantable cell-based biosensors that emit light signals corresponding to glucose concentrations. Such devices use genetically modified cells expressing chimeric genes with glucose binding properties. MSCs are good candidates as carrier cells, as they can be genetically engineered and expanded into large numbers. They also possess immunomodulatory properties that, by reducing local inflammation, may assist long operation time. Here, we generated a novel immortalized human MSC line co-expressing hTERT and a secreted glucose biosensor transgene using the Sleeping Beauty transposon technology. Genetically modified hMSCs retained their mesenchymal characteristics. Stable transgene expression was validated biochemically. Increased activity of hTERT was accompanied by elevated and constant level of stem cell pluripotency markers and subsequently, by MSC immortalization. Furthermore, these cells efficiently suppressed PBMC proliferation in MLR transwell assays, indicating that they possess immunomodulatory properties. Finally, biosensor protein produced by MSCs was used to quantify glucose in cell-free assays. Our results indicate that our immortalized MSCs are suitable for measuring glucose concentrations in a physiological range. Thus, they are appropriate for incorporation into a cell-based, immune-privileged, glucose-monitoring medical device.
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Meyer, Gesine; Hackemann, Annika; Reusch, Juergen; Badenhoop, Klaus
2012-05-01
Hypoglycemia can be a symptom in patients with Addison's disease. The common regimen of replacement therapy with oral glucocorticoids results in unphysiological low cortisol levels in the early morning, the time of highest insulin sensitivity. Therefore patients with Addison's disease are at risk for unrecognized and potentially severe nocturnal hypoglycemia also because of a disturbed counterregulatory function. Use of a continuous glucose monitoring system (CGMS) could help to adjust hydrocortisone treatment and to avoid nocturnal hypoglycemia in these patients. Thirteen patients with Addison's disease were screened for hypoglycemia wearing a CGMS for 3-5 days. In one patient we identified a hypoglycemic episode at 3:45 a.m. with a blood glucose level of 46 mg/dL, clearly beneath the 95% tolerance interval of minimal glucose levels between 2 and 4 a.m. (53.84 mg/dL). After the hydrocortisone replacement scheme was changed, the minimum blood glucose level between 2 and 4 a.m. normalized to 87 mg/dL. Continuous glucose monitoring can detect nocturnal hypoglycemia in patients with primary adrenal insufficiency and hence prevent in these patients an impaired quality of life and even serious adverse effects.
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Yamazaki, Masahiro; Hasegawa, Goji; Majima, Saori; Mitsuhashi, Kazuteru; Fukuda, Takuya; Iwase, Hiroya; Kadono, Mayuko; Asano, Mai; Senmaru, Takafumi; Tanaka, Muhei; Fukui, Michiaki; Nakamura, Naoto
2014-01-01
Hemoglobin A1c is the main treatment target for patients with type 2 diabetes. It has also been shown recently that postprandial glucose and daily glucose fluctuations affect the progression of diabetic complications and atherosclerotic damages. Continuous glucose monitoring was performed in patients with type 2 diabetes to evaluate the efficacy of repaglinide vs. glimepiride on postprandial glucose spikes and fluctuations. A total of 10 Japanese patients with type 2 diabetes treated with glimepiride monotherapy were enrolled. After observation period for 8 weeks, glimepiride was changed to repaglinide. Continuous glucose monitoring was performed whilst consuming calorie-restricted diets for two days at baseline and at the end of the 12-week trial. Blood and urine samples were collected for measurement of glucose control parameters and inflammatory and oxidative stress markers on the last day of taking either glimepiride or repaglinide. Nine patients completed the trial. Although the glucose control parameters were not significantly different between glimepiride and repaglinide, the mean amplitude of glycemic excursions measured by continuous glucose monitoring was significantly reduced by changing treatment from glimepiride to repaglinide. The levels of plasminogen activator inhibitor-1, high sensitivity C-reactive protein, and urinary 8-hydoroxydeoxyguanosine were reduced significantly by repaglinide treatment. These results suggest that repaglinide may decrease the risk of cardiovascular disease in type 2 diabetes by minimizing glucose fluctuations thereby reducing inflammation and oxidative stress.
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2014-01-01
Background Hemoglobin A1c is the main treatment target for patients with type 2 diabetes. It has also been shown recently that postprandial glucose and daily glucose fluctuations affect the progression of diabetic complications and atherosclerotic damages. Methods Continuous glucose monitoring was performed in patients with type 2 diabetes to evaluate the efficacy of repaglinide vs. glimepiride on postprandial glucose spikes and fluctuations. A total of 10 Japanese patients with type 2 diabetes treated with glimepiride monotherapy were enrolled. After observation period for 8 weeks, glimepiride was changed to repaglinide. Continuous glucose monitoring was performed whilst consuming calorie-restricted diets for two days at baseline and at the end of the 12-week trial. Blood and urine samples were collected for measurement of glucose control parameters and inflammatory and oxidative stress markers on the last day of taking either glimepiride or repaglinide. Results Nine patients completed the trial. Although the glucose control parameters were not significantly different between glimepiride and repaglinide, the mean amplitude of glycemic excursions measured by continuous glucose monitoring was significantly reduced by changing treatment from glimepiride to repaglinide. The levels of plasminogen activator inhibitor-1, high sensitivity C-reactive protein, and urinary 8-hydoroxydeoxyguanosine were reduced significantly by repaglinide treatment. Conclusion These results suggest that repaglinide may decrease the risk of cardiovascular disease in type 2 diabetes by minimizing glucose fluctuations thereby reducing inflammation and oxidative stress. PMID:24843385
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Glucose Disappearance in Biological Treatment Systems
Jeris, John S.; Cardenas, Raul R.
1966-01-01
Laboratory scale anaerobic and aerobic treatment units were conditioned with a daily slug-feed of glucose. After a period of acclimation and stabilization, glucose disappearance was monitored continuously after the slug feed. A continuous sampling apparatus is described. Mathematical analysis of the data indicate zero-order reactions for both biological treatment systems. PMID:16349685
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Continuous glucose monitoring for patients with diabetes: an evidence-based analysis.
2011-01-01
To determine the effectiveness and cost-effectiveness of continuous glucose monitoring combined with self-monitoring of blood glucose compared with self-monitoring of blood glucose alone in the management of diabetes. CONDITION AND TARGET POPULATION Diabetes is a chronic metabolic disorder that interferes with the body's ability to produce or effectively use insulin. In 2005, an estimated 816,000 Ontarians had diabetes representing 8.8% of the province's population. Type 1 or juvenile onset diabetes is a life-long disorder that commonly manifests in children and adolescents. It represents about 10% of the total diabetes population and involves immune-mediated destruction of insulin producing cells in the pancreas. The loss of these cells necessitates insulin therapy. Type 2 or "adult-onset" diabetes represents about 90% of the total diabetes population and is marked by a resistance to insulin or insufficient insulin secretion. The risk of developing type 2 diabetes increases with age, obesity and lack of physical activity. Approximately 30% of patients with type 2 diabetes eventually require insulin therapy. Continuous glucose monitors (CGM) measure glucose levels in the interstitial fluid surrounding skin cells. These measurements supplement conventional self monitoring of blood glucose (SMBG) by monitoring the glucose fluctuations continuously over a stipulated period of time, thereby identifying fluctuations that would not be identified with SMBG alone. To use a CGM, a sensor is inserted under the skin to measure glucose in the interstitial fluid. The sensor is wired to a transmitter. The device requires calibration using a capillary blood glucose measurement. Each sensor continuously measures glucose every 5-10 seconds averaging these values every 5 minutes and storing this data in the monitors memory. Depending on the device used, the algorithm in the device can measure glucose over a 3 or 6 day period using one sensor. After the 3 or 6 day period, a new sensor is required. The device is equipped with alarms which warn the patient of impending hypo-or hyperglycemia. Two types of CGM are available: Systems that is stored in a monitor and can be downloaded later.Real time systems that continuously provide the actual glucose concentration on a display. What is the effectiveness and cost-effectiveness of CGM combined with SMBG compared with SMBG alone in the management of diabetes? A literature search was performed on September 15, 2010 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, the Cumulative Index to Nursing & Allied Health Literature (CINAHL), the Cochrane Library, and the International Agency for Health Technology Assessment (INAHTA) for studies published from January 1, 2002 until September 15, 2010. Abstracts were reviewed by a single reviewer and, for those studies meeting the eligibility criteria, full-text articles were obtained. Reference lists were also examined for any additional relevant studies not identified through the search. Articles with unknown eligibility were reviewed with a second clinical epidemiologist, then a group of epidemiologists until consensus was established. The quality of evidence was assessed as high, moderate, low or very low according to GRADE methodology. English languageRandomized controlled trials (N>30 patients)Adults or pediatric patients with insulin dependent diabetes (type 1 or 2 or gestational)Studies comparing CGM plus SMBG versus SMBG alone Case studiesStudies that did not compare CGM plus SMBG versus SMBG aloneStudies that did not report statistical analysis of outcomes or data was unextractable Change in glycosylated hemoglobin (HbA1c)Frequency or duration of hypo-or hyperglycemic episodes or euglycemiaAdverse effects Moderate quality evidence that CGM + SMBG: is not more effective than self monitoring of blood glucose (SMBG) alone in the reduction of HbA1c using insulin infusion pumps for Type 1 diabetes.is not more effective than SMBG alone in the reduction of hypoglycemic or severe hypoglycemic events using insulin infusion pumps for Type 1 diabetes.
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A Fully Implantable, NFC Enabled, Continuous Interstitial Glucose Monitor
Anabtawi, Nijad; Freeman, Sabrina; Ferzli, Rony
2017-01-01
This work presents an integrated system-on-chip (SoC) that forms the core of a long-term, fully implantable, battery assisted, passive continuous glucose monitor. It integrates an amperometric glucose sensor interface, a near field communication (NFC) wireless front-end and a fully digital switched mode power management unit for supply regulation and on board battery charging. It uses 13.56 MHz (ISM) band to harvest energy and backscatter data to an NFC reader. System was implemented in 14nm CMOS technology and validated with post layout simulations. PMID:28702512
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A Fully Implantable, NFC Enabled, Continuous Interstitial Glucose Monitor.
Anabtawi, Nijad; Freeman, Sabrina; Ferzli, Rony
2016-02-01
This work presents an integrated system-on-chip (SoC) that forms the core of a long-term, fully implantable, battery assisted, passive continuous glucose monitor. It integrates an amperometric glucose sensor interface, a near field communication (NFC) wireless front-end and a fully digital switched mode power management unit for supply regulation and on board battery charging. It uses 13.56 MHz (ISM) band to harvest energy and backscatter data to an NFC reader. System was implemented in 14nm CMOS technology and validated with post layout simulations.
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Use of sensors in the treatment and follow-up of patients with diabetes mellitus.
Torres, Isabel; Baena, Maria G; Cayon, Manuel; Ortego-Rojo, Jose; Aguilar-Diosdado, Manuel
2010-01-01
Glucose control is the cornerstone of Diabetes Mellitus (DM) treatment. Although self-regulation using capillary glycemia (SRCG) still remains the best procedure in clinical practice, continuous glucose monitoring systems (CGM) offer the possibility of continuous and dynamic assessment of interstitial glucose concentration. CGM systems have the potential to improve glycemic control while decreasing the incidence of hypoglycemia but the efficiency, compared with SRCG, is still debated. CGM systems have the greatest potential value in patients with hypoglycemic unawareness and in controlling daily fluctuations in blood glucose. The implementation of continuous monitoring in the standard clinical setting has not yet been established but a new generation of open and close loop subcutaneous insulin infusion devices are emerging making insulin treatment and glycemic control more reliable.
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Use of Sensors in the Treatment and Follow-up of Patients with Diabetes Mellitus
Torres, Isabel; Baena, Maria G.; Cayon, Manuel; Ortego-Rojo, Jose; Aguilar-Diosdado, Manuel
2010-01-01
Glucose control is the cornerstone of Diabetes Mellitus (DM) treatment. Although self-regulation using capillary glycemia (SRCG) still remains the best procedure in clinical practice, continuous glucose monitoring systems (CGM) offer the possibility of continuous and dynamic assessment of interstitial glucose concentration. CGM systems have the potential to improve glycemic control while decreasing the incidence of hypoglycemia but the efficiency, compared with SRCG, is still debated. CGM systems have the greatest potential value in patients with hypoglycemic unawareness and in controlling daily fluctuations in blood glucose. The implementation of continuous monitoring in the standard clinical setting has not yet been established but a new generation of open and close loop subcutaneous insulin infusion devices are emerging making insulin treatment and glycemic control more reliable. PMID:22163609
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Wang, B; Sun, G; Qiao, W; Liu, Y; Qiao, J; Ye, W; Wang, H; Wang, X; Lindquist, R; Wang, Y; Xiao, Y-F
2017-09-01
Continuous blood glucose monitoring, especially long-term and remote, in diabetic patients or research is very challenging. Nonhuman primate (NHP) is an excellent model for metabolic research, because NHPs can naturally develop Type 2 diabetes mellitus (T2DM) similarly to humans. This study was to investigate blood glucose changes in conscious, moving-free cynomolgus monkeys (Macaca fascicularis) during circadian, meal, stress and drug exposure. Blood glucose, body temperature and physical activities were continuously and simultaneously recorded by implanted HD-XG telemetry device for up to 10 weeks. Blood glucose circadian changes in normoglycemic monkeys significantly differed from that in diabetic animals. Postprandial glucose increase was more obvious after afternoon feeding. Moving a monkey from its housing cage to monkey chair increased blood glucose by 30% in both normoglycemic and diabetic monkeys. Such increase in blood glucose declined to the pre-procedure level in 30 min in normoglycemic animals and >2 h in diabetic monkeys. Oral gavage procedure alone caused hyperglycemia in both normoglycemic and diabetic monkeys. Intravenous injection with the stress hormones, angiotensin II (2 μg/kg) or norepinephrine (0.4 μg/kg), also increased blood glucose level by 30%. The glucose levels measured by the telemetry system correlated significantly well with glucometer readings during glucose tolerance tests (ivGTT or oGTT), insulin tolerance test (ITT), graded glucose infusion (GGI) and clamp. Our data demonstrate that the real-time telemetry method is reliable for monitoring blood glucose remotely and continuously in conscious, stress-free, and moving-free NHPs with the advantages highly valuable to diabetes research and drug discovery.
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Hirsch, Irl B; Balo, Andrew K; Sayer, Kevin; Garcia, Arturo; Buckingham, Bruce A; Peyser, Thomas A
2017-06-01
The potential clinical benefits of continuous glucose monitoring (CGM) have been recognized for many years, but CGM is used by a small fraction of patients with diabetes. One obstacle to greater use of the technology is the lack of simplified tools for assessing glycemic control from CGM data without complicated visual displays of data. We developed a simple new metric, the personal glycemic state (PGS), to assess glycemic control solely from continuous glucose monitoring data. PGS is a composite index that assesses four domains of glycemic control: mean glucose, glycemic variability, time in range and frequency and severity of hypoglycemia. The metric was applied to data from six clinical studies for the G4 Platinum continuous glucose monitoring system (Dexcom, San Diego, CA). The PGS was also applied to data from a study of artificial pancreas comparing results from open loop and closed loop in adolescents and in adults. The new metric for glycemic control, PGS, was able to characterize the quality of glycemic control in a wide range of study subjects with various mean glucose, minimal, moderate, and excessive glycemic variability and subjects on open loop versus closed loop control. A new composite metric for the assessment of glycemic control based on CGM data has been defined for use in assessing glycemic control in clinical practice and research settings. The new metric may help rapidly identify problems in glycemic control and may assist with optimizing diabetes therapy during time-constrained physician office visits.
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Hehmke, Bernd; Berg, Sabine; Salzsieder, Eckhard
2017-05-01
Continuous standardized verification of the accuracy of blood glucose meter systems for self-monitoring after their introduction into the market is an important clinically tool to assure reliable performance of subsequently released lots of strips. Moreover, such published verification studies permit comparison of different blood glucose monitoring systems and, thus, are increasingly involved in the process of evidence-based purchase decision making.
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Hackemann, Annika; Reusch, Juergen; Badenhoop, Klaus
2012-01-01
Abstract Background Hypoglycemia can be a symptom in patients with Addison's disease. The common regimen of replacement therapy with oral glucocorticoids results in unphysiological low cortisol levels in the early morning, the time of highest insulin sensitivity. Therefore patients with Addison's disease are at risk for unrecognized and potentially severe nocturnal hypoglycemia also because of a disturbed counterregulatory function. Use of a continuous glucose monitoring system (CGMS) could help to adjust hydrocortisone treatment and to avoid nocturnal hypoglycemia in these patients. Methods Thirteen patients with Addison's disease were screened for hypoglycemia wearing a CGMS for 3–5 days. Results In one patient we identified a hypoglycemic episode at 3:45 a.m. with a blood glucose level of 46 mg/dL, clearly beneath the 95% tolerance interval of minimal glucose levels between 2 and 4 a.m. (53.84 mg/dL). After the hydrocortisone replacement scheme was changed, the minimum blood glucose level between 2 and 4 a.m. normalized to 87 mg/dL. Conclusions Continuous glucose monitoring can detect nocturnal hypoglycemia in patients with primary adrenal insufficiency and hence prevent in these patients an impaired quality of life and even serious adverse effects. PMID:22242902
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Consistency of Continuous Ambulatory Interstitial Glucose Monitoring Sensors.
Wu, Pei T; Segovia, David E; Lee, Cathy C; Nguyen, Kim-Lien
2018-05-16
The abdominal region is the most common location for continuous glucose monitor (CGM) sensor insertion. However, a paucity of post-marketing data is available to demonstrate intra-individual consistency of CGM readings at different abdominal insertion sites. Healthy adults (fasting glucose (FG) < 5.5 mmol/L; BMI < 30 kg/m²) were recruited and a CGM sensor was placed on each side of the abdomen. Postprandial and continuous 48-h interstitial glucose levels were analyzed. There was no significant difference in the 3-h postprandial glucose (PPG) level derived from the left versus right CGM, which remained non-significant after adjusting for waist circumference or FG. Among the glucose levels recorded over 48-h, values on the left site were greater in 3.6% of the data points ( p < 0.05). After adjusting for waist circumference, only 0.5% of the glucose values remained significantly greater on the left ( p < 0.05). When adjusted for FG, similar results were observed. For both PPG and 48-h readings, the mean absolute relative difference was not significant between the two abdominal sites. CGM-derived glucose measures were highly consistent between the left and right abdomen during both the postprandial and post-absorptive periods.
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Hydrogel-based electrochemical sensor for non-invasive and continuous glucose monitoring
NASA Astrophysics Data System (ADS)
Park, Habeen; Lee, Ji-Young; Kim, Dong-Chul; Koh, Younggook; Cha, Junhoe
2017-07-01
Monitoring blood glucose level of diabetic patients is crucial in diabetes care from life threating complications. Selfmonitoring blood glucose (SMBG) that involves finger prick to draw blood samples into the measurement system is a widely-used method of routine measurement of blood glucose levels to date. SMBG includes, however, unavoidable pain problems resulting from the repetitive measurements. We hereby present a hydrogel-based electrochemical (H-EC) sensor to monitor the glucose level, non-invasively. Glucose oxidase (GOx) was immobilized in the disc-type hydroxyethyl methacrylate (HEMA) based hydrogel and kept intact in the hydrogel. Fast electron transfer mediated by Prussian blue (PB, hexacyanoferrate) generated efficient signal amplifications to facilitate the detection of the extracted glucose from the interstitial fluid. The linear response and the selectivity against glucose of the H-EC sensor were validated by chronoamperometry. For the practical use, the outcomes from the correlation of the extracted glucose concentration and the blood glucose value by on-body extraction, as well as the validation of the hydrogel-based electrochemical (H-EC) device, were applied to the on-body glucose monitoring.
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Sparacino, Giovanni; Zanon, Mattia; Facchinetti, Andrea; Zecchin, Chiara; Maran, Alberto; Cobelli, Claudio
2012-01-01
Monitoring glucose concentration in the blood is essential in the therapy of diabetes, a pathology which affects about 350 million people around the World (three million in Italy), causes more than four million deaths per year and consumes a significant portion of the budget of national health systems (10% in Italy). In the last 15 years, several sensors with different degree of invasiveness have been proposed to monitor glycemia in a quasi-continuous way (up to 1 sample/min rate) for relatively long intervals (up to 7 consecutive days). These continuous glucose monitoring (CGM) sensors have opened new scenarios to assess, off-line, the effectiveness of individual patient therapeutic plans from the retrospective analysis of glucose time-series, but have also stimulated the development of innovative on-line applications, such as hypo/hyper-glycemia alert systems and artificial pancreas closed-loop control algorithms. In this review, we illustrate some significant Italian contributions, both from industry and academia, to the growth of the CGM sensors research area. In particular, technological, algorithmic and clinical developments performed in Italy will be discussed and put in relation with the advances obtained in the field in the wider international research community. PMID:23202020
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Sparacino, Giovanni; Zanon, Mattia; Facchinetti, Andrea; Zecchin, Chiara; Maran, Alberto; Cobelli, Claudio
2012-10-12
Monitoring glucose concentration in the blood is essential in the therapy of diabetes, a pathology which affects about 350 million people around the World (three million in Italy), causes more than four million deaths per year and consumes a significant portion of the budget of national health systems (10% in Italy). In the last 15 years, several sensors with different degree of invasiveness have been proposed to monitor glycemia in a quasi-continuous way (up to 1 sample/min rate) for relatively long intervals (up to 7 consecutive days). These continuous glucose monitoring (CGM) sensors have opened new scenarios to assess, off-line, the effectiveness of individual patient therapeutic plans from the retrospective analysis of glucose time-series, but have also stimulated the development of innovative on-line applications, such as hypo/hyper-glycemia alert systems and artificial pancreas closed-loop control algorithms. In this review, we illustrate some significant Italian contributions, both from industry and academia, to the growth of the CGM sensors research area. In particular, technological, algorithmic and clinical developments performed in Italy will be discussed and put in relation with the advances obtained in the field in the wider international research community.
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Song, Yonggui; Su, Dan; Shen, Yuan; Liu, Hongyu; Wang, Li
2017-01-01
A novel open circuit potential biosensor (OCPS) composed of a working electrode and a Ag/AgCl reference electrode was designed for in vivo continuous glucose monitoring in this work. The macroporous carbon derived from kenaf stem (KSC) was used to construct a KSC microelectrode (denoted as KSCME) which was subsequently used to load glucose oxidase (GOD) as the working electrode. The resulting GOD/KSCMEs could catalyze the oxidation of glucose directly to result in changes of the open circuit potential (V oc ) of the OCPS. The V oc of OCPS was dependent on the glucose concentration, showing a linear range of 0.03-10.0 mM (R = 0.999) with a detection limit of 10 μM. In addition, the OCPS exhibited good selectivity for glucose over other common endogenous interferences. The feasibility of the proposed OCPS for glucose detection in mice skin tumors and normal tissue homogenate samples (in vitro experiment) and rat subcutaneous glucose monitoring (in vivo experiment) was also demonstrated with satisfactory results. The biosensor represents a novel example of a superficial cancer diagnostic device, and the proposed OCPS also provides new ideas for the development of a simple and highly selective device for continuous glucose sensing.
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Continuous glucose monitoring on the ICU using a subcutaneous sensor.
Punke, M A; Decker, C; Wodack, K; Reuter, D A; Kluge, S
2015-06-01
Hypoglycemia is a frequent and feared complication of insulin therapy on the intensive care unit (ICU). Sedated patients in particular are at risk for hypoglycemia due to the absence of clinical symptoms. Furthermore, recent studies point to a correlation between the variability of blood glucose and mortality. Therefore, continuous glucose monitoring has the potential to influence outcome due to a better control of blood glucose in critically ill patients. We evaluated the efficacy, accuracy and safety of a new commercially available subcutaneous continuous glucose monitoring system (sCGM; Sentrino®, Medtronic) in a pilot study in critically ill adult patients. sCGM data were recorded for up to 72 h and values were compared with blood glucose values measured by cassette-based blood gas analyzer (BGA). A total of 14 patients (eight male, six female), with a mean age of 62.1 ± 9.8 years, referred to the ICU after major abdominal surgery were studied. The average simplified acute physiology score (SAPS II) was 35 ± 9. Three patients had known type II diabetes. The average runtime of sensors was 44.1 ± 22.1 h. In comparison to BGA, measurement of blood glucose by sCGM revealed an accuracy of 1.5 mg/dl, and a precision of +34.2 mg/dl to -31.2 mg/dl. Linn's concordance correlation coefficient yielded 0.74 with a 95% confidence interval of 0.68-0.78. No hypoglycemic events, defined as a blood glucose level below 70 mg/dl, occurred during treatment. sCGM monitoring via a subcutaneous sensor demonstrated high accuracy and considerable variability compared to blood gas samples, even in critically ill patients.
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Management of Hypoglycemia in Children and Adolescents with Type 1 Diabetes Mellitus.
McGill, Dayna E; Levitsky, Lynne L
2016-09-01
Hypoglycemia and fear of hypoglycemia limit appropriate glycemic control in many children and adolescents with type 1 diabetes. Traditional approaches to the prevention of hypoglycemia including patient education about modifiable risk factors for hypoglycemia (changes in insulin, diet, and exercise) and frequency of self glucose monitoring remain important for hypoglycemia prevention. Continuous glucose monitoring systems with or without a partial closed-loop control of insulin infusion have been very useful in the prevention of hypoglycemia. Oral carbohydrate and parenteral glucagon continue to be the mainstays of hypoglycemia treatment. In the future, we can look forward to regulatory approval of closed-loop insulin delivery and glucose monitoring systems to facilitate euglycemia, as well as glucagon administered by the intranasal route to treat hypoglycemia.
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ConA-based glucose sensing using the long-lifetime azadioxatriangulenium fluorophore
NASA Astrophysics Data System (ADS)
Cummins, Brian; Simpson, Jonathan; Gryczynski, Zygmunt; Sørensen, Thomas Just; Laursen, Bo W.; Graham, Duncan; Birch, David; Coté, Gerard
2014-02-01
Fluorescent glucose sensing technologies have been identified as possible alternatives to current continuous glucose monitoring approaches. We have recently introduced a new, smart fluorescent ligand to overcome the traditional problems of ConA-based glucose sensors. For this assay to be translated into a continuous glucose monitoring device where both components are free in solution, the molecular weight of the smart fluorescent ligand must be increased. We have identified ovalbumin as a naturally-occurring glycoprotein that could serve as the core-component of a 2nd generation smart fluorescent ligand. It has a single asparagine residue that is capable of displaying an N-linked glycan and a similar isoelectric point to ConA. Thus, binding between ConA and ovalbumin can potentially be monovalent and sugar specific. This work is the preliminary implementation of fluorescently-labeled ovalbumin in the ConA-based assay. We conjugate the red-emitting, long-lifetime azadioxatriangulenium (ADOTA+) dye to ovalbumin, as ADOTA have many advantageous properties to track the equilibrium binding of the assay. The ADOTA-labeled ovalbumin is paired with Alexa Fluor 647-labeled ConA to create a Förster Resonance Energy Transfer (FRET) assay that is glucose dependent. The assay responds across the physiologically relevant glucose range (0-500 mg/dL) with increasing intensity from the ADOTA-ovalbumin, showing that the strategy may allow for the translation of the smart fluorescent ligand concept into a continuous glucose monitoring device.
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Chen, Chen-Mei; Hung, Li-Chen; Chen, Yang-Lin; Yeh, Mei Chang
2018-04-01
To explore experiences of self-monitoring of blood glucose among patients with non-insulin-treated type 2 diabetes. Self-monitoring of blood glucose is essential to diabetes care and facilitates glycaemic control. Patients' perspectives of self-monitoring of blood glucose have seldom been discussed in the literature, and engagement in self-monitoring of blood glucose is consistently low. The descriptive phenomenological method was used. Purposive sampling was conducted to recruit participants from the endocrinology departments of medical institutions in Taiwan based on the following criteria: (i) having a medical diagnosis of type 2 diabetes, (ii) not being treated with insulin, (iii) having engaged in self-monitoring of blood glucose at least once within the preceding 6 months, (iv) being at least 20 years old and (v) not having any major mental or cognitive disorders. Data were collected in outpatient consultation rooms, the participants' homes and other settings where the participants felt secure and comfortable. In-depth interviews were conducted to collect data from 16 patients with diabetes. The participants perceived that lifestyle affected blood glucose levels and did not know how to handle high or low blood glucose levels. Their willingness to continue self-monitoring of blood glucose depended on whether healthcare professionals checked or discussed their blood glucose levels with them. The patients' knowledge regarding blood glucose variation and healthcare professionals' attitudes affected the patients' self-monitoring of blood glucose behaviours. The empirical findings illustrated self-monitoring of blood glucose experiences and recommended that healthcare professionals' closely attend to patients' requirements and responses to diabetes and incorporate the self-monitoring of blood glucose into therapy plans. Healthcare professionals should reinforce patients' knowledge on appropriate responses to high and low blood glucose levels, intervene appropriately, discuss self-monitoring of blood glucose results with patients and track these results. © 2017 John Wiley & Sons Ltd.
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Wagner, Julie; Armeli, Stephen; Tennen, Howard; Bermudez-Millan, Angela; Wolpert, Howard; Pérez-Escamilla, Rafael
2017-09-01
This study investigated between- and within-person associations among mean levels and variability in affect, diabetes self-care behaviors, and continuously monitored glucose in Latinos with type 2 diabetes. Fifty participants (M [SD] age = 57.8 [11.7] years, 74% women, mean [SD] glycosylated hemoglobin A1c = 8.3% [1.5%]) wore a "blinded" continuous glucose monitor for 7 days, and they responded to twice daily automated phone surveys regarding positive affect, negative affect, and self-care behaviors. Higher mean levels of NA were associated with higher mean glucose (r = .30), greater percent hyperglycemia (r = .34) and greater percentage of out-of-range glucose (r = .34). Higher NA variability was also related to higher mean glucose (r = .34), greater percent of hyperglycemia (r = .44) and greater percentage of out-of-range glucose (r = .43). Higher positive affect variability was related to lower percentage of hypoglycemia (r = -.33). Higher mean levels of self-care behaviors were related to lower glucose variability (r = -.35). Finally, higher self-care behavior variability was related to greater percentage of hyperglycemia (r = .31) and greater percentage of out-of-range glucose (r = -.28). In multilevel regression models, within-person increases from mean levels of self-care were associated with lower mean levels of glucose (b = -7.4, 95% confidence interval [CI] = -12.8 to -1.9), lower percentage of hyperglycemia (b = -0.04, 95% CI = -0.07 to -0.01), and higher percentage of hypoglycemia (b = 0.02, 95% CI = 0.01 to 0.03) in the subsequent 10-hour period. Near-to-real time sampling documented associations of glucose with affect and diabetes self-care that are not detectable with traditional measures.
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McGarraugh, Geoffrey V; Clarke, William L; Kovatchev, Boris P
2010-05-01
The purpose of the analysis was to compare the clinical utility of data from traditional self-monitoring of blood glucose (SMBG) to that of continuous glucose monitoring (CGM). A clinical study of the clinical accuracy of the FreeStyle Navigator CGM System (Abbott Diabetes Care, Alameda, CA), which includes SMBG capabilities, was conducted by comparison to the YSI blood glucose analyzer (YSI Inc., Yellow Springs, OH) using 58 subjects with type 1 diabetes. The Continuous Glucose-Error Grid Analysis (CG-EGA) was used as the analytical tool. Using CG-EGA, the "clinically accurate," "benign errors," and "clinical errors" were 86.8%, 8.7%, and 4.5% for SMBG and 92.7%, 3.7%, and 3.6% for CGM, respectively. If blood glucose is viewed as a process in time, SMBG would provide accurate information about this process 86.8% of the time, whereas CGM would provide accurate information about this process 92.7% of the time (P < 0.0001). In the hypoglycemic range, however, SMBG is more accurate as the "clinically accurate," "benign errors," and "clinical errors" were 83.5%, 6.4%, and 10.1% for SMBG and 57.1%, 8.4%, and 34.5% (P < 0.0001) for CGM, respectively. While SMBG produces more accurate instantaneous glucose values than CGM, control of blood glucose involves a system in flux, and CGM provides more detailed insight into the dynamics of that system. In the normal and elevated glucose ranges, the additional information about the direction and rate of glucose change provided by the FreeStyle Navigator CGM System increases the ability to make correct clinical decisions when compared to episodic SMBG tests.
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NASA Astrophysics Data System (ADS)
Lipani, Luca; Dupont, Bertrand G. R.; Doungmene, Floriant; Marken, Frank; Tyrrell, Rex M.; Guy, Richard H.; Ilie, Adelina
2018-06-01
Currently, there is no available needle-free approach for diabetics to monitor glucose levels in the interstitial fluid. Here, we report a path-selective, non-invasive, transdermal glucose monitoring system based on a miniaturized pixel array platform (realized either by graphene-based thin-film technology, or screen-printing). The system samples glucose from the interstitial fluid via electroosmotic extraction through individual, privileged, follicular pathways in the skin, accessible via the pixels of the array. A proof of principle using mammalian skin ex vivo is demonstrated for specific and `quantized' glucose extraction/detection via follicular pathways, and across the hypo- to hyper-glycaemic range in humans. Furthermore, the quantification of follicular and non-follicular glucose extraction fluxes is clearly shown. In vivo continuous monitoring of interstitial fluid-borne glucose with the pixel array was able to track blood sugar in healthy human subjects. This approach paves the way to clinically relevant glucose detection in diabetics without the need for invasive, finger-stick blood sampling.
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Patel, Jasbir N; Gray, Bonnie L; Kaminska, Bozena; Gates, Byron D
2011-09-01
Continuous glucose monitoring for patients with diabetes is of paramount importance to avoid severe health conditions resulting from hypoglycemia or hyperglycemia. Most available methods require an invasive setup and a health care professional. Handheld devices available on the market also require finger pricking for every measurement and do not provide continuous monitoring. Hence, continuous glucose monitoring from human tears using a glucose sensor embedded in a contact lens has been considered as a suitable option. However, the glucose concentration in human tears is very low in comparison with the blood glucose level (1/10-1/40 concentration). We propose a sensor that solves the sensitivity problem in a new way, is flexible, and is constructed onto the oxygen permeable contact lens material. To achieve such sensitivity while maintaining a small sensor footprint suitable for placement in a contact lens, we increased the active electrode area by using three-dimensional (3-D) electrode micropatterning. Fully flexible 3-D electrodes were realized utilizing ordered arrays of pillars with different shapes and heights. We successfully fabricated square and cylindrical pillars with different height (50, 100, and 200 μm) and uniform metal coverage to realize sensor electrodes. The increased surface area produces high amperometric current that increases sensor sensitivity up to 300% using 200 μm tall square pillars. The sensitivity improvement closely follows the improvement in the surface area of the electrode. The proposed flexible glucose sensors with 3-D microstructure electrodes are more sensitive to lower glucose concentrations and generate higher current signal than conventional glucose sensors. © 2011 Diabetes Technology Society.
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Wearable physiological systems and technologies for metabolic monitoring.
Gao, Wei; Brooks, George A; Klonoff, David C
2018-03-01
Wearable sensors allow continuous monitoring of metabolites for diabetes, sports medicine, exercise science, and physiology research. These sensors can continuously detect target analytes in skin interstitial fluid (ISF), tears, saliva, and sweat. In this review, we will summarize developments on wearable devices and their potential applications in research, clinical practice, and recreational and sporting activities. Sampling skin ISF can require insertion of a needle into the skin, whereas sweat, tears, and saliva can be sampled by devices worn outside the body. The most widely sampled metabolite from a wearable device is glucose in skin ISF for monitoring diabetes patients. Continuous ISF glucose monitoring allows estimation of the glucose concentration in blood without the pain, inconvenience, and blood waste of fingerstick capillary blood glucose testing. This tool is currently used by diabetes patients to provide information for dosing insulin and determining a diet and exercise plan. Similar technologies for measuring concentrations of other analytes in skin ISF could be used to monitor athletes, emergency responders, warfighters, and others in states of extreme physiological stress. Sweat is a potentially useful substrate for sampling analytes for metabolic monitoring during exercise. Lactate, sodium, potassium, and hydrogen ions can be measured in sweat. Tools for converting the concentrations of these analytes sampled from sweat, tears, and saliva into blood concentrations are being developed. As an understanding of the relationships between the concentrations of analytes in blood and easily sampled body fluid increases, then the benefits of new wearable devices for metabolic monitoring will also increase.
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Gellynck, Karolien; Kodeck, Valérie; Van De Walle, Elke; Kersemans, Ken; De Vos, Filip; Declercq, Heidi; Dubruel, Peter; Vlaminck, Lieven
2015-01-01
Continuous glucose monitoring (CGM) is crucial in diabetic care. Long-term CGM systems however require an accurate sensor as well as a suitable measuring environment. Since large intravenous sensors are not feasible, measuring inside the interstitial fluid is considered the best alternative. This option, unfortunately, has the drawback of a lag time with blood glucose values. A good strategy to circumvent this is to enhance tissue integration and enrich the peri-implant vasculature. Implants of different optically transparent biomaterials (poly(methyl-methacrylate) [PMMA] and poly(dimethylsiloxane) [PDMS]) – enabling glucose monitoring in the near-infrared (NIR) spectrum – were surface-treated and subsequently implanted in goats at various implantation sites for up to 3 months. The overall in vivo biocompatibility, tissue integration, and vascularization at close proximity of the surfaces of these materials were assessed. Histological screening showed similar tissue reactions independent of the implantation site. No significant inflammation reaction was observed. Tissue integration and vascularization correlated, to some extent, with the biomaterial composition. A modification strategy, in which a vascular endothelial-cadherin antibody was coupled to the biomaterials surface through a dopamine layer, showed significantly enhanced vascularization 3 months after subcutaneous implantation. Our results suggest that the developed strategy enables the creation of tissue interactive NIR transparent packaging materials, opening the possibility of continuous glucose monitoring. PMID:25304314
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Monte Carlo simulation of non-invasive glucose measurement based on FMCW LIDAR
NASA Astrophysics Data System (ADS)
Xiong, Bing; Wei, Wenxiong; Liu, Nan; He, Jian-Jun
2010-11-01
Continuous non-invasive glucose monitoring is a powerful tool for the treatment and management of diabetes. A glucose measurement method, with the potential advantage of miniaturizability with no moving parts, based on the frequency modulated continuous wave (FMCW) LIDAR technology is proposed and investigated. The system mainly consists of an integrated near-infrared tunable semiconductor laser and a detector, using heterodyne technology to convert the signal from time-domain to frequency-domain. To investigate the feasibility of the method, Monte Carlo simulations have been performed on tissue phantoms with optical parameters similar to those of human interstitial fluid. The simulation showed that the sensitivity of the FMCW LIDAR system to glucose concentration can reach 0.2mM. Our analysis suggests that the FMCW LIDAR technique has good potential for noninvasive blood glucose monitoring.
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Bergenstal, Richard M; Strock, Ellie; Mazze, Roger; Powers, Margaret A; Monk, Arlene M; Richter, Sara; Souhami, Elisabeth; Ahrén, Bo
2017-05-01
In the parent study of this analysis, patients with type 2 diabetes received lixisenatide before breakfast or the main meal of the day. This substudy was designed to examine the effect of lixisenatide administered before breakfast or the main meal of the day on continuously assessed 24-hour patient glucose profiles. A subset of patients from the parent study underwent 2 14-day periods of continuous glucose monitoring (CGM) at the start and end of the 24-week study. Ambulatory glucose profile analysis was used to measure changes over time in detailed aspects of the glucose profiles. The breakfast group consumed a standardized meal during both CGM periods to determine change in 4-hour glycemic response. Data were available for 69 patients in the substudy, 40 from the original breakfast group and 29 from the main meal group. Between baseline and end of study, mean (standard deviation) total glucose exposure decreased from 4198.1 (652.3) to 3681.2 (699.6) mg/dL*24 h in the breakfast group (P < .0001) and from 4127.9 (876.8) to 3880.9 (1165.0) mg/dL*24 h in the main meal group (P = .0224). For patients included in the substudy, HbA 1c decreased by approximately 0.6% in both groups. Mean (standard deviation) 4-hour total glucose exposure fell by 168.9 (158.4) mg/dL*4 h (P < .0001) from baseline. This analysis demonstrates that lixisenatide has beneficial effects on components of the 24-hour glucose profile, which endure beyond the meal at which it is administered. Continuous glucose monitoring analysis detects changes not captured using HbA 1c alone. Copyright © 2016 John Wiley & Sons, Ltd.
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Blood glucose monitoring in type 2 diabetes – Nepalese patients’ opinions and experiences
Sapkota, Sujata; Brien, Jo-anne E; Aslani, Parisa
2017-01-01
ABSTRACT Background: Blood glucose monitoring forms a vital component of diabetes care. Monitoring conducted at home using glucometers, and in laboratories by professionals, are two common methods of blood glucose monitoring in clinical practice. Objective: To investigate Nepalese patients’ perceptions and practices of blood glucose monitoring in diabetes. Methods: In-depth interviews were conducted with 48 Nepalese participants with type 2 diabetes in Sydney and Kathmandu. The interviews were audio-recorded, transcribed verbatim and thematically analysed. Results: In Australia, most participants perceived home monitoring as useful; and both home and laboratory monitoring were conducted at fairly regular intervals. In Nepal, only a small number conducted home monitoring and the laboratory method formed the primary method of day-to-day monitoring. The laboratory method was preferred due to easy access to laboratories, lack of faith in glucometers and perceptions that home monitoring is costlier. However, overall monitoring was irregular in Nepal. In addition to the healthcare system which enabled cheaper self-monitoring in Australia, Nepalese in Australia also tended to have a better understanding about the purpose of home monitoring. Conclusions: This study has highlighted the disparity in perceptions and practices related to blood glucose monitoring. Understanding the importance of blood glucose monitoring and access to affordable resources are critical facilitators for conducting regular monitoring. Both patient and health-system factors play a key role in ensuring continued diabetes monitoring and management. PMID:28585892
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Wang, Xiaolin; Ioacara, Sorin; DeHennis, Andrew
2015-11-01
This study analyzed the overall nocturnal performance during home use of a long-term subcutaneous implantable continuous glucose monitoring (CGM) sensor. In this study, 12 subjects with type 1 diabetes mellitus (T1DM) (mean±SD age, 37±8 years; mean±SD disease duration, 11±6 years) were implanted with an investigational continuous glucose sensor in the upper arm for up to 90 days. All subjects received full access to real-time glucose display and user programmable hypo- and hyperglycemic alarms. Subjects calibrated the sensors with a self-monitoring of blood glucose (SMBG) meter and continued to rely on their regular SMBG measurements for their diabetes management. Accuracy of the sensors during the home-use study was calculated using SMBG as the reference. The nocturnal sensor attenuation (NSA) concept was tested. Sensitivity and specificity of the nocturnal hypoglycemic alarm were calculated. Mean±SD glucose sensor life span was 87±7 days. The mean±SE absolute relative difference over the range of 40-400 mg/dL for the sensors in this home-use study was 12.3±0.7% using SMBG as the reference. The hypoglycemia alarms were set to be triggered when the glucose level went below 70 mg/dL. Percentage of nights with hypoglycemic alarms triggered for at least 10 min was 13.6%. Recovery into euglycemia within 30 min from the timestamp of the immediate confirmatory SMBG testing was obtained in 74% of all episodes (n=20). The implanted continuous glucose sensor showed a hypoglycemia detection sensitivity and specificity of 77% and 96%, respectively. The NSA-associated high negative rate of change of at least -4 mg/dL/min was not encountered during night use of the system. This home-use study of a fully implantable, long-term continuous glucose sensor shows excellent performance in nocturnal hypoglycemia detection in T1DM patients. The apparent lack of NSA affecting the implanted sensor and the high specificity of the hypoglycemic alarm expedite the recovery from nighttime hypoglycemia.
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Continuous Glucose Monitoring For Patients with Diabetes
2011-01-01
Executive Summary Objective To determine the effectiveness and cost-effectiveness of continuous glucose monitoring combined with self-monitoring of blood glucose compared with self-monitoring of blood glucose alone in the management of diabetes. Clinical Need: Condition and Target Population Diabetes is a chronic metabolic disorder that interferes with the body’s ability to produce or effectively use insulin. In 2005, an estimated 816,000 Ontarians had diabetes representing 8.8% of the province’s population. Type 1 or juvenile onset diabetes is a life-long disorder that commonly manifests in children and adolescents. It represents about 10% of the total diabetes population and involves immune-mediated destruction of insulin producing cells in the pancreas. The loss of these cells necessitates insulin therapy. Type 2 or “adult-onset” diabetes represents about 90% of the total diabetes population and is marked by a resistance to insulin or insufficient insulin secretion. The risk of developing type 2 diabetes increases with age, obesity and lack of physical activity. Approximately 30% of patients with type 2 diabetes eventually require insulin therapy. Technology Continuous glucose monitors (CGM) measure glucose levels in the interstitial fluid surrounding skin cells. These measurements supplement conventional self monitoring of blood glucose (SMBG) by monitoring the glucose fluctuations continuously over a stipulated period of time, thereby identifying fluctuations that would not be identified with SMBG alone. To use a CGM, a sensor is inserted under the skin to measure glucose in the interstitial fluid. The sensor is wired to a transmitter. The device requires calibration using a capillary blood glucose measurement. Each sensor continuously measures glucose every 5-10 seconds averaging these values every 5 minutes and storing this data in the monitors memory. Depending on the device used, the algorithm in the device can measure glucose over a 3 or 6 day period using one sensor. After the 3 or 6 day period, a new sensor is required. The device is equipped with alarms which warn the patient of impending hypo-or hyperglycemia. Two types of CGM are available: Systems that is stored in a monitor and can be downloaded later. Real time systems that continuously provide the actual glucose concentration on a display. Research Questions What is the effectiveness and cost-effectiveness of CGM combined with SMBG compared with SMBG alone in the management of diabetes? Research Methods Literature Search Search Strategy A literature search was performed on September 15, 2010 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, the Cumulative Index to Nursing & Allied Health Literature (CINAHL), the Cochrane Library, and the International Agency for Health Technology Assessment (INAHTA) for studies published from January 1, 2002 until September 15, 2010. Abstracts were reviewed by a single reviewer and, for those studies meeting the eligibility criteria, full-text articles were obtained. Reference lists were also examined for any additional relevant studies not identified through the search. Articles with unknown eligibility were reviewed with a second clinical epidemiologist, then a group of epidemiologists until consensus was established. The quality of evidence was assessed as high, moderate, low or very low according to GRADE methodology. Inclusion Criteria English language Randomized controlled trials (N>30 patients) Adults or pediatric patients with insulin dependent diabetes (type 1 or 2 or gestational) Studies comparing CGM plus SMBG versus SMBG alone Exclusion Criteria Case studies Studies that did not compare CGM plus SMBG versus SMBG alone Studies that did not report statistical analysis of outcomes or data was unextractable Outcomes of Interest Change in glycosylated hemoglobin (HbA1c) Frequency or duration of hypo-or hyperglycemic episodes or euglycemia Adverse effects Summary of Findings Moderate quality evidence that CGM + SMBG: is not more effective than self monitoring of blood glucose (SMBG) alone in the reduction of HbA1c using insulin infusion pumps for Type 1 diabetes. is not more effective than SMBG alone in the reduction of hypoglycemic or severe hypoglycemic events using insulin infusion pumps for Type 1 diabetes. PMID:23074416
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NASA Astrophysics Data System (ADS)
Larin, Kirill V.; Ashitkov, Taras V.; Larina, Irina V.; Petrova, Irina Y.; Eledrisi, Mohsen S.; Motamedi, Massoud; Esenaliev, Rinat O.
2002-06-01
Continuous noninvasive monitoring of blood glucose concentration can improve management of Diabetes Mellitus, reduce mortality, and considerably improve quality of life of diabetic patients. Recently, we proposed to use the OCT technique for noninvasive glucose monitoring. In this paper, we tested noninvasive blood glucose monitoring with the OCT technique in phantoms, animals, and human subjects. An OCT system with the wavelength of 1300 nm was used in our experiments. Phantom studies performed on aqueous suspensions of polystyrene microspheres and milk showed 3.2% decrease of exponential slope of OCT signals when glucose concentration increased from 0 to 100 mM. Theoretical calculations based on the Mie theory of scattering support the results obtained in phantoms. Bolus glucose injections and glucose clamping experiments were performed in animals (New Zealand rabbits and Yucatan micropigs). Good correlation between changes in the OCT signal slope and actual blood glucose concentration were observed in these experiments. First studies were performed in healthy human subjects (using oral glucose tolerance tests). Dependence of the slope of the OCT signals on the actual blood glucose concentration was similar to that obtained in animal studies. Our studies suggest that the OCT technique can potentially be used for noninvasive blood glucose monitoring.
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Optical glucose monitoring using vertical cavity surface emitting lasers (VCSELs)
NASA Astrophysics Data System (ADS)
Talebi Fard, Sahba; Hofmann, Werner; Talebi Fard, Pouria; Kwok, Ezra; Amann, Markus-Christian; Chrostowski, Lukas
2009-08-01
Diabetes Mellitus is a common chronic disease that has become a public health issue. Continuous glucose monitoring improves patient health by stabilizing the glucose levels. Optical methods are one of the painless and promising methods that can be used for blood glucose predictions. However, having accuracies lower than what is acceptable clinically has been a major concern. Using lasers along with multivariate techniques such as Partial Least Square (PLS) can improve glucose predictions. This research involves investigations for developing a novel optical system for accurate glucose predictions, which leads to the development of a small, low power, implantable optical sensor for diabetes patients.
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Zecchin, Chiara; Facchinetti, Andrea; Sparacino, Giovanni; Dalla Man, Chiara; Manohar, Chinmay; Levine, James A; Basu, Ananda; Kudva, Yogish C; Cobelli, Claudio
2013-10-01
In type 1 diabetes mellitus (T1DM), physical activity (PA) lowers the risk of cardiovascular complications but hinders the achievement of optimal glycemic control, transiently boosting insulin action and increasing hypoglycemia risk. Quantitative investigation of relationships between PA-related signals and glucose dynamics, tracked using, for example, continuous glucose monitoring (CGM) sensors, have been barely explored. In the clinic, 20 control and 19 T1DM subjects were studied for 4 consecutive days. They underwent low-intensity PA sessions daily. PA was tracked by the PA monitoring system (PAMS), a system comprising accelerometers and inclinometers. Variations on glucose dynamics were tracked estimating first- and second-order time derivatives of glucose concentration from CGM via Bayesian smoothing. Short-time effects of PA on glucose dynamics were quantified through the partial correlation function in the interval (0, 60 min) after starting PA. Correlation of PA with glucose time derivatives is evident. In T1DM, the negative correlation with the first-order glucose time derivative is maximal (absolute value) after 15 min of PA, whereas the positive correlation is maximal after 40-45 min. The negative correlation between the second-order time derivative and PA is maximal after 5 min, whereas the positive correlation is maximal after 35-40 min. Control subjects provided similar results but with positive and negative correlation peaks anticipated of 5 min. Quantitative information on correlation between mild PA and short-term glucose dynamics was obtained. This represents a preliminary important step toward incorporation of PA information in more realistic physiological models of the glucose-insulin system usable in T1DM simulators, in development of closed-loop artificial pancreas control algorithms, and in CGM-based prediction algorithms for generation of hypoglycemic alerts.
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Cheyne, E H; Cavan, D A; Kerr, D
2002-01-01
It has been suggested that the continuous glucose monitoring system may be a useful tool for detecting unrecognised hypoglycaemia, especially at times when finger prick testing is difficult or impossible (e.g., at night). Studies suggest that subcutaneous glucose levels closely mimic blood glucose levels with a lag time of only a few minutes. However, no studies have been published to show how well the sensor performs during sustained or in recovery from hypoglycaemia. This study involved using a hyperinsulinaemic glucose clamp (60 mU/m2) in nine healthy volunteers. Each subject had two sensors inserted the day before the study. Blood glucose levels were maintained at euglycaemia for the first 60 min, then decreased to 45 mg/dL (2.5 mmol/L) for 60 min, and finally restored to euglycaemia. Blood glucose measurements were compared with interstitial values recorded by the sensor. Sensor profiles showed acceptable agreement with blood glucose levels at each of the three plateaus with a correlation coefficient of 0.79, slope of 0.85, and mean absolute error of 7%. The sensor drop closely matched the drop in blood glucose, but the recovery from hypoglycaemia was delayed by an average of 26 min. Continuous glucose sensing provides a useful means of detecting unrecognised hypoglycaemia in type 1 diabetes, although the duration of hypoglycaemia may be overestimated.
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Progress toward the development of an implantable sensor for glucose.
Wilson, G S; Zhang, Y; Reach, G; Moatti-Sirat, D; Poitout, V; Thévenot, D R; Lemonnier, F; Klein, J C
1992-09-01
The development of an electrochemically based implantable sensor for glucose is described. The sensor is needle-shaped, about the size of a 28-gauge needle. It is flexible and must be implanted subcutaneously by using a 21-gauge catheter, which is then removed. When combined with a monitoring unit, this device, based on the glucose oxidase-catalyzed oxidation of glucose, reliably monitors glucose concentrations for as long as 10 days in rats. Various design considerations, including the decision to monitor the hydrogen peroxide produced in the enzymatic reaction, are discussed. Glucose constitutes the most important future target analyte for continuous monitoring, but the basic methodology developed for glucose could be applied to several other analytes such as lactate or ascorbate. The success in implementation of such a device depends on a reaction of the tissue surrounding the implant so as not to interfere with the proper functioning of the sensor. Histochemical evidence indicates that the tissue response leads to enhanced sensor performance.
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Metrics for glycaemic control - from HbA1c to continuous glucose monitoring.
Kovatchev, Boris P
2017-07-01
As intensive treatment to lower levels of HbA 1c characteristically results in an increased risk of hypoglycaemia, patients with diabetes mellitus face a life-long optimization problem to reduce average levels of glycaemia and postprandial hyperglycaemia while simultaneously avoiding hypoglycaemia. This optimization can only be achieved in the context of lowering glucose variability. In this Review, I discuss topics that are related to the assessment, quantification and optimal control of glucose fluctuations in diabetes mellitus. I focus on markers of average glycaemia and the utility and/or shortcomings of HbA 1c as a 'gold-standard' metric of glycaemic control; the notion that glucose variability is characterized by two principal dimensions, amplitude and time; measures of glucose variability that are based on either self-monitoring of blood glucose data or continuous glucose monitoring (CGM); and the control of average glycaemia and glucose variability through the use of pharmacological agents or closed-loop control systems commonly referred to as the 'artificial pancreas'. I conclude that HbA 1c and the various available metrics of glucose variability reflect the management of diabetes mellitus on different timescales, ranging from months (for HbA 1c ) to minutes (for CGM). Comprehensive assessment of the dynamics of glycaemic fluctuations is therefore crucial for providing accurate and complete information to the patient, physician, automated decision-support or artificial-pancreas system.
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Marics, Gábor; Koncz, Levente; Eitler, Katalin; Vatai, Barbara; Szénási, Boglárka; Zakariás, David; Mikos, Borbála; Körner, Anna; Tóth-Heyn, Péter
2015-03-19
Continuous glucose monitoring (CGM) originally was developed for diabetic patients and it may be a useful tool for monitoring glucose changes in pediatric intensive care unit (PICU). Its use is, however, limited by the lack of sufficient data on its reliability at insufficient peripheral perfusion. We aimed to correlate the accuracy of CGM with laboratory markers relevant to disturbed tissue perfusion. In 38 pediatric patients (age range, 0-18 years) requiring intensive care we tested the effect of pH, lactate, hematocrit and serum potassium on the difference between CGM and meter glucose measurements. Guardian® (Medtronic®) CGM results were compared to GEM 3000 (Instrumentation laboratory®) and point-of-care measurements. The clinical accuracy of CGM was evaluated by Clarke Error Grid -, Bland-Altman analysis and Pearson's correlation. We used Friedman test for statistical analysis (statistical significance was established as a p < 0.05). CGM values exhibited a considerable variability without any correlation with the examined laboratory parameters. Clarke, Bland-Altman analysis and Pearson's correlation coefficient demonstrated a good clinical accuracy of CGM (zone A and B = 96%; the mean difference between reference and CGM glucose was 1,3 mg/dL, 48 from the 780 calibration pairs overrunning the 2 standard deviation; Pearson's correlation coefficient: 0.83). The accuracy of CGM measurements is independent of laboratory parameters relevant to tissue hypoperfusion. CGM may prove a reliable tool for continuous monitoring of glucose changes in PICUs, not much influenced by tissue perfusion, but still not appropriate for being the base for clinical decisions.
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Cordeiro, C A; de Vries, M G; Ngabi, W; Oomen, P E; Cremers, T I F H; Westerink, B H C
2015-05-15
Enzyme-based amperometric biosensors are widely used for monitoring key biomarkers. In experimental neuroscience there is a growing interest in in vivo continuous and simultaneous monitoring of metabolism-related biomarkers, like glucose, lactate and pyruvate. The use of multiplex biosensors will provide better understanding of brain energy metabolism and its role in neuropathologies such as diabetes, ischemia, and epilepsy. We have developed and characterized an implantable multiplex microbiosensor device (MBD) for simultaneous and continuous in vivo monitoring of glucose, lactate, and pyruvate. First, we developed and characterized amperometric microbiosensors for monitoring lactate and pyruvate. In vitro evaluation allowed us to choose the most suitable biosensors for incorporation into the MBD, along with glucose and background biosensors. Fully assembled MBDs were characterized in vitro. The calculated performance parameters (LOD, LR, LRS, IMAX and appKM) showed that the multiplex MBD was highly selective and sensitive (LRS≥100 nA/mM) for each analyte and within an adequate range for in vivo application. Finally, MBDs were implanted in the mPFC of anesthetized adult male Wistar rats for in vivo evaluation. Following an equilibration period, baseline brain levels of glucose (1.3±0.2 mM), lactate (1.5±0.4 mM) and pyruvate (0.3±0.1 mM) were established. Subsequently, the MBDs recorded the responses of the animals when submitted to hyperglycemic (40% glucose i.v.) and hypoglycemic (5 U/kg insulin i.v.) challenges. Afterwards, MBDs were recalibrated to convert electrochemical readings into accurate substrate concentrations and to assess biofouling. The presented MBD can monitor simultaneously multiple biomarkers in vivo. Copyright © 2014 Elsevier B.V. All rights reserved.
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Towards a continuous glucose monitoring system using tunable quantum cascade lasers
NASA Astrophysics Data System (ADS)
Haase, Katharina; Müller, Niklas; Petrich, Wolfgang
2018-02-01
We present a reagent-free approach for long-term continuous glucose monitoring (cgm) of liquid samples using midinfrared absorption spectroscopy. This method could constitute an alternative to enzymatic glucose sensors in order to manage the widespread disease of Diabetes. In order to acquire spectra of the liquid specimen, we use a spectrally tunable external-cavity (EC-) quantum cascade laser (QCL) as radiation source in combination with a fiber-based in vitro sensor setup. Hereby we achieve a glucose sensitivity in pure glucose solutions of 3 mg/dL (RMSEP). Furthermore, the spectral tunability of the EC-QCL enables us to discriminate glucose from other molecules. We exemplify this by detecting glucose among other saccharides with an accuracy of 8 mg/dL (within other monosaccharides, RMSEVC) and 14 mg/dL (within other mono- and disaccharides, RMSECV). Moreover, we demonstrate a characterization of the significance of each wavenumber for an accurate prediction of glucose among other saccharides using an evolutionary algorithm. We show, that by picking 10 distinct wavenumbers we can achieve comparable accuracies to the use of a complete spectrum.
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Kumar, Rajiv B; Goren, Nira D; Stark, David E; Wall, Dennis P; Longhurst, Christopher A
2016-01-01
The diabetes healthcare provider plays a key role in interpreting blood glucose trends, but few institutions have successfully integrated patient home glucose data in the electronic health record (EHR). Published implementations to date have required custom interfaces, which limit wide-scale replication. We piloted automated integration of continuous glucose monitor data in the EHR using widely available consumer technology for 10 pediatric patients with insulin-dependent diabetes. Establishment of a passive data communication bridge via a patient’s/parent’s smartphone enabled automated integration and analytics of patient device data within the EHR between scheduled clinic visits. It is feasible to utilize available consumer technology to assess and triage home diabetes device data within the EHR, and to engage patients/parents and improve healthcare provider workflow. PMID:27018263
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Cell Based Metabolic Barriers to Glucose Diffusion: Macrophages and Continuous Glucose Monitoring
Klueh, Ulrike; Frailey, Jackman; Qiao, Yi; Antar, Omar; Kreutzer, Donald L.
2014-01-01
It is assumed that MQ are central to glucose sensor bio-fouling and therefore have a major negative impact on continuous glucose monitoring (CGM) performance in vivo. However to our knowledge there is no data in the literature to directly support or refute this assumption. Since glucose and oxygen (O2) are key to glucose sensor function in vivo, understanding and controlling glucose and O2 metabolic activity of MQ is likely key to successful glucose sensor performance. We hypothesized that the accumulation of MQ at the glucose sensor-tissue interface will act as “Cell Based Metabolic Barriers” (CBMB) to glucose diffusing from the interstitial tissue compartment to the implanted glucose sensor and as such creating an artificially low sensor output, thereby compromising sensor function and CGM. Our studies demonstrated that 1) direct injections of MQ at in vivo sensor implantation sites dramatically decreased sensor output (measured in nA), 2) addition of MQ to glucose sensors in vitro resulted in a rapid and dramatic fall in sensor output and 3) lymphocytes did not affect sensor function in vitro or in vivo. These data support our hypothesis that MQ can act as metabolic barriers to glucose and O2 diffusion in vivo and in vitro. PMID:24461328
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Cell based metabolic barriers to glucose diffusion: macrophages and continuous glucose monitoring.
Klueh, Ulrike; Frailey, Jackman T; Qiao, Yi; Antar, Omar; Kreutzer, Donald L
2014-03-01
It is assumed that MQ are central to glucose sensor bio-fouling and therefore have a major negative impact on continuous glucose monitoring (CGM) performance in vivo. However to our knowledge there is no data in the literature to directly support or refute this assumption. Since glucose and oxygen (O2) are key to glucose sensor function in vivo, understanding and controlling glucose and O2 metabolic activity of MQ is likely key to successful glucose sensor performance. We hypothesized that the accumulation of MQ at the glucose sensor-tissue interface will act as "Cell Based Metabolic Barriers" (CBMB) to glucose diffusing from the interstitial tissue compartment to the implanted glucose sensor and as such creating an artificially low sensor output, thereby compromising sensor function and CGM. Our studies demonstrated that 1) direct injections of MQ at in vivo sensor implantation sites dramatically decreased sensor output (measured in nA), 2) addition of MQ to glucose sensors in vitro resulted in a rapid and dramatic fall in sensor output and 3) lymphocytes did not affect sensor function in vitro or in vivo. These data support our hypothesis that MQ can act as metabolic barriers to glucose and O2 diffusion in vivo and in vitro. Copyright © 2014 Elsevier Ltd. All rights reserved.
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Siegelaar, Sarah E; Barwari, Temo; Hermanides, Jeroen; van der Voort, Peter H J; Hoekstra, Joost B L; DeVries, J Hans
2013-11-01
Continuous glucose monitoring could be helpful for glucose regulation in critically ill patients; however, its accuracy is uncertain and might be influenced by microcirculation. We investigated the microcirculation and its relation to the accuracy of 2 continuous glucose monitoring devices in patients after cardiac surgery. The present prospective, observational study included 60 patients admitted for cardiac surgery. Two continuous glucose monitoring devices (Guardian Real-Time and FreeStyle Navigator) were placed before surgery. The relative absolute deviation between continuous glucose monitoring and the arterial reference glucose was calculated to assess the accuracy. Microcirculation was measured using the microvascular flow index, perfused vessel density, and proportion of perfused vessels using sublingual sidestream dark-field imaging, and tissue oxygenation using near-infrared spectroscopy. The associations were assessed using a linear mixed-effects model for repeated measures. The median relative absolute deviation of the Navigator was 11% (interquartile range, 8%-16%) and of the Guardian was 14% (interquartile range, 11%-18%; P = .05). Tissue oxygenation significantly increased during the intensive care unit admission (maximum 91.2% [3.9] after 6 hours) and decreased thereafter, stabilizing after 20 hours. A decrease in perfused vessel density accompanied the increase in tissue oxygenation. Microcirculatory variables were not associated with sensor accuracy. A lower peripheral temperature (Navigator, b = -0.008, P = .003; Guardian, b = -0.006, P = .048), and for the Navigator, also a higher Acute Physiology and Chronic Health Evaluation IV predicted mortality (b = 0.017, P < .001) and age (b = 0.002, P = .037) were associated with decreased sensor accuracy. The results of the present study have shown acceptable accuracy for both sensors in patients after cardiac surgery. The microcirculation was impaired to a limited extent compared with that in patients with sepsis and healthy controls. This impairment was not related to sensor accuracy but the peripheral temperature for both sensors and patient age and Acute Physiology and Chronic Health Evaluation IV predicted mortality for the Navigator were. Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.
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Use of a continuous glucose sensor in an extracorporeal life support circuit.
Steil, Garry M; Alexander, Jamin; Papas, Alexandra; Monica, Langer; Modi, Biren P; Piper, Hannah; Jaksic, Tom; Gottlieb, Rebecca; Agus, Michael S D
2011-01-01
Standard care for infants on extracorporeal life support (ECLS) relies on intermittent measurement of blood glucose (BG); however, this can lead to significant changes in BG that go unrecognized for several hours. The present study was designed to assess performance and clinical applicability of a subcutaneous glucose sensor technology modified for use as a blood-contacting sensor within the ECLS circuit. Twelve children, aged 3 years or less, requiring ECLS support were studied. Three continuous glucose sensors (Medtronic MiniMed) were inserted into hubs placed in line with the ECLS circuit. Blood glucose was assessed with a laboratory analyzer (BG(LAB); Bayer Rapidlab 860) approximately every 5 h (mean 4.9 ± 3.3 h) with more frequent samples obtained with a bedside monitor (HemoCue) as needed. Sensor current (I(SIG)) was transmitted to a laptop computer and retrospectively calibrated using BGLAB. Sensor performance was assessed by mean absolute relative difference (MARD), linear regression slope and intercept, and correlation, all with BGLAB as reference. The BGLAB averaged 107.6 ± 36.4 mg/dl (mean ± standard deviation) ranging from 58 to 366 mg/dl. The MARD was 11.4%, with linear regression slope (0.86 ± 0.030) and intercept (9.0 ± 3.2 mg/dl) different from 1 and 0, respectively (p < .05), and correlation (r² = 0.76; p < .001). The system was not associated with any adverse events, and placement and removal into the hubs was easily accomplished. Instances in which more frequent BG values were obtained using a bedside HemoCue (BGHEMO) monitor showed the sensor to respond rapidly to changes. We conclude that continuous sensors can be adapted for use in an ECLS circuit with accuracy similar to or better than that achieved with the subcutaneous site. Continuous glucose monitoring in this population can rapidly detect changes in BG that would not otherwise be observed. Further studies will be needed to assess the benefit of continuous glucose monitoring in this population. © 2010 Diabetes Technology Society.
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NASA Astrophysics Data System (ADS)
Larin, Kirill V.
Approximately 14 million people in the USA and more than 140 million people worldwide suffer from diabetes mellitus. The current glucose sensing technique involves a finger puncture several times a day to obtain a droplet of blood for analysis. There have been enormous efforts by many scientific groups and companies to quantify glucose concentration noninvasively using different optical techniques. However, these techniques face limitations associated with low sensitivity, accuracy, and insufficient specificity of glucose concentrations over a physiological range. Optical coherence tomography (OCT), a new technology, is being applied for noninvasive imaging in tissues with high resolution. OCT utilizes sensitive detection of photons coherently scattered from tissue. The high resolution of this technique allows for exceptionally accurate measurement of tissue scattering from a specific layer of skin compared with other optical techniques and, therefore, may provide noninvasive and continuous monitoring of blood glucose concentration with high accuracy. In this dissertation work I experimentally and theoretically investigate feasibility of noninvasive, real-time, sensitive, and specific monitoring of blood glucose concentration using an OCT-based biosensor. The studies were performed in scattering media with stable optical properties (aqueous suspensions of polystyrene microspheres and milk), animals (New Zealand white rabbits and Yucatan micropigs), and normal subjects (during oral glucose tolerance tests). The results of these studies demonstrated: (1) capability of the OCT technique to detect changes in scattering coefficient with the accuracy of about 1.5%; (2) a sharp and linear decrease of the OCT signal slope in the dermis with the increase of blood glucose concentration; (3) the change in the OCT signal slope measured during bolus glucose injection experiments (characterized by a sharp increase of blood glucose concentration) is higher than that measured in the glucose clamping experiments (characterized by slow, controlled increase of the blood glucose concentration); and (4) the accuracy of glucose concentration monitoring may substantially be improved if optimal dimensions of the probed skin area are used. The results suggest that high-resolution OCT technique has a potential for noninvasive, accurate, and continuous glucose monitoring with high sensitivity.
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Fang, Lu; Liang, Bo; Yang, Guang; Hu, Yichuan; Zhu, Qin; Ye, Xuesong
2017-11-15
A minimally invasive glucose biosensor capable of continuous monitoring of subcutaneous glucose has been developed in this study. This sensor was prepared using electropolymerized conductive polymer polyaniline (PANI) nanofibers as an enzyme immobilization material and polyurethane (PU)/epoxy-enhanced polyurethane (E-PU) bilayer coating as a protective membrane. The sensor showed almost the same sensitivity (63nA/mM) and linearity (0-20mM with the correlation coefficient r 2 of 0.9997) in both PBS and bovine serum tests. When stored in 37°C bovine serum, the sensor's sensitivity gradually increased about 30% of the initial value within the first 13 days and then remained stable for the rest of the study period of 53 days. In vivo implantation experiments using mice models showed real-time response to the variation of blood glucose with an average signal delay of about 8min. Continuous monitoring showed that the sensor response increased for the first 12 days and then entered a stable period for 14 days. The sensor's baseline (530±10nA) and the total response to 1ml 50% dextrose injection were almost the same (267±15nA) in the stable period. The in vivo stable performances indicated that the sensor could be used as an implantable device for long-term invasive monitoring of blood glucose. Copyright © 2017 Elsevier B.V. All rights reserved.
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[Continuous glucose monitoring with type 1 diabetes mellitus].
López-Siguero, J P; García Arias, M J; del Pino de la Fuente, A; Moreno Molina, J A
2003-03-01
Appropriate metabolic control of children with type 1 diabetes mellitus (DM) is based on frequent measurements of capillary glycemia. However, this method offers only partial information on fluctuations in glycemia during the day, while episodes of postprandial hyperglycemia and hypoglycemia, mainly nocturnal, go unnoticed. To analyze pre- and postprandial blood glucose levels, as well as the presence and duration of hypoglycemic episodes in diabetic children aged more than 8 years old with more than one year of disease duration. Seventeen patients of both sexes (mean age: 12 years old) with type 1 DM were monitored with the continuous glucose monitoring system (CGMS) during working days. Maximum values of pre- and postprandial glucose (1-3 hours after breakfast, lunch and dinner) were registered. Data were downloaded with a Com-station. The mean duration of sensor-wearing was 2.97 days. Pre- and postprandial values were high: mean preprandial values were between 144.9 and 160.5 mg % and mean postprandial values were between 230.4 and 248.8 mg %. The mean number of hypoglycemic episodes detected with the sensor was 4.9 compared with 1.8 detected with the glucometer (p < 0.05). Episodes of mainly nocturnal asymptomatic hypoglycemia were detected with a mean duration of 145 minutes during the night and 75 minutes during the day. The use of continuous subcutaneous glucose monitoring demonstrates that glycemic objectives are not achieved by conventional insulin therapy. It also shows that there are a high number of hypoglycemic episodes, most of which are asymptomatic.
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Mortellaro, Mark; DeHennis, Andrew
2014-11-15
A continuous glucose monitoring (CGM) system consisting of a wireless, subcutaneously implantable glucose sensor and a body-worn transmitter is described and clinical performance over a 28 day implant period in 12 type 1 diabetic patients is reported. The implantable sensor is constructed of a fluorescent, boronic-acid based glucose indicating polymer coated onto a miniaturized, polymer-encased optical detection system. The external transmitter wirelessly communicates with and powers the sensor and contains Bluetooth capability for interfacing with a Smartphone application. The accuracy of 19 implanted sensors were evaluated over 28 days during 6 in-clinic sessions by comparing the CGM glucose values to venous blood glucose measurements taken every 15 min. Mean absolute relative difference (MARD) for all sensors was 11.6 ± 0.7%, and Clarke error grid analysis showed that 99% of paired data points were in the combined A and B zones. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.
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Sensor-Augmented Insulin Pumps and Hypoglycemia Prevention in Type 1 Diabetes.
Steineck, Isabelle; Ranjan, Ajenthen; Nørgaard, Kirsten; Schmidt, Signe
2017-01-01
Hypoglycemia can lead to seizures, unconsciousness, or death. Insulin pump treatment reduces the frequency of severe hypoglycemia compared with multiple daily injections treatment. The addition of a continuous glucose monitor, so-called sensor-augmented pump (SAP) treatment, has the potential to further limit the duration and severity of hypoglycemia as the system can detect and in some systems act on impending and prevailing low blood glucose levels. In this narrative review we summarize the available knowledge on SAPs with and without automated insulin suspension, in relation to hypoglycemia prevention. We present evidence from randomized trials, observational studies, and meta-analyses including nonpregnant individuals with type 1 diabetes mellitus. We also outline concerns regarding SAPs with and without automated insulin suspension. There is evidence that SAP treatment reduces episodes of moderate and severe hypoglycemia compared with multiple daily injections plus self-monitoring of blood glucose. There is some evidence that SAPs both with and without automated suspension reduces the frequency of severe hypoglycemic events compared with insulin pumps without continuous glucose monitoring.
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Galderisi, Alfonso; Schlissel, Elise; Cengiz, Eda
2017-09-23
Decades after the invention of insulin pump, diabetes management has encountered a technology revolution with the introduction of continuous glucose monitoring, sensor-augmented insulin pump therapy and closed-loop/artificial pancreas systems. In this review, we discuss the significance of the 2016 Endocrine Society Guidelines for insulin pump therapy and continuous glucose monitoring and summarize findings from relevant diabetes technology studies that were conducted after the publication of the 2016 Endocrine Society Guidelines. The 2016 Endocrine Society Guidelines have been a great resource for clinicians managing diabetes in this new era of diabetes technology. There is good body of evidence indicating that using diabetes technology systems safely tightens glycemic control while managing both type 1 and type 2 diabetes. The first-generation diabetes technology systems will evolve as we gain more experience and collaboratively work to improve them with an ultimate goal of keeping people with diabetes complication and burden-free until the cure for diabetes becomes a reality.
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Factory-Calibrated Continuous Glucose Sensors: The Science Behind the Technology.
Hoss, Udo; Budiman, Erwin Satrya
2017-05-01
The use of commercially available continuous glucose monitors for diabetes management requires sensor calibrations, which until recently are exclusively performed by the patient. A new development is the implementation of factory calibration for subcutaneous glucose sensors, which eliminates the need for user calibrations and the associated blood glucose tests. Factory calibration means that the calibration process is part of the sensor manufacturing process and performed under controlled laboratory conditions. The ability to move from a user calibration to factory calibration is based on several technical requirements related to sensor stability and the robustness of the sensor manufacturing process. The main advantages of factory calibration over the conventional user calibration are: (a) more convenience for the user, since no more fingersticks are required for calibration and (b) elimination of use errors related to the execution of the calibration process, which can lead to sensor inaccuracies. The FreeStyle Libre ™ and FreeStyle Libre Pro ™ flash continuous glucose monitoring systems are the first commercially available sensor systems using factory-calibrated sensors. For these sensor systems, no user calibrations are required throughout the sensor wear duration.
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Factory-Calibrated Continuous Glucose Sensors: The Science Behind the Technology
Budiman, Erwin Satrya
2017-01-01
Abstract The use of commercially available continuous glucose monitors for diabetes management requires sensor calibrations, which until recently are exclusively performed by the patient. A new development is the implementation of factory calibration for subcutaneous glucose sensors, which eliminates the need for user calibrations and the associated blood glucose tests. Factory calibration means that the calibration process is part of the sensor manufacturing process and performed under controlled laboratory conditions. The ability to move from a user calibration to factory calibration is based on several technical requirements related to sensor stability and the robustness of the sensor manufacturing process. The main advantages of factory calibration over the conventional user calibration are: (a) more convenience for the user, since no more fingersticks are required for calibration and (b) elimination of use errors related to the execution of the calibration process, which can lead to sensor inaccuracies. The FreeStyle Libre™ and FreeStyle Libre Pro™ flash continuous glucose monitoring systems are the first commercially available sensor systems using factory-calibrated sensors. For these sensor systems, no user calibrations are required throughout the sensor wear duration. PMID:28541139
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Glucose-sensitive silicone hydrogel contact lens toward tear glucose monitoring.
Badugu, Ramachandram; Reece, Edward Albert; Lakowicz, Joseph R
2018-05-01
Accurate and reliable monitoring of blood glucose is needed for the treatment of diabetes, which has many challenges, including lack of patient compliance. Measuring tear glucose is an alternative to traditional finger-stick tests used to track blood sugar levels, but glucose sensing using tears has yet to be achieved. We report a methodology for possible tear glucose monitoring using glucose-sensitive silicone hydrogel (SiHG) contact lenses, the primary type of lenses available in today's market. Initially, we assessed the interpenetrating polymer network, with nearly pure silicone and water regions, existing in the SiHGs using a polarity-sensitive probe Prodan. We then synthesized a glucose-sensitive fluorophore Quin-C18 with a hydrophobic side chain for localization of probe at the interfacial region. Using our glucose-sensing contact lens, we were able to measure varying concentrations of glucose in an in-vitro system. The Quin-C18 strongly bound to the lenses with insignificant leaching even after multiple rinses. The lenses displayed a similar response to glucose after three months of storage in water. This study demonstrates that it may be possible to develop a contact lens for continuous glucose monitoring in the near term, using our concept of fluorophore binding at the silicone-water interface. (2018) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).
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Müller, Achim Josef; Knuth, Monika; Nikolaus, Katharina Sibylle; Krivánek, Roland; Küster, Frank; Hasslacher, Christoph
2013-01-01
This article describes a new fiber-coupled, percutaneous fluorescent continuous glucose monitoring (CGM) system that has shown 14 days of functionality in a human clinical trial. The new optical CGM system (FiberSense) consists of a transdermal polymer optical fiber containing a biochemical glucose sensor and a small fluorescence photometer optically coupled to the fiber. The glucose-sensitive optical fiber was implanted in abdominal and upper-arm subcutaneous tissue of six diabetes patients and remained there for up to 14 days. The performance of the system was monitored during six visits to the study center during the trial. Blood glucose changes were induced by oral carbohydrate intake and insulin injections, and capillary blood glucose samples were obtained from the finger tip. The data were analyzed using linear regression and the consensus error grid analysis. The FiberSense worn at the upper arm exhibited excellent results during 14 wearing days, with an overall mean absolute relative difference (MARD) of 8.3% and 94.6% of the data in zone A of the consensus error grid. At the abdominal application site, FiberSense resulted in a MARD of 11.4 %, with 93.8% of the data in zone A. The FiberSense CGM system provided consistent, reliable measurements of subcutaneous glucose levels in human clinical trial patients with diabetes for up to 14 days. © 2013 Diabetes Technology Society.
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Psychology, technology, and diabetes management.
Gonder-Frederick, Linda A; Shepard, Jaclyn A; Grabman, Jesse H; Ritterband, Lee M
2016-10-01
Use of technology in diabetes management is rapidly advancing and has the potential to help individuals with diabetes achieve optimal glycemic control. Over the past 40 years, several devices have been developed and refined, including the blood glucose meter, insulin pump, and continuous glucose monitor. When used in tandem, the insulin pump and continuous glucose monitor have prompted the Artificial Pancreas initiative, aimed at developing control system for fully automating glucose monitoring and insulin delivery. In addition to devices, modern technology, such as the Internet and mobile phone applications, have been used to promote patient education, support, and intervention to address the behavioral and emotional challenges of diabetes management. These state-of-the-art technologies not only have the potential to improve clinical outcomes, but there are possible psychological benefits, such as improved quality of life, as well. However, practical and psychosocial limitations related to advanced technology exist and, in the context of several technology-related theoretical frameworks, can influence patient adoption and continued use. It is essential for future diabetes technology research to address these barriers given that the clinical benefits appear to largely depend on patient engagement and consistence of technology use. (PsycINFO Database Record (c) 2016 APA, all rights reserved).
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McGarraugh, Geoffrey
2010-01-01
Continuous glucose monitoring (CGM) devices available in the United States are approved for use as adjuncts to self-monitoring of blood glucose (SMBG). Alarm evaluation in the Clinical and Laboratory Standards Institute (CLSI) guideline for CGM does not specifically address devices that employ both CGM and SMBG. In this report, an alarm evaluation method is proposed for these devices. The proposed method builds on the CLSI method using data from an in-clinic study of subjects with type 1 diabetes. CGM was used to detect glycemic events, and SMBG was used to determine treatment. To optimize detection of a single glucose level, such as 70 mg/dl, a range of alarm threshold settings was evaluated. The alarm characterization provides a choice of alarm settings that trade off detection and false alarms. Detection of a range of high glucose levels was similarly evaluated. Using low glucose alarms, detection of 70 mg/dl within 30 minutes increased from 64 to 97% as alarm settings increased from 70 to 100 mg/dl, and alarms that did not require treatment (SMBG >85 mg/dl) increased from 18 to 52%. Using high glucose alarms, detection of 180 mg/dl within 30 minutes increased from 87 to 96% as alarm settings decreased from 180 to 165 mg/dl, and alarms that did not require treatment (SMBG <180 mg/dl) increased from 24 to 42%. The proposed alarm evaluation method provides information for choosing appropriate alarm thresholds and reflects the clinical utility of CGM alarms. 2010 Diabetes Technology Society.
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... transmit- ter sends information about glucose levels via radio waves from the sensor to a pagerlike wireless ... 703–738–4929 Email: ndep@mail.nih.gov Internet: www.ndep.nih.gov American Diabetes Association 1701 ...
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Johnson, P J; Wiedmeyer, C E; LaCarrubba, A; Messer, N T; Dingfelder, H A; Cogswell, A M; Amorim, J R R; Ganjam, V K
2011-01-01
The combined glucose-insulin test (CGIT) is helpful for evaluating insulin sensitivity. A continuous glucose monitoring system (CGMS) reports changes in interstitial glucose concentrations as they occur in the blood. Use of the CGMS minimizes animal contact and may be useful when performing a CGIT. Results obtained using a CGMS are useful for the evaluation of glucose responses during the evaluation of insulin sensitivity in equids. Seven mature, obese ponies. Ponies were equipped with CGMS for determination of interstitial glucose concentrations. Glucose (150 mg/kg, i.v.) and insulin (0.1 U/kg, i.v.) were administered and blood glucose concentrations determined at (minutes after time zero) 1, 5, 15, 25, 35, 45, 60, 75, 90, 105, and 120 with a hand-held glucometer. Blood chemistry results were compared with simultaneously obtained results using CGMS. Concordance coefficients determined for comparison of blood glucose concentrations determined by a hand-held glucometer and those determined by CGMS after the zero time point were 0.623, 0.764, 0.834, 0.854, and 0.818 (for delays of 0, 5, 10, 15, and 20 minutes, respectively). Interstitial glucose concentrations obtained by the CGMS compared favorably to blood glucose concentrations. CGMS may be useful for assessment of glucose dynamics in the CGIT. Copyright © 2010 by the American College of Veterinary Internal Medicine.
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Accuracy of a continuous glucose monitoring system in dogs and cats with diabetic ketoacidosis.
Reineke, Erica L; Fletcher, Daniel J; King, Lesley G; Drobatz, Kenneth J
2010-06-01
(1) To determine the ability of a continuous interstitial glucose monitoring system (CGMS) to accurately estimate blood glucose (BG) in dogs and cats with diabetic ketoacidosis. (2) To determine the effect of perfusion, hydration, body condition score, severity of ketosis, and frequency of calibration on the accuracy of the CGMS. Prospective study. University Teaching Hospital. Thirteen dogs and 11 cats diagnosed with diabetic ketoacidosis were enrolled in the study within 24 hours of presentation. Once BG dropped below 22.2 mmol/L (400 mg/dL), a sterile flexible glucose sensor was placed aseptically in the interstitial space and attached to the continuous glucose monitoring device for estimation of the interstitial glucose every 5 minutes. BG measurements were taken with a portable BG meter every 2-4 hours at the discretion of the primary clinician and compared with CGMS glucose measurements. The CGMS estimates of BG and BG measured on the glucometer were strongly associated regardless of calibration frequency (calibration every 8 h: r=0.86, P<0.001; calibration every 12 h: r=0.85, P<0.001). Evaluation of this data using both the Clarke and Consensus error grids showed that 96.7% and 99% of the CGMS readings, respectively, were deemed clinically acceptable (Zones A and B errors). Interpatient variability in the accuracy of the CGMS glucose measurements was found but was not associated with body condition, perfusion, or degree of ketosis. A weak association between hydration status of the patient as assessed with the visual analog scale and absolute percent error (Spearman's rank correlation, rho=-0.079, 95% CI=-0.15 to -0.01, P=0.03) was found, with the device being more accurate in the more hydrated patients. The CGMS provides clinically accurate estimates of BG in patients with diabetic ketoacidosis.
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Czupryniak, Leszek; Loba, Jerzy; Pawlowski, Maciej; Nowak, Dariusz; Bialasiewicz, Piotr
2005-05-01
Obstructive sleep apnea syndrome (OSAS) is often associated with impaired glucose metabolism. Data on the effects of OSAS treatment with continuous positive airway pressure (CPAP) on blood glucose and insulin resistance are conflicting. The study aimed at assessing the immediate effect of CPAP on glucose control measured with a continuous glucose monitoring system (CGMS). Nine non-diabetes subjects with OSAS (mean age 53.0 +/- 8.0 years; body mass index 34.8 +/- 5.3 kg/m2) underwent 2 overnight polysomnographic examinations: a diagnostic study and one with CPAP treatment. Continuous glucose monitoring system (CGMS) was applied overnight on both occasions. Glucose metabolism was assessed with a 75-g oral glucose tolerance test, plasma insulin and homeostatic model assessment of insulin resistance (HOMA-IR) index. The mean (+/- SD) apnoea-hypopnea index (AHI) at diagnostic polysomnography was 54.3 +/- 29.3 (range 16-81). Fasting plasma insulin levels in patients with OSAS was 84.3 +/- 43.4 pM at baseline, and the HOMA-IR was 3.6 +/- 2.2. CPAP treatment in the subjects with OSAS resulted in a significant reduction in the AHI to 4.5 +/- 7.1. All of the major saturation parameters improved significantly on CPAP. CGMS showed mean glucose values significantly higher during the CPAP night than during the diagnostic night: 80 +/- 11 mg/dL versus 63 +/- 7 mg/dL (P < .01). Fasting insulin and HOMA-IR measured after the CPAP night tended to be higher than at baseline (98.4 +/- 51.0 pmol vs 84.3 +/- 43.4 pmol and 3.9 pmol +/- 2.6 vs 3.6 +/- 2.2 pmol, respectively, P > .05). CPAP treatment in nondiabetic obese patients with OSAS may have an immediate elevating effect on blood glucose.
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A minimally invasive chip based near infrared sensor for continuous glucose monitoring
NASA Astrophysics Data System (ADS)
Ben Mohammadi, L.; Sigloch, S.; Frese, I.; Stein, V.; Welzel, K.; Schmitz, F.; Klotzbücher, T.
2012-06-01
Assessment of glycaemia in diabetes is crucially important for prevention of both, acute and long term complications. Continuous glucose monitoring (CGM) is certainly the most appropriate way for optimizing the glycaemic control, since it prevents or delays the progression of complications associated with hypo- or hyperglycaemic events, reducing morbidity, mortality, and overall costs in health care systems. In this paper we describe the concept and first in vitro results of a minimally invasive, chip-based NIR-Sensor for continuous glucose monitoring. The sensor concept is based on difference infrared absorption spectroscopy, which was evaluated within laboratory measurements of D+-Glucose dissolved in water. The laboratory measurements revealed a linear relationship between glucose concentration and the integrated difference spectroscopy signal with a coefficient of determination of 99.6% in the concentration range of 0- 500 mg/dL. Suitable wavelength bands were identified in which the correlation is preserved and commercial light sources are available for realisation of a spectrometer-less, integrated NIR-sensor. In the designed sensor the component area (non-disposable) is separated from the detection area (disposable, low-cost). The disposable part of the sensor is fluidically connected to a micro-dialyses needle, accessing glucose subcutaneously via the ISF (interstitial fluid) or intravascularly. The non-disposable part contains all the optical elements, like LED's and photo-detectors. The in- and out-coupling of the optical signal is achieved across the plane of the chip by using total internal reflection on mirrors integrated into the fluidic chip. The glucose is continuously measured by considering the difference signals of light at the corresponding wavelengths, as a function of time or in defined intervals if the light sources are modulated. The in-vitro measurements show an absolute error of about 5 mg/dL with a relative error of 5% for glucose concentrations larger than 50 mg/dL and about 12 % in the hypoglycemic range (<50 mg /dL).
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Noninvasive Diagnostic Devices for Diabetes through Measuring Tear Glucose
Zhang, Jin; Hodge, William; Hutnick, Cindy; Wang, Xianbin
2011-01-01
This article reviews the development of a noninvasive diagnostic for diabetes by detecting ocular glucose. Early diagnosis and daily management are very important to diabetes patients to ensure a healthy life. Commercial blood glucose sensors have been used since the 1970s. Millions of diabetes patients have to prick their finger for a drop of blood 4–5 times a day to check blood glucose levels—almost 1800 times annually. There is a strong need to have a noninvasive device to help patients to manage the disease easily and painlessly. Instead of detecting the glucose in blood, monitoring the glucose level in other body fluids may provide a feasible approach for noninvasive diagnosis and diabetes control. Tear glucose has been studied for several decades. This article reviews studies on ocular glucose and its monitoring methods. Attempts to continuously monitor the concentration of tear glucose by using contact lens-based sensors are discussed as well as our current development of a nanostructured lens-based sensor for diabetes. This disposable biosensor for the detection of tear glucose may provide an alternative method to help patients manage the disease conveniently. PMID:21303640
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Wagner, Julie A; Tennen, Howard; Feinn, Richard; Osborn, Chandra Y
2015-04-01
We investigated whether self-reported racial discrimination was associated with continuous glucose levels and variability in individuals with diabetes, and whether diabetes distress mediated these associations. Seventy-four Black and White women with type 2 diabetes completed the Experience of Discrimination scale, a measure of lifetime racial discrimination, and the Problem Areas in Diabetes, a measure of diabetes distress. Participants wore a continuous glucose monitor for 24 h after 8 h of fasting, a standard meal, and a 4-h run in period. Higher discrimination predicted higher continuous mean glucose and higher standard deviation of glucose. For both mean and standard deviation of glucose, a race × discrimination interaction indicated a stronger relationship between discrimination and glucose for Whites than for Blacks. Diabetes distress mediated the discrimination-mean glucose relationship. Whites who report discrimination may be uniquely sensitive to distress. These preliminary findings suggest that racial discrimination adversely affects glucose control in women with diabetes, and does so indirectly through diabetes distress. Diabetes distress may be an important therapeutic target to reduce the ill effects of racial discrimination in persons with diabetes.
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Can continuous glucose monitoring be used for the treatment of diabetes.
Reach, G; Wilson, G S
1992-03-15
In the case of the glucose sensor, clinicians and chemists must cooperate in interdisciplinary research to carefully define the analytical problem. Although not specifically discussed in this article, another group that must participate in this effort is engineers. Their expertise is needed to design the monitoring and control unit that contains the alarm and pump systems. The glucose sensor must operate reliably in an in vivo environment, provide the clinical information needed, and be easy to operate and manufacture.
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Lucisano, Joseph Y; Routh, Timothy L; Lin, Joe T; Gough, David A
2017-09-01
The use of a fully implanted first-generation prototype sensor/telemetry system is described for long-term monitoring of subcutaneous tissue glucose in a small cohort of people with diabetes. Sensors are based on a membrane containing immobilized glucose oxidase and catalase coupled to oxygen electrodes and a telemetry system, integrated as an implant. The devices remained implanted for up to 180 days, with signals transmitted every 2 min to external receivers. The data include signal recordings from glucose clamps and spontaneous glucose excursions, matched, respectively, to reference blood glucose and finger-stick values. The sensor signals indicate dynamic tissue glucose, for which there is no independent standard, and a model describing the relationship between blood glucose and the signal is, therefore, included. The values of all model parameters have been estimated, including the permeability of adjacent tissues to glucose, and equated to conventional mass transfer parameters. As a group, the sensor calibration varied randomly at an average rate of -2.6%/week. Statistical correlation indicated strong association between the sensor signals and reference glucose values. Continuous long-term glucose monitoring in individuals with diabetes is feasible with this system. All therapies for diabetes are based on glucose control, and therefore, require glucose monitoring. This fully implanted long-term sensor/telemetry system may facilitate a new era of management of the disease.
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Lucisano, Joseph Y.; Routh, Timothy L.; Lin, Joe T.; Gough, David A.
2017-01-01
Objective The use of a fully implanted, first-generation prototype sensor/telemetry system is described for long-term monitoring of subcutaneous tissue glucose in a small cohort of people with diabetes. Methods Sensors are based on a membrane containing immobilized glucose oxidase and catalase coupled to oxygen electrodes and a telemetry system, integrated as an implant. The devices remained implanted for up to 180 days, with signals transmitted every 2 minutes to external receivers. Results The data include signal recordings from glucose clamps and spontaneous glucose excursions, matched respectively to reference blood glucose and finger-stick values. The sensor signals indicate dynamic tissue glucose, for which there is no independent standard, and a model describing the relationship between blood glucose and the signal is therefore included. The values of all model parameters have been estimated, including the permeability of adjacent tissues to glucose, and equated to conventional mass transfer parameters. As a group, the sensor calibration varied randomly at an average rate of −2.6%/week. Statistical correlation indicated strong association between the sensor signals and reference glucose values. Conclusions Continuous, long-term glucose monitoring in individuals with diabetes is feasible with this system. Significance All therapies for diabetes are based on glucose control and therefore require glucose monitoring. This fully implanted, long-term sensor/telemetry system may facilitate a new era of management of the disease. PMID:27775510
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Wentholt, I M E; Maran, A; Masurel, N; Heine, R J; Hoekstra, J B L; DeVries, J H
2007-05-01
We quantified the occurrence and duration of nocturnal hypoglycaemia in individuals with Type 1 diabetes treated with continuous subcutaneous insulin infusion (CSII) or multiple-injection therapy (MIT) using a continuous subcutaneous glucose sensor. A microdialysis sensor was worn at home by 24 patients on CSII (mean HbA(1c) 7.8 +/- 0.9%) and 33 patients on MIT (HbA(1c) 8.7 +/- 1.3%) for 48 h. Occurrence and duration of nocturnal hypoglycaemia were assessed and using multivariate regression analysis, the association between HbA(1c), diabetes duration, treatment type (CSII vs. MIT), fasting and bedtime blood glucose values, total daily insulin dose and mean nocturnal glucose concentrations, and hypoglycaemia occurrence and duration was investigated. Nocturnal hypoglycaemia < or = 3.9 mmol/l occurred in 33.3% of both the CSII- (8/24) and MIT-treated patients (11/33). Mean (+/- sd; median, interquartile range) duration of hypoglycaemia < or = 3.9 mmol/l was 78 (+/- 76; 57, 23-120) min per night for the CSII- and 98 (+/- 80; 81, 32-158) min per night for the MIT-treated group. Multivariate regression analysis showed that bedtime glucose value had the strongest association with the occurrence (P = 0.026) and duration (P = 0.032) of nocturnal hypoglycaemia. Microdialysis continuous glucose monitoring has enabled more precise quantification of nocturnal hypoglycaemia occurrence and duration in Type 1 diabetic patients. Occurrence and duration of nocturnal hypoglycaemia were mainly associated with bedtime glucose value.
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El Awwa, A; Soliman, A; Al-Ali, M; Yassin, M; De Sanctis, V
2012-09-01
In obese adolescents pancreatic beta-cells may not be able to cope with insulin resistance leading to hyperglycemia and type2 diabetes (T2DM To assess oral glucose tolerance, 72-h continuous blood glucose concentrations (CGM) and calculate homeostatic model assessment (HOMA), and the quantitative insulin sensitivity check index (QUICKI) in 13 adolescents with simple obesity (BMI SDS=4 ± 1.06). OGTT performed in 13 obese adolescents (13.47 ± 3 years) revealed 3 cases (23%) with impaired fasting glucose (IFG: fasting glucose >5.6 mmol/L), 4 cases (30%) with impaired glucose tolerance (IGT: 2h blood glucose >7.8 <11.1 mmol/L), and none with diabetes. Using the continuous glucose monitoring system ( CGMS), IFG was detected in 4 cases, the maximum serum blood glucose (BG : 2h or more after meal) was >7.8 and <11.1 mmol/L (IGT) in 9 children (69%) and >11.1 mmol/L (diabetes) in one case (7.6%). Five cases had a minimum BG recorded of <2.7 mmol/L (hypoglycemia). No glycemic abnormality was detected using HbA1C (5.7 ± 0.3%). 11/13 patients had HOMA values >2.6 and QUICKI values <0.35 denoting insulin resistance. Beta cell mass percent (B %) = 200 ± 94.8% and insulin sensitivity values (IS)=50.4 ± 45.5% denoted insulin resistance with hyper-insulinaemia and preserved beta cell mass. In obese adolescents, CGMS is superior to OGTT and HbA1C in detecting glycemic abnormalities, which appears to be secondary to insulin resistance.
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Toward minimally invasive, continuous glucose monitoring in vivo
NASA Astrophysics Data System (ADS)
Vrancic, Christian; Gretz, Norbert; Kröger, Niels; Neudecker, Sabine; Pucci, Annemarie; Petrich, Wolfgang
2012-01-01
Diabetes mellitus is a disorder of glucose metabolism and it is one of the most challenging diseases, both from a medical and economic perspective. People with diabetes can benefit from a frequent or even continuous monitoring of their blood glucose concentrations. The approach presented here takes advantage of the observational nature of biomedical vibrational spectroscopy in contrast to chemical reactions which consume glucose. The particular technique employed here is based on the high sensitivity of mid-infrared transmission spectroscopy where strong vibrational bands of glucose can be monitored at wavelengths around 10 μm. The strong absorption of water in this spectral region was mitigated by the use of quantum cascade lasers and very short interaction path lengths below 50 μm. Various sensor concepts have been explored. In one of the concepts, the interaction of mid-infrared radiation with glucose is established within a miniature measurement cavity, formed by a gap between two silver halide fibers. In recent experiments, an additional quantum cascade laser was used for reference purposes. The long-term drift could significantly be reduced for time intervals > 1000 s, e. g., by more than 60% for a 3 hour interval. This extension for the compensation of long-term drifts of the measurement system in vitro is an important contribution towards the applicability in vivo.
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Byers, S R; Beemer, O M; Lear, A S; Callan, R J
2014-01-01
Persistent hyperglycemia is common in alpacas and typically requires insulin administration for resolution; however, little is known about alpacas' response to different insulin formulations. To evaluate the effects of 3 insulin formulations on blood glucose concentrations and the use of a continuous glucose monitoring (CGM) system in alpacas. Six healthy alpacas. The CGM was installed in the left paralumbar fossa at the start of this crossover study and recorded data every 5 minutes. Regular insulin, NPH insulin, insulin glargine, and dextrose were administered to each alpaca over a 2-week period. Blood samples were collected for glucose testing at 0, 1, 2, 4, 6, 8, and 12 hours, and then every 6 hours after each administration of insulin or dextrose. Data were compared by using method comparison techniques, error grid plots, and ANOVA. Blood glucose concentrations decreased most rapidly after regular insulin administration when administered IV or SC as compared to the other formulations. The NPH insulin produced the longest suppression of blood glucose. The mean CGM interstitial compartment glucose concentrations were typically lower than the intravascular compartment glucose concentrations. The alpacas had no adverse reactions to the different insulin formulations. The NPH insulin might be more appropriate for long-term use in hyperglycemic alpacas because of its extended duration of action. A CGM is useful in monitoring glucose trends and reducing blood collection events, but it should not be the sole method for determining treatment protocols. Copyright © 2014 by the American College of Veterinary Internal Medicine.
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International Consensus on Use of Continuous Glucose Monitoring.
Danne, Thomas; Nimri, Revital; Battelino, Tadej; Bergenstal, Richard M; Close, Kelly L; DeVries, J Hans; Garg, Satish; Heinemann, Lutz; Hirsch, Irl; Amiel, Stephanie A; Beck, Roy; Bosi, Emanuele; Buckingham, Bruce; Cobelli, Claudio; Dassau, Eyal; Doyle, Francis J; Heller, Simon; Hovorka, Roman; Jia, Weiping; Jones, Tim; Kordonouri, Olga; Kovatchev, Boris; Kowalski, Aaron; Laffel, Lori; Maahs, David; Murphy, Helen R; Nørgaard, Kirsten; Parkin, Christopher G; Renard, Eric; Saboo, Banshi; Scharf, Mauro; Tamborlane, William V; Weinzimer, Stuart A; Phillip, Moshe
2017-12-01
Measurement of glycated hemoglobin (HbA 1c ) has been the traditional method for assessing glycemic control. However, it does not reflect intra- and interday glycemic excursions that may lead to acute events (such as hypoglycemia) or postprandial hyperglycemia, which have been linked to both microvascular and macrovascular complications. Continuous glucose monitoring (CGM), either from real-time use (rtCGM) or intermittently viewed (iCGM), addresses many of the limitations inherent in HbA 1c testing and self-monitoring of blood glucose. Although both provide the means to move beyond the HbA 1c measurement as the sole marker of glycemic control, standardized metrics for analyzing CGM data are lacking. Moreover, clear criteria for matching people with diabetes to the most appropriate glucose monitoring methodologies, as well as standardized advice about how best to use the new information they provide, have yet to be established. In February 2017, the Advanced Technologies & Treatments for Diabetes (ATTD) Congress convened an international panel of physicians, researchers, and individuals with diabetes who are expert in CGM technologies to address these issues. This article summarizes the ATTD consensus recommendations and represents the current understanding of how CGM results can affect outcomes. © 2017 by the American Diabetes Association.
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Kamann, Stefanie; Aerts, Olivier; Heinemann, Lutz
2018-05-01
In the past decade, new diabetes technologies, including continuous glucose monitoring (CGM) systems, support patients with diabetes in their daily struggle with achieving a good glucose control. However, shortly after the first CGM systems appeared on the market, also the first concerns about adverse skin reactions were raised. Most patients claimed to suffer from (sometimes severe) skin irritation, or even allergy, which they related to the (acrylate-based) adhesive part of the device. For a long time the actual substance that caused these skin reactions with, for example, the Flash Glucose Monitoring system (iscCGM; Freestyle® Libre) could not be identified; however, recently Belgian and Swedish dermatologists reported that the majority of their patients that have developed a contact-allergic while using iscCGM react sensitively to a specific acrylate, that is, isobornyl acrylate (IBOA). Subsequently they showed by means of gas chromatography-mass spectrometry that this substance is present in the case of the glucose sensor attached by an adhesive to the skin. We report three additional cases from Germany, including a 10-year-old boy, suffering from severe allergic contact dermatitis to IBOA.
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NASA Astrophysics Data System (ADS)
Birkholz, M.; Ehwald, K.-E.; Basmer, T.; Kulse, P.; Reich, C.; Drews, J.; Genschow, D.; Haak, U.; Marschmeyer, S.; Matthus, E.; Schulz, K.; Wolansky, D.; Winkler, W.; Guschauski, T.; Ehwald, R.
2013-06-01
The progressive scaling in semiconductor technology allows for advanced miniaturization of intelligent systems like implantable biosensors for low-molecular weight analytes. A most relevant application would be the monitoring of glucose in diabetic patients, since no commercial solution is available yet for the continuous and drift-free monitoring of blood sugar levels. We report on a biosensor chip that operates via the binding competition of glucose and dextran to concanavalin A. The sensor is prepared as a fully embedded micro-electromechanical system and operates at GHz frequencies. Glucose concentrations derive from the assay viscosity as determined by the deflection of a 50 nm TiN actuator beam excited by quasi-electrostatic attraction. The GHz detection scheme does not rely on the resonant oscillation of the actuator and safely operates in fluidic environments. This property favorably combines with additional characteristics—(i) measurement times of less than a second, (ii) usage of biocompatible TiN for bio-milieu exposed parts, and (iii) small volume of less than 1 mm3—to qualify the sensor chip as key component in a continuous glucose monitor for the interstitial tissue.
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Zhou, Jian; Lv, Xiaofeng; Mu, Yiming; Wang, Xianling; Li, Jing; Zhang, Xingguang; Wu, Jinxiao; Bao, Yuqian; Jia, Weiping
2012-08-01
The purpose of this multicenter study was to investigate the accuracy of a real-time continuous glucose monitoring sensor in Chinese diabetes patients. In total, 48 patients with type 1 or 2 diabetes from three centers in China were included in the study. The MiniMed Paradigm(®) 722 insulin pump (Medtronic, Northridge, CA) was used to monitor the real-time continuous changes of blood glucose levels for three successive days. Venous blood of the subjects was randomly collected every 15 min for seven consecutive hours on the day when the subjects were wearing the sensor. Reference values were provided by the YSI(®) 2300 STAT PLUS™ glucose and lactate analyzer (YSI Life Sciences, Yellow Springs, OH). In total, 1,317 paired YSI-sensor values were collected from the 48 patients. Of the sensor readings, 88.3% (95% confidence interval, 0.84-0.92) were within±20% of the YSI values, and 95.7% were within±30% of the YSI values. Clarke and consensus error grid analyses showed that the ratios of the YSI-sensor values in Zone A to the values in Zone B were 99.1% and 99.9%, respectively. Continuous error grid analysis showed that the ratios of the YSI-sensor values in the region of accurate reading, benign errors, and erroneous reading were 96.4%, 1.8%, and 1.8%, respectively. The mean absolute relative difference (ARD) for all subjects was 10.4%, and the median ARD was 7.8%. Bland-Altman analysis detected a mean blood glucose level of 3.84 mg/dL. Trend analysis revealed that 86.1% of the difference of the rates of change between the YSI values and the sensor readings occurred within the range of 1 mg/dL/min. The Paradigm insulin pump has high accuracy in both monitoring the real-time continuous changes and predicting the trend of changes in blood glucose level. However, actual clinical manifestations should be taken into account for diagnosis of hypoglycemia.
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Zhu, Weidong; Jiang, Libing; Jiang, Shouyin; Ma, Yuefeng; Zhang, Mao
2015-01-23
Stress-induced hyperglycaemia, which has been shown to be associated with an unfavourable prognosis, is common among critically ill patients. Additionally, it has been reported that hypoglycaemia and high glucose variabilities are also associated with adverse outcomes. Thus, continuous glucose monitoring (CGM) may be the optimal method to detect severe hypoglycaemia, hyperglycaemia and decrease glucose excursion. However, the overall accuracy and reliability of CGM systems and the effects of CGM systems on glucose control and prognosis in critically ill patients remain inconclusive. Therefore, we will conduct a systematic review and meta-analysis to clarify the associations between CGM systems and clinical outcome. We will search PubMed, EMBASE and the Cochrane Library from inception to October 2014. Studies comparing CGM systems with any other glucose monitoring methods in critically ill patients will be eligible for our meta-analysis. The primary endpoints include the incidence of hypoglycaemia and hyperglycaemia, mean glucose level, and percentage of time within the target range. The second endpoints include intensive care unit (ICU) mortality, hospital mortality, duration of mechanical ventilation, length of ICU and hospital stay, and the Pearson correlation coefficient and the results of error grid analysis. In addition, we will record all complications (eg, acquired infections) in control and intervention groups and local adverse events in intervention groups (eg, bleeding or infections). Ethics approval is not required as this is a protocol for a systematic review. The findings will be disseminated in a peer-reviewed journal and presented at a relevant conference. PROSPERO registration number: CRD42014013488. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
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A label-free fiber-optic Turbidity Affinity Sensor (TAS) for continuous glucose monitoring.
Dutt-Ballerstadt, Ralph; Evans, Colton; Pillai, Arun P; Gowda, Ashok
2014-11-15
In this paper, we describe the concept of a novel implantable fiber-optic Turbidity Affinity Sensor (TAS) and report on the findings of its in-vitro performance for continuous glucose monitoring. The sensing mechanism of the TAS is based on glucose-specific changes in light scattering (turbidity) of a hydrogel suspension consisting of small particles made of crosslinked dextran (Sephadex G100), and a glucose- and mannose-specific binding protein - Concanavalin A (ConA). The binding of ConA to Sephadex particles results in a significant turbidity increase that is much greater than the turbidity contribution by the individual components. The turbidity of the TAS was measured by determining the intensity of light passing through the suspension enclosed within a small semi-permeable hollow fiber (OD: 220 μm, membrane thickness: 20 μm, molecular weight cut-off: 10 kDa) using fiber optics. The intensity of measured light of the TAS was proportional to the glucose concentration over the concentration range from 50mg/dL to 400mg/dL in PBS and whole blood at 37°C (R>0.96). The response time was approximately 4 min. The stability of the glucose response of the TAS decreased only slightly (by 20%) over an 8-day study period at 37°C. In conclusion, this study demonstrated proof-of-concept of the TAS for interstitial glucose monitoring. Due to the large signal amplitude of the turbidity change, and the lack of need for wavelength-specific emission and excitation filters, a very small, robust and compact TAS device with an extremely short optical pathlength could be feasibly designed and implemented for in-vivo glucose monitoring in people with diabetes. Copyright © 2014 Elsevier B.V. All rights reserved.
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Kerr, David; Olateju, Tolu
2010-06-01
Pascal's Wager is a suggestion posed by the French Philosopher, Blaise Pascal, that even though the existence of God cannot be determined through reason, a person should wager that God exists because he or she has everything to gain and nothing to lose. In the area of consideration here, the optimum experimental trial of the combined use of continuous subcutaneous insulin infusion and real-time continuous glucose monitoring in free-living individuals with type 1 diabetes providing rock-solid evidence of clinical benefit has not been performed. Nevertheless, there is considerable enthusiasm for combining the technologies among healthcare professionals, patients, and manufacturers based on the belief that this approach to diabetes care must be beneficial beyond the available evidence (i.e., reason).
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Kumar, Rajiv B; Goren, Nira D; Stark, David E; Wall, Dennis P; Longhurst, Christopher A
2016-05-01
The diabetes healthcare provider plays a key role in interpreting blood glucose trends, but few institutions have successfully integrated patient home glucose data in the electronic health record (EHR). Published implementations to date have required custom interfaces, which limit wide-scale replication. We piloted automated integration of continuous glucose monitor data in the EHR using widely available consumer technology for 10 pediatric patients with insulin-dependent diabetes. Establishment of a passive data communication bridge via a patient's/parent's smartphone enabled automated integration and analytics of patient device data within the EHR between scheduled clinic visits. It is feasible to utilize available consumer technology to assess and triage home diabetes device data within the EHR, and to engage patients/parents and improve healthcare provider workflow. © The Author 2016. Published by Oxford University Press on behalf of the American Medical Informatics Association.
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An Implantable RFID Sensor Tag toward Continuous Glucose Monitoring.
Xiao, Zhibin; Tan, Xi; Chen, Xianliang; Chen, Sizheng; Zhang, Zijian; Zhang, Hualei; Wang, Junyu; Huang, Yue; Zhang, Peng; Zheng, Lirong; Min, Hao
2015-05-01
This paper presents a wirelessly powered implantable electrochemical sensor tag for continuous blood glucose monitoring. The system is remotely powered by a 13.56-MHz inductive link and utilizes an ISO 15693 radio frequency identification (RFID) standard for communication. This paper provides reliable and accurate measurement for changing glucose level. The sensor tag employs a long-term glucose sensor, a winding ferrite antenna, an RFID front-end, a potentiostat, a 10-bit sigma-delta analog to digital converter, an on-chip temperature sensor, and a digital baseband for protocol processing and control. A high-frequency external reader is used to power, command, and configure the sensor tag. The only off-chip support circuitry required is a tuned antenna and a glucose microsensor. The integrated chip fabricated in SMIC 0.13-μm CMOS process occupies an area of 1.2 mm ×2 mm and consumes 50 μW. The power sensitivity of the whole system is -4 dBm. The sensor tag achieves a measured glucose range of 0-30 mM with a sensitivity of 0.75 nA/mM.
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López Gutiérrez, Sònia; Pavía Sesma, Carlos
2010-10-01
At present times, Continuous Glucose Monitoring is a recommended method to detect glucemia fluctuations in patients who have diabetes, due to the fine correlation between interstitial glucose and capillary glucemia. The objective of this project is obtain a glucose register during a 48 hour period in a group of Type I diabetes patients who have an irregular metabolic control and to evaluate effectiveness of treatment employed, as well as evaluating compliance of the therapeutic norms established for each patient. At the same time, the authors plan to test the usefulness of a graphical register for diabetic education. After applying an anesthetic cream in the lateral umbilical zone, a subcutaneous catheter connected to a GLUCODAY, Menarini Diagnostics glucose sensor is inserted which, by means of a continuous sequence taking measures in interstitial liquid, registers a value every three minutes for as long as this connection is maintained. After a maximum 48 hour period, data are transferred to a computer and by means of the corresponding computer program, a graphic register for each patient is produced. Informed consent has been obtained from each patient. There were 23 patients in this study group, each diagnosed to have Type I diabetes; eight of these patients, two girls and six boys, were pre-puberty aged while 15, six girls and nine boys, were adolescents. Two of the pre-puberty patients had pathological antecedents, in one case celiac and the other thyroid disease. Two of the puberty aged patients had a history of chronic lymphocytic thyroid disease under opo-therapeutic treatment. Individual analysis of each case permits health professionals to detect a series of facts: it is difficult to comply with glucemic objectives in this group of adolescents having diabetes, with insulin treatment installed and researchers detect postprandial hyper-glucemia which do not appear when using capillary glucemias carried out by habitual methods. Study observations manifest a lack of compliance in indicated agreed upon schedules and researchers detect dietary transgressions. Continuous Glucose Monitoring makes it possible to obtain a graphic which can include those incidences which have occurred, facilitate commenting on the errors detected with adolescent patients and permit proposing a series of therapeutic modifications based on concrete, real data. Continuous Glucose Monitoring promises to be a useful tool to educate patients about diabetes.
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Sensor-Augmented Insulin Pumps and Hypoglycemia Prevention in Type 1 Diabetes
Steineck, Isabelle; Ranjan, Ajenthen; Nørgaard, Kirsten; Schmidt, Signe
2016-01-01
Hypoglycemia can lead to seizures, unconsciousness, or death. Insulin pump treatment reduces the frequency of severe hypoglycemia compared with multiple daily injections treatment. The addition of a continuous glucose monitor, so-called sensor-augmented pump (SAP) treatment, has the potential to further limit the duration and severity of hypoglycemia as the system can detect and in some systems act on impending and prevailing low blood glucose levels. In this narrative review we summarize the available knowledge on SAPs with and without automated insulin suspension, in relation to hypoglycemia prevention. We present evidence from randomized trials, observational studies, and meta-analyses including nonpregnant individuals with type 1 diabetes mellitus. We also outline concerns regarding SAPs with and without automated insulin suspension. There is evidence that SAP treatment reduces episodes of moderate and severe hypoglycemia compared with multiple daily injections plus self-monitoring of blood glucose. There is some evidence that SAPs both with and without automated suspension reduces the frequency of severe hypoglycemic events compared with insulin pumps without continuous glucose monitoring. PMID:28264173
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Moreno-Fernandez, Jesus; Pazos-Couselo, Marcos; González-Rodriguez, Maria; Rozas, Pedro; Delgado, Manuel; Aguirre, Miguel; Garcia-Lopez, Jose Manuel
2018-06-12
To analyze the clinical impact of the Flash glucose monitoring system in patients with type 1 diabetes mellitus (T1DM) treated with continuous subcutaneous insulin infusion (CSII). A 24-week retrospective cohort study in CSII-treated T1DM patients exposed (1:1) to the Flash glucose monitoring system vs. self-monitoring of capillary blood glucose (SMBG). The primary outcome was the difference in hemoglobin A1c (HbA1c) levels between both groups at the end of the study. Thirty-six patients with a mean age of 38.2 years (range 22-55) and a mean T1DM duration of 20.9±7.8 years, treated with CSII for 7.1±5.4 years, were enrolled into the study. At the end of the study, mean HbA1c levels improved in patients in the Flash group (7.1±0.7 vs. 7.8±1.0, p=0.04). Only the Flash group showed a significant decrease in HbA1c levels of -0.4% (95% CI, -0.6, -0.2; p=0.004) during follow-up. Flash patients captured 93.9% of data through 17.8±9.9 scans daily. In fact, the Flash cohort showed a three-fold increase in daily self-monitoring of glucose, while daily frequency of SMBG decreased during the study (-1.8 tests/24h (95% CI -3, -0.7; p=0.01). No safety issues related to Flash use were recorded. The Flash glucose monitoring system is a novel approach to improve blood glucose control in CSII-treated T1DM patients. Randomized controlled trials are needed to assess the effectiveness of this system in CSII-treated T1DM patients. Copyright © 2018 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.
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Glucose metabolism disorder in obese children assessed by continuous glucose monitoring system.
Zou, Chao-Chun; Liang, Li; Hong, Fang; Zhao, Zheng-Yan
2008-02-01
Continuous glucose monitoring system (CGMS) can measure glucose levels at 5-minute intervals over a few days, and may be used to detect hypoglycemia, guide insulin therapy, and control glucose levels. This study was undertaken to assess the glucose metabolism disorder by CGMS in obese children. Eighty-four obese children were studied. Interstitial fluid (ISF) glucose levels were measured by CGMS for 24 hours covering the time for oral glucose tolerance test (OGTT). Impaired glucose tolerance (IGT), impaired fasting glucose (IFG), type 2 diabetic mellitus (T2DM) and hypoglycemia were assessed by CGMS. Five children failed to complete CGMS test. The glucose levels in ISF measured by CGMS were highly correlated with those in capillary samples (r=0.775, P<0.001). However, the correlation between ISF and capillary glucose levels was lower during the first hour than that in the later time period (r=0.722 vs r=0.830), and the ISF glucose levels in 69.62% of children were higher than baseline levels in the initial 1-3 hours. In 79 obese children who finished the CGMS, 2 children had IFG, 2 had IGT, 3 had IFG + IGT, and 2 had T2DM. Nocturnal hypoglycemia was noted during the overnight fasting in 11 children (13.92%). Our data suggest that glucose metabolism disorder including hyperglycemia and hypoglycemia is very common in obese children. Further studies are required to improve the precision of the CGMS in children.
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Franzese, Adriana; Valerio, Giuliana; Buono, Pietro; Spagnuolo, Maria Immacolata; Sepe, Angela; Mozzillo, Enza; De Simone, Ilaria; Raia, Valeria
2008-02-01
In cystic fibrosis (CF), diabetes mellitus (DM) is associated with progression of pulmonary disease and nutritional impairment. To compare oral glucose tolerance test (OGTT) and continuous glucose monitoring system (CGMS) in patients with CF with early glucose derangements. Thirty-two patients with CF (5-20 years) with intermediate glucose values > 7.7 mmol/l during OGTT received a CGMS registration. Patients were classified into those with normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and DM, according to glucose values at 120 min of OGTT and during CGMS. Furthermore BMI z-scores, forced expiratory volume in 1 second (FEV1%), number of respiratory infections/year, enzyme supplementation, and HbA1c were evaluated. OGTT and CGMS derangements were in agreement in 43.7% of the patients. BMI z-scores, FEV1%, number of respiratory infections/ year, enzyme supplementation, and HbA1c did not differ among the three groups. HbA1c, correlated positively with 120 min OGTT (r = 0.34; p = 0.059), CGMS area (r = 0.35; p = 0.048) and the number of respiratory infections, and negatively with FEV1%. Intermediate glucose values during OGTT should be considered as a screening test in patients with CF. CGMS can be useful in studying the early occurrence of glucose derangements in selected patients.
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NASA Astrophysics Data System (ADS)
Li, Dachao; Xu, Qingmei; Liu, Yu; Wang, Ridong; Xu, Kexin; Yu, Haixia
2017-11-01
A high-accuracy microdialysis method that can provide the reference values of glucose concentration in interstitial fluid for the accurate evaluation of non-invasive and minimally invasive continuous glucose monitoring is reported in this study. The parameters of the microdialysis process were firstly optimized by testing and analyzing three main factors that impact microdialysis recovery, including the perfusion rate, temperature, and glucose concentration in the area surrounding the microdialysis probe. The precision of the optimized microdialysis method was then determined in a simulation system that was designed and established in this study to simulate variations in continuous glucose concentration in the human body. Finally, the microdialysis method was tested for in vivo interstitial glucose concentration measurement.
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... costs will be covered. What is an artificial pancreas? A CGM is one part of the “artificial pancreas” systems that are beginning to reach people with ... has played an important role in developing artificial pancreas technology. An artificial pancreas replaces manual blood glucose ...
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Noninvasive diagnostic devices for diabetes through measuring tear glucose.
Zhang, Jin; Hodge, William; Hutnick, Cindy; Wang, Xianbin
2011-01-01
This article reviews the development of a noninvasive diagnostic for diabetes by detecting ocular glucose. Early diagnosis and daily management are very important to diabetes patients to ensure a healthy life. Commercial blood glucose sensors have been used since the 1970s. Millions of diabetes patients have to prick their finger for a drop of blood 4-5 times a day to check blood glucose levels--almost 1800 times annually. There is a strong need to have a noninvasive device to help patients to manage the disease easily and painlessly. Instead of detecting the glucose in blood, monitoring the glucose level in other body fluids may provide a feasible approach for noninvasive diagnosis and diabetes control. Tear glucose has been studied for several decades. This article reviews studies on ocular glucose and its monitoring methods. Attempts to continuously monitor the concentration of tear glucose by using contact lens-based sensors are discussed as well as our current development of a nanostructured lens-based sensor for diabetes. This disposable biosensor for the detection of tear glucose may provide an alternative method to help patients manage the disease conveniently. © 2010 Diabetes Technology Society.
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Lishova, E A; Nikoda, V V; Bondarenko, A V; Ragozin, A K; Skipenko, O G
2013-01-01
Recently new technologies of diagnostics and correction of carbohydrates metabolism disturbances are introduced in the ICU to improve the safety for patients during intensive care. 33 patients after pancreas surgery were included into the study 13 patients (39%) had underlying diabetes mellitus. Glucose level changes in the interstitial liquid of the subcutaneous fat during postoperative period were monitored by system of CGM Medtronic MiniMed Guardian RT, MiniMed Paradigm Real-time. Valid values of glucose were from 4.1 to 10.1 mmol/L. Episodes of glucose level increasing occurred in 94% of patients in postoperative period after pancreas surgery. Average level of glucose was within the limits of valid values. However in 64% of cases patients needed insulin therapy Used systems of continuous glucose monitoring in the ICU allow improving the safety for patients receiving artificial nutrition and intravenous insulin therapy.
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Recent Advances in Fluorescent Arylboronic Acids for Glucose Sensing
Hansen, Jon Stefan; Christensen, Jørn Bolstad
2013-01-01
Continuous glucose monitoring (CGM) is crucial in order to avoid complications caused by change in blood glucose for patients suffering from diabetes mellitus. The long-term consequences of high blood glucose levels include damage to the heart, eyes, kidneys, nerves and other organs, among others, caused by malign glycation of vital protein structures. Fluorescent monitors based on arylboronic acids are promising candidates for optical CGM, since arylboronic acids are capable of forming arylboronate esters with 1,2-cis-diols or 1,3-diols fast and reversibly, even in aqueous solution. These properties enable arylboronic acid dyes to provide immediate information of glucose concentrations. Thus, the replacement of the commonly applied semi-invasive and non-invasive techniques relying on glucose binding proteins, such as concanavalin A, or enzymes, such as glucose oxidase, glucose dehydrogenase and hexokinases/glucokinases, might be possible. The recent progress in the development of fluorescent arylboronic acid dyes will be emphasized in this review. PMID:25586415
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Banting Memorial Lecture 2014* Technology and diabetes care: appropriate and personalized.
Pickup, J C
2015-01-01
Continuous subcutaneous insulin infusion was initially developed as a research procedure in the 1970s but quickly became a routine treatment for selected people with Type 1 diabetes. Continuous subcutaneous insulin infusion and other diabetes technologies, such as continuous glucose monitoring, are now an established and evidence-based part of diabetes care, but there has been some confusion about effectiveness and best use, particularly because of conflicting results from meta-analyses. This is because literature summary meta-analyses (including all trials) are inappropriate for therapeutic and economic decision-making; such meta-analyses should only include trials representative of groups likely to benefit. For example, for continuous subcutaneous insulin infusion, this would be those with continued disabling hypoglycaemia or elevated HbA1c levels. Alternatively, individual patient data meta-analysis allows modelling of covariates that determine effect size, e.g. in the case of continuous glucose monitoring, baseline HbA1c and frequency of sensor usage. Diabetes technology is therefore an example of personalized medicine, where evaluation and use should be both appropriate and targeted. This will also apply to future technologies such as new 'patch' pumps for Type 2 diabetes, closed-loop insulin delivery systems and nanomedicine applications in diabetes that we are currently researching. These include fluorescence lifetime-based non-invasive glucose monitoring and nanoencapsulation of islets for improved post-transplant survival. © 2014 The Author. Diabetic Medicine © 2014 Diabetes UK.
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Peters, Anne L; Ahmann, Andrew J; Battelino, Tadej; Evert, Alison; Hirsch, Irl B; Murad, M Hassan; Winter, William E; Wolpert, Howard
2016-11-01
To formulate clinical practice guidelines for the use of continuous glucose monitoring and continuous subcutaneous insulin infusion in adults with diabetes. The participants include an Endocrine Society-appointed Task Force of seven experts, a methodologist, and a medical writer. The American Association for Clinical Chemistry, the American Association of Diabetes Educators, and the European Society of Endocrinology co-sponsored this guideline. The Task Force developed this evidence-based guideline using the Grading of Recommendations, Assessment, Development, and Evaluation system to describe the strength of recommendations and the quality of evidence. The Task Force commissioned one systematic review and used the best available evidence from other published systematic reviews and individual studies. One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of the Endocrine Society, the American Association for Clinical Chemistry, the American Association of Diabetes Educators, and the European Society of Endocrinology reviewed and commented on preliminary drafts of these guidelines. Continuous subcutaneous insulin infusion and continuous glucose monitoring have an important role in the treatment of diabetes. Data from randomized controlled trials are limited on the use of medical devices, but existing studies support the use of diabetes technology for a wide variety of indications. This guideline presents a review of the literature and practice recommendations for appropriate device use.
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Afandi, Bachar O; Hassanein, Mohamed M; Majd, Lina M; Nagelkerke, Nico J D
2017-01-01
Women with gestational diabetes mellitus (GDM) are categorized as at high risk for adverse events during Ramadan fasting. However, this is largely based on clinical opinion. In this study, we shed some light on what happens to glucose levels during Ramadan fasting. This is a prospective observational study. A total of 32 patients with GDM were recruited; 10 patients, treated with diet only (group 1), to observe their glucose levels before fasting and 22 patients who insisted on fasting the month of Ramadan, 13 treated with diet only (group 2) and nine treated with diet plus metformin 500 mg twice daily (group 3), to evaluate their glucose levels during fasting. Interstitial glucose was monitored in all by using the iPro2 Professional continuous glucose monitoring (CGM) system. Mean glucose level was 116±21 mg/dL (6.16±1.16 mmol/L), 106±9 mg/dL (5.88±0.49 mmol/L) and 99±7 mg/dL (5.49±0.34 mmol/L) in groups 1, 2 and 3, respectively. Patients in group 1 had the lowest rate of hypoglycemia (50%), followed by patients in group 2 (60%), whereas patients in group 3 had the highest rate of hypoglycemia (78%). CGM data indicates that Ramadan fasting in women with GDM treated with diet alone or with diet plus metformin was associated with lower mean glucose levels and higher rates of hypoglycemia when compared with non-fasting glucose levels. Women with GDM should be advised against fasting during Ramadan until further data is available.
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Predictive Monitoring for Improved Management of Glucose Levels
Reifman, Jaques; Rajaraman, Srinivasan; Gribok, Andrei; Ward, W. Kenneth
2007-01-01
Background Recent developments and expected near-future improvements in continuous glucose monitoring (CGM) devices provide opportunities to couple them with mathematical forecasting models to produce predictive monitoring systems for early, proactive glycemia management of diabetes mellitus patients before glucose levels drift to undesirable levels. This article assesses the feasibility of data-driven models to serve as the forecasting engine of predictive monitoring systems. Methods We investigated the capabilities of data-driven autoregressive (AR) models to (1) capture the correlations in glucose time-series data, (2) make accurate predictions as a function of prediction horizon, and (3) be made portable from individual to individual without any need for model tuning. The investigation is performed by employing CGM data from nine type 1 diabetic subjects collected over a continuous 5-day period. Results With CGM data serving as the gold standard, AR model-based predictions of glucose levels assessed over nine subjects with Clarke error grid analysis indicated that, for a 30-minute prediction horizon, individually tuned models yield 97.6 to 100.0% of data in the clinically acceptable zones A and B, whereas cross-subject, portable models yield 95.8 to 99.7% of data in zones A and B. Conclusions This study shows that, for a 30-minute prediction horizon, data-driven AR models provide sufficiently-accurate and clinically-acceptable estimates of glucose levels for timely, proactive therapy and should be considered as the modeling engine for predictive monitoring of patients with type 1 diabetes mellitus. It also suggests that AR models can be made portable from individual to individual with minor performance penalties, while greatly reducing the burden associated with model tuning and data collection for model development. PMID:19885110
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Osonoi, Takeshi; Saito, Miyoko; Tamasawa, Atsuko; Ishida, Hidenori; Osonoi, Yusuke
2014-07-01
Postprandial hyperglycemia and blood glucose fluctuations increase the risk of macroangiopathy in patients with type 2 diabetes mellitus (T2DM). However, few studies have examined the effects of oral hypoglycemic drugs on blood glucose fluctuations in daily life. Twenty-nine T2DM patients treated with acarbose were randomized to receive either sitagliptin (14 patients) or mitiglinide (15 patients) together with acarbose for 4 weeks. Patients were then switched to a combination of 10 mg mitiglinide and 0.2 mg voglibose for 4 weeks. All patients wore a continuous glucose monitoring (CGM) device for 5 - 7 days in week 3 of each treatment period. The percentage of blood glucose levels in the hyperglycemic range, blood glucose indices derived from 24-h CGM profiles and the glycemic parameters (HbA1c, glycated albumin and fasting plasma glucose) were significantly improved by adding sitagliptin or mitiglinide to ongoing acarbose therapy. These parameters also tended to improve in the mitiglinide/voglibose combination period. Daily blood glucose fluctuations were significantly improved by adding sitagliptin or mitiglinide to acarbose, and improved after switching to the mitiglinide/voglibose combination. Larger controlled studies are needed to verify the effects of adding sitagliptin or mitiglinide to acarbose on glucose fluctuations.
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Lawton, J; Blackburn, M; Allen, J; Campbell, F; Elleri, D; Leelarathna, L; Rankin, D; Tauschmann, M; Thabit, H; Hovorka, R
2018-02-20
Continuous glucose monitoring (CGM) enables users to view real-time interstitial glucose readings and provides information on the direction and rate of change of blood glucose levels. Users can also access historical data to inform treatment decisions. While the clinical and psychological benefits of CGM are well established, little is known about how individuals use CGM to inform diabetes self-management. We explored participants' experiences of using CGM in order to provide recommendations for supporting individuals to make optimal use of this technology. In-depth interviews (n = 24) with adults, adolescents and parents who had used CGM for ≥4 weeks; data were analysed thematically. Participants found CGM an empowering tool because they could access blood glucose data effortlessly, and trend arrows enabled them to see whether blood glucose was rising or dropping and at what speed. This predicative information aided short-term lifestyle planning and enabled individuals to take action to prevent hypoglycaemia and hyperglycaemia. Having easy access to blood glucose data on a continuous basis also allowed participants to develop a better understanding of how insulin, activity and food impacted on blood glucose. This understanding was described as motivating individuals to make dietary changes and break cycles of over-treating hypoglycaemia and hyperglycaemia. Participants also described how historical CGM data provided a more nuanced picture of blood glucose control than was possible with blood glucose self-monitoring and, hence, better information to inform changes to background insulin doses and mealtime ratios. However, while participants expressed confidence making immediate adjustments to insulin and lifestyle to address impending hypoglycaemia and hypoglycaemia, most described needing and expecting health professionals to interpret historical CGM data and determine changes to background insulin doses and mealtime ratios. While alarms could reinforce a sense of hypoglycaemic safety, some individuals expressed ambivalent views, especially those who perceived alarms as signalling personal failure to achieve optimal glycaemic control. CGM can be an empowering and motivational tool which enables participants to fine-tune and optimize their blood glucose control. However, individuals may benefit from psycho-social education, training and/or technological support to make optimal use of CGM data and use alarms appropriately.
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Bailey, Kaitlyn J; Little, Jonathan P; Jung, Mary E
2016-03-01
Exercise helps individuals with prediabetes or type 2 diabetes (T2D) manage their blood glucose (BG); however, exercise adherence in this population is dismal. In this pilot study we tested the efficacy of a self-monitoring group-based intervention using continuous glucose monitors (CGMs) at increasing exercise adherence in individuals with impaired BG. Thirteen participants with prediabetes or T2D were randomized to an 8-week standard care exercise program (CON condition) (n = 7) or self-monitoring exercise intervention (SM condition) (n = 6). Participants in the SM condition were taught how to self-monitor their exercise and BG, to goal set, and to use CGM to observe how exercise influences BG. We hypothesized that compared with the CON condition, using a real-time CGM would facilitate self-monitoring behavior, resulting in increased exercise adherence. Repeated-measures analysis of variance revealed significant Condition × Time interactions for self-monitoring (P < 0.01), goal setting (P = 0.01), and self-efficacy to self-monitor (P = 0.01), such that the SM condition showed greater increases in these outcomes immediately after the program and at the 1-month follow-up compared with the CON condition. The SM condition had higher program attendance rates (P = 0.03), and a greater proportion of participants reregistered for additional exercise programs (P = 0.048) compared with the CON condition. Participants in both conditions experienced improvements in health-related quality of life, waist circumference, and fitness (P values <0.05). These findings provide promising initial support for the use of a real-time CGM to foster self-monitoring and exercise behavior in individuals living with prediabetes or T2D.
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Fang, Yuxin; Wang, Shenjun; Liu, Yangyang; Xu, Zhifang; Zhang, Kuo; Guo, Yi
2018-07-01
A minimally invasive glucose microbiosensor based the flexibly integrated electrode for continuous monitoring glucose in vivo has been developed in this study. This was achieved by coating needle-type microelectrode with Cu nanoflowers, nafion, glucose oxidase (GOD) and polyurethane (PU) membranes, successfully prepared with layer-by-layer deposition. The Cu nanomaterials provided a large specific surface area and electrocatalytic activity for glucose detection. The PU layers as mass-transport limiting membranes significantly enhanced the linearity and stability of sensors. The resulting biosensor exhibited a wide linear range of 0-20 mM, with a good sensitivity of 42.38 nA mM -1 (correlation coefficient r 2 was 0.99) and a fast response time of less than 15 s. In vivo implantable experiments using anesthetized rats showed excellent real-time response to the variation of blood glucose concentration. And the variation tendency of sensor output was consistent with that using the glucose meter. Overall, the results supported the suitability of this microsensor for measuring rapid changes of glucose in vivo. This work offers a promising approach in implantable device applications related to diabetes management as well as other medical diagnosis. Copyright © 2018 Elsevier B.V. All rights reserved.
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Utility of different glycemic control metrics for optimizing management of diabetes.
Kohnert, Klaus-Dieter; Heinke, Peter; Vogt, Lutz; Salzsieder, Eckhard
2015-02-15
The benchmark for assessing quality of long-term glycemic control and adjustment of therapy is currently glycated hemoglobin (HbA1c). Despite its importance as an indicator for the development of diabetic complications, recent studies have revealed that this metric has some limitations; it conveys a rather complex message, which has to be taken into consideration for diabetes screening and treatment. On the basis of recent clinical trials, the relationship between HbA1c and cardiovascular outcomes in long-standing diabetes has been called into question. It becomes obvious that other surrogate and biomarkers are needed to better predict cardiovascular diabetes complications and assess efficiency of therapy. Glycated albumin, fructosamin, and 1,5-anhydroglucitol have received growing interest as alternative markers of glycemic control. In addition to measures of hyperglycemia, advanced glucose monitoring methods became available. An indispensible adjunct to HbA1c in routine diabetes care is self-monitoring of blood glucose. This monitoring method is now widely used, as it provides immediate feedback to patients on short-term changes, involving fasting, preprandial, and postprandial glucose levels. Beyond the traditional metrics, glycemic variability has been identified as a predictor of hypoglycemia, and it might also be implicated in the pathogenesis of vascular diabetes complications. Assessment of glycemic variability is thus important, but exact quantification requires frequently sampled glucose measurements. In order to optimize diabetes treatment, there is a need for both key metrics of glycemic control on a day-to-day basis and for more advanced, user-friendly monitoring methods. In addition to traditional discontinuous glucose testing, continuous glucose sensing has become a useful tool to reveal insufficient glycemic management. This new technology is particularly effective in patients with complicated diabetes and provides the opportunity to characterize glucose dynamics. Several continuous glucose monitoring (CGM) systems, which have shown usefulness in clinical practice, are presently on the market. They can broadly be divided into systems providing retrospective or real-time information on glucose patterns. The widespread clinical application of CGM is still hampered by the lack of generally accepted measures for assessment of glucose profiles and standardized reporting of glucose data. In this article, we will discuss advantages and limitations of various metrics for glycemic control as well as possibilities for evaluation of glucose data with the special focus on glycemic variability and application of CGM to improve individual diabetes management.
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Caduff, A; Dewarrat, F; Talary, M; Stalder, G; Heinemann, L; Feldman, Yu
2006-12-15
The aim of this work was to evaluate the performance of a novel non-invasive continuous glucose-monitoring system based on impedance spectroscopy (IS) in patients with diabetes. Ten patients with type 1 diabetes (mean+/-S.D., age 28+/-8 years, BMI 24.2+/-3.2 kg/m(2) and HbA(1C) 7.3+/-1.6%) and five with type 2 diabetes (age 61+/-8 years, BMI 27.5+/-3.2 kg/m(2) and HbA(1C) 8.3+/-1.8%) took part in this study, which comprised a glucose clamp experiment followed by a 7-day outpatient evaluation. The measurements obtained by the NI-CGMD and the reference blood glucose-measuring techniques were evaluated using retrospective data evaluation procedures. Under less controlled outpatient conditions a correlation coefficient of r=0.640 and a standard error of prediction (SEP) of 45 mg dl(-1) with a total of 590 paired glucose measurements was found (versus r=0.926 and a SEP of 26 mg dl(-1) under controlled conditions). Clark error grid analyses (EGA) showed 56% of all values in zone A, 37% in B and 7% in C-E. In conclusion, these results indicate that IS in the used technical setting allows retrospective, continuous and truly non-invasive glucose monitoring under defined conditions for patients with diabetes. Technical advances and developments are needed to expand on this concept to bring the results from the outpatient study closer to those in the experimental section of the study. Further studies will not only help to evaluate the performance and limitations of using such a technique for non non-invasive glucose monitoring but also help to verify technical extensions towards a IS-based concept that offers improved performance under real life operating conditions.
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Glucose monitoring system using nanopellets.
Rajasekaran, C; Nirmala, Madian; Jayanthi, K B
2017-02-01
The combination of the fields of software engineering, gadgets, and science has stood out among the most revolutionary future innovations. Health issues have been the focus of various engaging and explanatory studies. One such health-related dilemma is diabetes. Diabetes at its serious stage results in impaired vision. Increase in the glucose level is a critical parameter that could result in hyperglycaemia, hypoglycaemia, massive heart attack, strokes, and aneurysms. Monitoring the glucose level in blood is one of the control measures for diabetes in the affected population. A glucose monitoring framework interminably measures and screens the glucose level in blood. A novel framework for measuring the glucose level is proposed in this study. This study employs nanopellets that evaluate the glucose level. When the glucose level increases or decreases, it is continuously recorded and displayed using a microcontroller (mixed signal processor (MSP) 430). The data are then sent to the physician through global system for mobile communication. The typical blood glucose level of human being ranges from 70 to 110 mg/dl. When the insulin level builds up to certain point, hyperglycaemia occurs. When decreases, hypoglycaemia occurs. Hyperglycaemia leads to cataracts, oedema, hypertension, polyuria, and polydipsia. Hypoglycaemia causes perplexity, energy, insensateness, coma, and death.
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Borot, S; Benhamou, P Y; Atlan, C; Bismuth, E; Bonnemaison, E; Catargi, B; Charpentier, G; Farret, A; Filhol, N; Franc, S; Gouet, D; Guerci, B; Guilhem, I; Guillot, C; Jeandidier, N; Joubert, M; Melki, V; Merlen, E; Penfornis, A; Picard, S; Renard, E; Reznik, Y; Riveline, J P; Rudoni, S; Schaepelynck, P; Sola-Gazagnes, A; Tubiana-Rufi, N; Verier-Mine, O; Hanaire, H
2018-02-01
The use by diabetes patients of real-time continuous interstitial glucose monitoring (CGM) or the FreeStyle Libre ® (FSL) flash glucose monitoring (FGM) system is becoming widespread and has changed diabetic practice. The working group bringing together a number of French experts has proposed the present practical consensus. Training of professionals and patient education are crucial for the success of CGM. Also, institutional recommendations must pay particular attention to the indications for and reimbursement of CGM devices in populations at risk of hypoglycaemia. The rules of good practice for CGM are the precursors of those that need to be enacted, given the oncoming emergence of artificial pancreas devices. It is necessary to have software combining user-friendliness, multiplatform usage and average glucose profile (AGP) presentation, while integrating glucose and insulin data as well as events. Expression of CGM data must strive for standardization that facilitates patient phenotyping and their follow-up, while integrating indicators of variability. The introduction of CGM involves a transformation of treatment support, rendering it longer and more complex as it also includes specific educational and technical dimensions. This complexity must be taken into account in discussions of organization of diabetes care. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
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Continuous glucose monitoring: A review of the technology and clinical use.
Klonoff, David C; Ahn, David; Drincic, Andjela
2017-11-01
Continuous glucose monitoring (CGM) is an increasingly adopted technology for insulin-requiring patients that provides insights into glycemic fluctuations. CGM can assist patients in managing their diabetes with lifestyle and medication adjustments. This article provides an overview of the technical and clinical features of CGM based on a review of articles in PubMed on CGM from 1999 through January 31, 2017. A detailed description is presented of three professional (retrospective), three personal (real-time) continuous glucose monitors, and three sensor integrated pumps (consisting of a sensor and pump that communicate with each other to determine an optimal insulin dose and adjust the delivery of insulin) that are currently available in United States. We have reviewed outpatient CGM outcomes, focusing on hemoglobin A1c (A1C), hypoglycemia, and quality of life. Issues affecting accuracy, detection of glycemic variability, strategies for optimal use, as well as cybersecurity and future directions for sensor design and use are discussed. In conclusion, CGM is an important tool for monitoring diabetes that has been shown to improve outcomes in patients with type 1 diabetes mellitus. Given currently available data and technological developments, we believe that with appropriate patient education, CGM can also be considered for other patient populations. Copyright © 2017 Elsevier B.V. All rights reserved.
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Rigla, Mercedes
2011-01-01
Although current systems for continuous glucose monitoring (CGM) are the result of progressive technological improvement, and although a beneficial effect on glucose control has been demonstrated, few patients are using them. Something similar has happened to telemedicine (TM); in spite of the long-term experience, which began in the early 1980s, no TM system has been widely adopted, and presential visits are still almost the only way diabetologists and patients communicate. The hypothesis developed in this article is that neither CGM nor TM will ever be routinely implemented separately, and their consideration as essential elements for standard diabetes care will one day come from their integration as parts of a telemedical monitoring platform. This platform, which should include artificial intelligence for giving decision support to patients and physicians, will represent the core of a more complex global agent for diabetes care, which will provide control algorithms and risk analysis among other essential functions. © 2010 Diabetes Technology Society.
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Uemura, Mei; Suzuki, Toshinari; Yasuma, Taro; Sato, Toshiyuki; Morimoto, Aya; Hosoya, Samiko; Suminaka, Chihiro; Nakajima, Hiromu; Gabazza, Esteban C.; Takei, Yoshiyuki
2017-01-01
Background Continuous glucose monitoring (CGM) is reported to be a useful technique, but difficult or inconvenient for some patients and institutions. We are developing a glucose area under the curve (AUC) monitoring system without blood sampling using a minimally invasive interstitial fluid extraction technology (MIET). Here we evaluated the accuracy of interstitial fluid glucose (IG) AUC measured by MIET in patients with diabetes for an extended time interval and the potency of detecting hyperglycemia using CGM data as a reference. Methods Thirty-eight inpatients with diabetes undergoing CGM were enrolled. MIET comprised a pretreatment step using a plastic microneedle array and glucose accumulation step with a hydrogel patch, which was placed on two sites from 9:00 AM to 5:00 PM or from 10:00 PM to 6:00 AM. IG AUC was calculated by accumulated glucose extracted by hydrogel patches using sodium ion as standard. Results A significant correlation was observed between the predicted AUC by MIET and CGM in daytime (r=0.76) and nighttime (r=0.82). The optimal cutoff for the IG AUC value of MIET to predict hyperglycemia over 200 mg/dL measured by CGM for 8 hours was 1,067.3 mg·hr/dL with 88.2% sensitivity and 81.5% specificity. Conclusion We showed that 8-hour IG AUC levels using MIET were valuable in estimating the blood glucose AUC without blood sampling. The results also supported the concept of using this technique for evaluating glucose excursion and for screening hyperglycemia during 8 hours in patients with diabetes at any time of day. PMID:28868824
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Uemura, Mei; Yano, Yutaka; Suzuki, Toshinari; Yasuma, Taro; Sato, Toshiyuki; Morimoto, Aya; Hosoya, Samiko; Suminaka, Chihiro; Nakajima, Hiromu; Gabazza, Esteban C; Takei, Yoshiyuki
2017-08-01
Continuous glucose monitoring (CGM) is reported to be a useful technique, but difficult or inconvenient for some patients and institutions. We are developing a glucose area under the curve (AUC) monitoring system without blood sampling using a minimally invasive interstitial fluid extraction technology (MIET). Here we evaluated the accuracy of interstitial fluid glucose (IG) AUC measured by MIET in patients with diabetes for an extended time interval and the potency of detecting hyperglycemia using CGM data as a reference. Thirty-eight inpatients with diabetes undergoing CGM were enrolled. MIET comprised a pretreatment step using a plastic microneedle array and glucose accumulation step with a hydrogel patch, which was placed on two sites from 9:00 AM to 5:00 PM or from 10:00 PM to 6:00 AM. IG AUC was calculated by accumulated glucose extracted by hydrogel patches using sodium ion as standard. A significant correlation was observed between the predicted AUC by MIET and CGM in daytime (r=0.76) and nighttime (r=0.82). The optimal cutoff for the IG AUC value of MIET to predict hyperglycemia over 200 mg/dL measured by CGM for 8 hours was 1,067.3 mg·hr/dL with 88.2% sensitivity and 81.5% specificity. We showed that 8-hour IG AUC levels using MIET were valuable in estimating the blood glucose AUC without blood sampling. The results also supported the concept of using this technique for evaluating glucose excursion and for screening hyperglycemia during 8 hours in patients with diabetes at any time of day. Copyright © 2017 Korean Diabetes Association
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The application of simple metrics in the assessment of glycaemic variability.
Monnier, L; Colette, C; Owens, D R
2018-03-06
The assessment of glycaemic variability (GV) remains a subject of debate with many indices proposed to represent either short- (acute glucose fluctuations) or long-term GV (variations of HbA 1c ). For the assessment of short-term within-day GV, the coefficient of variation for glucose (%CV) defined as the standard deviation adjusted on the 24-h mean glucose concentration is easy to perform and with a threshold of 36%, recently adopted by the international consensus on use of continuous glucose monitoring, separating stable from labile glycaemic states. More complex metrics such as the Low Blood Glucose Index (LBGI) or High Blood Glucose Index (HBGI) allow the risk of hypo or hyperglycaemic episodes, respectively to be assessed although in clinical practice its application is limited due to the need for more complex computation. This also applies to other indices of short-term intraday GV including the mean amplitude of glycemic excursions (MAGE), Shlichtkrull's M-value and CONGA. GV is important clinically as exaggerated glucose fluctuations are associated with an enhanced risk of adverse cardiovascular outcomes due primarily to hypoglycaemia. In contrast, there is at present no compelling evidence that elevated short-term GV is an independent risk factor of microvascular complications of diabetes. Concerning long-term GV there are numerous studies supporting its association with an enhanced risk of cardiovascular events. However, this association raises the question as to whether the impact of long-term variability is not simply the consequence of repeated exposure to short-term GV or ambient chronic hyperglycaemia. The renewed emphasis on glucose monitoring with the introduction of continuous glucose monitoring technologies can benefit from the introduction and application of simple metrics for describing GV along with supporting recommendations. Copyright © 2018 Elsevier Masson SAS. All rights reserved.
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Simulation of an enzyme-based glucose sensor
NASA Astrophysics Data System (ADS)
Sha, Xianzheng; Jablecki, Michael; Gough, David A.
2001-09-01
An important biosensor application is the continuous monitoring blood or tissue fluid glucose concentration in people with diabetes. Our research focuses on the development of a glucose sensor based on potentiostatic oxygen electrodes and immobilized glucose oxidase for long- term application as an implant in tissues. As the sensor signal depends on many design variables, a trial-and-error approach to sensor optimization can be time-consuming. Here, the properties of an implantable glucose sensor are optimized by a systematic computational simulation approach.
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Improved blood glucose estimation through multi-sensor fusion.
Xiong, Feiyu; Hipszer, Brian R; Joseph, Jeffrey; Kam, Moshe
2011-01-01
Continuous glucose monitoring systems are an integral component of diabetes management. Efforts to improve the accuracy and robustness of these systems are at the forefront of diabetes research. Towards this goal, a multi-sensor approach was evaluated in hospitalized patients. In this paper, we report on a multi-sensor fusion algorithm to combine glucose sensor measurements in a retrospective fashion. The results demonstrate the algorithm's ability to improve the accuracy and robustness of the blood glucose estimation with current glucose sensor technology.
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Harris, Deborah L; Weston, Philip J; Williams, Christopher E; Pleasants, Anthony B; Battin, Malcolm R; Spooner, Claire G; Harding, Jane E
2011-11-01
To determine whether there is a relationship between electroencephalography patterns and hypoglycemia, by using simultaneous cot-side amplitude integrated electroencephalography (aEEG) and continuous interstitial glucose monitoring, and whether non-glucose cerebral fuels modified these patterns. Eligible babies were ≥ 32 weeks gestation, at risk for hypoglycemia, and admitted to the neonatal intensive care unit. Electrodes were placed in C3-P3, C4-P4 O1-O2 montages. A continuous interstitial glucose sensor was placed subcutaneously, and blood glucose was measured by using the glucose oxidase method. Non-glucose cerebral fuels were measured at study entry, exit, and during recognized hypoglycemia. A total of 101 babies were enrolled, with a median weight of 2179 g and gestation of 35 weeks. Twenty-four of the babies had aEEG recordings, and glucose concentrations were low (< 2.6 mM). There were 103 episodes of low glucose concentrations lasting 5 to 475 minutes, but no observable changes in aEEG variables. Plasma concentrations of lactate, beta-hydroxybutyrate, and glycerol were low and did not alter during hypoglycemia. Cot-side aEEG was not useful for the detection of neurological changes during mild hypoglycemia. Plasma concentrations of non-glucose cerebral fuels were low and unlikely to provide substantial neuroprotection. Copyright © 2011 Mosby, Inc. All rights reserved.
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NASA Astrophysics Data System (ADS)
Larin, Kirill V.; Ashitkov, Taras V.; Motamedi, Massoud; Esenaliev, Rinat O.
2003-10-01
Approximately 14 million people in the USA and more than 140 million people worldwide suffer from Diabetes Mellitus. The current glucose sensing technique involves a finger puncture several times a day to obtain a droplet of blood for chemical analysis. Recently we proposed to use optical coherence tomography (OCT) for continuous noninvasive blood glucose sensing through skin. In this paper we tested the OCT technique for noninvasive monitoring of blood glucose concentration in lip tissue of New Zealand rabbits and Yucatan micropigs during glucose clamping experiments. Obtained results show good agreement with results obtained in skin studies, good correlation of changes in the OCT signal slope measured at the depth of 250 to 500 μm with changes in blood glucose concentration, and higher stability of the OCT data points than that obtained from skin.
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Valletta, J J; Chipperfield, A J; Clough, G F; Byrne, C D
2012-06-01
Constant moderate intensity physical exertion in humid environments at altitude poses a considerable challenge to maintaining euglycaemia with Type 1 diabetes. Blood glucose concentrations and energy expenditure were continuously recorded in a person trekking at altitude in a tropical climate to quantify changes in glucose concentrations in relation to energy expenditure. Blood glucose concentrations and energy expenditure were continuously monitored with a Guardian® real-time continuous glucose monitoring system (CGMS) and a SenseWear® Pro3 armband (BodyMedia Inc., USA), in a 27-year-old woman with Type 1 diabetes, during her climb up Mount Kinabalu in Borneo (c. 4095 m). Comparative control data from the same person was collected in the UK (temperate climate at sea level) and Singapore (tropical climate at sea level). Maximum physical effort during the climb was < 60% VO(2MAX) (maximal oxygen consumption). Mean daily calorific intakes were 2300 kcal (UK), 2370 kcal (Singapore) and 2274 kcal (Mount Kinabalu), and mean daily insulin doses were 54 U (UK), 40 U (Singapore) and 47 U (Mount Kinabalu). Despite markedly increased energy expenditure during the climb [4202 kcal (Mount Kinabalu) vs. 2948 kcal (UK) and 2662 kcal (Singapore)], mean blood glucose was considerably higher during the trek up Mount Kinabalu [13.2 ± 5.9 mmol/l, vs. 7.9 ± 3.8 mmol/l (UK) and 8.6 ± 4.0 mmol/l (Singapore)]. Marked unexpected hyperglycaemia occurred while trekking on Mount Kinabalu, despite similar calorie consumption and insulin doses to control conditions. Because of the risk of unexpected hyperglycaemia in these conditions, we recommend that patients embarking on similar activity holidays undertake frequent blood glucose monitoring. © 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.
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Moser, Othmar; Yardley, Jane E.; Bracken, Richard M.
2018-01-01
Continuous and flash glucose monitoring systems measure interstitial fluid glucose concentrations within a body compartment that is dramatically altered by posture and is responsive to the physiological and metabolic changes that enable exercise performance in individuals with type 1 diabetes. Body fluid redistribution within the interstitial compartment, alterations in interstitial fluid volume, changes in rate and direction of fluid flow between the vasculature, interstitium and lymphatics, as well as alterations in the rate of glucose production and uptake by exercising tissues, make for caution when interpreting device read-outs in a rapidly changing internal environment during acute exercise. We present an understanding of the physiological and metabolic changes taking place with acute exercise and detail the blood and interstitial glucose responses with different forms of exercise, namely sustained endurance, high-intensity, and strength exercises in individuals with type 1 diabetes. Further, we detail novel technical information on currently available patient devices. As more health services and insurance companies advocate their use, understanding continuous and flash glucose monitoring for its strengths and limitations may offer more confidence for patients aiming to manage glycemia around exercise. PMID:29342932
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Continuous glucose monitors: current status and future developments.
Lane, Jennifer E; Shivers, Joseph P; Zisser, Howard
2013-04-01
Advances in diabetes technologies allow patients to manage their diabetes with greater precision and flexibility. Many recent studies show that continuous glucose monitors (CGMs) can be used to tighten glycemic control safely and to ease certain burdens of diabetes self-management. The following summary reflects the most recent findings in CGM and provides an overall review of who would most benefit from CGM use. Benefits of CGM may vary based on age, type of diabetes, pregnancy, health, sleep, or heart rate. Accuracy and reliability are critical in current uses of CGM and especially for new and future systems that automate insulin partially (e.g., low glucose suspend) or entirely (e.g., 'fully closed-loop' artificial pancreas). Clinicians are simultaneously testing available products in new patient groups such as the critically ill and type 2 diabetes patients not using mealtime insulin. In a widening set of circumstances, use of CGM has been shown to promote safer and more effective glycemic control than self-monitoring of blood glucose. Imperfections remain in certain scenarios such as hypoglycemia and in certain populations such as young children. Ongoing research on sensors and calibration software should translate to better systems.
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A diabetes-specific enteral formula improves glycemic variability in patients with type 2 diabetes.
Alish, Carolyn J; Garvey, W Timothy; Maki, Kevin C; Sacks, Gordon S; Hustead, Deborah S; Hegazi, Refaat A; Mustad, Vikkie A
2010-06-01
Well-controlled studies have demonstrated that inpatient hyperglycemia is an indicator of poor clinical outcomes, but the use of diabetes-specific enteral formulas in hospitalized patients remains a topic of great debate. In two different protocols, postprandial glycemia and insulinemia were measured in 22 subjects with diabetes fed a diabetes-specific or standard formula (protocol 1). Continuous glucose monitoring was used to assess glucose levels in 12 enterally fed patients with diabetes receiving the standard formula followed by the diabetes-specific formula continuously for 5 days each (protocol 2). End points included postprandial glycemia and insulinemia, glycemic variability (mean amplitude of glycemic excursions [MAGE]), mean glucose, and insulin use. In the postprandial response protocol, the diabetes-specific formula resulted in lower positive areas under the postprandial curve (P < 0.001) and peak glucose (P < 0.001) and insulin (P = 0.017) levels. In the protocol using continuous glucose monitoring, glycemic variability (as measured by MAGE) was lower with continuous administration of the diabetes-specific than the standard formula (64.6 +/- 6.8 mg/dL vs. 110.6 +/-15.3 mg/dL, P = 0.003). Also, administration of the diabetes-specific formula resulted in lower mean glucose concentrations during feeding (171.1 +/- 16.1 vs. 202.1 +/- 17.4 mg/dL, P = 0.024) and insulin requirements (7.8 +/- 2.3 vs. 10.9 +/- 3.3 units/day, P = 0.039) than the standard formula. Relative to the standard formula, the diabetes-specific formula reduced postprandial glycemia, mean glucose, glycemic variability, and short-acting insulin requirements. These results suggest potential clinical usefulness of a diabetes-specific enteral formula for minimizing glycemic excursions in hospitalized patients.
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Susceptibility of interstitial continuous glucose monitor performance to sleeping position.
Mensh, Brett D; Wisniewski, Natalie A; Neil, Brian M; Burnett, Daniel R
2013-07-01
Developing a round-the-clock artificial pancreas requires accurate and stable continuous glucose monitoring. The most widely used continuous glucose monitors (CGMs) are percutaneous, with the sensor residing in the interstitial space. Inaccuracies in percutaneous CGM readings during periods of lying on the devices (e.g., in various sleeping positions) have been anecdotally reported but not systematically studied. In order to assess the impact of sleep and sleep position on CGM performance, we conducted a study in human subjects in which we measured the variability of interstitial CGM data at night as a function of sleeping position. Commercially available sensors were placed for 4 days in the abdominal subcutaneous tissue in healthy, nondiabetic volunteers (four sensors per person, two per side). Nocturnal sleeping position was determined from video recordings and correlated to sensor data. We observed that, although the median of the four sensor readings was typically 70-110 mg/dl during sleep, individual sensors intermittently exhibited aberrant glucose readings (>25 mg/dl away from median) and that these aberrant readings were strongly correlated with subjects lying on the sensors. We expected and observed that most of these aberrant sleep-position-related CGM readings were sudden decreases in reported glucose values, presumably due to local blood-flow decreases caused by tissue compression. Curiously, in rare cases, the aberrant CGM readings were elevated values. These findings highlight limitations in our understanding of interstitial fluid physiology in the subcutaneous space and have significant implications for the utilization of sensors in the construction of an artificial pancreas. © 2013 Diabetes Technology Society.
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Chan, Christine L; Pyle, Laura; Newnes, Lindsey; Nadeau, Kristen J; Zeitler, Philip S; Kelsey, Megan M
2015-03-01
The optimal screening test for diabetes and prediabetes in obese youth is controversial. We examined whether glycosylated hemoglobin (HbA1c) or the oral glucose tolerance test (OGTT) is a better predictor of free-living glycemia as measured by continuous glucose monitoring (CGM). This was a cross-sectional study of youth 10-18 years old, body mass index (BMI) 85th percentile or greater, with diabetes risk factors. Participants (n = 118) with BMI 85th percentile or greater, not on medications for glucose management, were recruited from primary care and pediatric endocrinology clinics around Denver, Colorado. HbA1c, fasting plasma glucose, and 2-hour glucose were collected and all participants wore a blinded CGM for 72 hours. CGM outcomes were determined and descriptive statistics calculated. Performance characteristics at current American Diabetes Association cutpoints were compared with CGM outcomes. CGM data were successfully collected on 98 obese youth. Those with prediabetes had significantly higher average glucose, area under the curve (AUC), peak glucose, and time greater than 120 and greater than 140 mg/dL (P < .01) on CGM than youth with normal HbA1c or OGTT. HbA1c had a greater magnitude of correlation to CGM average glucose, AUC, and minimum glucose; 2-hour glucose had a greater magnitude of correlation to CGM SD, peak glucose, and time greater than 140 and greater than 200 mg/dL. However, there were no overall differences in the strength comparisons between 2-hour glucose and HbA1c correlations to CGM outcomes. In obese youth, HbA1c and 2-hour glucose performed equally well at predicting free-living glycemia on CGM, suggesting that both are valid tests for dysglycemia screening.
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Madrid, Lola; Sitoe, Antonio; Varo, Rosauro; Nhampossa, Tacilta; Lanaspa, Miguel; Nhama, Abel; Acácio, Sozinho; Riaño, Isolina; Casellas, Aina; Bassat, Quique
2017-05-02
Hypoglycaemia is a frequent complication among admitted children, particularly in malaria-endemic areas. This study aimed to estimate the occurrence of hypoglycaemia not only upon admission but throughout the first 72 h of hospitalization in children admitted with malaria. A simple pilot study to continuously monitor glycaemia in children aged 0-10 years, admitted with malaria in a rural hospital was conducted in Southern Mozambique by inserting continuous glucose monitors (CGMs) in subcutaneous tissue of the abdominal area, producing glycaemia readings every 5 min. Glucose was continuously monitored during a mean of 48 h, in 74 children. Continuous measurements of blood glucose were available for 72/74 children (97.3%). Sixty-five of them were admitted with density-specific malaria diagnosis criteria (17 severe, 48 uncomplicated). Five children (7.7%) had hypoglycaemia (<54 mg/dL) on admission as detected by routine capillary determination. Analysing the data collected by the CGMs, hypoglycaemia episodes (<54 mg/dL) were detected in 10/65 (15.4%) of the children, of which 7 (10.8%) could be classified as severe (≤45 mg/dL). No risk factors were independently associated with the presence of at least one episode of hypoglycaemia (<54 mg/dL) during hospitalization. Only one death occurred among a normoglycaemic child. All episodes of hypoglycaemia detected by CGMs were subclinical episodes or not perceived by caregivers or clinical staff. Hypoglycaemia beyond admission in children with malaria appears to be much more frequent than what had been previously described. The clinical relevance of these episodes of hypoglycaemia in the medium or long term remains to be determined.
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Nanopillar based electrochemical biosensor for monitoring microfluidic based cell culture
NASA Astrophysics Data System (ADS)
Gangadharan, Rajan
In-vitro assays using cultured cells have been widely performed for studying many aspects of cell biology and cell physiology. These assays also form the basis of cell based sensing. Presently, analysis procedures on cell cultures are done using techniques that are not integrated with the cell culture system. This approach makes continuous and real-time in-vitro measurements difficult. It is well known that the availability of continuous online measurements for extended periods of time will help provide a better understanding and will give better insight into cell physiological events. With this motivation we developed a highly sensitive, selective and stable microfluidic electrochemical glucose biosensor to make continuous glucose measurements in cell culture media. The performance of the microfluidic biosensor was enhanced by adding 3D nanopillars to the electrode surfaces. The microfluidic glucose biosensor consisted of three electrodes---Enzyme electrode, Working electrode, and Counter electrode. All these electrodes were enhanced with nanopillars and were optimized in their respective own ways to obtain an effective and stable biosensing device in cell culture media. For example, the 'Enzyme electrode' was optimized for enzyme immobilization via either a polypyrrole-based or a self-assembled-monolayer-based immobilization method, and the 'Working electrode' was modified with Prussian Blue or electropolymerized Neutral Red to reduce the working potential and also the interference from other interacting electro-active species. The complete microfluidic biosensor was tested for its ability to monitor glucose concentration changes in cell culture media. The significance of this work is multifold. First, the developed device may find applications in continuous and real-time measurements of glucose concentrations in in-vitro cell cultures. Second, the development of a microfluidic biosensor will bring technical know-how toward constructing continuous glucose monitoring devices. Third, the methods used to develop 3D electrodes incorporated with nanopillars can be used for other applications such as neural probes, fuel cells, solar cells etc., and finally, the knowledge obtained from the immobilization of enzymes onto nanostructures sheds some new insight into nanomaterial/biomolecule interactions.
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Chen, Jin-Long; Chen, Pin-Fan; Wang, Hung-Ming
2014-07-15
Parameters of glucose dynamics recorded by the continuous glucose monitoring system (CGMS) could help in the control of glycemic fluctuations, which is important in diabetes management. Multiscale entropy (MSE) analysis has recently been developed to measure the complexity of physical and physiological time sequences. A reduced MSE complexity index indicates the increased repetition patterns of the time sequence, and, thus, a decreased complexity in this system. No study has investigated the MSE analysis of glucose dynamics in diabetes. This study was designed to compare the complexity of glucose dynamics between the diabetic patients (n = 17) and the control subjects (n = 13), who were matched for sex, age, and body mass index via MSE analysis using the CGMS data. Compared with the control subjects, the diabetic patients revealed a significant increase (P < 0.001) in the mean (diabetic patients 166.0 ± 10.4 vs. control subjects 93.3 ± 1.5 mg/dl), the standard deviation (51.7 ± 4.3 vs. 11.1 ± 0.5 mg/dl), and the mean amplitude of glycemic excursions (127.0 ± 9.2 vs. 27.7 ± 1.3 mg/dl) of the glucose levels; and a significant decrease (P < 0.001) in the MSE complexity index (5.09 ± 0.23 vs. 7.38 ± 0.28). In conclusion, the complexity of glucose dynamics is decreased in diabetes. This finding implies the reactivity of glucoregulation is impaired in the diabetic patients. Such impairment presenting as an increased regularity of glycemic fluctuating pattern could be detected by MSE analysis. Thus, the MSE complexity index could potentially be used as a biomarker in the monitoring of diabetes.
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Nanotechnology in glucose monitoring: advances and challenges in the last 10 years.
Scognamiglio, Viviana
2013-09-15
In the last decades, a wide multitude of research activity has been focused on the development of biosensors for glucose monitoring, devoted to overcome the challenges associated with smart analytical performances with commercial implications. Crucial issues still nowadays elude biosensors to enter the market, such as sensitivity, stability, miniaturisation, continuous and in situ monitoring in a complex matrix. A noteworthy tendency of biosensor technology is likely to push towards nanotechnology, which allows to reduce dimensions at the nanoscale, consenting the construction of arrays for high throughput analysis with the integration of microfluidics, and enhancing the performance of the biological components by using new nanomaterials. This review aims to highlight current trends in biosensors for glucose monitoring based on nanotechnology, reporting widespread representative examples of the recent approaches for nanobiosensors over the past 10 years. Progress in nanotechnology for the development of biosensing systems for blood glucose level monitoring will be discussed, in view of their design and construction on the bases of the new materials offered by nanotechnology. Copyright © 2013 Elsevier B.V. All rights reserved.
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Non-invasive blood glucose monitor based on spectroscopy using a smartphone.
Dantu, Vishnu; Vempati, Jagannadh; Srivilliputhur, Srinivasan
2014-01-01
Development of a novel method for non-invasive measurement of blood glucose concentration using smartphone is discussed. Our research work has three major contributions to society and science. First, we modified and extended the Beer-Lambert's law in physics to accommodate for multiple wavelengths. This extension can aid researchers who wish to perform optical spectroscopy. Second, we successfully developed a creative and non-invasive way for diabetic patients to measure glucose levels via a smartphone. Researchers and chemists can now use their smartphones to determine the absorbance and, therefore, concentration of a chemical. Third, we created an inexpensive way to perform optical spectroscopy by using a smartphone. Monitoring blood glucose using a smartphone application that simply uses equipment already available on smartphones will improve the lives of diabetic patients who can continuously check their blood glucose levels while avoiding the current inconvenient, unhygienic, and costly invasive glucose meters.
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Yajima, Takahiro; Yajima, Kumiko; Hayashi, Makoto; Takahashi, Hiroshi; Yasuda, Keigo
2016-12-01
Appropriate glycemic control without hypoglycemia is important in patients with type 2 diabetes on hemodialysis. Teneligliptin, a novel dipeptidyl peptidase-4 inhibitor, can be used without dose adjustment for these patients. Using continuous glucose monitoring (CGM), we evaluated the efficacy and safety of adding teneligliptin to insulin therapy. Twenty-one type 2 diabetes mellitus patients on hemodialysis treated with insulin were enrolled. After the adjustment of insulin dose, their blood glucose level was monitored by CGM. Insulin dose was reduced after teneligliptin administration. The median total daily insulin dose significantly reduced from 18 (9-24)U to 6 (0-14)U (p<0.0001). Maximum, mean, and standard deviation of blood glucose level on the hemodialysis and non-hemodialysis days did not change after teneligliptin administration. However, minimum blood glucose level was significantly elevated on the hemodialysis day after teneligliptin administration (from 3.9±1.0mmol/L to 4.4±0.9mmol/L, p=0.040). The incidence of asymptomatic hypoglycemia on the hemodialysis day detected by CGM significantly decreased from 38.1% to 19.0% (p=0.049). Teneligliptin may contribute toward reducing the total daily insulin dose and preventing hypoglycemic events on the hemodialysis day in type 2 diabetes mellitus patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
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Freckmann, Guido; Hagenlocher, Sven; Baumstark, Annette; Jendrike, Nina; Gillen, Ralph C; Rössner, Katja; Haug, Cornelia
2007-09-01
This study investigated continuous glucose profiles in nondiabetic subjects. Continuous interstitial glucose measurement was performed under everyday life conditions (2 days) and after ingestion of four meals with standardized carbohydrate content (50 grams), but with different types of carbohydrates and variable protein and fat content. Twenty-four healthy volunteers (12 female, 12 male, age 27.1 +/- 3.6 years) participated in the study. Each subject wore two microdialysis devices (SCGM1, Roche Diagnostics) simultaneously. The mean 24-hour interstitial glucose concentration under everyday life conditions was 89.3 +/- 6.2 mg/dl (mean +/- SD, n = 21), and mean interstitial glucose concentrations at daytime and during the night were 93.0 +/- 7.0 and 81.8 +/- 6.3 mg/dl, respectively. The highest postprandial glucose concentrations were observed after breakfast: 132.3 +/- 16.7 mg/dl (range 101-168 mg/dl); peak concentrations after lunch and dinner were 118.2 +/- 13.4 and 123.0 +/- 16.9 mg/dl, respectively. Mean time to peak glucose concentration was between 46 and 50 minutes. After ingestion of standardized meals with fast absorption characteristics, peak interstitial glucose concentrations were 133.2 +/- 14.4 and 137.2 +/- 21.1 mg/dl, respectively. Meals with a higher fiber, protein, and fat content induced a smaller increase and a slower decrease of postprandial glucose concentrations with peak values of 99.2 +/- 10.5 and 122.1 +/- 20.4 mg/dl, respectively. This study provided continuous glucose profiles in nondiabetic subjects and demonstrated that differences in meal composition are reflected in postprandial interstitial glucose concentrations. Regarding the increasing application of continuous glucose monitoring in diabetic patients, these data suggest that detailed information about the ingested meals is important for adequate interpretation of postprandial glucose profiles.
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New Criteria for Assessing the Accuracy of Blood Glucose Monitors Meeting, October 28, 2011
Walsh, John; Roberts, Ruth; Vigersky, Robert A.; Schwartz, Frank
2012-01-01
Glucose meters (GMs) are routinely used for self-monitoring of blood glucose by patients and for point-of-care glucose monitoring by health care providers in outpatient and inpatient settings. Although widely assumed to be accurate, numerous reports of inaccuracies with resulting morbidity and mortality have been noted. Insulin dosing errors based on inaccurate GMs are most critical. On October 28, 2011, the Diabetes Technology Society invited 45 diabetes technology clinicians who were attending the 2011 Diabetes Technology Meeting to participate in a closed-door meeting entitled New Criteria for Assessing the Accuracy of Blood Glucose Monitors. This report reflects the opinions of most of the attendees of that meeting. The Food and Drug Administration (FDA), the public, and several medical societies are currently in dialogue to establish a new standard for GM accuracy. This update to the FDA standard is driven by improved meter accuracy, technological advances (pumps, bolus calculators, continuous glucose monitors, and insulin pens), reports of hospital and outpatient deaths, consumer complaints about inaccuracy, and research studies showing that several approved GMs failed to meet FDA or International Organization for Standardization standards in post-approval testing. These circumstances mandate a set of new GM standards that appropriately match the GMs’ analytical accuracy to the clinical accuracy required for their intended use, as well as ensuring their ongoing accuracy following approval. The attendees of the New Criteria for Assessing the Accuracy of Blood Glucose Monitors meeting proposed a graduated standard and other methods to improve GM performance, which are discussed in this meeting report. PMID:22538160
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New Criteria for Assessing the Accuracy of Blood Glucose Monitors meeting, October 28, 2011.
Walsh, John; Roberts, Ruth; Vigersky, Robert A; Schwartz, Frank
2012-03-01
Glucose meters (GMs) are routinely used for self-monitoring of blood glucose by patients and for point-of-care glucose monitoring by health care providers in outpatient and inpatient settings. Although widely assumed to be accurate, numerous reports of inaccuracies with resulting morbidity and mortality have been noted. Insulin dosing errors based on inaccurate GMs are most critical. On October 28, 2011, the Diabetes Technology Society invited 45 diabetes technology clinicians who were attending the 2011 Diabetes Technology Meeting to participate in a closed-door meeting entitled New Criteria for Assessing the Accuracy of Blood Glucose Monitors. This report reflects the opinions of most of the attendees of that meeting. The Food and Drug Administration (FDA), the public, and several medical societies are currently in dialogue to establish a new standard for GM accuracy. This update to the FDA standard is driven by improved meter accuracy, technological advances (pumps, bolus calculators, continuous glucose monitors, and insulin pens), reports of hospital and outpatient deaths, consumer complaints about inaccuracy, and research studies showing that several approved GMs failed to meet FDA or International Organization for Standardization standards in postapproval testing. These circumstances mandate a set of new GM standards that appropriately match the GMs' analytical accuracy to the clinical accuracy required for their intended use, as well as ensuring their ongoing accuracy following approval. The attendees of the New Criteria for Assessing the Accuracy of Blood Glucose Monitors meeting proposed a graduated standard and other methods to improve GM performance, which are discussed in this meeting report. © 2012 Diabetes Technology Society.
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Basement Membrane-Based Glucose Sensor Coatings Enhance Continuous Glucose Monitoring in Vivo.
Klueh, Ulrike; Qiao, Yi; Czajkowski, Caroline; Ludzinska, Izabela; Antar, Omar; Kreutzer, Donald L
2015-08-25
Implantable glucose sensors demonstrate a rapid decline in function that is likely due to biofouling of the sensor. Previous efforts directed at overcoming this issue has generally focused on the use of synthetic polymer coatings, with little apparent effect in vivo, clearly a novel approach is required. We believe that the key to extending sensor life span in vivo is the development of biocompatible basement membrane (BM) based bio-hydrogels as coatings for glucose sensors. BM based bio-hydrogel sensor coatings were developed using purified BM preparations (ie, Cultrex from Trevigen Inc). Modified Abbott sensors were coated with Cultrex BM extracts. Sensor performance was evaluated for the impact of these coatings in vitro and in vivo in a continuous glucose monitoring (CGM) mouse model. In vivo sensor function was assessed over a 28-day time period expressed as mean absolute relative difference (MARD) values. Tissue reactivity of both Cultrex coated and uncoated glucose sensors was evaluated at 7, 14, 21 and 28 days post-sensor implantation with standard histological techniques. The data demonstrate that Cultrex-based sensor coatings had no effect on glucose sensor function in vitro. In vivo glucose sensor performance was enhanced following BM coating as determined by MARD analysis, particularly in weeks 2 and 3. In vivo studies also demonstrated that Cultrex coatings significantly decreased sensor-induced tissue reactions at the sensor implantation sites. Basement-membrane-based sensor coatings enhance glucose sensor function in vivo, by minimizing or preventing sensor-induced tissues reactions. © 2015 Diabetes Technology Society.
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Umbrello, M; Salice, V; Spanu, P; Formenti, P; Barassi, A; Melzi d'Eril, G V; Iapichino, G
2014-10-01
The optimal level and modality of glucose control in critically ill patients is still debated. A protocolized approach and the use of nearly-continuous technologies are recommended to manage hyperglycemia, hypoglycemia and glycemic variability. We recently proposed a pato-physiology-based glucose control protocol which takes into account patient glucose/carbohydrate intake and insulin resistance. Aim of the present investigation was to assess the performance of our protocol with an automated intermittent plasma glucose monitoring device (OptiScanner™ 5000). OptiScanner™ was used in 6 septic patients, providing glucose measurement every 15' from a side-port of an indwelling central venous catheter. Target level of glucose was 80-150 mg/dL. Insulin infusion and kcal with nutritional support were also recorded. 6 septic patients were studied for 319 h (1277 measurements); 58 [45-65] hours for each patient (measurements/patient: 231 [172-265]). Blood glucose was at target for 93 [90-98]% of study time. Mean plasma glucose was 126 ± 11 mg/dL. Only 3 hypoglycemic episodes (78, 78, 69 mg/dL) were recorded. Glucose variability was limited: plasma glucose coefficient of variation was 11.7 ± 4.0% and plasma glucose standard deviation was 14.3 ± 5.5 mg/dL. The local glucose control protocol achieved satisfactory glucose control in septic patients along with a high degree of safeness. Automated intermittent plasma glucose monitoring seemed useful to assess the performance of the protocol. Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
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A glucose oxidase-coupled DNAzyme sensor for glucose detection in tears and saliva.
Liu, Chengcheng; Sheng, Yongjie; Sun, Yanhong; Feng, Junkui; Wang, Shijin; Zhang, Jin; Xu, Jiacui; Jiang, Dazhi
2015-08-15
Biosensors have been widely investigated and utilized in a variety of fields ranging from environmental monitoring to clinical diagnostics. Glucose biosensors have triggered great interest and have been widely exploited since glucose determination is essential for diabetes diagnosis. In here, we designed a novel dual-enzyme biosensor composed of glucose oxidase (GOx) and pistol-like DNAzyme (PLDz) to detect glucose levels in tears and saliva. First, GOx, as a molecular recognition element, catalyzes the oxidation of glucose forming H2O2; then PLDz recognizes the produced H2O2 as a secondary signal and performs a self-cleavage reaction promoted by Mn(2+), Co(2+) and Cu(2+). Thus, detection of glucose could be realized by monitoring the cleavage rate of PLDz. The slope of the cleavage rate of PLDz versus glucose concentration curve was fitted with a Double Boltzmann equation, with a range of glucose from 100 nM to 10mM and a detection limit of 5 μM. We further applied the GOx-PLDz 1.0 biosensor for glucose detection in tears and saliva, glucose levels in which are 720±81 μM and 405±56 μM respectively. Therefore, the GOx-PLDz 1.0 biosensor is able to determine glucose levels in tears and saliva as a noninvasive glucose biosensor, which is important for diabetic patients with frequent/continuous glucose monitoring requirements. In addition, induction of DNAzyme provides a new approach in the development of glucose biosensors. Copyright © 2015 Elsevier B.V. All rights reserved.
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An In-Line Photonic Biosensor for Monitoring of Glucose Concentrations
Al-Halhouli, Ala'aldeen; Demming, Stefanie; Alahmad, Laila; LIobera, Andreu; Büttgenbach, Stephanus
2014-01-01
This paper presents two PDMS photonic biosensor designs that can be used for continuous monitoring of glucose concentrations. The first design, the internally immobilized sensor, consists of a reactor chamber, micro-lenses and self-alignment structures for fiber optics positioning. This sensor design allows optical detection of glucose concentrations under continuous glucose flow conditions of 33 μL/h based on internal co-immobilization of glucose oxidase (GOX) and horseradish peroxidase (HRP) on the internal PDMS surface of the reactor chamber. For this design, two co-immobilization methods, the simple adsorption and the covalent binding (PEG) methods were tested. Experiments showed successful results when using the covalent binding (PEG) method, where glucose concentrations up to 5 mM with a coefficient of determination (R2) of 0.99 and a limit of detection of 0.26 mM are detectable. The second design is a modified version of the internally immobilized sensor, where a microbead chamber and a beads filling channel are integrated into the sensor. This modification enabled external co-immobilization of enzymes covalently onto functionalized silica microbeads and allows binding a huge amount of HRP and GOX enzymes on the microbeads surfaces which increases the interaction area between immobilized enzymes and the analyte. This has a positive effect on the amount and rate of chemical reactions taking place inside the chamber. The sensor was tested under continuous glucose flow conditions and was found to be able to detect glucose concentrations up to 10 mM with R2 of 0.98 and a limit of detection of 0.7 mM. Such results are very promising for the application in photonic LOC systems used for online analysis. PMID:25157552
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Hybrid CARS for Non-Invasive Blood Glucose Monitoring
NASA Astrophysics Data System (ADS)
Wang, Xi; Pestov, Dmitry; Zhang, Aihua; Murawski, Robert; Sokolov, Alexei; Welch, George; Laane, Jaan; Scully, Marlan
2007-10-01
We develop a spectroscopy technique that combines the advantages of both the frequency-resolved coherent anti-Stokes Raman scattering (CARS) and the time-resolved CARS. We use broadband preparation pulses to get an instantaneous coherent excitation of multiplex molecular vibration levels and subsequent optically shaped time-delayed narrowband probing pulse to detect these vibrations. This technique can suppress the nonresonant background and retrieve the molecular fingerprint signal efficiently and rapidly. We employ this technique to glucose detection, the final goal of which is accurate, non-invasive (i.e. painless) and continuous monitoring of blood glucose concentration in the Diabetes diagnosis to replace the current glucose measurement process, which requires painful fingerpricks and therefore cannot be performed more than a few times a day. We have gotten the CARS spectra of glucose aqueous solution down to 2 mM.
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Valletta, John Joseph; Chipperfield, Andrew J; Byrne, Christopher D
2009-01-01
Good blood glucose control is important to people with type 1 diabetes to prevent diabetes-related complications. Too much blood glucose (hyperglycaemia) causes long-term micro-vascular complications, while a severe drop in blood glucose (hypoglycaemia) can cause life-threatening coma. Finding the right balance between quantity and type of food intake, physical activity levels and insulin dosage, is a daily challenge. Increased physical activity levels often cause changes in blood glucose due to increased glucose uptake into tissues such as muscle. To date we have limited knowledge about the minute by minute effects of exercise on blood glucose levels, in part due to the difficulty in measuring glucose and physical activity levels continuously, in a free-living environment. By using a light and user-friendly armband we can record physical activity energy expenditure on a minute-by-minute basis. Simultaneously, by using a continuous glucose monitoring system we can record glucose concentrations. In this paper, Gaussian Processes are used to model the glucose excursions in response to physical activity data, to study its effect on glycaemic control.
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Logtenberg, Susan J J; Kleefstra, Nanne; Groenier, Klaas H; Gans, Rijk O B; Bilo, Henk J G
2009-05-01
In diabetes, strict glycemic control reduces risk of complications. One mode of therapy is continuous intraperitoneal insulin infusion (CIPII). With CIPII, like all intensified treatment strategies, frequent assessment of glucose levels is mandatory. Real-time (RT)-continuous glucose monitoring (CGM) gives RT information without the need for multiple invasive measurements. In theory, CIPII combined with RT-CGM could provide near normal glucose profiles. The objective of this study is to investigate effectiveness and safety of RT-CGM in patients treated with intraperitoneal insulin through an implanted pump. In an open-label, crossover, randomized study, effects of 6-day open RT-CGM use were studied in 12 type 1 diabetes patients on CIPII, with blinded RT-CGM used as a control. Primary outcome was time in euglycemia. Secondary outcomes included time in other glucose ranges, incidence of adverse events, and patient satisfaction. Agreement of self-measurement of blood glucose (SMBG) and RT-CGM measurements was assessed. Median time spent in euglycemia was 68.2% (55.9-72.3%) with open RT-CGM and 64.9% (55.3-71.2%) with blinded RT-CGM (P = 0.25). Time spent in other glucose ranges did not differ (P > 0.05). There were no serious adverse events. Patient satisfaction was good. Median relative absolute difference of SMBG and RT-CGM values was 13.9%. Bland-Altman analysis showed a mean difference of -0.31 mg/dL with lower and upper limits of agreement of -77.0 and +76.4 mg/dL, respectively. Short-term use of RT-CGM, although safe and with good patient satisfaction, does not result in more time spent in euglycemia, nor does it change time spent in other glucose ranges in our population of type 1 diabetes patients receiving CIPII.
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Technology to optimize pediatric diabetes management and outcomes.
Markowitz, Jessica T; Harrington, Kara R; Laffel, Lori M B
2013-12-01
Technology for diabetes management is rapidly developing and changing. With each new development, there are numerous factors to consider, including medical benefits, impact on quality of life, ease of use, and barriers to use. It is also important to consider the interaction between developmental stage and technology. This review considers a number of newer diabetes-related technologies and explores issues related to their use in the pediatric diabetes population (including young adults), with a focus on psychosocial factors. Areas include trend technology in blood glucose monitoring, continuous glucose monitoring, sensor-augmented insulin pumps and low glucose suspend functions, internet applications including videoconferencing, mobile applications (apps), text messaging, and online gaming.
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Price, David
2017-01-01
The FDA recently expanded the approved use of Dexcom’s G5 Mobile continuous glucose monitoring (CGM) system to allow for diabetes treatment decisions. This decision is expected to reduce the burden of SMBG testing and increase the adoption and persistent use of CGM. The safety of nonadjunctive CGM use was questioned because of sporadic large discrepancies between CGM and SMBG values. These data were viewed in the context of complaints found in the FDA MAUDE database and social media postings. This commentary provides additional perspective on the inferences that can be drawn from these reports and the risk of nonadjunctive use of CGM data. PMID:28654305
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Britton, Katherine E; Britton-Colonnese, Jennifer D
2017-03-01
Being able to track, analyze, and use data from continuous glucose monitors (CGMs) and through platforms and apps that communicate with CGMs helps achieve better outcomes and can advance the understanding of diabetes. The risks to patients' expectation of privacy are great, and their ability to control how their information is collected, stored, and used is virtually nonexistent. Patients' physical security is also at risk if adequate cybersecurity measures are not taken. Currently, data privacy and security protections are not robust enough to address the privacy and security risks and stymies the current and future benefits of CGM and the platforms and apps that communicate with them.
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Britton, Katherine E.; Britton-Colonnese, Jennifer D.
2017-01-01
Being able to track, analyze, and use data from continuous glucose monitors (CGMs) and through platforms and apps that communicate with CGMs helps achieve better outcomes and can advance the understanding of diabetes. The risks to patients’ expectation of privacy are great, and their ability to control how their information is collected, stored, and used is virtually nonexistent. Patients’ physical security is also at risk if adequate cybersecurity measures are not taken. Currently, data privacy and security protections are not robust enough to address the privacy and security risks and stymies the current and future benefits of CGM and the platforms and apps that communicate with them. PMID:28264188
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Capoccia, D; Coccia, F; Guida, A; Rizzello, M; De Angelis, F; Silecchia, G; Leonetti, F
2015-01-01
The study was carried out on type 2 diabetic obese patients who underwent laparoscopic sleeve gastrectomy (LSG). Patients underwent regular glycemic controls throughout 3 years and all patients were defined cured from diabetes according to conventional criteria defined as normalization of fasting glucose levels and glycated hemoglobin in absence of antidiabetic therapy. After 3 years of follow-up, Continuous Glucose Monitoring (CGM) was performed in each patient to better clarify the remission of diabetes. In this study, we found that the diabetes resolution after LSG occurred in 40% of patients; in the other 60%, even if they showed a normal fasting glycemia and A1c, patients spent a lot of time in hyperglycemia. During the oral glucose tolerance test (OGTT), we found that 2 h postload glucose determinations revealed overt diabetes only in a small group of patients and might be insufficient to exclude the diagnosis of diabetes in the other patients who spent a lot of time in hyperglycemia, even if they showed a normal glycemia (<140 mg/dL) at 120 minutes OGTT. These interesting data could help clinicians to better individualize patients in which diabetes is not resolved and who could need more attention in order to prevent chronic complications of diabetes.
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Karstoft, Kristian; Winding, Kamilla; Knudsen, Sine H; Nielsen, Jens S; Thomsen, Carsten; Pedersen, Bente K; Solomon, Thomas P J
2013-02-01
To evaluate the feasibility of free-living walking training in type 2 diabetic patients and to investigate the effects of interval-walking training versus continuous-walking training upon physical fitness, body composition, and glycemic control. Subjects with type 2 diabetes were randomized to a control (n = 8), continuous-walking (n = 12), or interval-walking group (n = 12). Training groups were prescribed five sessions per week (60 min/session) and were controlled with an accelerometer and a heart-rate monitor. Continuous walkers performed all training at moderate intensity, whereas interval walkers alternated 3-min repetitions at low and high intensity. Before and after the 4-month intervention, the following variables were measured: VO(2)max, body composition, and glycemic control (fasting glucose, HbA(1c), oral glucose tolerance test, and continuous glucose monitoring [CGM]). Training adherence was high (89 ± 4%), and training energy expenditure and mean intensity were comparable. VO(2)max increased 16.1 ± 3.7% in the interval-walking group (P < 0.05), whereas no changes were observed in the continuous-walking or control group. Body mass and adiposity (fat mass and visceral fat) decreased in the interval-walking group only (P < 0.05). Glycemic control (elevated mean CGM glucose levels and increased fasting insulin) worsened in the control group (P < 0.05), whereas mean (P = 0.05) and maximum (P < 0.05) CGM glucose levels decreased in the interval-walking group. The continuous walkers showed no changes in glycemic control. Free-living walking training is feasible in type 2 diabetic patients. Continuous walking offsets the deterioration in glycemia seen in the control group, and interval walking is superior to energy expenditure-matched continuous walking for improving physical fitness, body composition, and glycemic control.
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Long-term microfluidic glucose and lactate monitoring in hepatic cell culture
Prill, Sebastian; Jaeger, Magnus S.; Duschl, Claus
2014-01-01
Monitoring cellular bioenergetic pathways provides the basis for a detailed understanding of the physiological state of a cell culture. Therefore, it is widely used as a tool amongst others in the field of in vitro toxicology. The resulting metabolic information allows for performing in vitro toxicology assays for assessing drug-induced toxicity. In this study, we demonstrate the value of a microsystem for the fully automated detection of drug-induced changes in cellular viability by continuous monitoring of the metabolic activity over several days. To this end, glucose consumption and lactate secretion of a hepatic tumor cell line were continuously measured using microfluidically addressed electrochemical sensors. Adapting enzyme-based electrochemical flat-plate sensors, originally designed for human whole-blood samples, to their use with cell culture medium supersedes the common manual and laborious colorimetric assays and off-line operated external measurement systems. The cells were exposed to different concentrations of the mitochondrial inhibitor rotenone and the cellular response was analyzed by detecting changes in the rates of the glucose and lactate metabolism. Thus, the system provides real-time information on drug-induced liver injury in vitro. PMID:24926387
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Uettwiller, Florence; Chemin, Aude; Bonnemaison, Elisabeth; Favrais, Géraldine; Saliba, Elie; Labarthe, François
2015-01-01
Objectives Hypoglycemia is frequent in very low birth weight (VLBW) neonates and compromises their neurological outcome. The aim of this study was to compare real-time continuous glucose monitoring system (RT-CGMS) to standard methods by intermittent capillary blood glucose testing in detecting and managing hypoglycemia. Study design Forty-eight VLBW neonates were enrolled in this prospective study. During their 3 first days of life, their glucose level was monitored either by RT-CGMS (CGM-group), or by intermittent capillary glucose testing (IGM-group) associated with a blind-CGMS to detect retrospectively missed hypoglycemia. Outcomes were the number and duration of hypoglycemic (≤50mg/dl) episodes per patient detected by CGMS. Results Forty-three monitorings were analyzed (IGM n = 21, CGM n = 22), with a median recording time of 72 hours. In the IGM group, blind-CGMS revealed a significantly higher number of hypoglycemia episodes than capillary blood glucose testing (1.2±0.4 vs 0.4±0.2 episode/patient, p<0.01). In the CGM-group, the use of RT-CGMS made it possible (i) to detect the same number of hypoglycemia episodes as blind-CGMS (1.2±0.4 episode/patient), (ii) to adapt the glucose supply in neonates with hypoglycemia (increased supply during days 1 and 2), and (iii) to significantly reduce the duration of hypoglycemia episodes per patient (CGM 44[10–140] min versus IGM 95[15–520] min, p<0.05). Furthermore, it reduced the number of blood samples (CGM 16.9±1.0 vs IGM 21.9±1.0 blood sample/patient, p<0.001). Conclusion RT-CGMS played a beneficial role in managing hypoglycemia in VLBW neonates by adjusting the carbohydrate supply to the individual needs and by reducing the duration of hypoglycemia episodes. The clinical significance of the biological differences observed in our study need to be explored. PMID:25590334
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Leal, Yenny; Gonzalez-Abril, Luis; Lorencio, Carol; Bondia, Jorge; Vehi, Josep
2013-07-01
Support vector machines (SVMs) are an attractive option for detecting correct and incorrect measurements in real-time continuous glucose monitoring systems (RTCGMSs), because their learning mechanism can introduce a postprocessing strategy for imbalanced datasets. The proposed SVM considers the geometric mean to obtain a more balanced performance between sensitivity and specificity. To test this approach, 23 critically ill patients receiving insulin therapy were monitored over 72 h using an RTCGMS, and a dataset of 537 samples, classified according to International Standards Organization (ISO) criteria (372 correct and 165 incorrect measurements), was obtained. The results obtained were promising for patients with septic shock or with sepsis, for which the proposed system can be considered as reliable. However, this approach cannot be considered suitable for patients without sepsis.
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Rawlings, Renata A; Shi, Hang; Yuan, Lo-Hua; Brehm, William; Pop-Busui, Rodica; Nelson, Patrick W
2011-12-01
Several metrics of glucose variability have been proposed to date, but an integrated approach that provides a complete and consistent assessment of glycemic variation is missing. As a consequence, and because of the tedious coding necessary during quantification, most investigators and clinicians have not yet adopted the use of multiple glucose variability metrics to evaluate glycemic variation. We compiled the most extensively used statistical techniques and glucose variability metrics, with adjustable hyper- and hypoglycemic limits and metric parameters, to create a user-friendly Continuous Glucose Monitoring Graphical User Interface for Diabetes Evaluation (CGM-GUIDE©). In addition, we introduce and demonstrate a novel transition density profile that emphasizes the dynamics of transitions between defined glucose states. Our combined dashboard of numerical statistics and graphical plots support the task of providing an integrated approach to describing glycemic variability. We integrated existing metrics, such as SD, area under the curve, and mean amplitude of glycemic excursion, with novel metrics such as the slopes across critical transitions and the transition density profile to assess the severity and frequency of glucose transitions per day as they move between critical glycemic zones. By presenting the above-mentioned metrics and graphics in a concise aggregate format, CGM-GUIDE provides an easy to use tool to compare quantitative measures of glucose variability. This tool can be used by researchers and clinicians to develop new algorithms of insulin delivery for patients with diabetes and to better explore the link between glucose variability and chronic diabetes complications.
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Rawlings, Renata A.; Shi, Hang; Yuan, Lo-Hua; Brehm, William; Pop-Busui, Rodica
2011-01-01
Abstract Background Several metrics of glucose variability have been proposed to date, but an integrated approach that provides a complete and consistent assessment of glycemic variation is missing. As a consequence, and because of the tedious coding necessary during quantification, most investigators and clinicians have not yet adopted the use of multiple glucose variability metrics to evaluate glycemic variation. Methods We compiled the most extensively used statistical techniques and glucose variability metrics, with adjustable hyper- and hypoglycemic limits and metric parameters, to create a user-friendly Continuous Glucose Monitoring Graphical User Interface for Diabetes Evaluation (CGM-GUIDE©). In addition, we introduce and demonstrate a novel transition density profile that emphasizes the dynamics of transitions between defined glucose states. Results Our combined dashboard of numerical statistics and graphical plots support the task of providing an integrated approach to describing glycemic variability. We integrated existing metrics, such as SD, area under the curve, and mean amplitude of glycemic excursion, with novel metrics such as the slopes across critical transitions and the transition density profile to assess the severity and frequency of glucose transitions per day as they move between critical glycemic zones. Conclusions By presenting the above-mentioned metrics and graphics in a concise aggregate format, CGM-GUIDE provides an easy to use tool to compare quantitative measures of glucose variability. This tool can be used by researchers and clinicians to develop new algorithms of insulin delivery for patients with diabetes and to better explore the link between glucose variability and chronic diabetes complications. PMID:21932986
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Bode, Bruce; Gross, Kenneth; Rikalo, Nancy; Schwartz, Sherwyn; Wahl, Timothy; Page, Casey; Gross, Todd; Mastrototaro, John
2004-04-01
The purposes of this study were to demonstrate the accuracy and effectiveness of the Guardian Continuous Monitoring System (Medtronic MiniMed, Northridge, California) and to demonstrate that the application of real-time alarms to continuous monitoring alerts users to hypo and hyperglycemia and reduces excursions in people with diabetes. A total of 71 subjects with type 1 diabetes, mean hemoglobin A1c of 7.6 +/- 1.1%, age 44.0 +/- 11.4 years, and duration of diabetes 23.6 +/- 10.6 years were enrolled in this two-period, randomized, multicenter study. Subjects were randomized into either an Alert group or a Control group. The accuracy of the Guardian was evaluated by treating the study data as a single-sample correlational design. Effectiveness of the Guardian alerts was evaluated by comparing the Alert group with the Control group. The mean (median) absolute relative error between home blood glucose meter readings and sensor values was 21.3% (17.3%), and the Guardian, on average, read 12.8 mg/dL below the concurrent home blood glucose meter readings. The hypoglycemia alert was able to distinguished glucose values < or =70 mg/dL with 67% sensitivity, 90% specificity, and 47% false alerts. The hyperglycemia alert showed a similar ability to detect sensor values > or =250 mg/dL with 63% sensitivity, 97% specificity, and 19% false alerts. The Alert group demonstrated a median decrease in the duration of hypoglycemic excursions (-27.8 min) that was significantly greater than the median decrease in the duration of hypoglycemic excursions in the Control group (-4.5 min) (P = 0.03). A marginally significant increase in the frequency of hyperglycemic excursions (P = 0.07) between Period 1 and Period 2 was accompanied by a decrease of 9.6 min in the duration of hyperglycemic excursions in the Alert group. Glucose measurements differ between blood samples taken from the finger and interstitial fluid, especially when levels are changing rapidly; however, these results demonstrate that the Guardian is reasonably accurate while performing continuous glucose monitoring. The subjects' responses to hypoglycemia alerts resulted in a significant reduction in the duration of hypoglycemic excursions; however, overtreating hypoglycemia may have resulted in a marginally significant increase in the frequency of hyperglycemic excursions.
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Recent Updates on Type 1 Diabetes Mellitus Management for Clinicians
Iqbal, Ahmed; Novodvorsky, Peter
2018-01-01
Type 1 diabetes mellitus (T1DM) is a chronic autoimmune condition that requires life-long administration of insulin. Optimal management of T1DM entails a good knowledge and understanding of this condition both by the physician and the patient. Recent introduction of novel insulin preparations, technological advances in insulin delivery and glucose monitoring, such as continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring and improved understanding of the detrimental effects of hypoglycaemia and hyperglycaemia offer new opportunities and perspectives in T1DM management. Evidence from clinical trials suggests an important role of structured patient education. Our efforts should be aimed at improved metabolic control with concomitant reduction of hypoglycaemia. Despite recent advances, these goals are not easy to achieve and can put significant pressure on people with T1DM. The approach of physicians should therefore be maximally supportive. In this review, we provide an overview of the recent advances in T1DM management focusing on novel insulin preparations, ways of insulin administration and glucose monitoring and the role of metformin or sodium-glucose co-transporter 2 inhibitors in T1DM management. We then discuss our current understanding of the effects of hypoglycaemia on human body and strategies aimed at mitigating the risks associated with hypoglycaemia. PMID:29504302
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Application of optical lens of a CD writer for detecting the blood glucose semi-invasively
NASA Astrophysics Data System (ADS)
Meshram, N. D.; Dahikar, P. B.
2014-10-01
Recent technological advancements in the photonics industry have led to a resurgence of interest in optical glucose sensing and to realistic progress toward the development of an optical glucose sensor. Such a sensor has the potential to significantly improve the quality of life for the estimated 16 million diabetics in this country by making routine glucose measurements more convenient. Currently over 100 small companies and universities are working to develop noninvasive or minimally invasive glucose sensing technologies, and optical methods play a large role in these efforts. It has become overwhelmingly clear that frequent monitoring and tight control of blood sugar levels are requisite for effective management of Diabetes mellitus and reduction of the complications associated with this disease. The pain and trouble associated with current "finger-stick" methods for blood glucose monitoring result in decreased patient compliance and a failure to control blood sugar levels. Thus, the development of a convenient noninvasive blood glucose monitor holds the potential to significantly reduce the morbidity and mortality associated with Diabetes. A method and apparatus for noninvasive measurement of blood glucose concentration based on transilluminated laser beam via the Index Finger has been reported in this paper. This method depends on photodiode based laser operating at 632.8 nm wavelength. During measurement, the index finger is inserted into the glucose sensing unit, the transilluminated optical signal is converted into an electrical signal, compared with the reference electrical signal, and the obtained difference signal is processed by signal processing unit which presents the results in the form of blood glucose concentration. This method would enable the monitoring blood glucose level of the diabetic patient continuously, safely and noninvasively..
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Application of optical lens of a CD writer for detecting the blood glucose semi-invasively
DOE Office of Scientific and Technical Information (OSTI.GOV)
Meshram, N. D., E-mail: meshramnileshsd@gmail.com; Dahikar, P. B., E-mail: pbdahikar@rediffmail.com
Recent technological advancements in the photonics industry have led to a resurgence of interest in optical glucose sensing and to realistic progress toward the development of an optical glucose sensor. Such a sensor has the potential to significantly improve the quality of life for the estimated 16 million diabetics in this country by making routine glucose measurements more convenient. Currently over 100 small companies and universities are working to develop noninvasive or minimally invasive glucose sensing technologies, and optical methods play a large role in these efforts. It has become overwhelmingly clear that frequent monitoring and tight control of bloodmore » sugar levels are requisite for effective management of Diabetes mellitus and reduction of the complications associated with this disease. The pain and trouble associated with current “finger-stick” methods for blood glucose monitoring result in decreased patient compliance and a failure to control blood sugar levels. Thus, the development of a convenient noninvasive blood glucose monitor holds the potential to significantly reduce the morbidity and mortality associated with Diabetes. A method and apparatus for noninvasive measurement of blood glucose concentration based on transilluminated laser beam via the Index Finger has been reported in this paper. This method depends on photodiode based laser operating at 632.8 nm wavelength. During measurement, the index finger is inserted into the glucose sensing unit, the transilluminated optical signal is converted into an electrical signal, compared with the reference electrical signal, and the obtained difference signal is processed by signal processing unit which presents the results in the form of blood glucose concentration. This method would enable the monitoring blood glucose level of the diabetic patient continuously, safely and noninvasively.« less
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Signal, Matthew; Thomas, Felicity; Shaw, Geoffrey M.; Chase, J. Geoffrey
2013-01-01
Background Critically ill patients often experience high levels of insulin resistance and stress-induced hyperglycemia, which may negatively impact outcomes. However, evidence surrounding the causes of negative outcomes remains inconclusive. Continuous glucose monitoring (CGM) devices allow researchers to investigate glucose complexity, using detrended fluctuation analysis (DFA), to determine whether it is associated with negative outcomes. The aim of this study was to investigate the effects of CGM device type/calibration and CGM sensor location on results from DFA. Methods This study uses CGM data from critically ill patients who were each monitored concurrently using Medtronic iPro2s on the thigh and abdomen and a Medtronic Guardian REAL-Time on the abdomen. This allowed interdevice/calibration type and intersensor site variation to be assessed. Detrended fluctuation analysis is a technique that has previously been used to determine the complexity of CGM data in critically ill patients. Two variants of DFA, monofractal and multifractal, were used to assess the complexity of sensor glucose data as well as the precalibration raw sensor current. Monofractal DFA produces a scaling exponent (H), where H is inversely related to complexity. The results of multifractal DFA are presented graphically by the multifractal spectrum. Results From the 10 patients recruited, 26 CGM devices produced data suitable for analysis. The values of H from abdominal iPro2 data were 0.10 (0.03–0.20) higher than those from Guardian REAL-Time data, indicating consistently lower complexities in iPro2 data. However, repeating the analysis on the raw sensor current showed little or no difference in complexity. Sensor site had little effect on the scaling exponents in this data set. Finally, multifractal DFA revealed no significant associations between the multifractal spectrums and CGM device type/calibration or sensor location. Conclusions Monofractal DFA results are dependent on the device/calibration used to obtain CGM data, but sensor location has little impact. Future studies of glucose complexity should consider the findings presented here when designing their investigations. PMID:24351175
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Klueh, Ulrike; Antar, Omar; Qiao, Yi; Kreutzer, Donald L.
2014-01-01
The concept of increased blood vessel (BV) density proximal to glucose sensors implanted in the interstitial tissue increases the accuracy and lifespan of sensors is accepted, despite limited existing experimental data. Interestingly, there is no previous data or even conjecture in the literature on the role of lymphatic vessels (LV) alone, or in combination with BV, in enhancing continuous glucose monitoring (CGM) in vivo. To investigate the impact of inducing vascular networks (BV and LV) at sites of glucose sensor implantation, we utilized adenovirus based local gene therapy of vascular endothelial cell growth factor-A (VEGF-A) to induce vessels at sensor implantation sites. The results of these studies demonstrated that 1) VEGF-A based local gene therapy increases vascular networks (blood vessels and lymphatic vessels) at sites of glucose sensor implantation; and 2) this local increase of vascular networks enhances glucose sensor function in vivo from 7 days to greater than 28 days post sensor implantation. This data provides “proof of concept” for the effective usage of local angiogenic factor (AF) gene therapy in mammalian models in an effort to extend CGM in vivo. It also supports the practice of a variety of viral and non-viral vectors as well as gene products (e.g. anti-inflammatory and anti-fibrosis genes) to engineer “implant friendly tissues” for the usage with implantable glucose sensors as well as other implantable devices. PMID:24243850
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BioMEMS for multiparameter clinical monitoring
NASA Astrophysics Data System (ADS)
Moser, Isabella
2003-01-01
For diabetes patients glucose monitoring means an important improvement of their life quality and additionally it is a $3-billion-a-year business. Continuous glucose monitoring provides gapless glucose level control, an early warning of hypoglycemia, and is intended to control insulin pumps. An upgrading to multi-parameter monitoring would not only benefit patients with severe metabolism defects but also the metabolism of diabetes patient could be better controlled by monitoring an additional parameter like lactate. Multi-parameter monitoring devices are not commercially available, one of the complications in the integration of different biosensors using the same detecting molecule for all analytes is chemical cross talk between adjacent amperometric biosensors. Recently some integrated biosensors were published but either they were not mass producible or they were realized in an expensive silicon based technology. In addition to it most of them were not tested under monitoring conditions but their integration principles will be discussed. As an example a low cost multi- parameter microsystem and some applications of it in clinical diagnosis will be presented. Also an overlook of non-invasive methods and (minimal) invasive methods will be given with a focus on microdialysis.
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Helminen, Olli; Pokka, Tytti; Tossavainen, Päivi; Ilonen, Jorma; Knip, Mikael; Veijola, Riitta
2016-10-01
Continuous glucose monitoring (CGM) parameters, self-monitored blood glucose (SMBG), HbA1c and oral glucose tolerance test (OGTT) were studied during preclinical type 1 diabetes mellitus. Ten asymptomatic children with multiple (⩾2) islet autoantibodies (cases) and 10 age and sex-matched autoantibody-negative controls from the Type 1 Diabetes Prediction and Prevention (DIPP) Study were invited to 7-day CGM with Dexcom G4 Platinum Sensor. HbA1c and two daily SMBG values (morning and evening) were analyzed. Five-point OGTTs were performed and carbohydrate intake was assessed by food records. The matched pairs were compared with the paired sample t-test. The cases showed higher mean values and higher variation in glucose levels during CGM compared to the controls. The time spent ⩾7.8mmol/l was 5.8% in the cases compared to 0.4% in the controls (p=0.040). Postprandial CGM values were similar except after the dinner (6.6mmol/l in cases vs. 6.1mmol/l in controls; p=0.023). When analyzing the SMBG values higher mean level, higher evening levels, as well as higher variation were observed in the cases when compared to the controls. HbA1c was significantly higher in the cases [5.7% (39mmol/mol) vs. 5.3% (34mmol/mol); p=0.045]. No differences were observed in glucose or C-peptide levels during OGTT. Daily carbohydrate intake was slightly higher in the cases (254.2g vs. 217.7g; p=0.034). Glucose levels measured by CGM and SMBG are useful indicators of dysglycemia during preclinical type 1 diabetes mellitus. Increased evening glucose values seem to be common in children with preclinical type 1 diabetes mellitus. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
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Fonseca, Vivian A; Grunberger, George; Anhalt, Henry; Bailey, Timothy S; Blevins, Thomas; Garg, Satish K; Handelsman, Yehuda; Hirsch, Irl B; Orzeck, Eric A; Roberts, Victor Lawrence; Tamborlane, William
2016-08-01
Barriers to continuous glucose monitoring (CGM) use continue to hamper adoption of this valuable technology for the management of diabetes. The American Association of Clinical Endocrinologists and the American College of Endocrinology convened a public consensus conference February 20, 2016, to review available CGM data and propose strategies for expanding CGM access. Conference participants agreed that evidence supports the benefits of CGM in type 1 diabetes and that these benefits are likely to apply whenever intensive insulin therapy is used, regardless of diabetes type. CGM is likely to reduce healthcare resource utilization for acute and chronic complications, although real-world analyses are needed to confirm potential cost savings and quality of life improvements. Ongoing technological advances have improved CGM accuracy and usability, but more innovations in human factors, data delivery, reporting, and interpretation are needed to foster expanded use. The development of a standardized data report using similar metrics across all devices would facilitate clinician and patient understanding and utilization of CGM. Expanded CGM coverage by government and private payers is an urgent need. CGM improves glycemic control, reduces hypoglycemia, and may reduce overall costs of diabetes management. Expanding CGM coverage and utilization is likely to improve the health outcomes of people with diabetes. A1C = glycated hemoglobin AACE = American Association of Clinical Endocrinologists ACE = American College of Endocrinology ASPIRE = Automation to Simulate Pancreatic Insulin Response CGM = continuous glucose monitoring HRQOL = health-related quality of life ICER = incremental cost-effectiveness ratio JDRF = Juvenile Diabetes Research Foundation MARD = mean absolute relative difference MDI = multiple daily injections QALY = quality-adjusted life years RCT = randomized, controlled trial SAP = sensor-augmented pump SMBG = self-monitoring of blood glucose STAR = Sensor-Augmented Pump Therapy for A1C Reduction T1D = type 1 diabetes T2D = type 2 diabetes.
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Leelarathna, Lalantha; English, Shane W; Thabit, Hood; Caldwell, Karen; Allen, Janet M; Kumareswaran, Kavita; Wilinska, Malgorzata E; Nodale, Marianna; Haidar, Ahmad; Evans, Mark L; Burnstein, Rowan; Hovorka, Roman
2014-02-01
Accurate real-time continuous glucose measurements may improve glucose control in the critical care unit. We evaluated the accuracy of the FreeStyle(®) Navigator(®) (Abbott Diabetes Care, Alameda, CA) subcutaneous continuous glucose monitoring (CGM) device in critically ill adults using two methods of calibration. In a randomized trial, paired CGM and reference glucose (hourly arterial blood glucose [ABG]) were collected over a 48-h period from 24 adults with critical illness (mean±SD age, 60±14 years; mean±SD body mass index, 29.6±9.3 kg/m(2); mean±SD Acute Physiology and Chronic Health Evaluation score, 12±4 [range, 6-19]) and hyperglycemia. In 12 subjects, the CGM device was calibrated at variable intervals of 1-6 h using ABG. In the other 12 subjects, the sensor was calibrated according to the manufacturer's instructions (1, 2, 10, and 24 h) using arterial blood and the built-in point-of-care glucometer. In total, 1,060 CGM-ABG pairs were analyzed over the glucose range from 4.3 to 18.8 mmol/L. Using enhanced calibration median (interquartile range) every 169 (122-213) min, the absolute relative deviation was lower (7.0% [3.5, 13.0] vs. 12.8% [6.3, 21.8], P<0.001), and the percentage of points in the Clarke error grid Zone A was higher (87.8% vs. 70.2%). Accuracy of the Navigator CGM device during critical illness was comparable to that observed in non-critical care settings. Further significant improvements in accuracy may be obtained by frequent calibrations with ABG measurements.
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Leelarathna, Lalantha; English, Shane W.; Thabit, Hood; Caldwell, Karen; Allen, Janet M.; Kumareswaran, Kavita; Wilinska, Malgorzata E.; Nodale, Marianna; Haidar, Ahmad; Evans, Mark L.; Burnstein, Rowan
2014-01-01
Abstract Objective: Accurate real-time continuous glucose measurements may improve glucose control in the critical care unit. We evaluated the accuracy of the FreeStyle® Navigator® (Abbott Diabetes Care, Alameda, CA) subcutaneous continuous glucose monitoring (CGM) device in critically ill adults using two methods of calibration. Subjects and Methods: In a randomized trial, paired CGM and reference glucose (hourly arterial blood glucose [ABG]) were collected over a 48-h period from 24 adults with critical illness (mean±SD age, 60±14 years; mean±SD body mass index, 29.6±9.3 kg/m2; mean±SD Acute Physiology and Chronic Health Evaluation score, 12±4 [range, 6–19]) and hyperglycemia. In 12 subjects, the CGM device was calibrated at variable intervals of 1–6 h using ABG. In the other 12 subjects, the sensor was calibrated according to the manufacturer's instructions (1, 2, 10, and 24 h) using arterial blood and the built-in point-of-care glucometer. Results: In total, 1,060 CGM–ABG pairs were analyzed over the glucose range from 4.3 to 18.8 mmol/L. Using enhanced calibration median (interquartile range) every 169 (122–213) min, the absolute relative deviation was lower (7.0% [3.5, 13.0] vs. 12.8% [6.3, 21.8], P<0.001), and the percentage of points in the Clarke error grid Zone A was higher (87.8% vs. 70.2%). Conclusions: Accuracy of the Navigator CGM device during critical illness was comparable to that observed in non–critical care settings. Further significant improvements in accuracy may be obtained by frequent calibrations with ABG measurements. PMID:24180327
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Thomas, Felicity; Signal, Matthew; Chase, J. Geoffrey
2015-01-01
Patients admitted to critical care often experience dysglycemia and high levels of insulin resistance, various intensive insulin therapy protocols and methods have attempted to safely normalize blood glucose (BG) levels. Continuous glucose monitoring (CGM) devices allow glycemic dynamics to be captured much more frequently (every 2-5 minutes) than traditional measures of blood glucose and have begun to be used in critical care patients and neonates to help monitor dysglycemia. In an attempt to obtain a better insight relating biomedical signals and patient status, some researchers have turned toward advanced time series analysis methods. In particular, Detrended Fluctuation Analysis (DFA) has been a topic of many recent studies in to glycemic dynamics. DFA investigates the “complexity” of a signal, how one point in time changes relative to its neighboring points, and DFA has been applied to signals like the inter-beat-interval of human heartbeat to differentiate healthy and pathological conditions. Analyzing the glucose metabolic system with such signal processing tools as DFA has been enabled by the emergence of high quality CGM devices. However, there are several inconsistencies within the published work applying DFA to CGM signals. Therefore, this article presents a review and a “how-to” tutorial of DFA, and in particular its application to CGM signals to ensure the methods used to determine complexity are used correctly and so that any relationship between complexity and patient outcome is robust. PMID:26134835
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Continuous Glucose Monitoring and Trend Accuracy
Gottlieb, Rebecca; Le Compte, Aaron; Chase, J. Geoffrey
2014-01-01
Continuous glucose monitoring (CGM) devices are being increasingly used to monitor glycemia in people with diabetes. One advantage with CGM is the ability to monitor the trend of sensor glucose (SG) over time. However, there are few metrics available for assessing the trend accuracy of CGM devices. The aim of this study was to develop an easy to interpret tool for assessing trend accuracy of CGM data. SG data from CGM were compared to hourly blood glucose (BG) measurements and trend accuracy was quantified using the dot product. Trend accuracy results are displayed on the Trend Compass, which depicts trend accuracy as a function of BG. A trend performance table and Trend Index (TI) metric are also proposed. The Trend Compass was tested using simulated CGM data with varying levels of error and variability, as well as real clinical CGM data. The results show that the Trend Compass is an effective tool for differentiating good trend accuracy from poor trend accuracy, independent of glycemic variability. Furthermore, the real clinical data show that the Trend Compass assesses trend accuracy independent of point bias error. Finally, the importance of assessing trend accuracy as a function of BG level is highlighted in a case example of low and falling BG data, with corresponding rising SG data. This study developed a simple to use tool for quantifying trend accuracy. The resulting trend accuracy is easily interpreted on the Trend Compass plot, and if required, performance table and TI metric. PMID:24876437
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Basement Membrane-Based Glucose Sensor Coatings Enhance Continuous Glucose Monitoring in Vivo
Klueh, Ulrike; Qiao, Yi; Czajkowski, Caroline; Ludzinska, Izabela; Antar, Omar; Kreutzer, Donald L.
2015-01-01
Background: Implantable glucose sensors demonstrate a rapid decline in function that is likely due to biofouling of the sensor. Previous efforts directed at overcoming this issue has generally focused on the use of synthetic polymer coatings, with little apparent effect in vivo, clearly a novel approach is required. We believe that the key to extending sensor life span in vivo is the development of biocompatible basement membrane (BM) based bio-hydrogels as coatings for glucose sensors. Method: BM based bio-hydrogel sensor coatings were developed using purified BM preparations (ie, Cultrex from Trevigen Inc). Modified Abbott sensors were coated with Cultrex BM extracts. Sensor performance was evaluated for the impact of these coatings in vitro and in vivo in a continuous glucose monitoring (CGM) mouse model. In vivo sensor function was assessed over a 28-day time period expressed as mean absolute relative difference (MARD) values. Tissue reactivity of both Cultrex coated and uncoated glucose sensors was evaluated at 7, 14, 21 and 28 days post–sensor implantation with standard histological techniques. Results: The data demonstrate that Cultrex-based sensor coatings had no effect on glucose sensor function in vitro. In vivo glucose sensor performance was enhanced following BM coating as determined by MARD analysis, particularly in weeks 2 and 3. In vivo studies also demonstrated that Cultrex coatings significantly decreased sensor-induced tissue reactions at the sensor implantation sites. Conclusion: Basement-membrane-based sensor coatings enhance glucose sensor function in vivo, by minimizing or preventing sensor-induced tissues reactions. PMID:26306494
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Micro-Electromechanical Affinity Sensor for the Monitoring of Glucose in Bioprocess Media
Theuer, Lorenz; Lehmann, Micha; Junne, Stefan; Neubauer, Peter; Birkholz, Mario
2017-01-01
An affinity-viscometry-based micro-sensor probe for continuous glucose monitoring was investigated with respect to its suitability for bioprocesses. The sensor operates with glucose and dextran competing as binding partner for concanavalin A, while the viscosity of the assay scales with glucose concentration. Changes in viscosity are determined with a micro-electromechanical system (MEMS) in the measurement cavity of the sensor probe. The study aimed to elucidate the interactions between the assay and a typical phosphate buffered bacterial cultivation medium. It turned out that contact with the medium resulted in a significant long-lasting drift of the assay’s viscosity at zero glucose concentration. Adding glucose to the medium lowers the drift by a factor of eight. The cglc values measured off-line with the glucose sensor for monitoring of a bacterial cultivation were similar to the measurements with an enzymatic assay with a difference of less than ±0.15 g·L−1. We propose that lectin agglomeration, the electro-viscous effect, and constitutional changes of concanavalin A due to exchanges of the incorporated metal ions may account for the observed viscosity increase. The study has demonstrated the potential of the MEMS sensor to determine sensitive viscosity changes within very small sample volumes, which could be of interest for various biotechnological applications. PMID:28594350
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Cypryk, Katarzyna; Bartyzel, Lukasz; Zurawska-Klis, Monika; Mlynarski, Wojciech; Szadkowska, Agnieszka; Wilczynski, Jan; Nowakowska, Dorota; Wozniak, Lucyna A; Fendler, Wojciech
2015-09-01
Much evidence has shown that pregnancies in women with preexisting diabetes are affected by an increased risk of maternal and fetal adverse outcomes, probably linked to poor glycemic control. Despite great progress in medical care, the rate of stillbirths remains much higher in diabetes patients than in the general population. Recent technological advances in the field of glucose monitoring and noninvasive fetal heart rate monitoring made it possible to observe the fetal-maternal dependencies in a continuous manner. Fourteen type 1 diabetes patients were involved into the study and fitted with a blinded continuous glucose monitoring (CGM) recorder. Fetal electrocardiogram data were recorded using the Monica AN24™ device (Monica Healthcare Ltd., Nottingham, United Kingdom), the recordings of which were matched with CGM data. Statistical analysis was performed using a generalized mixed-effect logistic regression to account for individual factors. The mean number of paired data points per patient was 254±106, representing an observation period of 21.2±8.8 h. Mean glycemia equaled 5.64±0.68 mmol/L, and mean fetal heart rate was 135±6 beats/min. Higher glycemia correlated with fetal heart rate (R=0.32; P<0.0001) and was associated with higher odds of the fetus developing small accelerations (odds ratio=1.05; 95% confidence interval, 1.00-1.10; P=0.04). Elevated maternal glycemia of mothers with diabetes is associated with accelerations of fetal heart rate.
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Ebbeling, Cara B; Wadden, Thomas A; Ludwig, David S
2011-01-01
Background: The circumstances under which the glycemic index (GI) and glycemic load (GL) are derived do not reflect real-world eating behavior. Thus, the ecologic validity of these constructs is incompletely known. Objective: This study examined the relation of dietary intake to glycemic response when foods are consumed under free-living conditions. Design: Participants were 26 overweight or obese adults with type 2 diabetes who participated in a randomized trial of lifestyle modification. The current study includes baseline data, before initiation of the intervention. Participants wore a continuous glucose monitor and simultaneously kept a food diary for 3 d. The dietary variables included GI, GL, and intakes of energy, fat, protein, carbohydrate, sugars, and fiber. The glycemic response variables included AUC, mean and SD of continuous glucose monitoring (CGM) values, percentage of CGM values in euglycemic and hyperglycemic ranges, and mean amplitude of glycemic excursions. Relations between daily dietary intake and glycemic outcomes were examined. Results: Data were available from 41 d of monitoring. Partial correlations, controlled for energy intake, indicated that GI or GL was significantly associated with each glycemic response outcome. In multivariate analyses, dietary GI accounted for 10% to 18% of the variance in each glycemic variable, independent of energy and carbohydrate intakes (P < 0.01). Conclusions: The data support the ecologic validity of the GI and GL constructs in free-living obese adults with type 2 diabetes. GI was the strongest and most consistent independent predictor of glycemic stability and variability. PMID:22071699
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Technology to Optimize Pediatric Diabetes Management and Outcomes
Harrington, Kara R.; Laffel, Lori M. B.
2013-01-01
Technology for diabetes management is rapidly developing and changing. With each new development, there are numerous factors to consider, including medical benefits, impact on quality of life, ease of use, and barriers to use. It is also important to consider the interaction between developmental stage and technology. This review considers a number of newer diabetes-related technologies and explores issues related to their use in the pediatric diabetes population (including young adults), with a focus on psychosocial factors. Areas include trend technology in blood glucose monitoring, continuous glucose monitoring, sensor-augmented insulin pumps and low glucose suspend functions, internet applications including videoconferencing, mobile applications (apps), including text messaging, and online gaming. PMID:24046146
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New technologies in the treatment of type 1 diabetes.
Schmidt, Signe
2013-11-01
Type 1 diabetes is a chronic condition characterized by insufficient production of insulin, a hormone needed for proper control of blood glucose levels. People with type 1 diabetes must monitor their blood glucose throughout the day using a glucose meter or a continuous glucose monitor, calculate how much insulin is needed to maintain normal blood glucose levels, and administer the insulin dose by pen injection or insulin pump infusion into the subcutaneous tissue. In recent years, several new technologies for the treatment of type 1 diabetes have been developed. This PhD thesis covers two studies of the effects of commercially available technologies--sensor-augmented pump therapy and automated insulin bolus calculators--when used in clinical practice. Both studies demonstrated that these technologies have the potential to improve diabetes care. In addition, two in-clinic studies related to emerging technologies--closed-loop glucose control and virtual simulation environments--are included in the thesis. The results of these experiments provided proof of concept and will serve as a basis for further research in these fields.
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Bergenstal, Richard M; Bailey, Timothy S; Rodbard, David; Ziemen, Monika; Guo, Hailing; Muehlen-Bartmer, Isabel; Ahmann, Andrew J
2017-04-01
The objective of this study was to compare glucose control in participants with type 1 diabetes receiving insulin glargine 300 units/mL (Gla-300) or glargine 100 units/mL (Gla-100) in the morning or evening, in combination with mealtime insulin. In this 16-week, exploratory, open-label, parallel-group, two-period crossover study (clinicaltrials.gov identifier NCT01658579), 59 adults with type 1 diabetes were randomized (1:1:1:1) to once-daily Gla-300 or Gla-100 given in the morning or evening (with crossover in the injection schedule). The primary efficacy end point was the mean percentage of time in the target glucose range (80-140 mg/dL), as measured using continuous glucose monitoring (CGM), during the last 2 weeks of each 8-week period. Additional end points included other CGM glycemic control parameters, hypoglycemia (per self-monitored plasma glucose [SMPG]), and adverse events. The percentage of time within the target glucose range was comparable between the Gla-300 and Gla-100 groups. There was significantly less increase in CGM-based glucose during the last 4 h of the 24-h injection interval for Gla-300 compared with Gla-100 (least squares mean difference -14.7 mg/dL [95% CI -26.9 to -2.5]; P = 0.0192). Mean 24-h glucose curves for the Gla-300 group were smoother (lower glycemic excursions), irrespective of morning or evening injection. Four metrics of intrasubject interstitial glucose variability showed no difference between Gla-300 and Gla-100. Nocturnal confirmed (<54 mg/dL by SMPG) or severe hypoglycemia rate was lower for Gla-300 participants than for Gla-100 participants (4.0 vs. 9.0 events per participant-year; rate ratio 0.45 [95% CI 0.24-0.82]). Less increase in CGM-based glucose levels in the last 4 h of the 24-h injection interval, smoother average 24-h glucose profiles irrespective of injection time, and reduced nocturnal hypoglycemia were observed with Gla-300 versus Gla-100. © 2017 by the American Diabetes Association.
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Bila, Rubao; Varo, Rosauro; Madrid, Lola; Sitoe, Antonio; Bassat, Quique
2018-04-25
The appearance, over a decade ago, of continuous glucose monitoring (CGM) devices has triggered a patient-centred revolution in the control and management of diabetes mellitus and other metabolic conditions, improving the patient’s glycaemic control and quality of life. Such devices, the use of which remains typically restricted to high-income countries on account of their elevated costs, at present show very limited implantation in resource-constrained settings, where many other urgent health priorities beyond diabetes prevention and management still need to be resolved. In this commentary, we argue that such devices could have an additional utility in low-income settings, whereby they could be selectively used among severely ill children admitted to hospital for closer monitoring of paediatric hypoglycaemia, a life-threatening condition often complicating severe cases of malaria, malnutrition, and other common paediatric conditions.
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Mazze, Roger S; Strock, Ellie; Borgman, Sarah; Wesley, David; Stout, Philip; Racchini, Joel
2009-01-01
This study was designed to assess the accuracy, reliability, and contribution to clinical decision-making of two commercially available continuous glucose monitoring (CGM) devices using a novel analytical approach. Eleven individuals with type 1 diabetes and five with type 2 diabetes wore a Guardian RT (GRT) (Medtronic Minimed, Northridge, CA) or DexCom STS Continuous Monitoring System (DEX) (San Diego, CA) device for 200 h followed by an 8-h laboratory study. A subset of these subjects wore both devices simultaneously. Subjects produced 1,902 +/- 269 readings during the ambulatory phase. During the laboratory study we found: lag time of 21 +/- 5 min for GRT and 7 +/- 7 min for DEX (P < 0.005); mean absolute relative difference of 19.9% and 16.7%, respectively, for GRT and DEX; and glucose exposure (the ratio of study device/laboratory reference device [YSI Instruments, Inc., Yellow Springs, OH] area under the curve) of 95 +/- 6% for GRT and 101 +/- 13% for DEX. Reliability measured during laboratory study showed 82% for DEX and 99% for GRT. Clarke Error Grid analysis (YSI reference) showed for GRT 59% of values in zone A, 34% in zone B, and 7% in zone D and for DEX 70% in zone A, 28% in zone B, 1% in zone C, and 1% in zone D. Bland-Altman plots (YSI standard) yielded for DEX 3 mg/dL (95% confidence interval, -78 to 84 mg/dL) and for GRT -21 mg/dL (95% confidence interval, -124 to 82 mg/dL). Six of eight subjects completed both home and laboratory simultaneous use of DEX and GRT. Lag times were inconsistent between devices, ranging from 0 to 32 min; area under the curve revealed a tendency for DEX to report higher total glucose exposure than GRT for the same patient. CGM detects abnormalities in glycemic control in a manner heretofore impossible to obtain. However, our studies revealed sufficient incongruence between simultaneous laboratory blood glucose levels and interstitial fluid glucose (after calibrations) to question the fundamental assumption that interstitial fluid glucose and blood glucose could be made identical by resorting to algorithms based on concurrent blood glucose levels alone.
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Hovorka, Roman; Nodale, Marianna; Haidar, Ahmad; Wilinska, Malgorzata E
2013-01-01
We investigated whether continuous glucose monitoring (CGM) levels can accurately assess glycemic control while directing closed-loop insulin delivery. Data were analyzed retrospectively from 33 subjects with type 1 diabetes who underwent closed-loop and conventional pump therapy on two separate nights. Glycemic control was evaluated by reference plasma glucose and contrasted against three methods based on Navigator (Abbott Diabetes Care, Alameda, CA) CGM levels. Glucose mean and variability were estimated by unmodified CGM levels with acceptable clinical accuracy. Time when glucose was in target range was overestimated by CGM during closed-loop nights (CGM vs. plasma glucose median [interquartile range], 86% [65-97%] vs. 75% [59-91%]; P=0.04) but not during conventional pump therapy (57% [32-72%] vs. 51% [29-68%]; P=0.82) providing comparable treatment effect (mean [SD], 28% [29%] vs. 23% [21%]; P=0.11). Using the CGM measurement error of 15% derived from plasma glucose-CGM pairs (n=4,254), stochastic interpretation of CGM gave unbiased estimate of time in target during both closed-loop (79% [62-86%] vs. 75% [59-91%]; P=0.24) and conventional pump therapy (54% [33-66%] vs. 51% [29-68%]; P=0.44). Treatment effect (23% [24%] vs. 23% [21%]; P=0.96) and time below target were accurately estimated by stochastic CGM. Recalibrating CGM using reference plasma glucose values taken at the start and end of overnight closed-loop was not superior to stochastic CGM. CGM is acceptable to estimate glucose mean and variability, but without adjustment it may overestimate benefit of closed-loop. Stochastic CGM provided unbiased estimate of time when glucose is in target and below target and may be acceptable for assessment of closed-loop in the outpatient setting.
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Tappy, L; Berger, M; Schwarz, J M; McCamish, M; Revelly, J P; Schneiter, P; Jéquier, E; Chioléro, R
1999-01-01
The suppression of endogenous glucose production during parenteral nutrition is impaired in critically ill patients. It is, however, unknown whether enteral administration of carbohydrates, which normally promote hepatic glucose uptake, improves hepatic glucose metabolism in such patients. We studied two groups of 7 patients during a 3-day continuous isocaloric enteral nutrition. A high-carbohydrate, low-lipid (EN-C) or a high-lipid, low-carbohydrate (EN-L) nutrient mixture was administered. Endogenous glucose production assessed with [2H7]glucose was similarly increased in both groups, indicating absence of its suppression by carbohydrate feeding. Gluconeogenesis estimated from [13C]glucose synthesis during [13C]bicarbonate infusion also was not suppressed by EN-C compared with EN-L. Systemic appearance of exogenous glucose was monitored by enteral infusion of [6,6-2H]glucose and was not different from the rate of glucose equivalent administered enterally, indicating no significant hepatic uptake of glucose in both groups. Plasma glucose and insulin concentrations were slightly higher with EN-C, although not significantly, and plasma triglycerides were similar in both groups. Both nutrition formulas were well tolerated clinically. These results indicate that enteral carbohydrate administration, whatever its quantity, fails to suppress endogenous glucose production and to promote net splanchnic glucose uptake in critically ill patients.
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Hanaire, Helene; Bertrand, Monelle; Guerci, Bruno; Anduze, Yves; Guillaume, Eric; Ritz, Patrick
2011-06-01
Obesity surgery elicits complex changes in glucose metabolism that are difficult to observe with discontinuous glucose measurements. We aimed to evaluate glucose variability after gastric bypass by continuous glucose monitoring (CGM) in a real-life setting. CGM was performed for 4.2 ± 1.3 days in three groups of 10 subjects each: patients who had undergone gastric bypass and who were referred for postprandial symptoms compatible with mild hypoglycemia, nonoperated diabetes controls, and healthy controls. The maximum interstitial glucose (IG), SD of IG values, and mean amplitude of glucose excursions (MAGE) were significantly higher in operated patients and in diabetes controls than in healthy controls. The time to the postprandial peak IG was significantly shorter in operated patients (42.8 ± 6.0 min) than in diabetes controls (82.2 ± 11.1 min, P = 0.0002), as were the rates of glucose increase to the peak (2.4 ± 1.6 vs. 1.2 ± 0.3 mg/mL/min; P = 0.041). True hypoglycemia (glucose <60 mg/dL) was rare: the symptoms were probably more related to the speed of IG decrease than to the glucose level achieved. Half of the operated patients, mostly those with a diabetes background before surgery, had postprandial glucose concentrations above 200 mg/dL (maximum IG, 306 ± 59 mg/dL), in contrast to the normal glucose concentrations in the fasting state and 2 h postmeal. Glucose variability is exaggerated after gastric bypass, combining unusually high and early hyperglycemic peaks and rapid IG decreases. This might account for postprandial symptoms mimicking hypoglycemia but often seen without true hypoglycemia. Early postprandial hyperglycemia might be underestimated if glucose measurements are done 2 h postmeal.
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Klueh, Ulrike; Ludzinska, Izabela; Czajkowski, Caroline; Qiao, Yi; Kreutzer, Donald L
2018-01-01
Overcoming sensor-induced tissue reactions is an essential element of achieving successful continuous glucose monitoring (CGM) in the management of diabetes, particularly when used in closed loop technology. Recently, we demonstrated that basement membrane (BM)-based glucose sensor coatings significantly reduced tissue reactions at sites of device implantation. However, the biocompatible BM-based biohydrogel sensor coating rapidly degraded over a less than a 3-week period, which effectively eliminated the protective sensor coating. In an effort to increase the stability and effectiveness of the BM coating, we evaluated the impact of crosslinking BM utilizing glutaraldehyde as a crosslinking agent, designated as X-Cultrex. Sensor performance (nonrecalibrated) was evaluated for the impact of these X-Cultrex coatings in vitro and in vivo. Sensor performance was assessed over a 28-day time period in a murine CGM model and expressed as mean absolute relative difference (MARD) values. Tissue reactivity of Cultrex-coated, X-Cultrex-coated, and uncoated glucose sensors was evaluated over a 28-day time period in vivo using standard histological techniques. These studies demonstrated that X-Cultrex-based sensor coatings had no effect on glucose sensor function in vitro. In vivo, glucose sensor performance was significantly enhanced following X-Cultrex coating throughout the 28-day study. Histological evaluations of X-Cultrex-treated sensors demonstrated significantly less tissue reactivity when compared to uncoated sensors. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 7-16, 2018. © 2017 Wiley Periodicals, Inc.
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An investigation of spectral characteristics of water-glucose solutions
NASA Astrophysics Data System (ADS)
Lastovskaia, Elena A.; Gorbunova, Elena V.; Chertov, Aleksandr N.; Korotaev, Valery V.
2016-04-01
One of the problems of modern medical device engineering is the development of an instrument for non-invasive monitoring of glucose levels in the blood. The urgency of this task is ensured by the following facts: the increase in the incidence of diabetes, the need for regular monitoring of blood sugar, and pain of modern methods of glycemia measurement. The problem can be solved with the help of a spectrophotometric method. This report is devoted to the investigation of spectral characteristics of glucose solution with various molar concentrations. The authors proposed the methodology of experimental research and data processing algorithm. The results of the experimental studies confirmed potential opportunity of blood sugar control by spectrophotometric method. Further research is expected to continue by the way of complication of the composition of the object from an aqueous solution of glucose to biological object.
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A portable measuring system for a competitive binding glucose biosensor
NASA Astrophysics Data System (ADS)
Colvin, Lydia E.; Means, A. Kristen; Grunlan, Melissa A.; Coté, Gerard L.
2018-02-01
Central to minimizing the long- and short-term complications associated with diabetes is careful monitoring and maintenance of blood glucose at normal levels. Towards replacing conventionally used finger-prick glucose testing, indwelling continuous glucose monitors (CGMs) based on amperometric electrodes have been introduced to the market. Envisioned to lead to a CGM with an increased lifetime, we report herein a fluorescently-labeled competitive binding assay contained within a hydrogel membrane whose glucose response is measured via a novel portable system. The optical system design included a laser source, bifurcated fiber, laser filter and simple fiber coupled spectrometer to obtain the change in FRET pair ratio of the assay. Glucose response of the assay in free solution was measured using this system across the physiologic range (0-200 mg/dL). The FRET pair ratio signal was seen to increase with glucose and the standard error of calibration was 22.42 mg/dL with a MARD value of 14.85%. When the assay was contained within the hydrogel membrane's central cavity and similarly analyzed, the standard error increased but the assay maintained its reversibility.
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Unannounced Meals in the Artificial Pancreas: Detection Using Continuous Glucose Monitoring
Herrero, Pau; Bondia, Jorge
2018-01-01
The artificial pancreas (AP) system is designed to regulate blood glucose in subjects with type 1 diabetes using a continuous glucose monitor informed controller that adjusts insulin infusion via an insulin pump. However, current AP developments are mainly hybrid closed-loop systems that include feed-forward actions triggered by the announcement of meals or exercise. The first step to fully closing the loop in the AP requires removing meal announcement, which is currently the most effective way to alleviate postprandial hyperglycemia due to the delay in insulin action. Here, a novel approach to meal detection in the AP is presented using a sliding window and computing the normalized cross-covariance between measured glucose and the forward difference of a disturbance term, estimated from an augmented minimal model using an Unscented Kalman Filter. Three different tunings were applied to the same meal detection algorithm: (1) a high sensitivity tuning, (2) a trade-off tuning that has a high amount of meals detected and a low amount of false positives (FP), and (3) a low FP tuning. For the three tunings sensitivities 99 ± 2%, 93 ± 5%, and 47 ± 12% were achieved, respectively. A sensitivity analysis was also performed and found that higher carbohydrate quantities and faster rates of glucose appearance result in favorable meal detection outcomes. PMID:29547553
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[From insulin pump and continuous glucose monitoring to the artificial pancreas].
Apablaza, Pamela; Soto, Néstor; Codner, Ethel
2017-05-01
Technology for diabetes care has undergone major development during recent decades. These technological advances include continuous subcutaneous insulin infusion (CSII), also known as insulin pumps, and real-time continuous glucose monitoring system (RT-CGMS). The integration of CSII and RT-CGMS into a single device has led to sensor-augmented pump therapy and more recently, a technology that has automated delivery of basal insulin therapy, known as hybrid system. These new technologies have led to benefits in attaining better metabolic control and decreasing the incidence of severe hypoglycemia, especially in patients with type 1 diabetes. This review describes the types of technologies currently available or under investigation for these purposes, their benefits and disadvantages, recommendations and the appropriate patient selection for their use. The clinical use of the hybrid system and artificial pancreas seem to be possible in the near future.
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Choudhary, P; Geddes, J; Freeman, J V; Emery, C J; Heller, S R; Frier, B M
2010-06-01
Impaired awareness of hypoglycaemia (IAH) is a major risk factor for severe hypoglycaemia in Type 1 diabetes. Although biochemical hypoglycaemia is asserted to be more frequent in IAH, this has not been estimated accurately. The aim of this study was to use Continuous Glucose Monitoring (CGM) to quantify hypoglycaemia in IAH and evaluate its use in identifying impaired awareness of hypoglycaemia. Ninety-five patients with Type 1 diabetes were classified as having normal (n = 74) or impaired awareness (n = 21) using an established method of assessing hypoglycaemia awareness. Hypoglycaemia exposure was assessed prospectively over 9-12 months using weekly 4-point capillary home blood glucose monitoring (HBGM), 5 days of CGM and prospective reporting of severe hypoglycaemia. The frequencies of biochemical and severe hypoglycaemia were compared in patients with normal and impaired awareness of hypoglycaemia. Patients with impaired awareness had a 3-fold higher incidence of severe hypoglycaemia than those with normal awareness [incidence rate ratio (IRR) 3.37 (95% CI 1.30-8.7); P = 0.01] and 1.6-fold higher incidence of hypoglycaemia on weekly HBGM [IRR 1.63 (95% CI 1.09-2.44); P = 0.02]. No significant differences were observed with CGM [IRR for sensor glucose < or = 3.0 mmol/l 1.47 (95% CI 0.91-2.39); P = 0.12; IRR for sensor glucose < or = 2.2 mmol/l 1.23 (95% CI 0.76-1.98); P = 0.40]. Patients with Type 1 diabetes with impaired awareness had a 3-fold higher risk of severe hypoglycaemia and 1.6-fold higher incidence of biochemical hypoglycaemia measured with weekly glucose monitoring compared with normal awareness, but 5 days of CGM did not differentiate those with impaired from those with normal awareness.
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Evaluation of MOSFET-type glucose sensor using platinum electrode with glucose oxidase
NASA Astrophysics Data System (ADS)
Ooe, Katsutoshi; Hamamoto, Yasutaro; Hirano, Yoshiaki
2005-02-01
As the population ages, health management will be one of the important issues. The development of a safe medical machine based on MEMS technologies for the human body will be the primary research project in the future. We have developed the glucose sensor, as one of the medical based devices, for use in the Health Monitoring System (HMS). HMS is the device that continuously monitors human health conditions. For example, blood is the monitoring target of HMS. The glucose sensor specifically detects the glucose levels of the blood and monitors the glucose concentration as the blood sugar level. This glucose sensor has a "separated Au electrode", which immobilizes GOx. In our previous work, GOx was immobilized onto Au electrode by the SAMs (Self-Assembled Monolayer) method, and the sensor, using this working electrode, detected the glucose concentration of an aqueous glucose solution. In this report, we used a Pt electrode, which immobilized GOx, as a working electrode. Au electrode, which was used previously, was dissolved by the application of current in the presence of chloride ions. Based on the above-mentioned fact, a new working electrode, which immobilized GOx, was produced using Pt, which did not possess such characteristics. These Pt working electrodes were produced using the covalent binding method and the cross-link method, and both the electrodes displayed a good sensing property. In addition, the electrode using glutaraldehyde (GA) and bovine serum albumin (BSA) as crosslinking agents was produced, and it displayed better characteristics as compared with those displayed by the electrode that used only GA. Based on the above-mentioned techniques, the improvement in performance of the sensor was confirmed.
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Clinical Use of Continuous Glucose Monitoring in Adults with Type 2 Diabetes
Mullen, Deborah M.; Bergenstal, Richard M.
2017-01-01
Abstract Background: Hemoglobin A1c is an excellent population health measure for the risk of vascular complications in diabetes, while continuous glucose monitoring (CGM) is a tool to help personalize a diabetes treatment plan. The value of CGM in individuals with type 1 diabetes (T1D) has been well demonstrated when compared with utilizing self-monitoring of blood glucose (SMBG) to guide treatment decisions. CGM is a tool for patients and clinicians to visualize the important role that diet, exercise, stress management, and the appropriate selection of diabetes medications can have in managing type 2 diabetes (T2D). Several diabetes organizations have recently reviewed the literature on the appropriate use of CGM in diabetes management and concluded CGM may be a useful educational and management tool particularly for patients on insulin therapy. The indications for using CGM either as a clinic-based loaner distribution model for intermittent use (professional CGM) or a CGM system owned by the patient and used at home with real-time glucose reading (personal CGM) are only beginning to be addressed in T2D. Most summaries of CGM studies conclude that having a standardized glucose pattern report, such as the ambulatory glucose profile (AGP) report, should help facilitate effective shared decision-making sessions. The future of CGM indications for the use of CGM is evolving rapidly. In some instances, CGM is now approved for making medication adjustments without SMBG confirmation and it appears that some forms of CGM will be approved for use in the Medicare population in the United States in the near future. Many individuals with T1D and T2D and their care teams will come to depend on CGM as a key tool for diabetes management. PMID:28541137
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van den Bosch, Edith E.M.; de Bont, Nik H.M.; Qiu, Jun; Gelling, Onko-Jan
2013-01-01
Background Continuous glucose monitors (CGMs) measure glucose in real time, making it possible to improve glycemic control. A promising technique involves glucose sensors implanted in subcutaneous tissue measuring glucose concentration in interstitial fluid. A major drawback of this technique is sensor bioinstability, which can lead to unpredictable drift and reproducibility. The bioinstability is partly due to sensor design but is also affected by naturally occurring subcutaneous inflammations. Applying a nonbiofouling coating to the sensor membrane could be a means to enhancing sensocompatibility. Methods This study evaluates the suitability of a polyethylene-glycol-based coating on sensors in CGMs. Methods used include cross hatch, wet paper rub, paper double rub, bending, hydrophilicity, protein adsorption, bio-compatibility, hemocompatibility, and glucose/oxygen permeability testing. Results Results demonstrate that coating homogeneity, adhesion, integrity, and scratch resistance are good. The coating repels lysozyme and bovine serum albumin, and only a low level of fibrin and blood platelet adsorption to the coating was recorded when testing in whole human blood. Cytotoxicity, irritation, sensitization, and hemolysis were assessed, and levels suggested good biocompatibility of the coating in subcutaneous tissue. Finally, it was shown that the coating can be applied to cellulose acetate membranes of different porosity without changing their permeability for glucose and oxygen. Conclusions These results suggest that the mechanical properties of the coating are sufficient for the given application, that the coating is effective in preventing protein adsorption and blood clot formation on the sensor surface, and that the coating can be applied to membranes without hindering their glucose and oxygen transport. PMID:23567005
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Continuous Metabolic Monitoring Based on Multi-Analyte Biomarkers to Predict Exhaustion
Kastellorizios, Michail; Burgess, Diane J.
2015-01-01
This work introduces the concept of multi-analyte biomarkers for continuous metabolic monitoring. The importance of using more than one marker lies in the ability to obtain a holistic understanding of the metabolism. This is showcased for the detection and prediction of exhaustion during intense physical exercise. The findings presented here indicate that when glucose and lactate changes over time are combined into multi-analyte biomarkers, their monitoring trends are more sensitive in the subcutaneous tissue, an implantation-friendly peripheral tissue, compared to the blood. This unexpected observation was confirmed in normal as well as type 1 diabetic rats. This study was designed to be of direct value to continuous monitoring biosensor research, where single analytes are typically monitored. These findings can be implemented in new multi-analyte continuous monitoring technologies for more accurate insulin dosing, as well as for exhaustion prediction studies based on objective data rather than the subject’s perception. PMID:26028477
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Continuous metabolic monitoring based on multi-analyte biomarkers to predict exhaustion.
Kastellorizios, Michail; Burgess, Diane J
2015-06-01
This work introduces the concept of multi-analyte biomarkers for continuous metabolic monitoring. The importance of using more than one marker lies in the ability to obtain a holistic understanding of the metabolism. This is showcased for the detection and prediction of exhaustion during intense physical exercise. The findings presented here indicate that when glucose and lactate changes over time are combined into multi-analyte biomarkers, their monitoring trends are more sensitive in the subcutaneous tissue, an implantation-friendly peripheral tissue, compared to the blood. This unexpected observation was confirmed in normal as well as type 1 diabetic rats. This study was designed to be of direct value to continuous monitoring biosensor research, where single analytes are typically monitored. These findings can be implemented in new multi-analyte continuous monitoring technologies for more accurate insulin dosing, as well as for exhaustion prediction studies based on objective data rather than the subject's perception.
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Schiaffini, Riccardo; Liccardo, Daniela; Alisi, Anna; Benevento, Danila; Cappa, Marco; Cianfarani, Stefano; Nobili, Valerio
2016-01-01
Glucose derangement has been reported to increase oxidative stress, one of the most important factors underlying the progression of hepatic fibrosis in adults with nonalcoholic fatty liver disease (NAFLD). To date, careful evaluation of the glucose profile in pediatric NAFLD has not been performed. A total of 30 severely obese children (15 males; mean age 12.87 ± 2.19 years) with biopsy-proven NAFLD were enrolled in this study from September to December 2013. All patients underwent anthropometric and laboratory evaluation, including the oral glucose tolerance test (OGTT) and continuous glucose monitoring (CGM). Our study reveals some differences between OGTT and CGM in detecting NAFLD children with impaired fasting glucose (IFG) and impaired glucose tolerance (IGT). OGTT showed 2 (6.67%) patients with IFG and 1 (3.34%) with IGT, while CGM showed 5 (16.67%) patients with IFG and 6 (20%) with IGT. The daily blood glucose profile positively correlated with the baseline blood glucose (r = 0.39, p = 0.04) and the homeostatic model assessment (r = 0.56, p = 0.05). A positive correlation between hyperglycemia and liver fibrosis was found (r = 0.65, p < 0.05). Mean glucose values (F3-F4 group: 163.2 ± 35.92 mg/dl vs. F1 group: 136.58 ± 46.83 mg/dl and F2 group: 154.12 ± 22.51 mg/dl) and the difference between the minimum and maximum blood glucose levels (F3-F4 group: 110.21 ± 25.26 mg/dl vs. F1 group: 91.67 ± 15.97 mg/dl and F2 group: 92 ± 15.48 mg/dl) were significantly (p < 0.05) higher in the F3-F4 group compared to the F1 and F2 groups. Glucose profile derangement as detected by CGM is associated with the severity of hepatic fibrosis in children with NAFLD. © 2015 S. Karger AG, Basel.
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Lessan, N; Hannoun, Z; Hasan, H; Barakat, M T
2015-02-01
Ramadan fasting represents a major shift in meal timing and content for practicing Muslims. This study used continuous glucose monitoring (CGM) to assess changes in markers of glycaemic excursions during Ramadan fasting to investigate the short-term safety of this practice in different groups of patients with diabetes. A total of 63 subjects (56 with diabetes, seven healthy volunteers; 39 male, 24 female) had CGM performed during, before and after Ramadan fasting. Mean CGM curves were constructed for each group for these periods that were then used to calculate indicators of glucose control and excursions. Post hoc data analyses included comparisons of different medication categories (metformin/no medication, gliptin, sulphonylurea and insulin). Medication changes during Ramadan followed American Diabetes Association guidelines. Among patients with diabetes, there was a significant difference in mean CGM curve during Ramadan, with a slow fall during fasting hours followed by a rapid rise in glucose level after the sunset meal (iftar). The magnitude of this excursion was greatest in the insulin-treated group, followed by the sulphonylurea-treated group. Markers of control deteriorated in a small number (n=3) of patients. Overall, whether fasting or non-fasting, subjects showed no statistically significant changes in mean interstitial glucose (IG), mean amplitude of glycaemic excursion (MAGE), high and low blood glucose indices (HBGI/LBGI), and number of glucose excursions and rate of hypoglycaemia. The main change in glycaemic control with Ramadan fasting in patients with diabetes is in the pattern of excursions. Ramadan fasting caused neither overall deterioration nor improvement in the majority of patients with good baseline glucose control. Copyright © 2014 Elsevier Masson SAS. All rights reserved.
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Jones, Susan M; Quarry, Jill L; Caldwell-McMillan, Molly; Mauger, David T; Gabbay, Robert A
2005-04-01
We attempted to identify an optimal insulin pump meal bolus by comparing postprandial sensor glucose values following three methods of insulin pump meal bolusing for a consistent pizza meal. Twenty-four patients with type 1 diabetes participated in a study to compare postprandial glucose values following three meal bolus regimens for a consistent evening pizza meal. Each participant utilized the following insulin lispro regimens on consecutive evenings, and glucose values were tracked by the Continuous Glucose Monitoring System (CGMS, Medtronic MiniMed, Northridge, CA): (a) single-wave bolus (100% of insulin given immediately); (b) 4-h dual-wave bolus (50% of insulin given immediately and 50% given over a 4-h period); and (c) 8-h dual-wave bolus (50% of insulin given immediately and 50% given over a 8-h period). Total insulin bolus amount was kept constant for each pizza meal. Divergence in blood glucose among the regimens was greatest at 8-12 h. The 8-h dual-wave bolus provided the best glycemic control and lowest mean glucose values (singlewave bolus, 133 mg/dL; 4-h dual-wave bolus, 145 mg/dL; 8-h dual-wave bolus, 104 mg/dL), leading to a difference in mean glucose of 29 mg/dL for the single-wave bolus versus the 8-h dual-wave bolus and 42 mg/dL for the 4-h dual-wave bolus versus the 8-h dual-wave bolus. The lower mean glucose in the 8-h dual-wave bolus was not associated with any increased incidence of hypoglycemia. Use of a dual-wave bolus extended over an 8-h period following a pizza meal provided significantly less postprandial hyperglycemia in the late postprandial period (8-12 h) with no increased risk of hypoglycemia.
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Hypoglycemia incidence and risk factors assessment in hospitalized neonates.
Zhou, Wei; Yu, Jun; Wu, Yiqi; Zhang, Huawei
2015-03-01
To assess the incidence and risk factors of hypoglycemia in hospitalized neonates in China. Blood glucose level in hospitalized neonates was monitored routinely. Also, in high-risk newborns and neonates with abnormal blood glucose levels in initial detection, the blood sugar level was monitored daily until it was back to normal and stable. Hypoglycemia was detected in 113 out of 668 hospitalized neonates, and the incidence of hypoglycemia was 16.9%. The statistical analysis also showed that hypoglycemia always occurred within one week after birth, especially within three days after birth. Neonates with premature birth, low birth weight and perinatal asphyxia were susceptible to hypoglycemia. Active and continuous monitoring of blood glucose level should be performed in the early newborns, especially in high-risk children, and attention should be paid to timely feeding for the early diagnosis and treatment of neonatal hypoglycemia to reduce its impact on the newborns.
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Glucose sensor excludes hypoglycaemia as cause of death.
Schmidt, Signe; Nørgaard, Kirsten
2012-05-01
The cause of death can be difficult to verify post-mortem in unexpected deaths in patients with Type 1 diabetes. This report describes an unexpected death in a 44-year-old man with Type 1 diabetes treated with sensor-augmented pump therapy. Continuous glucose monitoring data proved useful in determining the cause of death. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
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Regulation Catches Up to Reality.
Edelman, Steven V
2017-01-01
The FDA recently conducted an Advisory Panel meeting to evaluate the safety, efficacy, and benefits of granting a nonadjunctive label claim for the DEXCOM G5 Mobile continuous glucose monitoring (CGM) system. If approved, this claim will allow users to make day-to-day treatment decisions, including insulin dosing directly from the glucose values and rate of changes arrows generated by the CGM device, without the requirement of a confirmatory measurement with a self-monitoring blood glucose (SMBG) meter. Sporadic SMBG testing gives limited data, while CGM gives a value every 5 minutes and has alerts, alarms, trending information and allows caregivers to follow the user in real time 24/7. This indication will lead to more wide spread use of CGM and improve overall care with protection of hypoglycemia.
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Standardization versus customization of glucose reporting.
Rodbard, David
2013-05-01
Bergenstal et al. (Diabetes Technol Ther 2013;15:198-211) described an important approach toward standardization of reporting and analysis of continuous glucose monitoring and self-monitoring of blood glucose (SMBG) data. The ambulatory glucose profile (AGP), a composite display of glucose by time of day that superimposes data from multiple days, is perhaps the most informative and useful of the many graphical approaches to display glucose data. However, the AGP has limitations; some variations are desirable and useful. Synchronization with respect to meals, traditionally used in glucose profiles for SMBG data, can improve characterization of postprandial glucose excursions. Several other types of graphical display are available, and recently developed ones can augment the information provided by the AGP. There is a need to standardize the parameters describing glycemic variability and cross-validate the available computer programs that calculate glycemic variability. Clinical decision support software can identify and prioritize clinical problems, make recommendations for modifications of therapy, and explain its justification for those recommendations. The goal of standardization is challenging in view of the diversity of clinical situations and of computing and display platforms and software. Standardization is desirable but must be done in a manner that permits flexibility and fosters innovation.
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Ribet, Federico; Stemme, Göran; Roxhed, Niclas
2017-04-15
An ultra-miniaturized electrochemical biosensor for continuous glucose monitoring (CGM) is presented. The aim of this work is to demonstrate the possibility of an overall reduction in sensor size to allow minimally invasive glucose monitoring in the interstitial fluid in the dermal region, in contrast to larger state-of-the-art systems, which are necessarily placed in the subcutaneous layer. Moreover, the reduction in size might be a key factor to improve the stability and reliability of transdermal sensors, due to the reduction of the detrimental foreign body reaction and of consequent potential failures. These advantages are combined with lower invasiveness and discomfort for patients. The realized device consists of a microfabricated three-electrode enzymatic sensor with a total surface area of the sensing portion of less than 0.04mm 2 , making it the smallest fully integrated planar amperometric glucose sensor area reported to date. The working electrode and counter electrode consist of platinum and are functionalized by drop casting of three polymeric membranes. The on-chip iridium oxide (IrOx) pseudo-reference electrode provides the required stability for measurements under physiological conditions. The device is able to dynamically and linearly measure glucose concentrations in-vitro over the relevant physiological range, while showing sufficient selectivity to known interfering species present in the interstitial fluid, with resolution and sensitivity (1.51nA/mM) comparable to that of state-of-art commercial CGM systems. This work can therefore enable less invasive and improved CGM in patients affected by diabetes. Copyright © 2016 Elsevier B.V. All rights reserved.
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Oxygen sensing glucose biosensors based on alginate nano-micro systems
NASA Astrophysics Data System (ADS)
Chaudhari, Rashmi; Joshi, Abhijeet; Srivastava, Rohit
2014-04-01
Clinically glucose monitoring in diabetes management is done by point-measurement. However, an accurate, continuous glucose monitoring, and minimally invasive method is desirable. The research aims at developing fluorescence-mediated glucose detecting biosensors based on near-infrared radiation (NIR) oxygen sensitive dyes. Biosensors based on Glucose oxidase (GOx)-Rudpp loaded alginate microspheres (GRAM) and GOx-Platinum-octaethylporphyrin (PtOEP)-PLAalginate microsphere system (GPAM) were developed using air-driven atomization and characterized using optical microscopy, CLSM, fluorescence spectro-photometry etc. Biosensing studies were performed by exposing standard solutions of glucose. Uniform sized GRAM and GPAM with size 50+/-10μm were formed using atomization. CLSM imaging of biosensors suggests that Rudpp and PtOEP nanoparticles are uniformly distributed in alginate microspheres. The GRAM and GPAM showed a good regression constant of 0.974 and of 0.9648 over a range of 0-10 mM of glucose with a high sensitivity of 3.349%/mM (625 nm) and 2.38%/mM (645 nm) at 10 mM of glucose for GRAM and GPAM biosensor. GRAM and GPAM biosensors show great potential in development of an accurate and minimally invasive glucose biosensor. NIR dye based assays can aid sensitive, minimally-invasive and interference-free detection of glucose in diabetic patients.
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NASA Astrophysics Data System (ADS)
Qiang, Liangliang
A miniature wireless implantable electrochemical glucose system for continuous glucose monitoring with good selectivity, sensitivity, linearity and long term stability was developed. First, highly sensitive, long-term stable and reusable planar H2O2 microelectrodes have been fabricated by microlithography. These electrodes composed of a 300 nm Pt black layer situated on a 5 um thick Au layer, provide effective protection to the underlying chromium adhesion layer. Using repeated cyclic voltammetric sweeps in flowing buffer solution, highly sensitive Pt black working electrodes were realized with five-decade linear dynamic range and low detection limit (10 nM) for H2O2 at low oxidation potentials. Second, a highly sensitive, low cost and flexible microwire biosensor was described using 25-mum thick gold wire as working electrode together with 125-mum thick Pt/Ir and Ag wires as counter and reference electrode, embedded within a PDMS-filled polyethylene tube. Surface area and activity of sensor was enhanced by converting gold electrode to nanoporous configuration followed by electrodeposition of platinum black. Glucose oxidase based biosensors by electrodeposition of poly(o-phenylenediamine) and glucose oxidase on the working electrode, displayed a higher glucose sensitivity (1.2 mA mM-1 cm-2) than highest literature reported. In addition it exhibits wide detection range (up to 20 mM) and selectivity (>95%). Third, novel miniaturized and flexible microelectrode arrays with 8 of 25 mum electrodes displayed the much needed 3D diffusion profiles similar to a single 25 mum microelectrode, but with one order increase in current levels. These microelectrode arrays displayed a H2O2 sensitivity of 13 mA mM-1 cm-2, a wide dynamic range of 100 nM to 10 mM, limit of detection of 10 nM. These microwire based edge plane microsensors incorporated flexibility, miniaturization and low operation potential are an promising approach for continuous in vivo metabolic monitoring. Fourth, homemade miniature wireless potentisotat was fabricated based on low power consumption integrated circuits and surface mount parts. The miniature wireless potentisotat with up to two week life-time for continuous glucose sensing has a size less than 9x22x10 mm and weight ˜3.4 grams. Primary in vivo experiment showed homemade system has the exactly same respond and trend as commercial glucose meter.
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Continuous Glucose Monitoring: Current Use in Diabetes Management and Possible Future Applications.
Vettoretti, Martina; Cappon, Giacomo; Acciaroli, Giada; Facchinetti, Andrea; Sparacino, Giovanni
2018-05-01
The recent announcement of the production of new low-cost continuous glucose monitoring (CGM) sensors, the approval of marketed CGM sensors for making treatment decisions, and new reimbursement criteria have the potential to revolutionize CGM use. After briefly summarizing current CGM applications, we discuss how, in our opinion, these changes are expected to extend CGM utilization beyond diabetes patients, for example, to subjects with prediabetes or even healthy individuals. We also elaborate on how the integration of CGM data with other relevant information, for example, health records and other medical device/wearable sensor data, will contribute to creating a digital data ecosystem that will improve our understanding of the etiology and complications of diabetes and will facilitate the development of data analytics for personalized diabetes management and prevention.
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Law, Graham R; Ellison, George T H; Secher, Anna L; Damm, Peter; Mathiesen, Elisabeth R; Temple, Rosemary; Murphy, Helen R; Scott, Eleanor M
2015-07-01
Continuous glucose monitoring (CGM) is increasingly used to assess glucose control in diabetes. The objective was to examine how analysis of glucose data might improve our understanding of the role temporal glucose variation has on large-for-gestational-age (LGA) infants born to women with diabetes. Functional data analysis (FDA) was applied to 1.68 million glucose measurements from 759 measurement episodes, obtained from two previously published randomized controlled trials of CGM in pregnant women with diabetes. A total of 117 women with type 1 diabetes (n = 89) and type 2 diabetes (n = 28) who used repeated CGM during pregnancy were recruited from secondary care multidisciplinary obstetric clinics for diabetes in the U.K. and Denmark. LGA was defined as birth weight ≥90th percentile adjusted for sex and gestational age. A total of 54 of 117 (46%) women developed LGA. LGA was associated with lower mean glucose (7.0 vs. 7.1 mmol/L; P < 0.01) in trimester 1, with higher mean glucose in trimester 2 (7.0 vs. 6.7 mmol/L; P < 0.001) and trimester 3 (6.5 vs. 6.4 mmol/L; P < 0.01). FDA showed that glucose was significantly lower midmorning (0900-1100 h) and early evening (1900-2130 h) in trimester 1, significantly higher early morning (0330-0630 h) and throughout the afternoon (1130-1700 h) in trimester 2, and significantly higher during the evening (2030-2330 h) in trimester 3 in women whose infants were LGA. FDA of CGM data identified specific times of day that maternal glucose excursions were associated with LGA. It highlights trimester-specific differences, allowing treatment to be targeted to gestational glucose patterns. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
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Vukovic, Rade; Milenkovic, Tatjana; Djordjevic, Maja; Mitrovic, Katarina; Todorovic, Sladjana; Sarajlija, Adrijan; Hussain, Khalid
2017-07-26
Postprandial hyperinsulinemic hypoglycemia (PHH) is an increasingly recognized complication of gastric bypass surgery in obese adults, distinct from the "dumping syndrome". Upon birth, primary repair of esophageal atresia was performed, and at the age of 14 months definite esophageal reconstruction was performed. At the age of 3 years, recurrent brief episodes of symptomatic hypoglycemia started. At the age of 5.7 years the girl was admitted to our clinic and investigations indicated hyperinsulinemic hypoglycemia. Oral glucose tolerance test (OGTT) and continuous glucose monitoring results revealed frequent postprandial hypoglycemic events, which were always preceded by early postprandial hyperglycemia. It was concluded that the patient had PHH caused by a delayed and hyperinsulinemic response to carbohydrate intake as a result of esophagogastric surgery. Treatment with acarbose was titrated using flash glucose monitoring, which resulted in satisfactory glucose regulation. This is the first described case of a child with PHH following esophageal reconstruction.
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Dutt-Ballerstadt, Ralph; Evans, Colton; Pillai, Arun P; Orzeck, Eric; Drabek, Rafal; Gowda, Ashok; McNichols, Roger
2012-03-01
We report results of a pilot clinical study of a subcutaneous fluorescence affinity sensor (FAS) for continuous glucose monitoring conducted in people with type 1 and type 2 diabetes. The device was assessed based on performance, safety, and comfort level under acute conditions (4 h). A second-generation FAS (BioTex Inc., Houston, TX) was subcutaneously implanted in the abdomens of 12 people with diabetes, and its acute performance to excursions in blood glucose was monitored over 4 h. After 30-60 min the subjects, who all had fasting blood glucose levels of less than 200 mg/dl, received a glucose bolus of 75 g/liter dextrose by oral administration. Capillary blood glucose samples were obtained from the finger tip. The FAS data were retrospectively evaluated by linear least squares regression analysis and by the Clarke error grid method. Comfort levels during insertion, operation, and sensor removal were scored by the subjects using an analog pain scale. After retrospective calibration of 17 sensors implanted in 12 subjects, error grid analysis showed 97% of the paired values in zones A and B and 1.5% in zones C and D, respectively. The mean absolute relative error between sensor signal and capillary blood glucose was 13% [±15% standard deviation (SD), 100-350 mg/dl] with an average correlation coefficient of 0.84 (±0.24 SD). The actual average "warm-up" time for the FAS readings, at which highest correlation with glucose readings was determined, was 65 (±32 SD) min. Mean time lag was 4 (±5 SD) min during the initial operational hours. Pain levels during insertion and operation were modest. The in vivo performance of the FAS demonstrates feasibility of the fluorescence affinity technology to determine blood glucose excursions accurately and safely under acute dynamic conditions in humans with type 1 and type 2 diabetes. Specific engineering challenges to sensor and instrumentation robustness remain. Further studies will be required to validate its promising performance over longer implantation duration (5-7 days) in people with diabetes. © 2012 Diabetes Technology Society.
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Development of glucose-responsive 'smart' insulin systems.
Rege, Nischay K; Phillips, Nelson F B; Weiss, Michael A
2017-08-01
The complexity of modern insulin-based therapy for type I and type II diabetes mellitus and the risks associated with excursions in blood-glucose concentration (hyperglycemia and hypoglycemia) have motivated the development of 'smart insulin' technologies (glucose-responsive insulin, GRI). Such analogs or delivery systems are entities that provide insulin activity proportional to the glycemic state of the patient without external monitoring by the patient or healthcare provider. The present review describes the relevant historical background to modern GRI technologies and highlights three distinct approaches: coupling of continuous glucose monitoring (CGM) to deliver devices (algorithm-based 'closed-loop' systems), glucose-responsive polymer encapsulation of insulin, and molecular modification of insulin itself. Recent advances in GRI research utilizing each of the three approaches are illustrated; these include newly developed algorithms for CGM-based insulin delivery systems, glucose-sensitive modifications of existing clinical analogs, newly developed hypoxia-sensitive polymer matrices, and polymer-encapsulated, stem-cell-derived pancreatic β cells. Although GRI technologies have yet to be perfected, the recent advances across several scientific disciplines that are described in this review have provided a path towards their clinical implementation.
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Choleau, C; Klein, J C; Reach, G; Aussedat, B; Demaria-Pesce, V; Wilson, G S; Gifford, R; Ward, W K
2002-08-01
Calibration, i.e. the transformation in real time of the signal I(t) generated by the glucose sensor at time t into an estimation of glucose concentration G(t), represents a key issue for the development of a continuous glucose monitoring system. To compare two calibration procedures. In the one-point calibration, which assumes that I(o) is negligible, S is simply determined as the ratio I/G, and G(t) = I(t)/S. The two-point calibration consists in the determination of a sensor sensitivity S and of a background current I(o) by plotting two values of the sensor signal versus the concomitant blood glucose concentrations. The subsequent estimation of G(t) is given by G(t) = (I(t)-I(o))/S. A glucose sensor was implanted in the abdominal subcutaneous tissue of nine type 1 diabetic patients during 3 (n = 2) and 7 days (n = 7). The one-point calibration was performed a posteriori either once per day before breakfast, or twice per day before breakfast and dinner, or three times per day before each meal. The two-point calibration was performed each morning during breakfast. The percentages of points present in zones A and B of the Clarke Error Grid were significantly higher when the system was calibrated using the one-point calibration. Use of two one-point calibrations per day before meals was virtually as accurate as three one-point calibrations. This study demonstrates the feasibility of a simple method for calibrating a continuous glucose monitoring system.
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Torimoto, Keiichi; Okada, Yosuke; Sugino, Sachiko; Tanaka, Yoshiya
2017-05-01
We investigated the relationship between blood glucose profile at hospital discharge, evaluated by continuous glucose monitoring (CGM), and hemoglobin A1c (HbA1c) level at 12 weeks after discharge in patients with type 2 diabetes who received inpatient diabetes education. This was a retrospective study. The participants were 54 patients with type 2 diabetes who did not change their medication after discharge. The mean blood glucose (MBG), standard deviation, coefficient of variation, mean postprandial glucose excursion, maximum blood glucose, minimum blood glucose, percentage of time with blood glucose at ≥180 mg/dL (time at ≥180), percentage of time with blood glucose at ≥140 mg/dL, and percentage of time with blood glucose at <70 mg/dL were measured at admission and discharge using CGM. The primary end-point was the relationship between CGM parameters and HbA1c level at 12 weeks after discharge. The HbA1c level at 12 weeks after discharge correlated with MBG level (r = 0.30, P = 0.029). Multivariate analysis showed that MBG level and disease duration were predictors of 12-week HbA1c level. Multivariate logistic regression analysis was carried out considering goal achievement as a HbA1c level <7.0% 12 weeks after discharge. Disease duration and time at ≥180 were associated with goal achievement. The present results suggested that blood glucose profile at discharge using CGM seems useful to predict HbA1c level after discharge in patients with type 2 diabetes who received inpatient diabetes education. Early treatment to improve MBG level, as well as postprandial hyperglycemia, is important to achieve strict glycemic control. © 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.
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Li, Jiang; Koinkar, Pankaj; Fuchiwaki, Yusuke; Yasuzawa, Mikito
2016-12-15
A low invasive type glucose sensor, which has a sensing region at the tip of a fine pointed electrode, was developed for continuous glucose monitoring. Platinum-iridium alloy electrode with a surface area of 0.045mm(2) was settled at the middle of pointed PEEK (Polyetheretherketone) tubing and was employed as sensing electrode. Electrodeposition of glucose oxidase in the presence of surfactant, Triton X-100, was performed for high-density enzyme immobilization followed by the electropolymerization of o-phenylenediamine for the formation of functional entrapping and permselective polymer membrane. Ag/AgCl film was coated on the surface of PEEK tubing as reference electrode. Amperometric responses of the prepared sensors to glucose were measured at a potential of 0.60V (vs. Ag/AgCl). The prepared electrode showed the sensitivity of 2.55μA/cm(2) mM with high linearity of 0.9986, within the glucose concentration range up to 21mM. The detection limit (S/N=3) was determined to be 0.11mM. The glucose sensor properties were evaluated in phosphate buffer solution and in vivo monitoring by the implantation of the sensors in rabbit, while conventional needle type sensors as a reference were used. The results showed that change in output current of the proposed sensor fluctuated similar with one in output current of the conventional needle type sensors, which was also in similar accordance with actual blood sugar level measured by commercially glucose meter. One-point calibration method was used to calibrate the sensor output current. Copyright © 2016 Elsevier B.V. All rights reserved.
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Pharmacology of the glucagon-like peptide-1 analog exenatide extended-release in healthy cats.
Rudinsky, A J; Adin, C A; Borin-Crivellenti, S; Rajala-Schultz, P; Hall, M J; Gilor, C
2015-04-01
Exenatide extended-release (ER) is a microencapsulated formulation of the glucagon-like peptide 1-receptor agonist exenatide. It has a protracted pharmacokinetic profile that allows a once-weekly injection with comparable efficacy to insulin with an improved safety profile in type II diabetic people. Here, we studied the pharmacology of exenatide ER in 6 healthy cats. A single subcutaneous injection of exenatide ER (0.13 mg/kg) was administered on day 0. Exenatide concentrations were measured for 12 wk. A hyperglycemic clamp (target = 225 mg/dL) was performed on days -7 (clamp I) and 21 (clamp II) with measurements of insulin and glucagon concentrations. Glucose tolerance was defined as the amount of glucose required to maintain hyperglycemia during the clamp. Continuous glucose monitoring was performed on weeks 0, 2, and 6 after injection. Plasma concentrations of exenatide peaked at 1 h and 4 wk after injection. Comparing clamp I with clamp II, fasting blood glucose decreased (mean ± standard deviation = -11 ± 8 mg/dL, P = 0.02), glucose tolerance improved (median [range] +33% [4%-138%], P = 0.04), insulin concentrations increased (+36.5% [-9.9% to 274.1%], P = 0.02), and glucagon concentrations decreased (-4.7% [0%-12.1%], P = 0.005). Compared with preinjection values on continuous glucose monitoring, glucose concentrations decreased and the frequency of readings <50 mg/dL increased at 2 and 6 wk after injection of exenatide ER. This did not correspond to clinical hypoglycemia. No other side effects were observed throughout the study. Exenatide ER was safe and effective in improving glucose tolerance 3 wk after a single injection. Further evaluation is needed to determine its safety, efficacy, and duration of action in diabetic cats. Copyright © 2015 Elsevier Inc. All rights reserved.
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Accuracy of continuous glucose monitoring during exercise in type 1 diabetes pregnancy.
Kumareswaran, Kavita; Elleri, Daniela; Allen, Janet M; Caldwell, Karen; Nodale, Marianna; Wilinska, Malgorzata E; Amiel, Stephanie A; Hovorka, Roman; Murphy, Helen R
2013-03-01
Performance of continuous glucose monitors (CGMs) may be lower when glucose levels are changing rapidly, such as occurs during physical activity. Our aim was to evaluate accuracy of a current-generation CGM during moderate-intensity exercise in type 1 diabetes (T1D) pregnancy. As part of a study of 24-h closed-loop insulin delivery in 12 women with T1D (disease duration, 17.6 years; glycosylated hemoglobin, 6.4%) during pregnancy (gestation, 21 weeks), we evaluated the Freestyle Navigator(®) sensor (Abbott Diabetes Care, Alameda, CA) during afternoon (15:00-18:00 h) and morning (09:30-12:30 h) exercise (55 min of brisk walking on a treadmill followed by a 2-h recovery), compared with sedentary conditions (18:00-09:00 h). Plasma (reference) glucose, measured at regular 15-30-min intervals with the YSI Ltd. (Fleet, United Kingdom) model YSI 2300 analyzer, was used to assess CGM performance. Sensor accuracy, as indicated by the larger relative absolute difference (RAD) between paired sensor and reference glucose values, was lower during exercise compared with rest (median RAD, 11.8% vs. 18.4%; P<0.001). These differences remained significant when correcting for plasma glucose relative rate of change (P<0.001). Analysis by glucose range showed lower accuracy during hypoglycemia for both sedentary (median RAD, 24.4%) and exercise (median RAD, 32.1%) conditions. Using Clarke error grid analysis, 96% of CGM values were clinically safe under resting conditions compared with only 87% during exercise. Compared with sedentary conditions, accuracy of the Freestyle Navigator CGM was lower during moderate-intensity exercise in pregnant women with T1D. This difference was particularly marked in hypoglycemia and could not be solely explained by the glucose rate of change associated with physical activity.
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Use of continuous glucose monitoring as an outcome measure in clinical trials.
Beck, Roy W; Calhoun, Peter; Kollman, Craig
2012-10-01
Although developed to be a management tool for individuals with diabetes, continuous glucose monitoring (CGM) also has potential value for the assessment of outcomes in clinical studies. We evaluated using CGM as such an outcome measure. Data were analyzed from six previously completed inpatient studies in which both CGM (Freestyle Navigator™ [Abbott Diabetes Care, Alameda, CA] or Guardian(®) [Medtronic, Northridge, CA]) and reference glucose measurements were available. The analyses included 97 days of data from 93 participants with type 1 diabetes (age range, 5-57 years; mean, 18 ± 12 years). Mean glucose levels per day were similar for the CGM and reference measurements (median, 148 mg/dL vs. 143 mg/dL, respectively; P = 0.92), and the correlation of the two was high (r = 0.89). Similarly, most glycemia metrics showed no significant differences comparing CGM and reference values, except that the nadir glucose tended to be slightly lower and peak glucose slightly higher with reference measurements than CGM measurements (respective median, 59 mg/dL vs. 66 mg/dL [P = 0.05] and 262 mg/dL vs. 257 mg/dL [P = 0.003]) and glucose variability as measured with the coefficient of variation was slightly lower with CGM than reference measurements (respective median, 31% vs. 35%; P<0.001). A reasonably high degree of concordance exists when comparing outcomes based on CGM measurements with outcomes based on reference blood glucose measurements. CGM inaccuracy and underestimation of the extremes of hyperglycemia and hypoglycemia can be accounted for in a clinical trial's study design. Thus, in appropriate settings, CGM can be a very meaningful and feasible outcome measure for clinical trials.
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Clinical update on optimal prandial insulin dosing using a refined run-to-run control algorithm.
Zisser, Howard; Palerm, Cesar C; Bevier, Wendy C; Doyle, Francis J; Jovanovic, Lois
2009-05-01
This article provides a clinical update using a novel run-to-run algorithm to optimize prandial insulin dosing based on sparse glucose measurements from the previous day's meals. The objective was to use a refined run-to-run algorithm to calculate prandial insulin-to-carbohydrate ratios (I:CHO) for meals of variable carbohydrate content in subjects with type 1 diabetes (T1DM). The open-labeled, nonrandomized study took place over a 6-week period in a nonprofit research center. Nine subjects with T1DM using continuous subcutaneous insulin infusion participated. Basal insulin rates were optimized using continuous glucose monitoring, with a target fasting blood glucose of 90 mg/dl. Subjects monitored blood glucose concentration at the beginning of the meal and at 60 and 120 minutes after the start of the meal. They were instructed to start meals with blood glucose levels between 70 and 130 mg/dl. Subjects were contacted daily to collect data for the previous 24-hour period and to give them the physician-approved, algorithm-derived I:CHO ratios for the next 24 hours. Subjects calculated the amount of the insulin bolus for each meal based on the corresponding I:CHO and their estimate of the meal's carbohydrate content. One- and 2-hour postprandial glucose concentrations served as the main outcome measures. The mean 1-hour postprandial blood glucose level was 104 +/- 19 mg/dl. The 2-hour postprandial levels (96.5 +/- 18 mg/dl) approached the preprandial levels (90.1 +/- 13 mg/dl). Run-to-run algorithms are able to improve postprandial blood glucose levels in subjects with T1DM. 2009 Diabetes Technology Society.
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Use of Continuous Glucose Monitoring as an Outcome Measure in Clinical Trials
Calhoun, Peter; Kollman, Craig
2012-01-01
Abstract Objective Although developed to be a management tool for individuals with diabetes, continuous glucose monitoring (CGM) also has potential value for the assessment of outcomes in clinical studies. We evaluated using CGM as such an outcome measure. Research Design and Methods Data were analyzed from six previously completed inpatient studies in which both CGM (Freestyle Navigator™ [Abbott Diabetes Care, Alameda, CA] or Guardian® [Medtronic, Northridge, CA]) and reference glucose measurements were available. The analyses included 97 days of data from 93 participants with type 1 diabetes (age range, 5–57 years; mean, 18±12 years). Results Mean glucose levels per day were similar for the CGM and reference measurements (median, 148 mg/dL vs. 143 mg/dL, respectively; P=0.92), and the correlation of the two was high (r=0.89). Similarly, most glycemia metrics showed no significant differences comparing CGM and reference values, except that the nadir glucose tended to be slightly lower and peak glucose slightly higher with reference measurements than CGM measurements (respective median, 59 mg/dL vs. 66 mg/dL [P=0.05] and 262 mg/dL vs. 257 mg/dL [P=0.003]) and glucose variability as measured with the coefficient of variation was slightly lower with CGM than reference measurements (respective median, 31% vs. 35%; P<0.001). Conclusions A reasonably high degree of concordance exists when comparing outcomes based on CGM measurements with outcomes based on reference blood glucose measurements. CGM inaccuracy and underestimation of the extremes of hyperglycemia and hypoglycemia can be accounted for in a clinical trial's study design. Thus, in appropriate settings, CGM can be a very meaningful and feasible outcome measure for clinical trials. PMID:23013201
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Tanaka, Kenichi; Okada, Yosuke; Mori, Hiroko; Torimoto, Keiichi; Arao, Tadashi; Tanaka, Yoshiya
2018-01-01
One adverse effect of methylprednisolone (MP) pulse therapy is an acute dose-dependent increase in the blood glucose level. Five patients with thyroid ophthalmopathy but normal glucose tolerance received MP pulse therapy (3 cycles, 3 days/week) and were assessed by continuous glucose monitoring. Steroid therapy increased the mean sensor glucose level, and all patients developed steroid-induced diabetes. The patients were treated alternately with mitiglinide (30 mg/day) and repaglinide (1.5 mg/day) during the second or third MP pulse therapy. The sensor glucose levels before lunch and dinner were more favorable during treatment with repaglinide than during treatment with mitiglinide. Repaglinide may be more clinically appropriate than mitiglinide.
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Continuous glucose monitoring systems for type 1 diabetes mellitus.
Langendam, Miranda; Luijf, Yoeri M; Hooft, Lotty; Devries, J Hans; Mudde, Aart H; Scholten, Rob J P M
2012-01-18
Self-monitoring of blood glucose is essential to optimise glycaemic control in type 1 diabetes mellitus. Continuous glucose monitoring (CGM) systems measure interstitial fluid glucose levels to provide semi-continuous information about glucose levels, which identifies fluctuations that would not have been identified with conventional self-monitoring. Two types of CGM systems can be defined: retrospective systems and real-time systems. Real-time systems continuously provide the actual glucose concentration on a display. Currently, the use of CGM is not common practice and its reimbursement status is a point of debate in many countries. To assess the effects of CGM systems compared to conventional self-monitoring of blood glucose (SMBG) in patients with diabetes mellitus type 1. We searched The Cochrane Library, MEDLINE, EMBASE and CINAHL for the identification of studies. Last search date was June 8, 2011. Randomised controlled trials (RCTs) comparing retrospective or real-time CGM with conventional self-monitoring of blood glucose levels or with another type of CGM system in patients with type 1 diabetes mellitus. Primary outcomes were glycaemic control, e.g. level of glycosylated haemoglobin A1c (HbA1c) and health-related quality of life. Secondary outcomes were adverse events and complications, CGM derived glycaemic control, death and costs. Two authors independently selected the studies, assessed the risk of bias and performed data-extraction. Although there was clinical and methodological heterogeneity between studies an exploratory meta-analysis was performed on those outcomes the authors felt could be pooled without losing clinical merit. The search identified 1366 references. Twenty-two RCTs meeting the inclusion criteria of this review were identified. The results of the meta-analyses (across all age groups) indicate benefit of CGM for patients starting on CGM sensor augmented insulin pump therapy compared to patients using multiple daily injections of insulin (MDI) and standard monitoring blood glucose (SMBG). After six months there was a significant larger decline in HbA1c level for real-time CGM users starting insulin pump therapy compared to patients using MDI and SMBG (mean difference (MD) in change in HbA1c level -0.7%, 95% confidence interval (CI) -0.8% to -0.5%, 2 RCTs, 562 patients, I(2)=84%). The risk of hypoglycaemia was increased for CGM users, but CIs were wide and included unity (4/43 versus 1/35; RR 3.26, 95% CI 0.38 to 27.82 and 21/247 versus 17/248; RR 1.24, 95% CI 0.67 to 2.29). One study reported the occurrence of ketoacidosis from baseline to six months; there was however only one event. Both RCTs were in patients with poorly controlled diabetes.For patients starting with CGM only, the average decline in HbA1c level six months after baseline was also statistically significantly larger for CGM users compared to SMBG users, but much smaller than for patients starting using an insulin pump and CGM at the same time (MD change in HbA1c level -0.2%, 95% CI -0.4% to -0.1%, 6 RCTs, 963 patients, I(2)=55%). On average, there was no significant difference in risk of severe hypoglycaemia or ketoacidosis between CGM and SMBG users. The confidence interval however, was wide and included a decreased as well as an increased risk for CGM users compared to the control group (severe hypoglycaemia: 36/411 versus 33/407; RR 1.02, 95% CI 0.65 to 1.62, 4 RCTs, I(2)=0% and ketoacidosis: 8/411 versus 8/407; RR 0.94, 95% CI 0.36 to 2.40, 4 RCTs, I(2)=0%).Health-related quality of life was reported in five of the 22 studies. In none of these studies a significant difference between CGM and SMBG was found. Diabetes complications, death and costs were not measured.There were no studies in pregnant women with diabetes type 1 and in patients with hypoglycaemia unawareness. There is limited evidence for the effectiveness of real-time continuous glucose monitoring (CGM) use in children, adults and patients with poorly controlled diabetes. The largest improvements in glycaemic control were seen for sensor-augmented insulin pump therapy in patients with poorly controlled diabetes who had not used an insulin pump before. The risk of severe hypoglycaemia or ketoacidosis was not significantly increased for CGM users, but as these events occurred infrequent these results have to be interpreted cautiously.There are indications that higher compliance of wearing the CGM device improves glycosylated haemoglobin A1c level (HbA1c) to a larger extent.
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Technologies for Continuous Glucose Monitoring: Current Problems and Future Promises
Vaddiraju, Santhisagar; Burgess, Diane J; Tomazos, Ioannis; Jain, Faquir C; Papadimitrakopoulos, Fotios
2010-01-01
Devices for continuous glucose monitoring (CGM) are currently a major focus of research in the area of diabetes management. It is envisioned that such devices will have the ability to alert a diabetes patient (or the parent or medical care giver of a diabetes patient) of impending hypoglycemic/hyperglycemic events and thereby enable the patient to avoid extreme hypoglycemic/hyperglycemic excursions as well as minimize deviations outside the normal glucose range, thus preventing both life-threatening events and the debilitating complications associated with diabetes. It is anticipated that CGM devices will utilize constant feedback of analytical information from a glucose sensor to activate an insulin delivery pump, thereby ultimately realizing the concept of an artificial pancreas. Depending on whether the CGM device penetrates/breaks the skin and/or the sample is measured extracorporeally, these devices can be categorized as totally invasive, minimally invasive, and noninvasive. In addition, CGM devices are further classified according to the transduction mechanisms used for glucose sensing (i.e., electrochemical, optical, and piezoelectric). However, at present, most of these technologies are plagued by a variety of issues that affect their accuracy and long-term performance. This article presents a critical comparison of existing CGM technologies, highlighting critical issues of device accuracy, foreign body response, calibration, and miniaturization. An outlook on future developments with an emphasis on long-term reliability and performance is also presented. PMID:21129353
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Correlation of continuous glucose monitoring profiles with pregnancy outcomes in nondiabetic women.
Sung, Joyce F; Kogut, Elizabeth A; Lee, Henry C; Mannan, Jana L; Navabi, Kasra; Taslimi, M Mark; El-Sayed, Yasser Y
2015-04-01
To determine whether hyperglycemic excursions detected by continuous glucose monitoring (CGM) correlate with birth weight percentile and other pregnancy outcomes, and whether CGM correlates better with these outcomes than a single glucose value from a 1-hour glucose challenge test (GCT). This was a prospective observational study of 55 pregnant patients without preexisting diabetes, who wore a CGM device for up to 7 days, between 24 and 28 weeks' gestation. The area under the curve (AUC) of hyperglycemic excursions above various thresholds (110, 120, 130, 140, and 180 mg/dL) was calculated. These AUC values, and results from a standard 50-g GCT, were correlated with our primary outcome of birth weight percentile, and secondary outcomes of unplanned operative delivery, pregnancy complications, delivery complications, fetal complications, and neonatal complications. A consistent correlation was seen between all AUC thresholds and birth weight percentile (r = 0.29, p < 0.05 for AUC-110, -120, -130, and -140; r = 0.25, p = 0.07 for AUC-180). This correlation was stronger than that of 1-hour oral GCT (r = -0.02, p = 0.88). There was no association between AUC values and other outcomes. Among nondiabetic pregnant patients, hyperglycemic excursions detected by CGM show a stronger correlation to birth weight percentile than blood glucose values obtained 1-hour after a 50-g oral GCT. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
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Malcolm, Gary; Rilstone, Sian; Sivasubramaniyam, Sivasujan; Jairam, Carol; Chew, Stephen; Oliver, Nick; Hill, Neil E
2017-01-01
Physical activity is important for well-being but can be challenging for people with diabetes. Data informing support of specialist activities such as climbing and high-altitude trekking are limited. A 42-year-old man with type 1 diabetes (duration 30 years) attended a Multidisciplinary Physical Activity and Diabetes Clinic planning to climb Mont Blanc during the summer and trek to Everest Base Camp in the autumn. His aims were to complete these adventures without his diabetes impacting on their success. We report the information provided that enabled him to safely facilitate his objectives, in particular, the requirement for frequent checking of blood glucose levels, the effects of altitude on insulin dose requirements, and recognition that acute mountain sickness may mimic the symptoms of hypoglycaemia and vice versa. Real-time continuous glucose monitoring was made available for his treks. The effects of high altitude on blood glucose results and glycaemic variability while treated on multiple daily injections of insulin are reported. In addition, we present a first-person account of his experience and lessons learnt from managing diabetes at high altitude. A dedicated Multidisciplinary Physical Activity and Diabetes Clinic delivering individualised, evidence-based, patient-focused advice on the effects of altitude on blood glucose levels, and provision of real-time continuous glucose monitoring enabled uneventful completion of a trek to Everest Base Camp in a person with type 1 diabetes.
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Dehennis, Andrew; Mortellaro, Mark A; Ioacara, Sorin
2015-07-29
Continuous glucose monitoring (CGM), which enables real-time glucose display and trend information as well as real-time alarms, can improve glycemic control and quality of life in patients with diabetes mellitus. Previous reports have described strategies to extend the useable lifetime of a single sensor from 1-2 weeks to 28 days. The present multisite study describes the characterization of a sensing platform achieving 90 days of continuous use for a single, fully implanted sensor. The Senseonics CGM system is composed of a long-term implantable glucose sensor and a wearable smart transmitter. Study subjects underwent subcutaneous implantation of sensors in the upper arm. Eight-hour clinic sessions were performed every 14 days, during which sensor glucose values were compared against venous blood lab reference measurements collected every 15 minutes using mean absolute relative differences (MARDs). All subjects (mean ± standard deviation age: 43.5 ± 11.0 years; with 10 sensors inserted in men and 14 in women) had type 1 diabetes mellitus. Most (22 of 24) sensors reported glucose values for the entire 90 days. The MARD value was 11.4 ± 2.7% (range, 8.1-19.5%) for reference glucose values between 40-400 mg/dl. There was no significant difference in MARD throughout the 90-day study (P = .31). No serious adverse events were noted. The Senseonics CGM, composed of an implantable sensor, external smart transmitter, and smartphone app, is the first system that uses a single sensor for continuous display of accurate glucose values for 3 months. © 2015 Diabetes Technology Society.
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Developing strategies to enhance loading efficiency of erythrosensors
NASA Astrophysics Data System (ADS)
Bustamante Lopez, Sandra C.; Ritter, Sarah C.; Meissner, Kenith E.
2014-02-01
For diabetics, continuous glucose monitoring and the resulting tighter control of glucose levels ameliorate serious complications from hypoglycemia and hyperglycemia. Diabetics measure their blood glucose levels multiple times a day by finger pricks, or use implantable monitoring devices. Still, glucose and other analytes in the blood fluctuate throughout the day and the current monitoring methods are invasive, immunogenic, and/or present biodegradation problems. Using carrier erythrocytes loaded with a fluorescent sensor, we seek to develop a biodegradable, efficient, and potentially cost effective method to continuously sense blood analytes. We aim to reintroduce sensor-loaded erythrocytes to the bloodstream and conserve the erythrocytes lifetime of 120 days in the circulatory system. Here, we compare the efficiency of two loading techniques: hypotonic dilution and electroporation. Hypotonic dilution employs hypotonic buffer to create transient pores in the erythrocyte membrane, allowing dye entrance and a hypertonic buffer to restore tonicity. Electroporation relies on controlled electrical pulses that results in reversible pores formation to allow cargo entrance, follow by incubation at 37°C to reseal. As part of the cellular characterization of loaded erythrocytes, we focus on cell size, shape, and hemoglobin content. Cell recovery, loading efficiency and cargo release measurements render optimal loading conditions. The detected fluorescent signal from sensor-loaded erythrocytes can be translated into a direct measurement of analyte levels in the blood stream. The development of a suitable protocol to engineer carrier erythrocytes has profound and lasting implications in the erythrosensor's lifespan and sensing capabilities.
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Occurence of adverse events due to continuous glucose monitoring.
Jadviscokova, Tereza; Fajkusova, Zuzana; Pallayova, Maria; Luza, Jiri; Kuzmina, Galina
2007-12-01
Continuous glucose monitoring (CGM) using transcutaneous sensors is becoming a sophisticated method to control and regulate glucose metabolism. The transcutaneous sensor of the CGM system (CGMS Medtronic Minimed, Northridge, CA, USA) is chosen to measure glucose concentration in interstitial fluid up to three days after insertion even though its function remains stable for a longer period. The question arises, which factors really limit the period of sensor insertion without unnecessary risk. The aim of this study was to assess any adverse events occurring in the course of 9 days after the sensor insertion. In a group of 22 healthy volunteers aged 21.8+/-1.30 y (mean +/- SE) a total of 26 sensors was inserted subcutaneously in gluteal or lumbar region for 9 days. Before insertion the site was sprayed with an antiseptic (Cutasept F, Bode Chemie, Hamburg, Germany). Local adverse reactions and disturbances in general condition were examined. In the course of 184 sensor-days, there were only minor local adverse events: hypersensitivity, itching, pain, redness, burning, subcutaneous hemorrhage. Additionally, sleep disturbances, attention deficits, problems related to the CGMS monitor, to adhesive tape and/or sensor were found. None of these resulted in sensor withdrawal. In 12 volunteers (55 %) no complications were observed. The sensor function measured according to electrical signals (ISIG) failed (always on day 1-2) in 4 cases (16 %). The present FDA approved 3-day insertion period for Medtronic transcutaneous sensor does not seem to limit its use and appears to be worth a careful revision.
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Yeh, Hsin-Chieh; Brown, Todd T; Maruthur, Nisa; Ranasinghe, Padmini; Berger, Zackary; Suh, Yong D; Wilson, Lisa M; Haberl, Elisabeth B; Brick, Jessica; Bass, Eric B; Golden, Sherita Hill
2012-09-04
Patients with diabetes mellitus need information about the effectiveness of innovations in insulin delivery and glucose monitoring. To review how intensive insulin therapy (multiple daily injections [MDI] vs. rapid-acting analogue-based continuous subcutaneous insulin infusion [CSII]) or method of monitoring (self-monitoring of blood glucose [SMBG] vs. real-time continuous glucose monitoring [rt-CGM]) affects outcomes in types 1 and 2 diabetes mellitus. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials through February 2012 without language restrictions. 33 randomized, controlled trials in children or adults that compared CSII with MDI (n=19), rt-CGM with SMBG (n=10), or sensor-augmented insulin pump use with MDI and SMBG (n=4). 2 reviewers independently evaluated studies for eligibility and quality and serially abstracted data. In randomized, controlled trials, MDI and CSII showed similar effects on hemoglobin A1c (HbA1c) levels and severe hypoglycemia in children or adults with type 1 diabetes mellitus and adults with type 2 diabetes mellitus. In adults with type 1 diabetes mellitus, HbA1c levels decreased more with CSII than with MDI, but 1 study heavily influenced these results. Compared with SMBG, rt-CGM achieved a lower HbA1c level (between-group difference of change, 0.26% [95% CI, 0.33% to 0.19%]) without any difference in severe hypoglycemia. Sensor-augmented insulin pump use decreased HbA1c levels more than MDI and SMBG did in persons with type 1 diabetes mellitus (between-group difference of change, 0.68% [CI, 0.81% to 0.54%]). Little evidence was available on other outcomes. Many studies were small, of short duration, and limited to white persons with type 1 diabetes mellitus. Continuous subcutaneous insulin infusion and MDI have similar effects on glycemic control and hypoglycemia, except CSII has a favorable effect on glycemic control in adults with type 1 diabetes mellitus. For glycemic control, rt-CGM is superior to SMBG and sensor-augmented insulin pumps are superior to MDI and SMBG without increasing the risk for hypoglycemia. Agency for Healthcare Research and Quality.
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Enzymatic glucose sensor compensation for variations in ambient oxygen concentration
NASA Astrophysics Data System (ADS)
Collier, Bradley B.; McShane, Michael J.
2013-02-01
Due to the increasing prevalence of diabetes, research toward painless glucose sensing continues. Oxygen sensitive phosphors with glucose oxidase (GOx) can be used to determine glucose levels indirectly by monitoring oxygen consumption. This is an attractive combination because of its speed and specificity. Packaging these molecules together in "smart materials" for implantation will enable non-invasive glucose monitoring. As glucose levels increase, oxygen levels decrease; consequently, the luminescence intensity and lifetime of the phosphor increase. Although the response of the sensor is dependent on glucose concentration, the ambient oxygen concentration also plays a key role. This could lead to inaccurate glucose readings and increase the risk of hyper- or hypoglycemia. To mitigate this risk, the dependence of hydrogel glucose sensor response on oxygen levels was investigated and compensation methods explored. Sensors were calibrated at different oxygen concentrations using a single generic logistic equation, such that trends in oxygen-dependence were determined as varying parameters in the equation. Each parameter was found to be a function of oxygen concentration, such that the correct glucose calibration equation can be calculated if the oxygen level is known. Accuracy of compensation will be determined by developing an overall calibration, using both glucose and oxygen sensors in parallel, correcting for oxygen fluctuations in real time by intentionally varying oxygen, and calculating the error in actual and predicted glucose levels. While this method was developed for compensation of enzymatic glucose sensors, in principle it can also be implemented with other kinds of sensors utilizing oxidases.
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Real-time improvement of continuous glucose monitoring accuracy: the smart sensor concept.
Facchinetti, Andrea; Sparacino, Giovanni; Guerra, Stefania; Luijf, Yoeri M; DeVries, J Hans; Mader, Julia K; Ellmerer, Martin; Benesch, Carsten; Heinemann, Lutz; Bruttomesso, Daniela; Avogaro, Angelo; Cobelli, Claudio
2013-04-01
Reliability of continuous glucose monitoring (CGM) sensors is key in several applications. In this work we demonstrate that real-time algorithms can render CGM sensors smarter by reducing their uncertainty and inaccuracy and improving their ability to alert for hypo- and hyperglycemic events. The smart CGM (sCGM) sensor concept consists of a commercial CGM sensor whose output enters three software modules, able to work in real time, for denoising, enhancement, and prediction. These three software modules were recently presented in the CGM literature, and here we apply them to the Dexcom SEVEN Plus continuous glucose monitor. We assessed the performance of the sCGM on data collected in two trials, each containing 12 patients with type 1 diabetes. The denoising module improves the smoothness of the CGM time series by an average of ∼57%, the enhancement module reduces the mean absolute relative difference from 15.1 to 10.3%, increases by 12.6% the pairs of values falling in the A-zone of the Clarke error grid, and finally, the prediction module forecasts hypo- and hyperglycemic events an average of 14 min ahead of time. We have introduced and implemented the sCGM sensor concept. Analysis of data from 24 patients demonstrates that incorporation of suitable real-time signal processing algorithms for denoising, enhancement, and prediction can significantly improve the performance of CGM applications. This can be of great clinical impact for hypo- and hyperglycemic alert generation as well in artificial pancreas devices.
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An Overview of Insulin Pumps and Glucose Sensors for the Generalist
McAdams, Brooke H.; Rizvi, Ali A.
2016-01-01
Continuous subcutaneous insulin, or the insulin pump, has gained popularity and sophistication as a near-physiologic programmable method of insulin delivery that is flexible and lifestyle-friendly. The introduction of continuous monitoring with glucose sensors provides unprecedented access to, and prediction of, a patient’s blood glucose levels. Efforts are underway to integrate the two technologies, from “sensor-augmented” and “sensor-driven” pumps to a fully-automated and independent sensing-and-delivery system. Implantable pumps and an early-phase “bionic pancreas” are also in active development. Fine-tuned “pancreas replacement” promises to be one of the many avenues that offers hope for individuals suffering from diabetes. Although endocrinologists and diabetes specialists will continue to maintain expertise in this field, it behooves the primary care physician to have a working knowledge of insulin pumps and sensors to ensure optimal clinical care and decision-making for their patients. PMID:26742082
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Distiller, Larry A; Cranston, Iain; Mazze, Roger
2016-11-01
In 2014, an innovative blinded continuous glucose monitoring system was introduced with automated ambulatory glucose profile (AGP) reporting. The clinical use and interpretation of this new technology has not previously been described. Therefore we wanted to understand its use in characterizing key factors related to glycemic control: glucose exposure, variability, and stability, and risk of hypoglycemia in clinical practice. Clinicians representing affiliated diabetes centers throughout South Africa were trained and subsequently were given flash glucose monitoring readers and 2-week glucose sensors to use at their discretion. After patient use, sensor data were collected and uploaded for AGP reporting. Complete data (sensor AGP with corresponding clinical information) were obtained for 50 patients with type 1 (70%) and type 2 diabetes (30%), irrespective of therapy. Aggregated analysis of AGP data comparing patients with type 1 versus type 2 diabetes, revealed that despite similar HbA1c values between both groups (8.4 ± 2 vs 8.6 ± 1.7%, respectively), those with type 2 diabetes had lower mean glucose levels (9.2 ± 3 vs 10.3 mmol/l [166 ± 54 vs 185 mg/dl]) and lower indices of glucose variability (3.0 ± 1.5 vs 5.0 ± 1.9 mmol/l [54 ± 27 vs 90 ± 34.2 mg/dl]). This highlights key areas for future focus. Using AGP, the characteristics of glucose exposure, variability, stability, and hypoglycemia risk and occurrence were obtained within a short time and with minimal provider and patient input. In a survey at the time of the follow-up visit, clinicians indicated that aggregated AGP data analysis provided important new clinical information and insights. © 2016 Diabetes Technology Society.
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Fleischer, Jesper; Laugesen, Esben; Cichosz, Simon Lebech; Hoeyem, Pernille; Dejgaard, Thomas Fremming; Poulsen, Per Loegstrup; Tarnow, Lise; Hansen, Troels Krarup
2017-09-01
Hyperglycemia as evaluated by HbA1c is a risk factor for the development of cardiovascular autonomic neuropathy (CAN). The aim of the present study was to investigate whether continuous glucose monitoring (CGM) may add information beyond HbA1c in patients with type 2 diabetes and CAN. 81 patients with type 2 diabetes (43 men, mean age 58±11year, HbA1c 6.6±0.5%). Patients were tested for CAN using cardiovascular reflex tests (response to standing, deep breathing and Valsalva maneuver) and underwent CGM for three days. CAN was defined as early (one test abnormal), or manifest (two or three tests abnormal). Twenty patients had early CAN and two patients had manifest CAN. Blood pressure, HbA1c, cholesterol levels and smoking habits were comparable in patients with vs. without CAN. Post-breakfast glycemic peak was significantly higher in patients with CAN (peak 207 vs 176mg/dL, P=0.009). Furthermore, the nocturnal glucose drop and dawn glucose was significantly higher in patients with CAN compared with patients without CAN (mean 134 vs. 118mg/dL, P=0.017 and mean 143 vs. 130mg/dL, P=0.045, respectively). Removing the two patients with manifest CAN from the statistical analysis didn't change the results. These findings emphasize the importance of monitoring glucose patterns over 24-h and not only rely on HbA1c as therapeutic target in patients with type 2 diabetes and CAN. Copyright © 2017 Elsevier Inc. All rights reserved.
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Blood glucose level reconstruction as a function of transcapillary glucose transport.
Koutny, Tomas
2014-10-01
A diabetic patient occasionally undergoes a detailed monitoring of their glucose levels. Over the course of a few days, a monitoring system provides a detailed track of their interstitial fluid glucose levels measured in their subcutaneous tissue. A discrepancy in the blood and interstitial fluid glucose levels is unimportant because the blood glucose levels are not measured continuously. Approximately five blood glucose level samples are taken per day, and the interstitial fluid glucose level is usually measured every 5min. An increased frequency of blood glucose level sampling would cause discomfort for the patient; thus, there is a need for methods to estimate blood glucose levels from the glucose levels measured in subcutaneous tissue. The Steil-Rebrin model is widely used to describe the relationship between blood and interstitial fluid glucose dynamics. However, we measured glucose level patterns for which the Steil-Rebrin model does not hold. Therefore, we based our research on a different model that relates present blood and interstitial fluid glucose levels to future interstitial fluid glucose levels. Using this model, we derived an improved model for calculating blood glucose levels. In the experiments conducted, this model outperformed the Steil-Rebrin model while introducing no additional requirements for glucose sample collection. In subcutaneous tissue, 26.71% of the calculated blood glucose levels had absolute values of relative differences from smoothed measured blood glucose levels less than or equal to 5% using the Steil-Rebrin model. However, the same difference interval was encountered in 63.01% of the calculated blood glucose levels using the proposed model. In addition, 79.45% of the levels calculated with the Steil-Rebrin model compared with 95.21% of the levels calculated with the proposed model had 20% difference intervals. Copyright © 2014 Elsevier Ltd. All rights reserved.
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Schrangl, Patrick; Reiterer, Florian; Heinemann, Lutz; Freckmann, Guido; Del Re, Luigi
2018-05-18
Systems for continuous glucose monitoring (CGM) are evolving quickly, and the data obtained are expected to become the basis for clinical decisions for many patients with diabetes in the near future. However, this requires that their analytical accuracy is sufficient. This accuracy is usually determined with clinical studies by comparing the data obtained by the given CGM system with blood glucose (BG) point measurements made with a so-called reference method. The latter is assumed to indicate the correct value of the target quantity. Unfortunately, due to the nature of the clinical trials and the approach used, such a comparison is subject to several effects which may lead to misleading results. While some reasons for the differences between the values obtained with CGM and BG point measurements are relatively well-known (e.g., measurement in different body compartments), others related to the clinical study protocols are less visible, but also quite important. In this review, we present a general picture of the topic as well as tools which allow to correct or at least to estimate the uncertainty of measures of CGM system performance.
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Update on Neonatal Hypoglycemia
Rozance, Paul J.
2014-01-01
Purpose of Review Neonatal hypoglycemia is one of the most common biochemical abnormalities encountered in the newborn. However, controversy remains surrounding its definition and management especially in asymptomatic patients. Recent Findings New information has been published that describes the incidence and timing of low glucose concentrations in the groups most at risk for asymptomatic neonatal hypoglycemia. Furthermore, one large prospective study failed to find an association between repetitive low glucose concentrations and poor neurodevelopmental outcomes in preterm infants. But hypoglycemia due to hyperinsulinism, especially genetic causes, continued to be associated with brain injury. New advances were made in the diagnosis and management of hyperinsulinism, including acquired hyperinsulinism in small for gestational age infants and others. Continuous glucose monitoring remains an attractive strategy for future research in this area. Summary The fundamental question of how best to manage asymptomatic newborns with low glucose concentrations remains unanswered. Balancing the risks of over treating newborns with low glucose concentrations who are undergoing a normal transition following birth against the risks of under treating those in whom low glucose concentrations are pathological, dangerous, and/or a harbinger of serious metabolic disease remains a challenge. PMID:24275620
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Update on neonatal hypoglycemia.
Rozance, Paul J
2014-02-01
Neonatal hypoglycemia is one of the most common biochemical abnormalities encountered in the newborn. However, controversy remains surrounding its definition and management especially in asymptomatic patients. New information has been published that describes the incidence and timing of low glucose concentrations in the groups most at risk for asymptomatic neonatal hypoglycemia. Furthermore, one large prospective study failed to find an association between repetitive low glucose concentrations and poor neurodevelopmental outcomes in preterm infants. But hypoglycemia due to hyperinsulinism, especially genetic causes, continued to be associated with brain injury. New advances were made in the diagnosis and management of hyperinsulinism, including acquired hyperinsulinism in small for gestational age infants and others. Continuous glucose monitoring remains an attractive strategy for future research in this area. The fundamental question of how best to manage asymptomatic newborns with low glucose concentrations remains unanswered. Balancing the risks of overtreating newborns with low glucose concentrations who are undergoing a normal transition following birth against the risks of undertreating those in whom low glucose concentrations are pathological, dangerous, and/or a harbinger of serious metabolic disease remains a challenge.
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Fox, Larry A; Balkman, Emilie; Englert, Kim; Hossain, Jobayer; Mauras, Nelly
2017-06-01
This study explored the safety of using real-time sensor glucose (SG) data for treatment decisions in adolescents with poorly controlled type 1 diabetes. Ten adolescents with type 1 diabetes, HbA1c ≥9% on insulin pumps were admitted to the clinical research center and a continuous glucose sensor was inserted. Plasma glucose was measured at least hourly using Yellow Springs Instrument's (YSI) glucose analyzer. Starting at dinner, SG rather than YSI was used for treatment decisions unless YSI was <70 mg/dL (<3.9 mmol/L) or specific criteria indicating SG and YSI were very discordant were met. Participants were discharged after lunch the next day. Ten participants (seven males; 15.2-17.8 year old) completed the study. The range of differences between high glucose correction doses using SG vs YSI for calculations was -2 (SG < YSI dose) to +1 (SG > YSI dose); this difference was two units in only 2 of 23 correction doses given (all SG < YSI dose). There were five episodes of mild hypoglycemia in two patients, two of which occurred after using SG for dose calculations. There was no severe hypoglycemia and no YSI glucose >350 mg/dL (19.4 mmol/L). Mean (±SE) pre- and postmeal YSI glucose were 163 ± 11 and 183 ± 12 mg/dL (9.1 ± 0.6 and 10.2 ± 0.7 mmol/L), respectively. Use of real-time continuous glucose monitoring for treatment decisions was safe and did not result in significant over- or undertreatment. Use of SG for treatment decisions under supervised inpatient conditions is a suitable alternative to repeated fingerstick glucose monitoring. Outpatient studies using SG in real-time are needed. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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Hatada, Mika; Loew, Noya; Inose-Takahashi, Yuka; Okuda-Shimazaki, Junko; Tsugawa, Wakako; Mulchandani, Ashok; Sode, Koji
2018-06-01
Enzyme based electrochemical biosensors are divided into three generations according to their type of electron transfer from the cofactors of the enzymes to the electrodes. Although the 3rd generation sensors using direct electron transfer (DET) type enzymes are ideal, the number of enzyme types which possess DET ability is limited. In this study, we report of a glucose sensor using mediator-modified glucose dehydrogenase (GDH), that was fabricated by a new quick-and-easy method using the pre-functionalized amine reactive phenazine ethosulfate (arPES). Thus mediator-modified GDH obtained the ability to transfer electrons to bulky electron acceptors as well as electrodes. The concentration of glucose was successfully measured using electrodes with immobilized PES-modified GDH, without addition of external electron mediators. Therefore, continuous monitoring systems can be developed based on this "2.5th generation" electron transfer principle utilizing quasi-DET. Furthermore, we successfully modified two other diagnostically relevant enzymes, glucoside 3-dehydrogenase and lactate oxidase, with PES. Therefore, various kinds of diagnostic enzymes can achieve quasi-DET ability simply by modification with arPES, suggesting that continuous monitoring systems based on the 2.5th generation principle can be developed for various target molecules. Copyright © 2018 Elsevier B.V. All rights reserved.
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Scholten, Kee; Meng, Ellis
2018-06-15
Closed-loop drug delivery promises autonomous control of pharmacotherapy through the continuous monitoring of biomarker levels. For decades, researchers have strived for portable closed-loop systems capable of treating ambulatory patients with chronic conditions such as diabetes mellitus. After years of development, the first of these systems have left the laboratory and entered commercial use. This long-awaited advance reflects recent development of chronically stable implantable biosensors able to accurately measure biomarker levels in vivo. This review discusses the role of implantable biosensors in closed-loop drug delivery applications, with the intent to provide a resource for engineers and researchers studying such systems. We provide an overview of common biosensor designs and review the principle challenges in implementing long indwelling sensors: namely device sensitivity, selectivity, and lifetime. This review examines novel advances in transducer design, biological interface, and material biocompatibility, with a focus on recent academic and commercial work which provide successful strategies to overcome perennial challenges. This review focuses primarily on the topics of closed-loop glucose control and continuous glucose monitoring biosensors, which make up the overwhelming majority of published research in this area. We conclude with an overview of recent advances in closed-loop systems targeting applications outside blood glucose management. Copyright © 2018 Elsevier B.V. All rights reserved.
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Impact of macrophage deficiency and depletion on continuous glucose monitoring in vivo
Klueh, Ulrike; Qiao, Yi; Frailey, Jackman T.; Kreutzer, Donald L.
2014-01-01
Although it is assumed that macrophages (MQ) have a major negative impact on continuous glucose monitoring (CGM), surprisingly there is no data in the literature to directly support or refute the role of MQ or related foreign body giant cells in the bio-fouling of glucose sensors in vivo. As such, we developed the hypothesis that MQ are key in controlling glucose sensor performance and CGM in vivo and MQ deficiencies or depletion would enhance CGM. To test this hypothesis we determined the presence/distribution of MQ at the sensor tissue interface over a 28-day time period using F4/80 antibody and immunohistochemical analysis. We also evaluated the impact of spontaneous MQ deficiency (op/op mice) and induced-transgenic MQ depletions (Diphtheria Toxin Receptor (DTR) mice) on sensor function and CGM utilizing our murine CGM system. The results of these studies demonstrated: 1) a time dependent increase in MQ accumulation (F4/80 positive cells) at the sensor tissue interface; and 2) MQ deficient mice and MQ depleted C57BL/6 mice demonstrated improved sensor performance (MARD) when compared to normal mice (C57BL/6). These studies directly demonstrate the importance of MQ in sensor function and CGM in vivo. PMID:24331705
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Rumpler, M; Mader, J K; Fischer, J P; Thar, R; Granger, J M; Deliane, F; Klimant, I; Aberer, F; Sinner, F; Pieber, T R; Hajnsek, M
2017-02-15
The combination of continuous glucose monitoring (CGM) and continuous subcutaneous insulin infusion can be used to improve the treatment of patients with diabetes. The aim of this study was to advance an existing preclinical single-port system for clinical application by integrating the sensors of a phosphorescence based CGM system into a standard insulin infusion set. The extracorporeal optical phase fluorimeter was miniaturised and is now comparable with commercial CGM systems regarding size, weight and wear comfort. Sensor chemistry was adapted to improve the adhesion of the sensor elements on the insulin infusion set. In-vitro tests showed a linear correlation of R 2 =0.998 between sensor values and reference glucose values in the range of 0-300mg/dl. Electrical and cytotoxicity tests showed no negative impact on human health. Two single-port devices were tested in each of 12 patients with type 1 diabetes mellitus in a clinical set-up for 12h. Without additional data processing, the overall median absolute relative difference (median ARD) was 22.5%. For some of the used devices the median ARD was even well below 10%. The present results show that individual glucose sensors performance of the single-port system is comparable with commercial CGM systems but further improvements are needed. The new system offers a high extent of safety and usability by combining insulin infusion and continuous glucose measurement in a single-port system which could become a central element in an artificial pancreas for an improved treatment of patients with type 1 diabetes mellitus. Copyright © 2016 Elsevier B.V. All rights reserved.
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In vivo continuous glucose monitoring using a chip based near infrared sensor
NASA Astrophysics Data System (ADS)
Ben Mohammadi, L.; Sigloch, S.; Frese, I.; Welzel, K.; Göddel, M.; Klotzbücher, T.
2014-05-01
Diabetes is a serious health condition considered to be one of the major healthcare epidemics of modern era. An effective treatment of this disease can be only achieved by reliable continuous information on blood glucose levels. In this work we present a minimally invasive, chip-based near infrared (NIR) sensor, combined with microdialysis, for continuous glucose monitoring (CGM). The sensor principle is based on difference absorption spectroscopy in the 1st overtone band of the near infrared spectrum. The device features a multi-emitter LED and InGaAs-Photodiodes, which are located on a single electronic board (non-disposable part), connected to a personal computer via Bluetooth. The disposable part consists of a chip containing the fluidic connections for microdialysis, two fluidic channels acting as optical transmission cells and total internally reflecting mirrors for in- and out-coupling of the LED light to the chip and to the detectors. The sensor is combined with an intraveneous microdialysis to separate the glucose from the cells and proteins in the blood and operates without any chemical consumption. In vitro measurements showed a linear relationship between glucose concentration and the integrated difference signal with a coefficient of determination of 99 % in the relevant physiological concentration range from 0 to 400 mg/dl. In vivo measurements on 10 patients showed that the NIR-CGM sensor data reflects the blood reference values adequately, if a proper calibration and signal drift compensation is applied. The MARE (mean absolute relative error) value taken over all patient data is 13.8 %. The best achieved MARE value is at 4.8 %, whereas the worst is 25.8 %, with a standard deviation of 5.5 %.
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Evaluation of the performance of a novel system for continuous glucose monitoring.
Zschornack, Eva; Schmid, Christina; Pleus, Stefan; Link, Manuela; Klötzer, Hans-Martin; Obermaier, Karin; Schoemaker, Michael; Strasser, Monika; Frisch, Gerhard; Schmelzeisen-Redeker, Günther; Haug, Cornelia; Freckmann, Guido
2013-07-01
The performance of a continuous glucose monitoring (CGM) system in the early stage of development was assessed in an inpatient setting that simulates daily life conditions of people with diabetes. Performance was evaluated at low glycemic, euglycemic, and high glycemic ranges as well as during phases with rapid glucose excursions. Each of the 30 participants with type 1 diabetes (15 female, age 47 ± 12 years, hemoglobin A1c 7.7% ± 1.3%) wore two sensors of the prototype system in parallel for 7 days. Capillary blood samples were measured at least 16 times per day (at least 15 times per daytime and at least once per night). On two subsequent study days, glucose excursions were induced. For performance evaluation, the mean absolute relative difference (MARD) between CGM readings and paired capillary blood glucose readings and precision absolute relative difference (PARD), i.e., differences between paired CGM readings were calculated. Overall aggregated MARD was 9.2% and overall aggregated PARD was 7.5%. During induced glucose excursions, MARD was 10.9% and PARD was 7.8%. Lowest MARD (8.5%) and lowest PARD (6.4%) were observed in the high glycemic range (euglycemic range, MARD 9.1% and PARD 7.4%; low glycemic range, MARD 12.3% and PARD 12.4%). The performance of this prototype CGM system was, particularly in the hypoglycemic range and during phases with rapid glucose fluctuations, better than performance data reported for other commercially available systems. In addition, performance of this prototype sensor was noticeably constant over the whole study period. This prototype system is not yet approved, and performance of this CGM system needs to be further assessed in clinical studies. © 2013 Diabetes Technology Society.
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Hajime, Maiko; Okada, Yosuke; Mori, Hiroko; Otsuka, Takashi; Kawaguchi, Mayuko; Miyazaki, Megumi; Kuno, Fumi; Sugai, Kei; Sonoda, Satomi; Tanaka, Kenichi; Kurozumi, Akira; Narisawa, Manabu; Torimoto, Keiichi; Arao, Tadashi; Tanaka, Yoshiya
2018-01-01
High fluctuations in blood glucose are associated with various complications. The correlation between glycated hemoglobin (HbA1c) level and fluctuations in blood glucose level has not been studied in Japanese patients with type 2 diabetes. In the present study, blood glucose profile stratified by HbA1c level was evaluated by continuous glucose monitoring (CGM) in Japanese type 2 diabetes patients. Our retrospective study included 294 patients with type 2 diabetes who were divided by HbA1c level into five groups (≥6.0 to <7.0%, ≥7.0 to <8.0%, ≥8.0 to <9.0%, ≥9.0 to <10.0% and ≥10%). The correlation between HbA1c level and CGM data was analyzed. The primary end-point was the difference in blood glucose fluctuations among the HbA1c groups. The mean blood glucose level increased significantly with increasing HbA1c (P trend < 0.01). The standard deviation increased with increases in HbA1c (P trend < 0.01). The mean amplitude of glycemic excursions did not vary significantly with HbA1c. The levels of maximum blood glucose, minimum blood glucose, each preprandial blood glucose, each postprandial maximum blood glucose, range of increase in postprandial glucose from pre-meal to after breakfast, the area under the blood concentration-time curve >180 mg/dL and percentage of the area under the blood concentration-time curve >180 mg/dL were higher with higher HbA1c. Mean glucose level and pre-breakfast blood glucose level were significant and independent determinants of HbA1c. In Japanese patients treated for type 2 diabetes, the mean amplitude of glycemic excursions did not correlate with HbA1c, making it difficult to assess blood glucose fluctuations using HbA1c. Parameters other than HbA1c are required to evaluate fluctuations in blood glucose level in patients receiving treatment for type 2 diabetes. © 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.
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Garg, Satish K; Smith, James; Beatson, Christie; Lopez-Baca, Benita; Voelmle, Mary; Gottlieb, Peter A
2009-02-01
This study evaluated the accuracy and safety of two continuous glucose monitoring (CGM) systems, the SEVEN (DexCom, San Diego, CA) and the Navigator (Abbott Diabetes Care, Alameda, CA), with the YSI laboratory measurements of blood glucose (blood glucose meter manufactured by YSI, Yellow Springs, OH), when worn concurrently in adults with type 1 diabetes. Fourteen subjects with type 1 diabetes, 33 +/- 6 (mean +/- SD) years old, were enrolled in this study. All subjects wore both sensors concurrently over three consecutive 5-day CGM sessions (15-day wear). On Days 5, 10, and 15, subjects participated in an 8-h in-clinic session where measurements from the CGM systems were collected and compared with YSI measurements every 15 min. At the end of Day 5 and 10 in-clinic sessions, the sensors were removed, and new sensors were inserted for the following CGM session despite the SEVEN system's recommended use for up to 7 days. The mean absolute relative difference (ARD) for the two CGM devices versus YSI was not different: 16.8% and 16.1% for SEVEN and Navigator, respectively (P = 0.38). In the hypoglycemic region (YSI value <80 mg/dL), the mean ARD for SEVEN was lower than for Navigator (21.5% vs. 29.8%, respectively; P = 0.001). The data analyses were similar when compared with self-monitoring of blood glucose (SMBG) values. Thirteen additional Navigator replacement devices were issued compared to two for the SEVEN. A total of three versus 14 skin reactions were reported with the SEVEN and Navigator insertion area, respectively. Glucose measurements with the SEVEN and Navigator were found to be similar compared with YSI and SMBG measurements, with the exception of the hypoglycemic range where the SEVEN performed better. However, the Navigator caused more skin area reactions.
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First Clinical Experience with Retrospective Flash Glucose Monitoring (FGM) Analysis in South Africa
Distiller, Larry A.; Cranston, Iain; Mazze, Roger
2016-01-01
Background: In 2014, an innovative blinded continuous glucose monitoring system was introduced with automated ambulatory glucose profile (AGP) reporting. The clinical use and interpretation of this new technology has not previously been described. Therefore we wanted to understand its use in characterizing key factors related to glycemic control: glucose exposure, variability, and stability, and risk of hypoglycemia in clinical practice. Methods: Clinicians representing affiliated diabetes centers throughout South Africa were trained and subsequently were given flash glucose monitoring readers and 2-week glucose sensors to use at their discretion. After patient use, sensor data were collected and uploaded for AGP reporting. Results: Complete data (sensor AGP with corresponding clinical information) were obtained for 50 patients with type 1 (70%) and type 2 diabetes (30%), irrespective of therapy. Aggregated analysis of AGP data comparing patients with type 1 versus type 2 diabetes, revealed that despite similar HbA1c values between both groups (8.4 ± 2 vs 8.6 ± 1.7%, respectively), those with type 2 diabetes had lower mean glucose levels (9.2 ± 3 vs 10.3 mmol/l [166 ± 54 vs 185 mg/dl]) and lower indices of glucose variability (3.0 ± 1.5 vs 5.0 ± 1.9 mmol/l [54 ± 27 vs 90 ± 34.2 mg/dl]). This highlights key areas for future focus. Conclusions: Using AGP, the characteristics of glucose exposure, variability, stability, and hypoglycemia risk and occurrence were obtained within a short time and with minimal provider and patient input. In a survey at the time of the follow-up visit, clinicians indicated that aggregated AGP data analysis provided important new clinical information and insights. PMID:27154973
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Alzaid, Aus; Schlaeger, Christof; Hinzmann, Rolf
2013-12-01
International experts in the fields of diabetes, diabetes technology, endocrinology, and pediatrics gathered for the 6(th) Annual Symposium on Self-Monitoring of Blood Glucose (SMBG) Applications and beyond. The aim of this meeting was to continue setting up a global network of experts in this field and provide an international platform for exchange of ideas to improve life for people with diabetes. The 2013 meeting comprised a comprehensive scientific program, parallel interactive workshops, and two keynote lectures. All these discussions were intended to help identify gaps and areas where further scientific work and clinical studies are warranted.
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Real-time, aptamer-based tracking of circulating therapeutic agents in living animals
Ferguson, B. Scott; Hoggarth, David A.; Maliniak, Dan; Ploense, Kyle; White, Ryan J.; Woodward, Nick; Hsieh, Kuangwen; Bonham, Andrew J.; Eisenstein, Michael; Kippin, Tod; Plaxco, Kevin W.; Soh, H. Tom
2014-01-01
A sensor capable of continuously measuring specific molecules in the bloodstream in vivo would give clinicians a valuable window into patients’ health and their response to therapeutics. Such technology would enable truly personalized medicine, wherein therapeutic agents could be tailored with optimal doses for each patient to maximize efficacy and minimize side effects. Unfortunately, continuous, real-time measurement is currently only possible for a handful of targets, such as glucose, lactose, and oxygen, and the few existing platforms for continuous measurement are not generalizable for the monitoring of other analytes, such as small-molecule therapeutics. In response, we have developed a real-time biosensor capable of continuously tracking a wide range of circulating drugs in living subjects. Our microfluidic electrochemical detector for in vivo continuous monitoring (MEDIC) requires no exogenous reagents, operates at room temperature, and can be reconfigured to measure different target molecules by exchanging probes in a modular manner. To demonstrate the system's versatility, we measured therapeutic in vivo concentrations of doxorubicin (a chemotherapeutic) and kanamycin (an antibiotic) in live rats and in human whole blood for several hours with high sensitivity and specificity at sub-minute temporal resolution. Importantly, we show that MEDIC can also obtain pharmacokineticparameters for individual animals in real-time. Accordingly, just as continuous glucose monitoring technology is currently revolutionizing diabetes care, we believe MEDIC could be a powerful enabler for personalized medicine by ensuring delivery of optimal drug doses for individual patients based on direct detection of physiological parameters. PMID:24285484
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Holmes-Walker, Deborah Jane; Gunton, Jenny E; Hawthorne, Wayne; Payk, Marlene; Anderson, Patricia; Donath, Susan; Loudovaris, Tom; Ward, Glenn M; Kay, Thomas Wh; OʼConnell, Philip J
2017-06-01
The aim was to compare efficacy of multiple daily injections (MDI), continuous subcutaneous insulin infusion (CSII) and islet transplantation to reduce hypoglycemia and glycemic variability in type 1 diabetes subjects with severe hypoglycemia. This was a within-subject, paired comparison of MDI and CSII and CSII with 12 months postislet transplantation in 10 type 1 diabetes subjects referred with severe hypoglycemia, suitable for islet transplantation. Individuals were assessed with HbA1c, Edmonton Hypoglycemia Score (HYPOscore), continuous glucose monitoring (CGM) and in 8 subjects measurements of glucose variability using standard deviation of glucose (SD glucose) from CGM and continuous overlapping net glycemic action using a 4 hour interval (CONGA4). After changing from MDI to CSII before transplantation, 10 subjects reduced median HYPOscore from 2028 to 1085 (P < 0.05) and hypoglycemia events from 24 to 8 per patient-year (P < 0.05). While HbA1c, mean glucose and median percent time hypoglycemic on CGM were unchanged with CSII, SD glucose and CONGA4 reduced significantly (P < 0.05). At 12 months posttransplant 9 of 10 were C-peptide positive, (5 insulin independent). Twelve months postislet transplantation, there were significant reductions in all baseline parameters versus CSII, respectively, HbA1c (6.4% cf 8.2%), median HYPOscore (0 cf 1085), mean glucose (7.1 cf 8.6 mmol L), SD glucose (1.7 cf 3.2 mmol/L), and CONGA4 (1.6 cf 3.0). In subjects with severe hypoglycemia suitable for islet transplantation, CSII decreased hypoglycemia frequency and glycemic variability compared with MDI whereas islet transplantation resolved hypoglycemia and further improved glycemic variability regardless of insulin independence.
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Electrochemistry in diabetes management.
Heller, Adam; Feldman, Ben
2010-07-20
Diabetes devastates lives and burdens society. Hypoglycemic (low glucose) episodes cause blackouts, and severe ones are life-threatening. Periods of hyperglycemia (high glucose) cause circulatory disease, stroke, amputations, blindness, kidney failure and nerve degeneration. In this Account, we describe the founding of TheraSense, now a major part of Abbott Diabetes Care, and the development of two products that have improved the lives of people with diabetes. The first, a virtually painless microcoulometer (300 nL volume), the FreeStyle blood glucose monitoring system, was approved by the FDA and became available in 2000. In 2009, this system was used in more than one billion blood assays. The second, the enzyme-wiring based, subcutaneously-implanted FreeStyle Navigator continuous glucose monitoring system, was approved by the FDA and became available in the United States in 2008. The strips of the FreeStyle blood glucose monitoring system comprise a printed parallel plate coulometer, with a 50 microm gap between two facing printed electrodes, a carbon electrode and a Ag/AgCl electrode. The volume of blood between the facing plates is accurately controlled. The glucose is electrooxidized through catalysis by a glucose dehydrogenase (GDH) and an Os(2+/3+) redox mediator, which is reduced by the glucose-reduced enzyme and is electrooxidized on the carbon electrode. Initially the system used pyrroloquinoline quinone (PQQ)-dependent GDH but now uses flavin adenine dinucleotide (FAD)-dependent GDH. Because the facing electrodes are separated by such a small distance, shuttling of electrons by the redox couple could interfere with the coulometric assay. However, the Os(2+/3+) redox mediator is selected to have a substantially negative formal potential, between 0.0 and -0.2 V, versus that of the facing Ag/AgCl electrode. This makes the flow of a shuttling current between the two electrodes virtually impossible because the oxidized Os(3+) complex cannot be appreciably reduced at the more positively poised Ag/AgCl electrode. The FreeStyle Navigator continuous glucose monitoring system uses a subcutaneously implanted miniature plastic sensor connected to a transmitter to measure glycemia amperometrically and sends the information to a PDA-like device every minute. The sensor consists of a narrow (0.6 mm wide) plastic substrate on which carbon-working, Ag/AgCl reference, and carbon counter electrodes are printed in a stacked geometry. The active wired enzyme sensing layer covers only about 0.1 mm(2) of the working electrode and is overlaid by a flux-limiting membrane. It resides at about 5 mm depth in the subcutaneous adipose tissue and monitors glucose concentrations over the range 20-500 mg/dL. Its core component, a miniature, disposable, amperometric glucose sensor, has an electrooxidation catalyst made from a crosslinked adduct of glucose oxidase (GOx) and a GOx wiring redox hydrogel containing a polymer-bound Os(2+/3+) complex. Because of the selectivity of the catalyst for glucose, very little current flows in the absence of glucose. That feature, either alone or in combination with other features of the sensor, facilitates the one-point calibration of the system. The sensor is implanted subcutaneously and replaced by the patient after 5 days use with minimal pain. The wearer does not feel its presence under the skin.
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A wire-based dual-analyte sensor for glucose and lactate: in vitro and in vivo evaluation.
Ward, W Kenneth; House, Jody L; Birck, Jonathan; Anderson, Ellen M; Jansen, Lawrence B
2004-06-01
Continuous measurement of lactate is potentially useful for detecting physical exhaustion and for monitoring critical care conditions characterized by hypoperfusion, such as heart failure. In some conditions, it may be desirable to monitor more than one metabolic parameter concurrently. For this reason, we designed and fabricated twisted wire-based microelectrodes that can measure both lactate and glucose. These dual-analyte sensors were characterized in vitro by measuring their response to the analyte of interest and to assess whether they were susceptible to interference from the other analyte. When measured in stirred aqueous buffer, lactate sensors detected a very small amount of crosstalk from glucose in vitro, although this signal was less than 3% of the response to lactate. Glucose sensors did not detect crosstalk from lactate. Sensors were implanted subcutaneously in rats and tested during infusions of lactate and glucose. Each sensing electrode responded rapidly to changes in its analyte concentration, and there was no evidence of in vivo crosstalk. This study constitutes proof of the concept that oxidase-based, amperometric wire microsensors can detect changes in glucose and lactate during subcutaneous implantation in rats.
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Terada, Tasuku; Loehr, Sarah; Guigard, Emmanuel; McCargar, Linda J; Bell, Gordon J; Senior, Peter; Boulé, Normand G
2014-08-01
This study determined the test-retest reliability of a continuous glucose monitoring system (CGMS) (iPro™2; Medtronic, Northridge, CA) under standardized conditions in individuals with type 2 diabetes (T2D). Fourteen individuals with T2D spent two nonconsecutive days in a calorimetry unit. On both days, meals, medication, and exercise were standardized. Glucose concentrations were measured continuously by CGMS, from which daily mean glucose concentration (GLU(mean)), time spent in hyperglycemia (t(>10.0 mmol/L)), and meal, exercise, and nocturnal mean glucose concentrations, as well as glycemic variability (SD(w), percentage coefficient of variation [%cv(w)], mean amplitude of glycemic excursions [MAGEc, MAGE(ave), and MAGE(abs.gos)], and continuous overlapping net glycemic action [CONGA(n)]) were estimated. Absolute and relative reliabilities were investigated using coefficient of variation (CV) and intraclass correlation, respectively. Relative reliability ranged from 0.77 to 0.95 (P<0.05) for GLU(mean) and meal, exercise, and nocturnal glycemia with CV ranging from 3.9% to 11.7%. Despite significant relative reliability (R=0.93; P<0.01), t(>10.0 mmol/L) showed larger CV (54.7%). Among the different glycemic variability measures, a significant between-day difference was observed in MAGEc, MAGE(ave), CONGA6, and CONGA12. The remaining measures (i.e., SD(w), %cv(w), MAGE(abs.gos), and CONGA1-4) indicated no between-day differences and significant relative reliability. In individuals with T2D, CGMS-estimated glycemic profiles were characterized by high relative and absolute reliability for both daily and shorter-term measurements as represented by GLUmean and meal, exercise, and nocturnal glycemia. Among the different methods to calculate glycemic variability, our results showed SD(w), %cv(w), MAGE(abs.gos), and CONGAn with n ≤ 4 were reliable measures. These results suggest the usefulness of CGMS in clinical trials utilizing repeated measured.
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Little, Jonathan P; Jung, Mary E; Wright, Amy E; Wright, Wendi; Manders, Ralph J F
2014-07-01
The purpose of this study was to examine the impact of acute high-intensity interval training (HIIT) compared with continuous moderate-intensity (CMI) exercise on postprandial hyperglycemia in overweight or obese adults. Ten inactive, overweight or obese adults (41 ± 11 yrs, BMI = 36 ± 7 kg/m(2)) performed an acute bout of HIIT (10 × 1 min at approximately 90% peak heart rate (HRpeak) with 1-min recovery periods) or matched work CMI (30 min at approximately 65% HRpeak) in a randomized, counterbalanced fashion. Exercise was performed 2 h after breakfast, and glucose control was assessed by continuous glucose monitoring under standardized dietary conditions over 24 h. Postprandial glucose (PPG) responses to lunch, dinner, and the following day's breakfast were analyzed and compared with a no-exercise control day. Exercise did not affect the PPG responses to lunch, but performing both HIIT and CMI in the morning significantly reduced the PPG incremental area under the curve (AUC) following dinner when compared with control (HIIT = 110 ± 35, CMI = 125 ± 34, control = 162 ± 46 mmol/L × 2 h, p < 0.05). The PPG AUC (HIIT = 125 ± 53, CMI = 186 ± 55, control = 194 ± 96 mmol/L × 2 h) and the PPG spike (HIIT = Δ2.1 ± 0.9, CMI = Δ3.0 ± 0.9, control = Δ3.0 ± 1.5 mmol/l) following breakfast on the following day were significantly lower following HIIT compared with both CMI and control (p < 0.05). Absolute AUC and absolute glucose spikes were not different between HIIT, CMI, or control for any meal (p > 0.05 for all). We conclude that a single session of HIIT has greater and more lasting effects on reducing incremental PPG when compared with CMI.
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Usability of Medical Devices for Patients With Diabetes Who Are Visually Impaired or Blind
Heinemann, Lutz; Drossel, Diana; Freckmann, Guido; Kulzer, Bernhard
2016-01-01
The estimation is that every third to fourth patient with diabetes suffers from some degree of diabetic retinopathy. Medical products for insulin administration (such as insulin pens and pumps) or glucose monitoring not optimized to the needs of these patients’ represent a high barrier for optimal diabetes therapy in daily practice. To date, the number of devices suitable for visually impaired and blind patients with diabetes is scarce. This manuscript outlines the specific needs of this patient group with regard to systems for insulin administration, blood glucose measurement, and continuous glucose monitoring. We see the clear need for a policy requirement for manufacturers to provide accessible/user friendly technical aids for visually impaired and blind patients with diabetes. This would represent an important step toward improving the situation for this impressively large patient group. PMID:27605593
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Riddell, Michael C; Milliken, Jill
2011-08-01
Real-time (RT) continuous glucose monitoring (CGM) offers the possibility to better manage glucose levels during exercise in active individuals with type 1 diabetes mellitus (T1DM). However, studies have yet to determine the appropriate actions to take when glucose levels are trending toward hypoglycemia. The purpose of this observational field study was to test the effectiveness of RT-GCM and a new carbohydrate intake algorithm designed for maintaining euglycemia during sports. During a 2-week sports camp, 25 adolescents (8-17 years old) with T1DM were fitted with a RT-CGM device and instructed to ingest fast-acting carbohydrates (8-20 g, depending on the concentration of glucose at the time of RT-CGM alert and rates of change in glycemia) when glucose levels were trending toward hypoglycemia. Rates of change in glucose were measured before and after algorithm use, and the incidence of hypoglycemia was documented. With RT-CGM and algorithm use, euglycemia was largely maintained with modest amounts of carbohydrate intake, even when glucose levels were initially dropping at an elevated rate (>0.55 mmol/L per 5 min). Mild biochemical hypoglycemia (3.0-3.9 mmol/L) occurred just twice out of 22 uses of the algorithm (9%) when trend arrows alerted the subjects that glucose levels were dropping. When glucose levels were already below target (<5.0 mmol/L), mild hypoglycemia occurred five times out of 13 events (38%), despite 16 g of carbohydrate being ingested. Average glucose levels during sports in the 60 min following algorithm use were 5.8 ± 1.2 mmol/L, 5.3 ± 1.0 mmol/L, and 6.2 ± 0.8 mmol/L in the 20-, 16-, and 8-g carbohydrate intake protocols when glucose levels were initially on target but dropping toward hypoglycemia. When coupled with RT-CGM, a new carbohydrate intake algorithm prevents hypoglycemia and maintains euglycemia during exercise, particularly if patients ingest carbohydrate when trend arrows alert them of a drop in glycemia.
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Nanomaterial-based Electrochemical Sensors for the Detection of Glucose and Cholesterol
NASA Astrophysics Data System (ADS)
Ahmadalinezhad, Asieh
Electrochemical detection methods are highly attractive for the monitoring of glucose, cholesterol, cancer, infectious diseases, and biological warfare agents due to their low cost, high sensitivity, functionality despite sample turbidity, easy miniaturization via microfabrication, low power requirements, and a relatively simple control infrastructure. The development of implantable biosensors is laden with great challenges, which include longevity and inherent biocompatibility, coupled with the continuous monitoring of analytes. Deficiencies in any of these areas will necessitate their surgical replacement. In addition, random signals arising from non-specific adsorption events can cause problems in diagnostic assays. Hence, a great deal of effort has been devoted to the specific control of surface structures. Nanotechnology involves the creation and design of structures with at least one dimension that is below 100 nm. The optical, magnetic, and electrical properties of nanostructures may be manipulated by altering their size, shape, and composition. These attributes may facilitate improvements in biocompatibility, sensitivity and the specific attachment of biomaterials. Thus, the central theme of this dissertation pertains to highlighting the critical roles that are played by the morphology and intrinsic properties of nanomaterials when they are applied in the development of electrochemical biosensors. For this PhD project, we initially designed and fabricated a novel amperometric glucose biosensor based on the immobilization of glucose oxidase (GOx) on a Prussian blue modified nanoporous gold surface, which exhibited a rapid response and a low detection limit of 2.5 microM glucose. The sensitivity of the biosensor was found to be very high (177 microA/mM) and the apparent Michaelis--Menten constant was calculated to be 2.1 mM. Our study has demonstrated that nanoporous gold provides an excellent matrix for enzyme immobilization. To adopt these advanced properties, we fabricated a highly sensitive and mediator-free electrochemical biosensor for the determination of total cholesterol. The developed biosensor possessed high selectivity and sensitivity (29.33 microA mM--1cm --2). The apparent Michaelis--Menten constant, KappM of this biosensor was very low (0.64 mM), which originated from both the effective immobilization process and the nanoporous structure of the substrate. The biosensor exhibited a wide linear range, up to 300 mg dL--1 , in a physiological environment (pH 7.4); making it a promising candidate for the clinical determination of cholesterol. The fabricated biosensor was tested further by utilizing actual food samples (e.g., margarine, butter and fish oil). The results indicated that it has the potential capacity to be employed as a facile cholesterol detection tool in the food industry and for supplement quality control. To enhance the stability of the biosensors in the continuous monitoring of glucose, we designed a novel platform that was based on buckypaper. The fabricated biosensor responded to glucose with a considerable functional lifetime of over 80 days and detected glucose with a dynamic linear range of over 9 mM with a detection limit of 0.01 mM. To investigate the effects of the physical dimensions of nanomaterials on electrochemical biosensing, we synthesized TiO2 nanowires with controllable dimensions via a facile thermal oxidation treatment of a Ti substrate. To improve the conductivity of the TiO2 nanowires and to facilitate the immobilization of enzymes, a thin layer of carbon was deposited onto the TiO2 nanowires via a chemical vapour deposition method. Upon the immobilization of glucose oxidase as a model protein, direct electron transfer was observed in a mediator-free biosensing environment. Our electrochemical studies have revealed that the electron transfer rate of the immobilized glucose oxidase is strongly dependent on the dimensions of the carbonized TiO 2 nanowires, and that the designed glucose biosensor exhibits a wide linear range, up to 18 mM glucose, as well as high sensitivity and selectivity. Glucose measurements of human serum using the developed biosensor showed excellent agreement with the data recorded by a commercial blood glucose monitoring assay. Finally, we fabricated an enzyme-free glucose sensor based on nanoporous palladium-cadmium (PdCd) networks. A hydrothermal method was applied in the synthesis of PdCd nanomaterials. The effect of the composition of the PdCd nanomaterials on the performance of the electrode was investigated by cyclic voltammetry (CV). Amperometric studies showed that the nanoporous PdCd electrode was responsive to the direct oxidation of glucose with high electrocatalytic activity. The sensitivity of the sensor for continuous glucose monitoring was 146.21 microAmM--1cm--2, with linearity up to 10 mM and a detection limit of 0.05 mM. In summary, the electrochemical biosensors proposed in my PhD study exhibited high sensitivity and selectivity for the continuous monitoring of analytes in the presence of common interference species. Our results have shown that the performance of the biosensors is significantly dependent on the dimensions and morphologies of nanostructured materials. The unique nanomaterials-based platforms proposed in this dissertation open the door to the design and fabrication of high-performance electrochemical biosensors for medical diagnostics.
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Bratina, Natasa; Battelino, Tadej
2010-08-01
The use of insulin pump and continuous glucose monitoring (CGM) therapies in children and adolescents with type 1 diabetes (T1DM) has increased over the last 10 years, including the group of children <7 years of age. When these young children use pumps and CGM, their families, teachers, school nurses and professional caregivers (who take the place of school nurses in many countries) in preschools, kindergartens and primary schools need to give them special attention since they depend completely on their help in succeeding with diabetes management. Written individualized diabetesrelated health-care plans should be agreed upon between parents, school nurses, professional caregivers and teachers, and the diabetes healthcare team. A structured educational program should be provided for preschools, kindergartens and primary schools that includes information about and practical training for the use of these new diabetes-related technologies.
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A data driven nonlinear stochastic model for blood glucose dynamics.
Zhang, Yan; Holt, Tim A; Khovanova, Natalia
2016-03-01
The development of adequate mathematical models for blood glucose dynamics may improve early diagnosis and control of diabetes mellitus (DM). We have developed a stochastic nonlinear second order differential equation to describe the response of blood glucose concentration to food intake using continuous glucose monitoring (CGM) data. A variational Bayesian learning scheme was applied to define the number and values of the system's parameters by iterative optimisation of free energy. The model has the minimal order and number of parameters to successfully describe blood glucose dynamics in people with and without DM. The model accounts for the nonlinearity and stochasticity of the underlying glucose-insulin dynamic process. Being data-driven, it takes full advantage of available CGM data and, at the same time, reflects the intrinsic characteristics of the glucose-insulin system without detailed knowledge of the physiological mechanisms. We have shown that the dynamics of some postprandial blood glucose excursions can be described by a reduced (linear) model, previously seen in the literature. A comprehensive analysis demonstrates that deterministic system parameters belong to different ranges for diabetes and controls. Implications for clinical practice are discussed. This is the first study introducing a continuous data-driven nonlinear stochastic model capable of describing both DM and non-DM profiles. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.
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Continuous glucose monitoring--a study of the Enlite sensor during hypo- and hyperbaric conditions.
Adolfsson, Peter; Örnhagen, Hans; Eriksson, Bengt M; Cooper, Ken; Jendle, Johan
2012-06-01
The performance and accuracy of the Enlite(™) (Medtronic, Inc., Northridge, CA) sensor may be affected by microbubble formation at the electrode surface during hypo- and hyperbaric conditions. The effects of acute pressure changes and of prewetting of sensors were investigated. On Day 1, 24 sensors were inserted on the right side of the abdomen and back in one healthy individual; 12 were prewetted with saline solution, and 12 were inserted dry. On Day 2, this procedure was repeated on the left side. All sensors were attached to an iPro continuous glucose monitoring (CGM) recorder. Hypobaric and hyperbaric tests were conducted in a pressure chamber, with each test lasting 105 min. Plasma glucose values were obtained at 5-min intervals with a HemoCue(®) (Ängelholm, Sweden) model 201 glucose analyzer for comparison with sensor glucose values. Ninety percent of the CGM systems operated during the tests. The mean absolute relative difference was lower during hyperbaric than hypobaric conditions (6.7% vs. 14.9%, P<0.001). Sensor sensitivity was slightly decreased (P<0.05) during hypobaric but not during hyperbaric conditions. Clarke Error Grid Analysis showed that 100% of the values were found in the A+B region. No differences were found between prewetted and dry sensors. The Enlite sensor performed adequately during acute pressure changes and was more accurate during hyperbaric than hypobaric conditions. Prewetting the sensors did not improve accuracy. Further studies on type 1 diabetes subjects are needed under various pressure conditions.
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Preechasuk, Lukana; Suwansaksri, Nattakarn; Ipichart, Nantawan; Vannasaeng, Sathit; Permpikul, Chairat; Sriwijitkamol, Apiradee
2017-04-01
The purpose was to compare glucose variability (GV) obtained via continuous glucose monitoring between nondiabetic sepsis patients and healthy subjects and to seek associations between GV and sepsis severity in nondiabetic sepsis patients. Nondiabetic sepsis inpatients and healthy controls received a 72-hour continuous glucose monitoring (iPro2, Medtronic) postadmission and post-oral glucose tolerance test, respectively. The mean glucose level (MGL) along with GV represented by standard deviation (SD) and the mean amplitude of glycemic excursion (MAGE) were calculated at 24 and 72 hours. Sepsis severity was evaluated with the Sepsis-related Organ Failure Assessment Score (SOFA). MGL and GV in patients with SOFA ≥9 and <9 were compared. Thirty nondiabetic sepsis and 10 healthy subjects were recruited. No differences were found between groups except for higher patient age in sepsis patients. The MGL and MAGE 72h of sepsis patients were significantly higher than those of healthy subjects. MGL and GV 24h were higher in patients with SOFA ≥9 than in patients with SOFA <9 (MGL 24h 195±17 vs 139±27, P<.001; SD 24h 32 [28, 36] vs 19 [5, 58], P=.02; and MAGE 24h 94 [58, 153] vs 54 [16, 179], P=.01). Nondiabetic sepsis patients had higher MGL and GV values than healthy subjects. MGL and GV 24h were associated with sepsis severity. Copyright © 2016 Elsevier Inc. All rights reserved.
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Surface Enhanced Raman Spectroscopy for Monitoring Lactate and Glucose
2005-07-01
lasers. We have successfully developed and tested these SERS active substances in vitro and in vivo in the subcutaneous space of a rat. Work continues in...using this system for detection in vitro and in vivo as specified in the original proposal. The specific aims, as proposed in the original "statement...assess performance. a. Control experiments. b. Use indwelling probes to quantitatively measure glucose levels in vivo . c. Use indwelling probes to
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Nonenzymatic Wearable Sensor for Electrochemical Analysis of Perspiration Glucose.
Zhu, Xiaofei; Ju, Yinhui; Chen, Jian; Liu, Deye; Liu, Hong
2018-05-25
We report a nonenzymatic wearable sensor for electrochemical analysis of perspiration glucose. Multipotential steps are applied on a Au electrode, including a high negative pretreatment potential step for proton reduction which produces a localized alkaline condition, a moderate potential step for electrocatalytic oxidation of glucose under the alkaline condition, and a positive potential step to clean and reactivate the electrode surface for the next detection. Fluorocarbon-based materials were coated on the Au electrode for improving the selectivity and robustness of the sensor. A fully integrated wristband is developed for continuous real-time monitoring of perspiration glucose during physical activities, and uploading the test result to a smartphone app via Bluetooth.
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Fabrication of nitric oxide-releasing polyurethane glucose sensor membranes
Koh, Ahyeon; Riccio, Daniel A.; Sun, Bin; Carpenter, Alexis W.; Nichols, Scott P.; Schoenfisch, Mark H.
2011-01-01
Despite clear evidence that polymeric nitric oxide (NO) release coatings reduce the foreign body response (FBR) and may thus improve the analytical performance of in vivo continuous glucose monitoring devices when used as sensor membranes, the compatibility of the NO release chemistry with that required for enzymatic glucose sensing remains unclear. Herein, we describe the fabrication and characterization of NO-releasing polyurethane sensor membranes using NO donor-modified silica vehicles embedded within the polymer. In addition to demonstrating tunable NO release as a function of the NO donor silica scaffold and polymer compositions and concentrations, we describe the impact of the NO release vehicle and its release kinetics on glucose sensor performance. PMID:21795038
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An Adaptive Nonlinear Basal-Bolus Calculator for Patients With Type 1 Diabetes
Boiroux, Dimitri; Aradóttir, Tinna Björk; Nørgaard, Kirsten; Poulsen, Niels Kjølstad; Madsen, Henrik; Jørgensen, John Bagterp
2016-01-01
Background: Bolus calculators help patients with type 1 diabetes to mitigate the effect of meals on their blood glucose by administering a large amount of insulin at mealtime. Intraindividual changes in patients physiology and nonlinearity in insulin-glucose dynamics pose a challenge to the accuracy of such calculators. Method: We propose a method based on a continuous-discrete unscented Kalman filter to continuously track the postprandial glucose dynamics and the insulin sensitivity. We augment the Medtronic Virtual Patient (MVP) model to simulate noise-corrupted data from a continuous glucose monitor (CGM). The basal rate is determined by calculating the steady state of the model and is adjusted once a day before breakfast. The bolus size is determined by optimizing the postprandial glucose values based on an estimate of the insulin sensitivity and states, as well as the announced meal size. Following meal announcements, the meal compartment and the meal time constant are estimated, otherwise insulin sensitivity is estimated. Results: We compare the performance of a conventional linear bolus calculator with the proposed bolus calculator. The proposed basal-bolus calculator significantly improves the time spent in glucose target (P < .01) compared to the conventional bolus calculator. Conclusion: An adaptive nonlinear basal-bolus calculator can efficiently compensate for physiological changes. Further clinical studies will be needed to validate the results. PMID:27613658
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[New developments in the treatment and monitoring of type 1 diabetes mellitus].
Otto-Buczkowska, Ewa; Jarosz-Chobot, Przemysława; Tucholski, Krzysztof
2008-01-01
In recent years, insulin analogues are the benefits of the use in functional intensive insulin therapy for the treatment of diabetes. Shortacting insulin (lispro, aspart and glulisine) and long-acting insulin (glargine and detemir) have been developed for the management of diabetes. Short-acting insulin analogues are an alternative to regular human insulin before meals. These new short-acting insulin analogues show more rapid onset of activity and a shorter duration of action. As a result of these pharmacokinetic differences, an improved postprandial glycemic control is achieved, without increasing the risk of hypoglycemia. In addition, these insulin analogues can be administered immediately before a meal. The long-acting insulin analogues provide basal insulin levels for 24 h when administered once (glargine) or two (detemir) daily. Compared with previous intermediate- or long-acting conventional insulin, these insulins shows a flat profile of plasma insulin levels . The use of these long-acting insulin analogues appears to be associated with a reduced incidence of hypoglycemia, especially at night. The availability of these new insulin analogues has the potential to significantly improve long-term control over blood glucose in diabetic patients. In recent years more and more frequently the method of multiple daily injections (MDI) of insulin is being replaced by the method of continuous subcutaneous insulin infusion (CSII). It is the most physiological way to administer insulin. In recent years treatment with insulin pumps has been used more frequently in the pediatric patients and in the treatment of diabetes in pregnancy. Use of continuous glucose monitoring systems enables detection of glycemia fluctuations unrevealed by selfmonitoring of blood glucose, such as night hypoglycemias and early postprandial hyperglycemias. Real-time systems allow to reduce HbA1c levels and limit number of excursions. Non-invasive glucose measurement devices are introduced. Fully automated continuous glucose monitoring systems integrated with insulin pumps operating in closed-loop model, requiring no patient assistance, are still being researched. Commercially available systems operate in open-loop model, where the patient has to decide on administration and dose of insulin.
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Mainguy, Catherine; Bellon, Gabriel; Delaup, Véronique; Ginoux, Tiphanie; Kassai-Koupai, Behrouz; Mazur, Stéphane; Rabilloud, Muriel; Remontet, Laurent; Reix, Philippe
2017-01-01
Cystic fibrosis-related diabetes (CFRD) is a late cystic fibrosis (CF)-associated comorbidity whose prevalence is increasing sharply lifelong. Guidelines for glucose metabolism (GM) monitoring rely on the oral glucose tolerance test (OGTT). However, this test is neither sensitive nor specific. The aim of this study was to compare sensitivity and specificity of different methods for GM monitoring in children and adolescents with CF. Continuous glucose monitoring system (CGMS), used as the reference method, was compared with the OGTT, intravenous glucose tolerance test (IGTT), homeostasis model assessment index of insulin resistance (HOMA-IR), homeostasis model assessment index of β-cell function (HOMA-%B) and glycated haemoglobin A1C. Patients were classified into three groups according to CGMS: normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and diabetes mellitus (DM). Twenty-nine patients (median age: 13.1 years) were recruited. According to CGMS, 11 had DM, 12 IGT and six NGT, whereas OGTT identified three patients with DM and five with IGT. While 13 of 27 had insulin deficiency according to IGTT, there was 19 of 28 according to HOMA-%B. According to HOMA-IR, 12 of 28 had insulin resistance. HOMA-%B was the most sensitive method for CFRD screening [sensitivity 91% (95% CI), specificity 47% (95% CI) and negative predictive value 89% (95% CI)]. OGTT showed the weak capacity to diagnose DM in CF and should no longer be considered as the reference method for CFRD screening in patients with CF. In our study, HOMA-%B showed promising metrics for CFRD screening. Finally, CGMS revealed that pathological glucose excursions were frequent even early in life.
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Setford, Steven; Grady, Mike; Mackintosh, Stephen; Donald, Robert; Levy, Brian
2018-05-01
MARD (mean absolute relative difference) is increasingly used to describe performance of glucose monitoring systems, providing a single-value quantitative measure of accuracy and allowing comparisons between different monitoring systems. This study reports MARDs for the OneTouch Verio® glucose meter clinical data set of 80 258 data points (671 individual batches) gathered as part of a 7.5-year self-surveillance program Methods: Test strips were routinely sampled from randomly selected manufacturer's production batches and sent to one of 3 clinic sites for clinical accuracy assessment using fresh capillary blood from patients with diabetes, using both the meter system and standard laboratory reference instrument. Evaluation of the distribution of strip batch MARD yielded a mean value of 5.05% (range: 3.68-6.43% at ±1.96 standard deviations from mean). The overall MARD for all clinic data points (N = 80 258) was also 5.05%, while a mean bias of 1.28 was recorded. MARD by glucose level was found to be consistent, yielding a maximum value of 4.81% at higher glucose (≥100 mg/dL) and a mean absolute difference (MAD) of 5.60 mg/dL at low glucose (<100 mg/dL). MARD by year of manufacture varied from 4.67-5.42% indicating consistent accuracy performance over the surveillance period. This 7.5-year surveillance program showed that this meter system exhibits consistently low MARD by batch, glucose level and year, indicating close agreement with established reference methods whilste exhibiting lower MARD values than continuous glucose monitoring (CGM) systems and providing users with confidence in the performance when transitioning to each new strip batch.
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Continuous glucose monitoring: 40 years, what we've learned and what's next.
Gifford, Raeann
2013-07-22
After 40 years of research and development, today continuous glucose monitoring (CGM) is demonstrating the benefit it provides for millions with diabetes. To provide in vivo accuracy, new permselective membranes and mediated systems have been developed to prevent enzyme saturation and to minimize interference signals. Early in vivo implanted sensor research clearly showed that the foreign body response was a more difficult issue to overcome. Understanding the biological interface and circumventing the inflammatory response continue to drive development of a CGM sensor with accuracy and reliability performance suitable in a closed-loop artificial pancreas. Along with biocompatible polymer development, other complimentary algorithm and data analysis techniques have improved the performance of commercial systems significantly. For example, the mean average relative difference of Dexcom's CGM system improved from 26 to 14% and its use-life was extended from 3 to 7 d. Significant gains in usability, including size, flexibility, insertion, calibration, and data interface, have been incorporated into new generations of commercial CGM systems. Besides Medtronic, Dexcom, and Abbott, other major players are also investing in CGM. Becton Dickinson is conducting clinical trials with an optical galactose glucose binding system. Development of fully implanted sensor systems fulfills the desire for a discreet, reliable CGM system. Research continues to find innovative ways to help make living with diabetes easier and more normal, and new segments are being pursued (intensive care unit, surgery, behavior modification) in which CGM is being utilized. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Moser, Othmar; Mader, Julia K; Tschakert, Gerhard; Mueller, Alexander; Groeschl, Werner; Pieber, Thomas R; Koehler, Gerd; Messerschmidt, Janin; Hofmann, Peter
2016-08-10
Continuous exercise (CON) and high-intensity interval exercise (HIIE) can be safely performed with type 1 diabetes mellitus (T1DM). Additionally, continuous glucose monitoring (CGM) systems may serve as a tool to reduce the risk of exercise-induced hypoglycemia. It is unclear if CGM is accurate during CON and HIIE at different mean workloads. Seven T1DM patients performed CON and HIIE at 5% below (L) and above (M) the first lactate turn point (LTP₁), and 5% below the second lactate turn point (LTP₂) (H) on a cycle ergometer. Glucose was measured via CGM and in capillary blood (BG). Differences were found in comparison of CGM vs. BG in three out of the six tests (p < 0.05). In CON, bias and levels of agreement for L, M, and H were found at: 0.85 (-3.44, 5.15) mmol·L(-1), -0.45 (-3.95, 3.05) mmol·L(-1), -0.31 (-8.83, 8.20) mmol·L(-1) and at 1.17 (-2.06, 4.40) mmol·L(-1), 0.11 (-5.79, 6.01) mmol·L(-1), 1.48 (-2.60, 5.57) mmol·L(-1) in HIIE for the same intensities. Clinically-acceptable results (except for CON H) were found. CGM estimated BG to be clinically acceptable, except for CON H. Additionally, using CGM may increase avoidance of exercise-induced hypoglycemia, but usual BG control should be performed during intense exercise.
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Prévoteau, Antonin; Geirnaert, Annelies; Arends, Jan B A; Lannebère, Sylvain; Van de Wiele, Tom; Rabaey, Korneel
2015-07-01
Monitoring in vitro the metabolic activity of microorganisms aids bioprocesses and enables better understanding of microbial metabolism. Redox mediators can be used for this purpose via different electrochemical techniques that are either complex or only provide non-continuous data. Hydrodynamic chronoamperometry using a rotating disc electrode (RDE) can alleviate these issues but was seldom used and is poorly characterized. The kinetics of Faecalibacterium prausnitzii A2-165, a beneficial gut microbe, were determined using a RDE with riboflavin as redox probe. This butyrate producer anaerobically ferments glucose and reduces riboflavin whose continuous monitoring on a RDE provided highly accurate kinetic measurements of its metabolism, even at low cell densities. The metabolic reaction rate increased linearly over a broad range of cell concentrations (9 × 10(4) to 5 × 10(7) cells.mL(-1)). Apparent Michaelis-Menten kinetics was observed with respect to riboflavin (KM = 6 μM; kcat = 5.3 × 10(5) s(-1), at 37 °C) and glucose (KM = 6 μM; kcat = 2.4 × 10(5) s(-1)). The short temporal resolution allows continuous monitoring of fast cellular events such as kinetics inhibition with butyrate. Furthermore, we detected for the first time riboflavin reduction by another potential probiotic, Butyricicoccus pullicaecorum. The ability of the RDE for fast, accurate, simple and continuous measurements makes it an ad hoc tool for assessing bioprocesses at high resolution.
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New-generation diabetes management: glucose sensor-augmented insulin pump therapy
Cengiz, Eda; Sherr, Jennifer L; Weinzimer, Stuart A; Tamborlane, William V
2011-01-01
Diabetes is one of the most common chronic disorders with an increasing incidence worldwide. Technologic advances in the field of diabetes have provided new tools for clinicians to manage this challenging disease. For example, the development of continuous subcutaneous insulin infusion systems have allowed for refinement in the delivery of insulin, while continuous glucose monitors provide patients and clinicians with a better understanding of the minute to minute glucose variability, leading to the titration of insulin delivery based on this variability when applicable. Merging of these devices has resulted in sensor-augmented insulin pump therapy, which became a major building block upon which the artificial pancreas (closed-loop systems) can be developed. This article summarizes the evolution of sensor-augmented insulin pump therapy until present day and its future applications in new-generation diabetes management. PMID:21728731
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New-generation diabetes management: glucose sensor-augmented insulin pump therapy.
Cengiz, Eda; Sherr, Jennifer L; Weinzimer, Stuart A; Tamborlane, William V
2011-07-01
Diabetes is one of the most common chronic disorders with an increasing incidence worldwide. Technologic advances in the field of diabetes have provided new tools for clinicians to manage this challenging disease. For example, the development of continuous subcutaneous insulin infusion systems have allowed for refinement in the delivery of insulin, while continuous glucose monitors provide patients and clinicians with a better understanding of the minute to minute glucose variability, leading to the titration of insulin delivery based on this variability when applicable. Merging of these devices has resulted in sensor-augmented insulin pump therapy, which became a major building block upon which the artificial pancreas (closed-loop systems) can be developed. This article summarizes the evolution of sensor-augmented insulin pump therapy until present day and its future applications in new-generation diabetes management.
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Matsuda, Erin; Brennan, Patricia
The review question is: Are metabolic outcomes improved in outpatient adolescents (aged 13 to 19 years) with type 1 diabetes on a Continuous Subcutaneous Insulin Infusion (CSII) when continuous glucose monitoring is used, compared to self-glucose monitoring alone? Type 1 diabetes is the most common childhood paediatric disease, characterised by impairment of insulin producing βeta-cells in the pancreas. Internationally, there is variation in the incidence of type 1 diabetes in paediatric patients. According to the Center for Disease Control and Prevention (CDC) and the SEARCH for Diabetes in Youth Study Group, the overall incidence rate of this autoimmune disease is 24.3/100,000 in those 19 years of age . Annually, more than 15,000 children and adolescents are diagnosed in the United States (US) . From 1990 to 1999, the World Health Organization (WHO) launched the Multinational Project for Childhood Diabetes (DIAMOND), which was tasked with assessing type 1 diabetes in those 14 years or younger worldwide . Finland was discovered to have the highest age-adjusted incidence at 40.9 cases per 100,000/year. The lowest age-adjusted incidence is in China and Venezuela at 0.1 cases per 100,000/year. Globally, the largest increase in incidence is in those aged 10 to 14 years . This systematic review will focus on adolescent patients with type 1 diabetes, aged 13 to 19 years who manage their diabetes with an insulin pump.Patients with type 1 diabetes mellitus typically present with a history of polydipsia, polyuria, polyphagia, and weight loss . Initial findings include hyperglycemia, glycosuria, and ketones in the blood or urine . In 2009, the International Expert Committee deemed a haemoglobin A1C (glycosylated haemoglobin) of 6.5% or higher to be the standard for diagnosis . The American Diabetes Association (ADA) as well as the International Diabetes Federation and the European Association Study of Diabetes (EASD) accept this measure as the diagnostic tool for diabetes. Haemoglobin A1C is the most commonly used measurement for patients with type 1 diabetes . It refers to the measurement of the amount of glucose bound to haemoglobin. It is an average of blood glucose levels for the last 120 days, which is consistent with the average life span of a red blood cell (RBC).Compensation for the lack of insulin-secreting βeta-cells is accomplished through administration of insulin. For adolescents, insulin dosing is based on pubescent status, age, weight, activity level, and amount of carbohydrates consumed . Insulin administration, carbohydrate counting, and correction of hyperglycemia are necessary for maintaining glycemic control. Insulin can be administered through multiple daily injections (MDI) of rapid, intermediate and long-acting insulin .Another form of insulin delivery is the Continuous Subcutaneous Insulin Infusion (CSII), also known as an insulin pump, which is designed to meet physiological requirements through programmable basal rates and bolus doses . CSII's utilise rapid-acting insulin and establish a basal rate, which replaces the need for long-acting insulin. Bolus dosing is accomplished through adjusting the pump and is utilised to account for nutritional intake as well as hyperglycemia correction. Adjustments are also made for physical activity and exercise, as this can affect glucose levels . All patients considered in this systematic review will be utilising insulin pumps.In 2006, the United States had more than 35,000 patients, under the age of 21 years, receiving insulin therapy through an insulin pump . In Europe, the percentage of people with type 1 diabetes utilising a CSII is lower, potentially due to variation in health care coverage . There are various forms of insulin pumps, all with similar capabilities including a dose calculator for high blood glucose correction and carbohydrate ratios, programming software, and several other features . Software and programming is specific to each manufacturer. Basal rate abilities vary in each model from 0.05 units/hour to 30 units/hour . Information from the pump can be uploaded to online registries allowing providers to review trends and usage. It is imperative the information is reviewed concurrently with glucose monitoring results in order to ensure appropriate dosing and treatment .The intervention considered in this systematic review is the use of continuous glucose monitoring (CGM) in conjunction with a CSII. CGM utilises a sensor placed in the interstitial subcutaneous tissue, which then measures glucose levels. This is accomplished with "electrochemical sensors that use glucose oxidase and measure an electric current generated when glucose reacts with oxygen. The sensors are coated with a specialised membrane to make them biocompatible" . The CGM has programmable high and low levels to alert the user when the limit is being reached. Information regarding continuous glucose levels can then be downloaded and reviewed. Based on the report, providers, patients, and caregivers may assess trends and consider changing basal rates or bolus doses .CGM sensors currently do not offer a closed-loop solution. The user must enter insulin dosing information into the pump, taking into account the present glucose level and duration of action of the insulin. Currently, CGMs are regarded as a supplemental method for assessing the effectiveness of glucose control. Existing studies are underway to improve accuracy and communication between the sensor and insulin pump with the goal to develop an artificial pancreas . Currently, CGM sensors must be calibrated with a glucometer, as specified by the manufacturer .The comparison for this review is the standard of care, self-glucose monitoring (SGM), in patients with insulin pumps . SGM is accomplished with a glucometer and blood sample typically obtained from a finger prick. The Diabetes Control and Complications Trial (DCCT) demonstrated frequency of monitoring improves glycemic control and decreases the risk of comorbidity . Data from this significant study continues to contribute to current diabetes management. According to the ADA, children and adolescents should monitor their blood glucose at least three or more times per day. Blood glucose data is utilised to calculate appropriate insulin doses. Similar to the CGM, information from the glucometers can be downloaded for assessment of results and trends. However, the result is dependent on the action of the patient to obtain the sample and only represents a specific moment in time whereas the CGM sensor continuously tracks the blood glucose level. Depending on the model, CGM can provide glucose levels every one to ten minutes. The sensor may last for up to 72 hours and results are available in real time .This systematic review will address two metabolic outcomes: a decrease in the number of hypoglycemic episodes and a haemoglobin A1C level <7.5%. These outcomes were chosen due to their significance as indicators in the management of type 1 diabetes. Glucose levels should be between 90 mg/dL and 130 mg/dL (5.0mmol/l and 7.2mmol/l) before meals and between 90 mg/dL and 150 mg/dL at night (5.0mmmol/l and 8.3mmol/l) . Optimal care of an adolescent with type 1 diabetes mellitus is to safely maintain glycemic control and avoid hypoglycemia.Haemoglobin A1C is an indicator of how well the disease is being managed and should be evaluated every three months. McCulloch recommends the haemoglobin A1C level should be compared to approximately 50 recent blood glucose readings to ensure the accuracy of patient SGM . The reliability and validity of this test is based on the evidence discovered by the DCCT demonstrating those with lower haemoglobin A1C levels have fewer complications . The target A1C for adolescents, aged 13 to 19 years of age, is <7.5% . This is consistent with the National Institute of Clinical Excellence (NICE) and diabetes management guidelines of the Australasian Paediatric Endocrine Group for the Department of Health and Ageing .An initial search for a systematic review regarding insulin pumps in adolescents with type 1 diabetes mellitus and concurrent use of CGM was conducted in the Joanna Briggs Institute Library of Systematic Reviews, Cochrane Database of Systematic Reviews, and PubMed. No systematic reviews were found.
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Diurnal glycemic profile in obese and normal weight nondiabetic pregnant women.
Yogev, Yariv; Ben-Haroush, Avi; Chen, Rony; Rosenn, Barak; Hod, Moshe; Langer, Oded
2004-09-01
A paucity of data exists concerning the normal glycemic profile in nondiabetic pregnancies. Using a novel approach that provides continuous measurement of blood glucose, we sought to evaluate the ambulatory daily glycemic profile in the second half of pregnancy in nondiabetic women. Fifty-seven obese and normal weight nondiabetic subjects were evaluated for 72 consecutive hours with continuous glucose monitoring by measurement interstitial glucose levels in subcutaneous tissue every 5 minutes. Subjects were instructed not to modify their lifestyle or to follow any dietary restriction. For each woman, mean and fasting blood glucose values were determined; for each meal during the study period, the first 180 minutes were analyzed. For the study group, the fasting blood glucose level was 75 +/- 12 mg/dL; the mean blood glucose level was 83.7 +/- 18 mg/dL; the postprandial peak glucose value level was 110 +/- 16 mg/dL, and the time interval that was needed to reach peak postprandial glucose level was 70 +/- 13 minutes. A similar postprandial glycemic profile was obtained for breakfast, lunch, and dinner. Obese women were characterized by a significantly higher postprandial glucose peak value, increased 1- and 2-hour postprandial glucose levels, increased time interval for glucose peak, and significantly lower mean blood glucose during the night. No difference was found in fasting and mean blood glucose between obese and nonobese subjects. Glycemic profile characterization in both obese and normal weight nondiabetic subjects provide a measure for the desired level of glycemic control in pregnancy that is complicated with diabetes mellitus.
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Hernandez, Teri L; Van Pelt, Rachael E; Anderson, Molly A; Daniels, Linda J; West, Nancy A; Donahoo, William T; Friedman, Jacob E; Barbour, Linda A
2014-01-01
The conventional diet approach to gestational diabetes mellitus (GDM) advocates carbohydrate restriction, resulting in higher fat (HF), also a substrate for fetal fat accretion and associated with maternal insulin resistance. Consequently, there is no consensus about the ideal GDM diet. We hypothesized that, compared with a conventional, lower-carbohydrate/HF diet (40% carbohydrate/45% fat/15% protein), consumption of a higher-complex carbohydrate (HCC)/lower-fat (LF) Choosing Healthy Options in Carbohydrate Energy (CHOICE) diet (60/25/15%) would result in 24-h glucose area under the curve (AUC) profiles within therapeutic targets and lower postprandial lipids. Using a randomized, crossover design, we provided 16 GDM women (BMI 34 ± 1 kg/m2) with two 3-day isocaloric diets at 31 ± 0.5 weeks (washout between diets) and performed continuous glucose monitoring. On day 4 of each diet, we determined postprandial (5 h) glucose, insulin, triglycerides (TGs), and free fatty acids (FFAs) following a controlled breakfast meal. There were no between-diet differences for fasting or mean nocturnal glucose, but 24-h AUC was slightly higher (∼6%) on the HCC/LF CHOICE diet (P = 0.02). The continuous glucose monitoring system (CGMS) revealed modestly higher 1- and 2-h postprandial glucose on CHOICE (1 h, 115 ± 2 vs. 107 ± 3 mg/dL, P ≤ 0.01; 2 h, 106 ± 3 vs. 97 ± 3 mg/dL, P = 0.001) but well below current targets. After breakfast, 5-h glucose and insulin AUCs were slightly higher (P < 0.05), TG AUC was no different, but the FFA AUC was significantly lower (∼19%; P ≤ 0.01) on the CHOICE diet. This highly controlled study randomizing isocaloric diets and using a CGMS is the first to show that liberalizing complex carbohydrates and reducing fat still achieved glycemia below current treatment targets and lower postprandial FFAs. This diet strategy may have important implications for preventing macrosomia.
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Klueh, Ulrike; Czajkowski, Caroline; Ludzinska, Izabela; Qiao, Yi; Frailey, Jackman; Kreutzer, Donald L.
2016-01-01
The accumulation of macrophages (MΦ) at the sensor-tissue interface is thought to be a major player in controlling tissue reactions and sensor performance in vivo. Nevertheless until recently no direct demonstration of the causal relationship between MΦ aggregation and loss of sensor function existed. Using a Continuous Glucose Monitoring (CGM) murine model we previously demonstrated that genetic deficiencies of MΦ or depletion of MΦ decreased MΦ accumulation at sensor implantation sites, which led to significantly enhanced CGM performance, when compared to normal mice. Additional studies in our laboratories have also demonstrated that MΦ can act as “metabolic sinks” by depleting glucose levels at the implanted sensors in vitro and in vivo. In the present study we extended these observations by demonstrating that MΦ chemokine (CCL2) and receptor (CCR2) knockout mice displayed a decrease in inflammation and MΦ recruitment at sensor implantation sites, when compared to normal mice. This decreased MΦ recruitment significantly enhanced CGM performance when compared to control mice. These studies demonstrated the importance of the CCL2 family of chemokines and related receptors in MΦ recruitment and sensor performance and suggest chemokine targets for enhancing CGM in vivo. PMID:27376197
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Therapeutics of diabetes mellitus: focus on insulin analogues and insulin pumps.
Valla, Vasiliki
2010-01-01
Inadequately controlled diabetes accounts for chronic complications and increases mortality. Its therapeutic management aims in normal HbA1C, prandial and postprandial glucose levels. This review discusses diabetes management focusing on the latest insulin analogues, alternative insulin delivery systems and the artificial pancreas. Intensive insulin therapy with multiple daily injections (MDI) allows better imitation of the physiological rhythm of insulin secretion. Longer-acting, basal insulin analogues provide concomitant improvements in safety, efficacy and variability of glycaemic control, followed by low risks of hypoglycaemia. Continuous subcutaneous insulin infusion (CSII) provides long-term glycaemic control especially in type 1 diabetic patients, while reducing hypoglycaemic episodes and glycaemic variability. Continuous subcutaneous glucose monitoring (CGM) systems provide information on postprandial glucose excursions and nocturnal hypo- and/or hyperglycemias. This information enhances treatment options, provides a useful tool for self-monitoring and allows safer achievement of treatment targets. In the absence of a cure-like pancreas or islets transplants, artificial "closed-loop" systems mimicking the pancreatic activity have been also developed. Individualized treatment plans for insulin initiation and administration mode are critical in achieving target glycaemic levels. Progress in these fields is expected to facilitate and improve the quality of life of diabetic patients.
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Usability of Medical Devices for Patients With Diabetes Who Are Visually Impaired or Blind.
Heinemann, Lutz; Drossel, Diana; Freckmann, Guido; Kulzer, Bernhard
2016-11-01
The estimation is that every third to fourth patient with diabetes suffers from some degree of diabetic retinopathy. Medical products for insulin administration (such as insulin pens and pumps) or glucose monitoring not optimized to the needs of these patients' represent a high barrier for optimal diabetes therapy in daily practice. To date, the number of devices suitable for visually impaired and blind patients with diabetes is scarce. This manuscript outlines the specific needs of this patient group with regard to systems for insulin administration, blood glucose measurement, and continuous glucose monitoring. We see the clear need for a policy requirement for manufacturers to provide accessible/user friendly technical aids for visually impaired and blind patients with diabetes. This would represent an important step toward improving the situation for this impressively large patient group. © 2016 Diabetes Technology Society.
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Self monitoring of glucose by people with diabetes: evidence based practice.
Gallichan, M.
1997-01-01
The inappropriate use of self monitoring of glucose is wasteful of NHS resources and can cause psychological harm. Although a few patients find that self monitoring enables them to understand and take control of their diabetes, many people with diabetes are performing inaccurate or unnecessary tests. There is no convincing evidence that self monitoring improves glycaemic control, nor that blood testing is necessarily better than urine testing. It may be appropriate for some patients not to monitor their own glucose but to rely instead on regular laboratory estimations of glycaemic control. Glucose self monitoring should be performed only when it serves an identified purpose. It is widely assumed that glucose self monitoring, preferably of blood glucose concentrations, is desirable or even essential for everyone with diabetes. It is common for patients who have previously tested their urine, or have done no glucose monitoring at home, to be taught to measure their blood glucose when they are admitted to hospital. In the community too, patients are often encouraged to monitor their blood glucose, and newly diagnosed patients of all ages are usually taught to measure their blood glucose concentrations. Self monitoring can sometimes be useful, but evidence is mounting that its indiscriminate use is of questionable value. In 1995, Pounds 42.6 million was spent on home monitoring of glucose in the United Kingdom (Intercontinental Medical Statistics, personal communication). Is this enormous cost justified? Is blood testing necessarily better than urine testing? Is glucose self monitoring always necessary, or is it sometimes a waste of time and money? Are recommendations for self monitoring based on sound evidence? PMID:9099125
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Schlaeger, Christof; Hinzmann, Rolf
2013-01-01
Abstract International experts in the fields of diabetes, diabetes technology, endocrinology, and pediatrics gathered for the 6th Annual Symposium on Self-Monitoring of Blood Glucose (SMBG) Applications and beyond. The aim of this meeting was to continue setting up a global network of experts in this field and provide an international platform for exchange of ideas to improve life for people with diabetes. The 2013 meeting comprised a comprehensive scientific program, parallel interactive workshops, and two keynote lectures. All these discussions were intended to help identify gaps and areas where further scientific work and clinical studies are warranted. PMID:24074038
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NASA Astrophysics Data System (ADS)
Vasudevan, Srivathsan; Chen, George Chung Kit; Andika, Marta; Agarwal, Shuchi; Chen, Peng; Olivo, Malini
2010-09-01
Red blood cells (RBCs) have been found to undergo ``programmed cell death,'' or eryptosis, and understanding this process can provide more information about apoptosis of nucleated cells. Photothermal (PT) response, a label-free photothermal noninvasive technique, is proposed as a tool to monitor the cell death process of living human RBCs upon glucose depletion. Since the physiological status of the dying cells is highly sensitive to photothermal parameters (e.g., thermal diffusivity, absorption, etc.), we applied linear PT response to continuously monitor the death mechanism of RBC when depleted of glucose. The kinetics of the assay where the cell's PT response transforms from linear to nonlinear regime is reported. In addition, quantitative monitoring was performed by extracting the relevant photothermal parameters from the PT response. Twofold increases in thermal diffusivity and size reduction were found in the linear PT response during cell death. Our results reveal that photothermal parameters change earlier than phosphatidylserine externalization (used for fluorescent studies), allowing us to detect the initial stage of eryptosis in a quantitative manner. Hence, the proposed tool, in addition to detection of eryptosis earlier than fluorescence, could also reveal physiological status of the cells through quantitative photothermal parameter extraction.
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Johansen, Mette Dencker; Gjerløv, Irene; Christiansen, Jens Sandahl; Hejlesen, Ole K
2012-03-01
In glycemic control, postprandial glycemia may be important to monitor and optimize as it reveals glycemic control quality, and postprandial hyperglycemia partly predicts late diabetic complications. Self-monitoring of blood glucose (SMBG) may be an appropriate technology to use, but recommendations on measurement time are crucial. We retrospectively analyzed interindividual and intraindividual variations in postprandial glycemic peak time. Continuous glucose monitoring (CGM) and carbohydrate intake were collected in 22 patients with type 1 diabetes mellitus. Meals were identified from carbohydrate intake data. For each meal, peak time was identified as time from meal to CGM zenith within 40-150 min after meal start. Interindividual (one-way Anova) and intraindividual (intraclass correlation coefficient) variation was calculated. Nineteen patients were included with sufficient meal data quality. Mean peak time was 87 ± 29 min. Mean peak time differed significantly between patients (p = 0.02). Intraclass correlation coefficient was 0.29. Significant interindividual and intraindividual variations exist in postprandial glycemia peak time, thus hindering simple and general advice regarding postprandial SMBG for detection of maximum values. © 2012 Diabetes Technology Society.
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Eborall, Helen C; Dallosso, Helen M; McNicol, Sarah; Speight, Jane; Khunti, Kamlesh; Davies, Melanie J; Heller, Simon R
2015-01-01
Abstract Background. The Diabetes Education and Self-Management for Ongoing and Newly Diagnosed (DESMOND) Self-monitoring Trial reported that people with newly diagnosed type 2 diabetes attending community-based structured education and randomized to self-monitoring of blood glucose (SMBG) or urine monitoring had comparable improvements in biomedical outcomes, but differences in satisfaction with, and continued use of monitoring method, well-being and perceived threat from diabetes. Objectives. To explore experiences of SMBG and urine monitoring following structured education. We specifically addressed the perceived usefulness of each monitoring method and the associated well-being. Methods. Qualitative semi-structured interviews with 18 adults with newly diagnosed type 2 diabetes participating in the DESMOND Self-monitoring Trial (SMBG, N = 10; urine monitoring, N = 8) ~12 months into the trial. Analysis was informed by the constant comparative approach. Results. Interviewees reported SMBG as accurate, convenient and useful. Declining use was explained by having established a pattern of managing blood glucose with less frequent monitoring or lack of feedback or encouragement from health care professionals. Many initially positive views of urine monitoring progressively changed due to perceived inaccuracy, leading some to switch to SMBG. Perceiving diabetes as less serious was attributable to lack of symptoms, treatment with diet alone and—in the urine-monitoring group—consistently negative readings. Urine monitoring also provided less visible evidence of diabetes and of the effect of behaviour on glucose. Conclusions. The findings highlight the importance for professionals of considering patients’ preferences when using self-monitoring technologies, including how these change over time, when supporting the self-care behaviours of people with type 2 diabetes. PMID:26160892
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Adolfsson, Peter; Örnhagen, Hans; Eriksson, Bengt M.; Gautham, Raghavendhar; Jendle, Johan
2012-01-01
Background There is a need for reliable methods of glucose measurement in different environmental conditions. The objective of this in vitro study was to evaluate the performance of the Enlite® Sensor when connected to either the iPro™ Continuous Glucose Monitor recording device or the Guardian® REAL-Time transmitting device, in hypobaric and hyperbaric conditions. Methods Sixteen sensors connected to eight iPro devices and eight Guardian REAL-Time devices were immersed in three beakers containing separate glucose concentrations: 52, 88, and 207 mg/dl (2.9, 4.9, and 11.3 mmol/liter). Two different pressure tests were conducted: a hypobaric test, corresponding to maximum 18000 ft/5500 m height, and a hyperbaric test, corresponding to maximum 100 ft/30 m depth. The linearity of the sensor signals in the different conditions was evaluated. Results The sensors worked continuously, and the sensor signals were collected without interruption at all pressures tested. When comparing the input signals for glucose (ISIGs) and the different glucose concentrations during altered pressure, linearity (R2) of 0.98 was found. During the hypobaric test, significant differences (p < .005) were seen when comparing the ISIGs during varying pressure at two of the glucose concentrations (52 and 207 mg/dl), whereas no difference was seen at the 88 mg/dl glucose concentration. During the hyperbaric test, no differences were found. Conclusions The Enlite Sensors connected to either the iPro or the Guardian REAL-Time device provided values continuously. In hyperbaric conditions, no significant differences were seen during changes in ambient pressure; however, during hypobaric conditions, the ISIG was significantly different in the low and high glucose concentrations. PMID:23294783
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Adolfsson, Peter; Ornhagen, Hans; Eriksson, Bengt M; Gautham, Raghavendhar; Jendle, Johan
2012-11-01
There is a need for reliable methods of glucose measurement in different environmental conditions. The objective of this in vitro study was to evaluate the performance of the Enlite® Sensor when connected to either the iPro™ Continuous Glucose Monitor recording device or the Guardian® REAL-Time transmitting device, in hypobaric and hyperbaric conditions. Sixteen sensors connected to eight iPro devices and eight Guardian REAL-Time devices were immersed in three beakers containing separate glucose concentrations: 52, 88, and 207 mg/dl (2.9, 4.9, and 11.3 mmol/liter). Two different pressure tests were conducted: a hypobaric test, corresponding to maximum 18000 ft/5500 m height, and a hyperbaric test, corresponding to maximum 100 ft/30 m depth. The linearity of the sensor signals in the different conditions was evaluated. The sensors worked continuously, and the sensor signals were collected without interruption at all pressures tested. When comparing the input signals for glucose (ISIGs) and the different glucose concentrations during altered pressure, linearity (R(2)) of 0.98 was found. During the hypobaric test, significant differences (p < .005) were seen when comparing the ISIGs during varying pressure at two of the glucose concentrations (52 and 207 mg/dl), whereas no difference was seen at the 88 mg/dl glucose concentration. During the hyperbaric test, no differences were found. The Enlite Sensors connected to either the iPro or the Guardian REAL-Time device provided values continuously. In hyperbaric conditions, no significant differences were seen during changes in ambient pressure; however, during hypobaric conditions, the ISIG was significantly different in the low and high glucose concentrations. © 2012 Diabetes Technology Society.
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Dunn, Timothy C; Hayter, Gary A; Doniger, Ken J; Wolpert, Howard A
2014-07-01
The objective was to develop an analysis methodology for generating diabetes therapy decision guidance using continuous glucose (CG) data. The novel Likelihood of Low Glucose (LLG) methodology, which exploits the relationship between glucose median, glucose variability, and hypoglycemia risk, is mathematically based and can be implemented in computer software. Using JDRF Continuous Glucose Monitoring Clinical Trial data, CG values for all participants were divided into 4-week periods starting at the first available sensor reading. The safety and sensitivity performance regarding hypoglycemia guidance "stoplights" were compared between the LLG method and one based on 10th percentile (P10) values. Examining 13 932 hypoglycemia guidance outputs, the safety performance of the LLG method ranged from 0.5% to 5.4% incorrect "green" indicators, compared with 0.9% to 6.0% for P10 value of 110 mg/dL. Guidance with lower P10 values yielded higher rates of incorrect indicators, such as 11.7% to 38% at 80 mg/dL. When evaluated only for periods of higher glucose (median above 155 mg/dL), the safety performance of the LLG method was superior to the P10 method. Sensitivity performance of correct "red" indicators of the LLG method had an in sample rate of 88.3% and an out of sample rate of 59.6%, comparable with the P10 method up to about 80 mg/dL. To aid in therapeutic decision making, we developed an algorithm-supported report that graphically highlights low glucose risk and increased variability. When tested with clinical data, the proposed method demonstrated equivalent or superior safety and sensitivity performance. © 2014 Diabetes Technology Society.
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Levy, J C; Davies, M J; Holman, R R
2017-09-01
Hypoglycaemia is a significant risk in insulin treated type 2 diabetes and has been associated with future risk of cardiovascular events. We compared the frequency of low-glucose events using continuous glucose monitoring (CGM) with that of self-reported hypoglycemic events at the end of the first and third years of the Treating to Target in Type 2 Diabetes Trial (4-T), which compared biphasic, prandial and basal insulin regimens added to sulfonylurea and metformin. CGM using a Medtronic Gold system was performed in a subgroup of 4-T participants. CGM detected low-glucose events were defined at thresholds of ≤3.0 (CGM3.0) and ≤2.2 (CGM2.2) mmol/l. Of the 110 participants, 106 and 70 had CGM analysable data at the end of years 1 and 3 respectively. In both years, the frequency of CGM detected low glucose events was several fold higher than that of self-reported hypoglycaemia (symptoms with blood glucose less than 3.1mmol/l [<56mg/dl]). At the end of the first year, CGM3.0 and CGM2.2 mean (95%CI) event frequencies, expressed at events per participant per year, were 120 (85, 155) and 41 (21, 61) compared with 17 (8, 29) self-reported events during CGM, each p=0.001. The disparity at the end of the third year was similar. These data demonstrate the likely under-reporting of hypoglycaemia and of potential hypoglycaemia unawareness in clinical trials. The clinical implications of these findings need to be explored further (ISRCTN No ISRCTN51125379). Copyright © 2017. Published by Elsevier B.V.
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Walker, Tomas C; Yucha, Carolyn B
2014-05-01
How patients are benefitting from continuous glucose monitoring (CGM) remains poorly understood. The focus on numerical glucose values persists, even though access to the glucose waveform and rate of change may contribute more to improved control. This pilot study compared outcomes of patients using CGMs with or without access to the numerical values on their CGM. Ten persons with type 1 diabetes, naïve to CGM use, enrolled in a 12-week study. Subjects were randomly assigned to either unmodified CGM receivers, or to CGM receivers that had their numerical values obscured but otherwise functioned normally. HbA1c, quality of life (QLI-D), and fear of hypoglycemia (HFS) were assessed, at baseline and at week 12. Baseline HbA1c for the entire group was 7.46 ± 1.27%. At week 12 the experimental group HbA1c reduction was 1.5 ± 0.9% (p < .05), the control group's reduction was 0.06 ± 0.61% (p > .05). Repeated measures testing revealed no significant difference in HbA1c reduction between groups. Both groups had reductions in HFS; these reductions were statistically significant within groups (p < .05), but not between groups. QLI-D indices demonstrated improvements (p < .05) in QLI-D total and the health and family subscales, but not between groups. The results of this pilot study suggest that benefits of CGM extend beyond reductions in HbA1c to reductions in fear of hypoglycemia and improvements in quality of life. The display of a numerical glucose value did not improve control when compared to numerically blinded units. © 2014 Diabetes Technology Society.
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Glucose Sensing Using Functionalized Amorphous In-Ga-Zn-O Field-Effect Transistors.
Du, Xiaosong; Li, Yajuan; Motley, Joshua R; Stickle, William F; Herman, Gregory S
2016-03-01
Recent advances in glucose sensing have focused on the integration of sensors into contact lenses to allow noninvasive continuous glucose monitoring. Current technologies focus primarily on enzyme-based electrochemical sensing which requires multiple nontransparent electrodes to be integrated. Herein, we leverage amorphous indium gallium zinc oxide (IGZO) field-effect transistors (FETs), which have found use in a wide range of display applications and can be made fully transparent. Bottom-gated IGZO-FETs can have significant changes in electrical characteristics when the back-channel is exposed to different environments. We have functionalized the back-channel of IGZO-FETs with aminosilane groups that are cross-linked to glucose oxidase and have demonstrated that these devices have high sensitivity to changes in glucose concentrations. Glucose sensing occurs through the decrease in pH during glucose oxidation, which modulates the positive charge of the aminosilane groups attached to the IGZO surface. The change in charge affects the number of acceptor-like surface states which can deplete electron density in the n-type IGZO semiconductor. Increasing glucose concentrations leads to an increase in acceptor states and a decrease in drain-source conductance due to a positive shift in the turn-on voltage. The functionalized IGZO-FET devices are effective in minimizing detection of interfering compounds including acetaminophen and ascorbic acid. These studies suggest that IGZO FETs can be effective for monitoring glucose concentrations in a variety of environments, including those where fully transparent sensing elements may be of interest.
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Continuous Glucose Monitoring Enables the Detection of Losses in Infusion Set Actuation (LISAs)
Howsmon, Daniel P.; Cameron, Faye; Baysal, Nihat; Ly, Trang T.; Forlenza, Gregory P.; Maahs, David M.; Buckingham, Bruce A.; Hahn, Juergen; Bequette, B. Wayne
2017-01-01
Reliable continuous glucose monitoring (CGM) enables a variety of advanced technology for the treatment of type 1 diabetes. In addition to artificial pancreas algorithms that use CGM to automate continuous subcutaneous insulin infusion (CSII), CGM can also inform fault detection algorithms that alert patients to problems in CGM or CSII. Losses in infusion set actuation (LISAs) can adversely affect clinical outcomes, resulting in hyperglycemia due to impaired insulin delivery. Prolonged hyperglycemia may lead to diabetic ketoacidosis—a serious metabolic complication in type 1 diabetes. Therefore, an algorithm for the detection of LISAs based on CGM and CSII signals was developed to improve patient safety. The LISA detection algorithm is trained retrospectively on data from 62 infusion set insertions from 20 patients. The algorithm collects glucose and insulin data, and computes relevant fault metrics over two different sliding windows; an alarm sounds when these fault metrics are exceeded. With the chosen algorithm parameters, the LISA detection strategy achieved a sensitivity of 71.8% and issued 0.28 false positives per day on the training data. Validation on two independent data sets confirmed that similar performance is seen on data that was not used for training. The developed algorithm is able to effectively alert patients to possible infusion set failures in open-loop scenarios, with limited evidence of its extension to closed-loop scenarios. PMID:28098839
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Continuous Glucose Monitoring Enables the Detection of Losses in Infusion Set Actuation (LISAs).
Howsmon, Daniel P; Cameron, Faye; Baysal, Nihat; Ly, Trang T; Forlenza, Gregory P; Maahs, David M; Buckingham, Bruce A; Hahn, Juergen; Bequette, B Wayne
2017-01-15
Reliable continuous glucose monitoring (CGM) enables a variety of advanced technology for the treatment of type 1 diabetes. In addition to artificial pancreas algorithms that use CGM to automate continuous subcutaneous insulin infusion (CSII), CGM can also inform fault detection algorithms that alert patients to problems in CGM or CSII. Losses in infusion set actuation (LISAs) can adversely affect clinical outcomes, resulting in hyperglycemia due to impaired insulin delivery. Prolonged hyperglycemia may lead to diabetic ketoacidosis-a serious metabolic complication in type 1 diabetes. Therefore, an algorithm for the detection of LISAs based on CGM and CSII signals was developed to improve patient safety. The LISA detection algorithm is trained retrospectively on data from 62 infusion set insertions from 20 patients. The algorithm collects glucose and insulin data, and computes relevant fault metrics over two different sliding windows; an alarm sounds when these fault metrics are exceeded. With the chosen algorithm parameters, the LISA detection strategy achieved a sensitivity of 71.8% and issued 0.28 false positives per day on the training data. Validation on two independent data sets confirmed that similar performance is seen on data that was not used for training. The developed algorithm is able to effectively alert patients to possible infusion set failures in open-loop scenarios, with limited evidence of its extension to closed-loop scenarios.
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A self-powered glucose biosensing system.
Slaughter, Gymama; Kulkarni, Tanmay
2016-04-15
A self-powered glucose biosensor (SPGS) system is fabricated and in vitro characterization of the power generation and charging frequency characteristics in glucose analyte are described. The bioelectrodes consist of compressed network of three-dimensional multi-walled carbon nanotubes with redox enzymes, pyroquinoline quinone glucose dehydrogenase (PQQ-GDH) and laccase functioning as the anodic and cathodic catalyst, respectively. When operated in 45 mM glucose, the biofuel cell exhibited an open circuit voltage and power density of 681.8 mV and 67.86 µW/cm(2) at 335 mV, respectively, with a current density of 202.2 µA/cm(2). Moreover, at physiological glucose concentration (5mM), the biofuel cell exhibits open circuit voltage and power density of 302.1 mV and 15.98 µW/cm(2) at 166.3 mV, respectively, with a current density of 100 µA/cm(2). The biofuel cell assembly produced a linear dynamic range of 0.5-45 mM glucose. These findings show that glucose biofuel cells can be further investigated in the development of a self-powered glucose biosensor by using a capacitor as the transducer element. By monitoring the capacitor charging frequencies, which are influenced by the concentration of the glucose analyte, a linear dynamic range of 0.5-35 mM glucose is observed. The operational stability of SPGS is monitored over a period of 63 days and is found to be stable with 15.38% and 11.76% drop in power density under continuous discharge in 10mM and 20mM glucose, respectively. These results demonstrate that SPGSs can simultaneously generate bioelectricity to power ultra-low powered devices and sense glucose. Copyright © 2015 Elsevier B.V. All rights reserved.
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Carreiro, Marina Pimenta; Lauria, Márcio W; Naves, Gabriel Nino T; Miranda, Paulo Augusto C; Leite, Ricardo Barsaglini; Rajão, Kamilla Maria Araújo Brandão; de Aguiar, Regina Amélia Lopes Pessoa; Nogueira, Anelise Impeliziere; Ribeiro-Oliveira, Antônio
2016-09-01
To study glucose profiles of gestational diabetes (GDM) patients with 72 h of continuous glucose monitoring (CGM) either before (GDM1) or after (GDM2) dietary counseling, comparing them with nondiabetic (NDM) controls. We performed CGM on 22 GDM patients; 11 before and 11 after dietary counseling and compared them to 11 healthy controls. Several physiological and clinical characteristics of the glucose profiles were compared across the groups, including comparisons for pooled 24-h measures and hourly median values, summary measures representing glucose exposure (area under the median curves) and variability (amplitude, standard deviation, interquartile range), and time points related to meals. Most women (81.8%) in the GDM groups had fasting glucose <95mg/dL, suggesting mild GDM. Variability, glucose levels 1 and 2h after breakfast and dinner, peak values after dinner and glucose levels between breakfast and lunch, were all significantly higher in GDM1 than NDM (P<0.05 for all comparisons). The GDM2 results were similar to NDM in all aforementioned comparisons (P>0.05). Both GDM groups spent more time with glucose levels above 140mg/dL when compared with the NDM group. No differences among the groups were found for: pooled measurements and hourly comparisons, exposure, nocturnal, fasting, between lunch and dinner and before meals, as well as after lunch (P>0.05 for all). The main differences between the mild GDM1 group and healthy controls were related to glucose variability and excursions above 140mg/dL, while glucose exposure was similar. Glucose levels after breakfast and dinner also discerned the GDM1 group. Dietary counseling was able to keep glucose levels to those of healthy patients. © 2016 European Society of Endocrinology.
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He, Y L; Foteinos, G; Neelakantham, S; Mattapalli, D; Kulmatycki, K; Forst, T; Taylor, A
2013-12-01
To assess whether there is a difference in the effects of vildagliptin and glimepiride on glucose fluctuation in patients with type 2 diabetes mellitus (T2DM) using continuous glucose monitoring (CGM). This was an open-label, randomized cross-over study conducted in T2DM patients. A total of 24 patients (age: 58.3 ± 5.56 years, baseline HbA1c: 7.6 ± 0.50%) who were on stable metformin monotherapy (500-3000 mg) were enrolled, and all completed the study. Each patient received two 5-day treatments (vildagliptin 50 mg b.i.d. or glimepiride 2 mg q.d.) in a cross-over manner. Various biomarkers and blood glucose concentrations were measured following breakfast. The 24-h glucose profiles were also measured using the CGM device at baseline and after 5 days of treatment, and fluctuations in glucose levels were estimated from CGM data. Both vildagliptin and glimepiride reduced postprandial glucose levels, based on both CGM data (15% vs. 16%) and measured plasma glucose (13% vs.17%). Vildagliptin showed lower glucose fluctuations than glimepiride as measured by mean amplitude of glycaemic excursions (MAGE, p = 0.1076), standard deviation (s.d., p = 0.1346) of blood glucose rate of change, but did not reach statistical significance attributed to the small sample size. MAGE was reduced by ∼20% with vildagliptin versus glimepiride. Vildagliptin led to statistically significant lowering of the rate of change in the median curve (RCMC) and interquartile range (IQR) of glucose. Treatment with vildagliptin significantly increased the levels of active glucagon-like peptide-1 by 2.36-fold (p ≤ 0.0001) and suppressed glucagon by 8% (p = 0.01), whereas glimepiride significantly increased the levels of insulin and C-peptide by 21% (p = 0.012) and 12% (p = 0.003), respectively. Vildagliptin treatment was associated with less fluctuation of glucose levels than glimepiride treatment as assessed by 24-h CGM device, suggesting vildagliptin may have the potential to offer long-term beneficial effects for patients with T2DM in preventing the development of complications of diabetes. © 2013 John Wiley & Sons Ltd.
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Recent Advances in Nanotechnology for Diabetes Treatment
DiSanto, Rocco Michael; Subramanian, Vinayak; Gu, Zhen
2015-01-01
Nanotechnology in diabetes research has facilitated the development of novel glucose measurement and insulin delivery modalities which hold the potential to dramatically improve quality of life for diabetics. Recent progress in the field of diabetes research at its interface with nanotechnology is our focus. In particular, we examine glucose sensors with nanoscale components including metal nanoparticles and carbon nanostructures. The addition of nanoscale components commonly increases glucose sensor sensitivity, temporal response, and can lead to sensors which facilitate continuous in vivo glucose monitoring. Additionally, we survey nanoscale approaches to “closed-loop” insulin delivery strategies which automatically release insulin in response to fluctuating blood glucose levels. “Closing the loop” between blood glucose level (BGL) measurements and insulin administration by removing the requirement of patient action holds the potential to dramatically improve the health and quality of life of diabetics. Advantages and limitations of current strategies, as well as future opportunities and challenges are also discussed. PMID:25641955
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PEGylation of Concanavalin A to decrease nonspecific interactions in a fluorescent glucose sensor
NASA Astrophysics Data System (ADS)
Abraham, Alexander A.; Cummins, Brian M.; Locke, Andrea K.; Grunlan, Melissa A.; Coté, Gerard L.
2014-02-01
The ability of people with diabetes to both monitor and regulate blood sugar levels is limited by the conventional "finger-prick" test that provides intermittent, single point measurements. Toward the development of a continuous glucose monitoring (CGM) system, the lectin, Concanavalin A (ConA), has been utilized as a component in a Förster resonance energy transfer (FRET), competitive glucose binding assay. Recently, to avoid reversibility problems associated with ConA aggregation, a suitable competing ligand labeled with 8-aminopyrene-1,3,6-trisulfonic acid trisodium salt (APTS) has been engineered. However, its ability to function as part of a glucose sensing assay is compromised due to the negative charge (at physiological pH) of native ConA that gives rise to non-specific binding with other ConA groups as well as with electrostatically charged assay-delivery carriers. To minimize these undesirable interactions, we have conjugated ConA with monomethoxy-poly(ethylene glycol) (mPEG) (i.e. "PEGylation"). In this preliminary research, fluorescently-labeled ConA was successfully PEGylated with mPEG-Nhydroxylsuccinimide( succinimidyl carbonate) (mPEG-NHS(SC)). The FRET response of APTS-labeled competing ligand (donor) conveyed an increase in the fluorescence intensity with increasing glucose concentrations.
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Real-time understanding of lignocellulosic bioethanol fermentation by Raman spectroscopy
2013-01-01
Background A substantial barrier to commercialization of lignocellulosic ethanol production is a lack of process specific sensors and associated control strategies that are essential for economic viability. Current sensors and analytical techniques require lengthy offline analysis or are easily fouled in situ. Raman spectroscopy has the potential to continuously monitor fermentation reactants and products, maximizing efficiency and allowing for improved process control. Results In this paper we show that glucose and ethanol in a lignocellulosic fermentation can be accurately monitored by a 785 nm Raman spectroscopy instrument and novel immersion probe, even in the presence of an elevated background thought to be caused by lignin-derived compounds. Chemometric techniques were used to reduce the background before generating calibration models for glucose and ethanol concentration. The models show very good correlation between the real-time Raman spectra and the offline HPLC validation. Conclusions Our results show that the changing ethanol and glucose concentrations during lignocellulosic fermentation processes can be monitored in real-time, allowing for optimization and control of large scale bioconversion processes. PMID:23425590
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Laffel, Lori
2016-02-01
This study was designed to evaluate accuracy, performance, and safety of the Dexcom (San Diego, CA) G4(®) Platinum continuous glucose monitoring (CGM) system (G4P) compared with the Dexcom G4 Platinum with Software 505 algorithm (SW505) when used as adjunctive management to blood glucose (BG) monitoring over a 7-day period in youth, 2-17 years of age, with diabetes. Youth wore either one or two sensors placed on the abdomen or upper buttocks for 7 days, calibrating the device twice daily with a uniform BG meter. Participants had one in-clinic session on Day 1, 4, or 7, during which fingerstick BG measurements (self-monitoring of blood glucose [SMBG]) were obtained every 30 ± 5 min for comparison with CGM, and in youth 6-17 years of age, reference YSI glucose measurements were obtained from arterialized venous blood collected every 15 ± 5 min for comparison with CGM. The sensor was removed by the participant/family after 7 days. In comparison of 2,922 temporally paired points of CGM with the reference YSI measurement for G4P and 2,262 paired points for SW505, the mean absolute relative difference (MARD) was 17% for G4P versus 10% for SW505 (P < 0.0001). In comparison of 16,318 temporally paired points of CGM with SMBG for G4P and 4,264 paired points for SW505, MARD was 15% for G4P versus 13% for SW505 (P < 0.0001). Similarly, error grid analyses indicated superior performance with SW505 compared with G4P in comparison of CGM with YSI and CGM with SMBG results, with greater percentages of SW505 results falling within error grid Zone A or the combined Zones A plus B. There were no serious adverse events or device-related serious adverse events for either the G4P or the SW505, and there was no sensor breakoff. The updated algorithm offers substantial improvements in accuracy and performance in pediatric patients with diabetes. Use of CGM with improved performance has potential to increase glucose time in range and improve glycemic outcomes for youth.
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A comparative effectiveness analysis of three continuous glucose monitors.
Damiano, Edward R; El-Khatib, Firas H; Zheng, Hui; Nathan, David M; Russell, Steven J
2013-02-01
To compare three continuous glucose monitoring (CGM) devices in subjects with type 1 diabetes under closed-loop blood glucose (BG) control. Six subjects with type 1 diabetes (age 52 ± 14 years, diabetes duration 32 ± 14 years) each participated in two 51-h closed-loop BG control experiments in the hospital. Venous plasma glucose (PG) measurements (GlucoScout, International Biomedical) obtained every 15 min (2,360 values) were paired in time with corresponding CGM glucose (CGMG) measurements obtained from three CGM devices, the Navigator (Abbott Diabetes Care), the Seven Plus (DexCom), and the Guardian (Medtronic), worn simultaneously by each subject. Errors in paired PG-CGMG measurements and data reporting percentages were obtained for each CGM device. The Navigator had the best overall accuracy, with an aggregate mean absolute relative difference (MARD) of all paired points of 11.8 ± 11.1% and an average MARD across all 12 experiments of 11.8 ± 3.8%. The Seven Plus and Guardian produced aggregate MARDs of all paired points of 16.5 ± 17.8% and 20.3 ± 18.0%, respectively, and average MARDs across all 12 experiments of 16.5 ± 6.7% and 20.2 ± 6.8%, respectively. Data reporting percentages, a measure of reliability, were 76% for the Seven Plus and nearly 100% for the Navigator and Guardian. A comprehensive head-to-head-to-head comparison of three CGM devices for BG values from 36 to 563 mg/dL revealed marked differences in performance characteristics that include accuracy, precision, and reliability. The Navigator outperformed the other two in these areas.
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Peterson, Karolina; Zapletalova, Jana; Kudlova, Pavla; Matuskova, Veronika; Bartek, Josef; Novotny, Dalibor; Chlup, Rudolf
2009-03-01
The latest Paradigm 722 insulin pump, Medtronic MiniMed, USA, enables daily reading of 288 interstitial fluid glucose concentrations determined by a sensor inserted into subcutaneous tissue; the sensor signals are transmitted into the insulin pump, enabling the patient to see real-time glucose concentration on the display and adapt further treatment. To assess the evolution of HbA1c over the course of a 3-month period in two cohorts of persons with type 1 (n=39) or type 2 (n=3) diabetes (PWD): 1) PWD on Paradigm 722 using sensors for continuous glucose monitoring (CGM group), 2) PWD on other types of insulin pumps performing intensive self-monitoring as before (3 to 6 times/d) on glucometer Linus, Wellion, Agamatrix (control group). Compliant PWDs using insulin pump with insulin aspart for several previous months were included in the study. Seventeen were put on Paradigm 722 with CGM and 25 were included in the control group. Paired t-test and the statistical program SPSS v.15.0 were used to analyze the data. There was no significant difference in age between the two groups (P=0.996), in diabetes duration (P=0.482) or in daily insulin dose (P=0.469). In the CGM group (but not in the control group) HbA1c/IFCC dropped from 6.98+/-0.43 % to 5.98+/-0.36 % (P=0.006) within 1 month and remained reduced. The use of the Paradigm 722 insulin pump with CGM resulted in significant improvement in HbA1c which appeared within one month and remained throughout the whole 3-month study period. No significant improvement in HbA1c was seen in the control group.
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Enhancing the accuracy of subcutaneous glucose sensors: a real-time deconvolution-based approach.
Guerra, Stefania; Facchinetti, Andrea; Sparacino, Giovanni; Nicolao, Giuseppe De; Cobelli, Claudio
2012-06-01
Minimally invasive continuous glucose monitoring (CGM) sensors can greatly help diabetes management. Most of these sensors consist of a needle electrode, placed in the subcutaneous tissue, which measures an electrical current exploiting the glucose-oxidase principle. This current is then transformed to glucose levels after calibrating the sensor on the basis of one, or more, self-monitoring blood glucose (SMBG) samples. In this study, we design and test a real-time signal-enhancement module that, cascaded to the CGM device, improves the quality of its output by a proper postprocessing of the CGM signal. In fact, CGM sensors measure glucose in the interstitium rather than in the blood compartment. We show that this distortion can be compensated by means of a regularized deconvolution procedure relying on a linear regression model that can be updated whenever a pair of suitably sampled SMBG references is collected. Tests performed both on simulated and real data demonstrate a significant accuracy improvement of the CGM signal. Simulation studies also demonstrate the robustness of the method against departures from nominal conditions, such as temporal misplacement of the SMBG samples and uncertainty in the blood-to-interstitium glucose kinetic model. Thanks to its online capabilities, the proposed signal-enhancement algorithm can be used to improve the performance of CGM-based real-time systems such as the hypo/hyper glycemic alert generators or the artificial pancreas.
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Kovatchev, Boris P; Clarke, William L; Breton, Marc; Brayman, Kenneth; McCall, Anthony
2005-12-01
Continuous glucose monitors (CGMs) collect detailed blood glucose (BG) time series, which carry significant information about the dynamics of BG fluctuations. In contrast, the methods for analysis of CGM data remain those developed for infrequent BG self-monitoring. As a result, important information about the temporal structure of the data is lost during the translation of raw sensor readings into clinically interpretable statistics and images. The following mathematical methods are introduced into the field of CGM data interpretation: (1) analysis of BG rate of change; (2) risk analysis using previously reported Low/High BG Indices and Poincare (lag) plot of risk associated with temporal BG variability; and (3) spatial aggregation of the process of BG fluctuations and its Markov chain visualization. The clinical application of these methods is illustrated by analysis of data of a patient with Type 1 diabetes mellitus who underwent islet transplantation and with data from clinical trials. Normative data [12,025 reference (YSI device, Yellow Springs Instruments, Yellow Springs, OH) BG determinations] in patients with Type 1 diabetes mellitus who underwent insulin and glucose challenges suggest that the 90%, 95%, and 99% confidence intervals of BG rate of change that could be maximally sustained over 15-30 min are [-2,2], [-3,3], and [-4,4] mg/dL/min, respectively. BG dynamics and risk parameters clearly differentiated the stages of transplantation and the effects of medication. Aspects of treatment were clearly visualized by graphs of BG rate of change and Low/High BG Indices, by a Poincare plot of risk for rapid BG fluctuations, and by a plot of the aggregated Markov process. Advanced analysis and visualization of CGM data allow for evaluation of dynamical characteristics of diabetes and reveal clinical information that is inaccessible via standard statistics, which do not take into account the temporal structure of the data. The use of such methods improves the assessment of patients' glycemic control.
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Hu, Yu-Ming; Zhao, Li-Hua; Zhang, Xiu-Lin; Cai, Hong-Li; Huang, Hai-Yan; Xu, Feng; Chen, Tong; Wang, Xue-Qin; Guo, Ai-Song; Li, Jian-An; Su, Jian-Bin
2018-05-01
Diabetic peripheral neuropathy (DPN), a common microvascular complication of diabetes, is linked to glycaemic derangements. Glycaemic variability, as a pattern of glycaemic derangements, is a key risk factor for diabetic complications. We investigated the association of glycaemic variability with DPN in a large-scale sample of type 2 diabetic patients. In this cross-sectional study, we enrolled 982 type 2 diabetic patients who were screened for DPN and monitored by a continuous glucose monitoring (CGM) system between February 2011 and January 2017. Multiple glycaemic variability parameters, including the mean amplitude of glycaemic excursions (MAGE), mean of daily differences (MODD), standard deviation of glucose (SD), and 24-h mean glucose (24-h MG), were calculated from glucose profiles obtained from CGM. Other possible risks for DPN were also examined. Of the recruited type 2 diabetic patients, 20.1% (n = 197) presented with DPN, and these patients also had a higher MAGE, MODD, SD, and 24-h MG than patients without DPN (p < 0.001). Using univariate and multiple logistic regression analyses, MAGE and conventional risks including diabetic duration, HOMA-IR, and hemoglobin A1c (HbA1c) were found to be independent contributors to DPN, and the corresponding odds ratios (95% confidence interval) were 4.57 (3.48-6.01), 1.10 (1.03-1.17), 1.24 (1.09-1.41), and 1.33 (1.15-1.53), respectively. Receiver operating characteristic analysis indicated that the optimal MAGE cutoff value for predicting DPN was 4.60 mmol/L; the corresponding sensitivity was 64.47%, and the specificity was 75.54%. In addition to conventional risks including diabetic duration, HOMA-IR and HbA1c, increased glycaemic variability assessed by MAGE is a significant independent contributor to DPN in type 2 diabetic patients.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Zhao Qingliang; Guo Zhouyi; Wei Huajiang
2011-10-31
Depth-resolved monitoring with differentiation and quantification of glucose diffusion in healthy and abnormal esophagus tissues has been studied in vitro. Experiments have been performed using human normal esophagus and esophageal squamous cell carcinoma (ESCC) tissues by the optical coherence tomography (OCT). The images have been continuously acquired for 120 min in the experiments, and the depth-resolved and average permeability coefficients of the 40 % glucose solution have been calculated by the OCT amplitude (OCTA) method. We demonstrate the capability of the OCT technique for depth-resolved monitoring, differentiation, and quantifying of glucose diffusion in normal esophagus and ESCC tissues. It ismore » found that the permeability coefficients of the 40 % glucose solution are not uniform throughout the normal esophagus and ESCC tissues and increase from (3.30 {+-} 0.09) Multiplication-Sign 10{sup -6} and (1.57 {+-} 0.05) Multiplication-Sign 10{sup -5} cm s{sup -1} at the mucous membrane of normal esophagus and ESCC tissues to (1.82 {+-} 0.04) Multiplication-Sign 10{sup -5} and (3.53 {+-} 0.09) Multiplication-Sign 10{sup -5} cm s{sup -1} at the submucous layer approximately 742 {mu}m away from the epithelial surface of normal esophagus and ESCC tissues, respectively. (optical coherence tomography)« less
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Rich, Alisa L; Patel, Jay T; Al-Angari, Samiah S
2016-01-01
Carbon disulfide (CS2) has been historically associated with the manufacturing of rayon, cellophane, and carbon tetrachloride production. This study is one of the first to identify elevated atmospheric levels of CS2 above national background levels and its mechanisms to dysregulate normal glucose metabolism. Interference in glucose metabolism can indirectly cause other complications (diabetes, neurodegenerative disease, and retinopathy), which may be preventable if proper precautions are taken. Rich et al found CS2 and 12 associated sulfide compounds present in the atmosphere in residential areas where unconventional shale oil and gas extraction and processing operations were occurring. Ambient atmospheric concentrations of CS2 ranged from 0.7 parts per billion by volume (ppbv) to 103 ppbv over a continuous 24-hour monitoring period. One-hour ambient atmospheric concentrations ranged from 3.4 ppbv to 504.6 ppbv. Using the U.S. Environmental Protection Agency Urban Air Toxic Monitoring Program study as a baseline comparison for atmospheric CS2 concentrations found in this study, it was determined that CS2 atmospheric levels were consistently elevated in areas where unconventional oil and gas extraction and processing occurred. The mechanisms by which CS2 interferes in normal glucose metabolism by dysregulation of the tryptophan metabolism pathway are presented in this study. The literature review found an increased potential for alteration of normal glucose metabolism in viscose rayon occupational workers exposed to CS2. Occupational workers in the energy extraction industry exposed to CS2 and other sulfide compounds may have an increased potential for glucose metabolism interference, which has been an indicator for diabetogenic effect and other related health impacts. The recommendation of this study is for implementation of regular monitoring of blood glucose levels in CS2-exposed populations as a preventative health measure.
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Hypo- and Hyperglycemic Alarms
Howsmon, Daniel; Bequette, B. Wayne
2015-01-01
Soon after the discovery that insulin regulates blood glucose by Banting and Best in 1922, the symptoms and risks associated with hypoglycemia became widely recognized. This article reviews devices to warn individuals of impending hypo- and hyperglycemia; biosignals used by these devices include electroencephalography, electrocardiography, skin galvanic resistance, diabetes alert dogs, and continuous glucose monitors (CGMs). While systems based on other technology are increasing in performance and decreasing in size, CGM technology remains the best method for both reactive and predictive alarming of hypo- or hyperglycemia. PMID:25931581
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Fortin, Nicolas; Klok, Harm-Anton
2015-03-04
Tight regulation of blood glucose levels of diabetic patients requires durable and robust continuous glucose sensing schemes. This manuscript reports the fabrication of ultrathin, phenylboronic acid (PBA) functionalized polymer brushes that swell upon glucose binding and which were integrated as the sensing interface in a new polypropylene hollow fiber (PPHF)-based hydraulic flow glucose sensor prototype. The polymer brushes were prepared via surface-initiated atom transfer radical polymerization of sodium methacrylate followed by postpolymerization modification with 3-aminophenyl boronic acid. In a first series of experiments, the glucose-response of PBA-functionalized poly(methacrylic acid) (PMAA) brushes grafted from planar silicon surfaces was investigated by quartz crystal microbalance with dissipation (QCM-D) and atomic force microscopy (AFM) experiments. The QCM-D experiments revealed a more or less linear change of the frequency shift for glucose concentrations up to ∼10 mM and demonstrated that glucose binding was completely reversible for up to seven switching cycles. The AFM experiments indicated that glucose binding was accompanied by an increase in the film thickness of the PBA functionalized PMAA brushes. The PBA functionalized PMAA brushes were subsequently grafted from the surface of PPHF membranes. The hydraulic permeability of these porous fibers depends on the thickness and swelling of the PMAA brush coating. PBA functionalized brush-coated PPHFs showed a decrease in flux upon exposure to glucose, which is consistent with swelling of the brush coating. Because they avoid the use of enzymes and do not rely on an electrochemical transduction scheme, these PPHF-based hydraulic flow sensors could represent an interesting alternative class of continuous glucose sensors.
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Measurement of Glucose in Blood with a Phenylboronic Acid Optical Sensor
Worsley, Graham J.; Tourniaire, Guilhem A.; Medlock, Kathryn E. S.; Sartain, Felicity K.; Harmer, Hazel E.; Thatcher, Michael; Horgan, Adrian M.; Pritchard, John
2008-01-01
Background Current methods of glucose monitoring rely predominantly on enzymes such as glucose oxidase for detection. Phenylboronic acid receptors have been proposed as alternative glucose binders. A unique property of these molecules is their ability to bind glucose in a fully reversible covalent manner that facilitates direct continuous measurements. We examined (1) the ability of a phenylboronic-based sensor to measure glucose in blood and blood plasma and (2) the effect on measurement accuracy of a range of potential interferents. We also showed that the sensor is able to track glucose fluctuations occurring at rates mimicking those experienced in vivo. Method In vitro static measurements of glucose in blood and blood plasma were conducted using holographic sensors containing acrylamide, N,N′-methylenebisacrylamide, 3-acrylamidophenylboronic acid, and (3-acrylamidopropyl) trimethylammonium chloride. The same sensors were also used for in vitro measurements performed under flow conditions. Results The opacity of the liquid had no affect on the ability of the optical sensor to measure glucose in blood or blood plasma. The presence of common antibiotics, diabetic drugs, pain killers, and endogenous substances did not affect the measurement accuracy, as shown by error grid analysis. Ex vivo flow experiments showed that the sensor is able to track changes accurately in concentration occurring in real time without lag or evidence of hysteresis. Conclusions The ability of phenylboronic acid sensors to measure glucose in whole blood was demonstrated for the first time. Holographic sensors are ideally suited to continuous blood glucose measurements, being physically and chemically robust and potentially calibration free. PMID:19885345
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An Optical Biosensing Platform using Reprecipitated Polyaniline Microparticles
NASA Astrophysics Data System (ADS)
Nemzer, Louis; Epstein, Arthur
2009-03-01
A great deal of effort remains focused on the goal of developing a continuous in vivo glucose monitoring system for patients with diabetes mellitus. We report a proof-of-concept study on a reagentless optical biosensing platform that circumvents the problems usually associated with direct glucose detection by utilizing the UV-VIS absorption properties of polyaniline, a biocompatible polymer. When the enzyme glucose oxidase is entrapped within reprecipitated polyaniline microparticles, a glucose molecule readily donates two protons and two electrons to the polyaniline, reversibly altering the polymer's oxidation state. The resultant change can be monitored by measuring the absorption at wavelengths that fall within the ``optical window'' for skin. The micro-structured morphology also insures a high surface-area to volume ratio. Data from in vitro prototype devices indicate that in the low enzyme-loading regime, the response can be fit to the Michaelis-Menten model for enzyme kinetics, but at higher enzyme loading, diffusion effects dominate. As a biosensing platform, the system also has the potential to be adapted to detect other biologically relevant analytes, including cholesterol and ethanol.
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Middle infrared optoelectronic absorption systems for monitoring physiological glucose solutions
NASA Astrophysics Data System (ADS)
Martin, W. Blake
Tight monitoring of the glucose levels for diabetic individuals is essential to control long-term complications. A definitive diabetes management system has yet to be developed for the diabetic. This research investigates the application of middle infrared absorption frequencies for monitoring glucose levels in biological solutions. Three frequencies were identified using a Fourier transform infrared spectrometer and correlated to changes in glucose concentrations. The 1035 +/- 1 cm-1 frequency was determined to be the best representative frequency. Other biological molecules contributed no significant interference to monitoring glucose absorption. A second frequency at 1193 cm-1 was suggested as a representative background absorption frequency, which could be used for more accurate glucose absorption values. Next, a quantum cascade laser optoelectronic absorption system was designed and developed to monitor glucose. After careful alignment and design, the system was used to monitor physiological glucose concentrations. Correlation at 1036 cm-1 with glucose changes was comparable to the previous results. The use of the background absorption frequency was verified. This frequency essentially acts as a calibrating frequency to adjust in real-time to any changes in the background absorption that may alter the accuracy of the predicted glucose value. An evanescent wave cavity ring-down spectroscopy technique was explored to monitor molecules in a biological solution. Visible light at 425 nm was used to monitor hemoglobin in control urine samples. An adsorption isotherm for hemoglobin was detectable to limit of 5.8 nM. Evanescent wave cavity ring-down spectroscopy would be useful for a glucose solution. Given an equivalent system designed for the middle infrared, the molar extinction coefficient of glucose allows for a detectable limit of 45 mg/dl for a free-floating glucose solution, which is below normal physiological concentrations. The future use of a hydrophobic coating could limit the adsorption of glucose to the surface but still allow physiological monitoring. Three middle infrared optoelectronic absorption systems have been designed for monitoring glucose in a physiological solution. The systems are applicable for the monitoring of glucose. These systems may lead to a useful monitoring device for the diabetic so that the universal complications associated with the disease may be limited.
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Tran, Nam K; Godwin, Zachary R; Steele, Amanda N; Wolf, Steven E; Palmieri, Tina L
2016-09-01
The goal of this study was to retrospectively evaluate the clinical impact of an accurate autocorrecting blood glucose monitoring system in children with severe burns. Blood glucose monitoring system accuracy is essential for providing appropriate intensive insulin therapy and achieving tight glycemic control in critically ill patients. Unfortunately, few comparison studies have been performed to evaluate the clinical impact of accurate blood glucose monitoring system monitoring in the high-risk pediatric burn population. Retrospective analysis of an electronic health record system. Pediatric burn ICU at an academic medical center. Children (aged < 18 yr) with severe burns (≥ 20% total body surface area) receiving intensive insulin therapy guided by either a noncorrecting (blood glucose monitoring system-1) or an autocorrecting blood glucose monitoring system (blood glucose monitoring system-2). Patient demographics, insulin rates, and blood glucose monitoring system measurements were collected. The frequency of hypoglycemia and glycemic variability was compared between the two blood glucose monitoring system groups. A total of 122 patient charts from 2001 to 2014 were reviewed. Sixty-three patients received intensive insulin therapy using blood glucose monitoring system-1 and 59 via blood glucose monitoring system-2. Patient demographics were similar between the two groups. Mean insulin infusion rates (5.1 ± 3.8 U/hr; n = 535 paired measurements vs 2.4 ± 1.3 U/hr; n = 511 paired measurements; p < 0.001), glycemic variability, and frequency of hypoglycemic events (90 vs 12; p < 0.001) were significantly higher in blood glucose monitoring system-1-treated patients. Compared with laboratory measurements, blood glucose monitoring system-2 yielded the most accurate results (mean ± SD bias: -1.7 ± 6.9 mg/dL [-0.09 ± 0.4 mmol/L] vs 7.4 ± 13.5 mg/dL [0.4 ± 0.7 mmol/L]). Blood glucose monitoring system-2 patients achieve glycemic control more quickly (5.7 ± 4.3 vs 13.1 ± 6.9 hr; p< 0.001) and stayed within the target glycemic control range longer compared with blood glucose monitoring system-1 patients (85.2% ± 13.9% vs 57.9% ± 29.1%; p < 0.001). Accurate autocorrecting blood glucose monitoring system optimizes intensive insulin therapy, improves tight glycemic control, and reduces the risk of hypoglycemia and glycemic variability. The use of an autocorrecting blood glucose monitoring system for intensive insulin therapy may improve glycemic control in severely burned children.
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Optical microsensor for continuous glucose measurements in interstitial fluid
NASA Astrophysics Data System (ADS)
Olesberg, Jonathon T.; Cao, Chuanshun; Yager, Jeffrey R.; Prineas, John P.; Coretsopoulos, Chris; Arnold, Mark A.; Olafsen, Linda J.; Santilli, Michael
2006-02-01
Tight control of blood glucose levels has been shown to dramatically reduce the long-term complications of diabetes. Current invasive technology for monitoring glucose levels is effective but underutilized by people with diabetes because of the pain of repeated finger-sticks, the inconvenience of handling samples of blood, and the cost of reagent strips. A continuous glucose sensor coupled with an insulin delivery system could provide closed-loop glucose control without the need for discrete sampling or user intervention. We describe an optical glucose microsensor based on absorption spectroscopy in interstitial fluid that can potentially be implanted to provide continuous glucose readings. Light from a GaInAsSb LED in the 2.2-2.4 μm wavelength range is passed through a sample of interstitial fluid and a linear variable filter before being detected by an uncooled, 32-element GaInAsSb detector array. Spectral resolution is provided by the linear variable filter, which has a 10 nm band pass and a center wavelength that varies from 2.18-2.38 μm (4600-4200 cm -1) over the length of the detector array. The sensor assembly is a monolithic design requiring no coupling optics. In the present system, the LED running with 100 mA of drive current delivers 20 nW of power to each of the detector pixels, which have a noise-equivalent-power of 3 pW/Hz 1/2. This is sufficient to provide a signal-to-noise ratio of 4500 Hz 1/2 under detector-noise limited conditions. This signal-to-noise ratio corresponds to a spectral noise level less than 10 μAU for a five minute integration, which should be sufficient for sub-millimolar glucose detection.
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Wireless connection of continuous glucose monitoring system to the electronic patient record
NASA Astrophysics Data System (ADS)
Murakami, Alexandre; Gutierrez, Marco A.; Lage, Silvia G.; Rebelo, Marina S.; Granja, Luiz A. R.; Ramires, Jose A. F.
2005-04-01
The control of blood sugar level (BSL) at near-normal levels has been documented to reduce both acute and chronic complications of diabetes mellitus. Recent studies suggested, the reduction of mortality in a surgical intensive care unit (ICU), when the BSL are maintained at normal levels. Despite of the benefits appointed by these and others clinical studies, the strict BSL control in critically ill patients suffers from some difficulties: a) medical staff need to measure and control the patient"s BSL using blood sample at least every hour. This is a complex and time consuming task; b) the inaccuracy of standard capillary glucose monitoring (fingerstick) in hypotensive patients and, if frequently used to sample arterial or venous blood, may lead to excess phlebotomy; c) there is no validated procedure for continuously monitoring of BSL levels. This study used the MiniMed CGMS in ill patients at ICU to send, in real-time, BSL values to a Web-Based Electronic Patient Record. The BSL values are parsed and delivered through a wireless network as an HL7 message. The HL7 messages with BSL values are collected, stored into the Electronic Patient Record and presented into a bed-side monitor at the ICU together with other relevant patient information.
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Blood Glucose Monitoring Before and After Type 1 Diabetes Clinic Visits.
Driscoll, Kimberly A; Johnson, Suzanne Bennett; Wang, Yuxia; Wright, Nancy; Deeb, Larry C
2017-12-23
To determine patterns of blood glucose monitoring in children and adolescents with type 1 diabetes (T1D) before and after routine T1D clinic visits. Blood glucose monitoring data were downloaded at four consecutive routine clinic visits from children and adolescents aged 5-18 years. Linear mixed models were used to analyze patterns of blood glucose monitoring in patients who had at least 28 days of data stored in their blood glucose monitors. In general, the frequency of blood glucose monitoring decreased across visits, and younger children engaged in more frequent blood glucose monitoring. Blood glucose monitoring increased before the T1D clinic visits in younger children, but not in adolescents. It declined after the visit regardless of age. Members of the T1D care team need to consider that a T1D clinic visit may prompt an increase in blood glucose monitoring when making treatment changes and recommendations. Tailored interventions are needed to maintain that higher level of adherence across time. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com
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Moser, Othmar; Mader, Julia K.; Tschakert, Gerhard; Mueller, Alexander; Groeschl, Werner; Pieber, Thomas R.; Koehler, Gerd; Messerschmidt, Janin; Hofmann, Peter
2016-01-01
Continuous exercise (CON) and high-intensity interval exercise (HIIE) can be safely performed with type 1 diabetes mellitus (T1DM). Additionally, continuous glucose monitoring (CGM) systems may serve as a tool to reduce the risk of exercise-induced hypoglycemia. It is unclear if CGM is accurate during CON and HIIE at different mean workloads. Seven T1DM patients performed CON and HIIE at 5% below (L) and above (M) the first lactate turn point (LTP1), and 5% below the second lactate turn point (LTP2) (H) on a cycle ergometer. Glucose was measured via CGM and in capillary blood (BG). Differences were found in comparison of CGM vs. BG in three out of the six tests (p < 0.05). In CON, bias and levels of agreement for L, M, and H were found at: 0.85 (−3.44, 5.15) mmol·L−1, −0.45 (−3.95, 3.05) mmol·L−1, −0.31 (−8.83, 8.20) mmol·L−1 and at 1.17 (−2.06, 4.40) mmol·L−1, 0.11 (−5.79, 6.01) mmol·L−1, 1.48 (−2.60, 5.57) mmol·L−1 in HIIE for the same intensities. Clinically-acceptable results (except for CON H) were found. CGM estimated BG to be clinically acceptable, except for CON H. Additionally, using CGM may increase avoidance of exercise-induced hypoglycemia, but usual BG control should be performed during intense exercise. PMID:27517956
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Levitt, David L; Spanakis, Elias K; Ryan, Kathleen A; Silver, Kristi D
2018-01-01
Insulin pumps and continuous glucose monitoring (CGM) are commonly used by patients with diabetes mellitus in the outpatient setting. The efficacy and safety of initiating inpatient insulin pumps and CGM in the nonintensive care unit setting is unknown. In a prospective pilot study, inpatients with type 2 diabetes were randomized to receive standard subcutaneous basal-bolus insulin and blinded CGM (group 1, n = 5), insulin pump and blinded CGM (group 2, n = 6), or insulin pump and nonblinded CGM (group 3, n = 5). Feasibility, glycemic control, and patient satisfaction were evaluated among groups. Group 1 had lower mean capillary glucose levels, 144.5 ± 19.5 mg/dL, compared with groups 2 and 3, 191.5 ± 52.3 and 182.7 ± 59.9 mg/dL (P 1 vs. 2+3 = 0.05). CGM detected 19 hypoglycemic episodes (glucose <70 mg/dL) among all treatment groups, compared with 12 episodes detected by capillary testing, although not statistically significant. No significant differences were found for the total daily dose of insulin or percentage of time spent below target glucose range (<90 mg/dL), in target glucose range (90-180 mg/dL), or above target glucose range (>180 mg/dL). On the Diabetes Treatment Satisfaction Questionnaire-Change, group 3 reported increased hyperglycemia and decreased hypoglycemia frequency compared with the other two groups, although the differences did not reach statistical significance. Insulin pump and CGM initiation are feasible during hospitalization, although they are labor intensive. Although insulin pump initiation may not lead to improved glycemic control, there is a trend toward CGM detecting a greater number of hypoglycemic episodes. Larger studies are needed to determine whether use of this technology can lower inpatient morbidity and mortality.
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Diagnosing cystic fibrosis-related diabetes: current methods and challenges.
Prentice, Bernadette; Hameed, Shihab; Verge, Charles F; Ooi, Chee Y; Jaffe, Adam; Widger, John
2016-07-01
Cystic fibrosis-related diabetes (CFRD) is the end-point of a spectrum of glucose abnormalities in cystic fibrosis that begins with early insulin deficiency and ultimately results in accelerated nutritional decline and loss of lung function. Current diagnostic and management regimens are unable to entirely reverse this clinical decline. This review summarises the current understanding of the pathophysiology of CFRD, the issues associated with using oral glucose tolerance tests in CF and the challenges faced in making the diagnosis of CFRD. Medline database searches were conducted using search terms "Cystic Fibrosis Related Diabetes", "Cystic Fibrosis" AND "glucose", "Cystic Fibrosis" AND "insulin", "Cystic Fibrosis" AND "Diabetes". Additionally, reference lists were studied. Expert commentary: Increasing evidence points to early glucose abnormalities being clinically relevant in cystic fibrosis and as such novel diagnostic methods such as continuous glucose monitoring or 30 minute sampled oral glucose tolerance test (OGTT) may play a key role in the future in the screening and diagnosis of early glucose abnormalities in CF.
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Xie, Yiqiong; Agiro, Abiy; Bowman, Kevin; DeVries, Andrea
2017-08-01
Not much is known about the extent to which lower cost share for blood glucose strips is associated with persistent filling. To evaluate the relationship between cost sharing for blood glucose testing strips and continued use of testing strips. This is a retrospective observational study using medical and pharmacy claims data integrated with laboratory hemoglobin A1c (A1c) values for patients using insulin and blood glucose testing strips. Diabetic patients using insulin who had at least 1 fill of blood glucose testing strips between 2010 and 2012 were included. Patients were divided into a low cost-share group (out-of-pocket cost percentage of total testing strip costs over a 1-year period from the initial fill < 20%; n = 3,575) and a high cost-share group (out-of-pocket cost percentage ≥ 20%; n = 3,580). We compared the likelihood of continued testing strip fills after the initial fill between the 2 groups by using modified Poisson regression models. Patients with low cost share had higher rates of continued testing strip fills compared with those with high cost share (89% vs. 82%, P < 0.001). Lower cost share was associated with greater probability of continued fills (adjusted risk ratio [aRR] = 1.05, 95% CI = 1.03-1.07, P < 0.001). Other patient characteristics associated with continued fills included type 1 diabetes diagnosis, types of insulin regimens, and health insurance plan type. In a subset analysis of patients whose A1c values at baseline were above the target level (8%) set by the National Committee for Quality Assurance guidelines, we saw a slight increase in magnitude of relationship between cost share and continued fills (RR = 1.06, 95% CI = 1.03-1.10, P < 0.01). There was a statistically significant association between cost share for testing strips and continued blood glucose self-monitoring. Among patients not achieving A1c control at baseline, there was an increase in the magnitude of relationship. Lowering cost share for testing strips can remove a barrier to persistence in diabetes self-management. Funding for this study was provided by Anthem, which had no role in the study design, data interpretation, or preparation or review of the manuscript. The decision to publish was strictly that of the authors. Xie, Agiro, and DeVries are employees of HealthCore, a wholly owned subsidiary of Anthem. Bowman is an employee of Anthem. Study concept and design were contributed by all the authors. Xie took the lead in data collection, along with Agiro, and data interpretation was performed by all the authors. The manuscript was written by Xie and Agiro, along with DeVries, and revised by Xie, Agiro, and Devries, along with Bowman.
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Golden, Sherita Hill; Sapir, Tamar
2012-08-01
Diabetes mellitus is defined as a group of metabolic diseases characterized by hyperglycemia, which when untreated can lead to long-term complications, including micro- and macrovascular complications. Tight glycemic control with intensive insulin therapy has been suggested to reduce the risk of such complications in several diabetes populations; however, such an approach can also be associated with risks and challenges. There are currently several modalities available to deliver insulin and monitor glucose levels to achieve glycemic goals in diabetic patients. In July 2012, the Agency for Healthcare Research and Quality (AHRQ) published a systematic review on the comparative effectiveness of insulin delivery systems and glucose-monitoring modalities in diabetic patients receiving intensive insulin therapy. Studies from 44 publications included in the review compared the effects of continuous subcutaneous insulin infusion (CSII) with multiple daily injections (MDI) and/or real time-continuous glucose monitoring (rt-CGM) with self-monitoring of blood glucose (SMBG) among children, adolescents, or adults with either type 1 (T1DM) or type 2 diabetes (T2DM), or pregnant women with pre-existing diabetes (either T1DM or T2DM). This comparative effectiveness review evaluated which modality results in improved glycemic control, less hypoglycemia, better quality of life, and/or improved clinical outcomes. The numerous technologies and the challenges that clinicians face when determining which patient population may benefit from different insulin delivery systems and glucose-monitoring approaches motivated AHRQ to synthesize the available information to assist health professionals in making evidence-based practice decisions for their patients. The review also delineates advances in insulin delivery and glucose-monitoring systems, practical methods to achieve tight glycemic control and strategies to minimize associated risks, as well as highlights gaps in research and areas that need to be addressed in the future. To (a) educate health care professionals on the findings from AHRQ's 2012 comparative effectiveness review on insulin delivery and glucose-monitoring modalities in patients with diabetes; (b) apply review findings to make treatment decisions in clinical practice; and (c) identify shortcomings in the current research and future directions relating to the comparative effectiveness of insulin delivery and glucose-monitoring modalities for patients with diabetes. The AHRQ systematic review of randomized clinical trials reveals that both insulin delivery modalities (CSII and MDI) demonstrate similar effectiveness on glycemic control and severe hypoglycemia in children and adolescents with T1DM and in adults with T2DM. In adults with T1DM, hemoglobin A1c decreased more with CSII than with MDI with low strength of evidence, but one study heavily influenced these results. In children and adults with T1DM, the use of CSII was associated with improved quality of life compared with MDI, with low strength of evidence, while there was insufficient strength of evidence to make conclusions regarding the quality of life for adults with T2DM. The study investigators suggest that the modality to deliver intensive insulin therapy can be individualized to patient preference in order to maximize quality of life. On all measured outcomes, there was insufficient or low strength of evidence regarding pregnant women with pre-existing diabetes.The AHRQ investigators found studies comparing the effectiveness of glucose-monitoring modalities in individuals with T1DM only. The systematic review demonstrates that rt-CGM is associated with greater lowering of A1c compared with SMBG (high strength of evidence) without affecting the risk of severe hypoglycemia (low strength of evidence) or quality of life (low strength of evidence) in nonpregnant individuals with T1DM, particularly when compliance with device use is high. Additional findings suggest that the use of sensor-augmented insulin pumps (rt-CGM + CSII) is superior to the use of MDI/SMBG use in lowering A1c in nonpregnant individuals with T1DM (moderate strength of evidence). Comparison of other outcome measures did not yield firm conclusions due to low or insufficient evidence.
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NASA Astrophysics Data System (ADS)
Prévoteau, Antonin; Geirnaert, Annelies; Arends, Jan B. A.; Lannebère, Sylvain; van de Wiele, Tom; Rabaey, Korneel
2015-07-01
Monitoring in vitro the metabolic activity of microorganisms aids bioprocesses and enables better understanding of microbial metabolism. Redox mediators can be used for this purpose via different electrochemical techniques that are either complex or only provide non-continuous data. Hydrodynamic chronoamperometry using a rotating disc electrode (RDE) can alleviate these issues but was seldom used and is poorly characterized. The kinetics of Faecalibacterium prausnitzii A2-165, a beneficial gut microbe, were determined using a RDE with riboflavin as redox probe. This butyrate producer anaerobically ferments glucose and reduces riboflavin whose continuous monitoring on a RDE provided highly accurate kinetic measurements of its metabolism, even at low cell densities. The metabolic reaction rate increased linearly over a broad range of cell concentrations (9 × 104 to 5 × 107 cells.mL-1). Apparent Michaelis-Menten kinetics was observed with respect to riboflavin (KM = 6 μM kcat = 5.3×105 s-1, at 37 °C) and glucose (KM = 6 μM kcat = 2.4 × 105 s-1). The short temporal resolution allows continuous monitoring of fast cellular events such as kinetics inhibition with butyrate. Furthermore, we detected for the first time riboflavin reduction by another potential probiotic, Butyricicoccus pullicaecorum. The ability of the RDE for fast, accurate, simple and continuous measurements makes it an ad hoc tool for assessing bioprocesses at high resolution.
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Unger, Jeff; Parkin, Christopher
2011-07-01
Hypoglycemia is the key barrier that prevents patients from optimizing glycemic control with the use of pharmacotherapeutic interventions. Optimal glycemic control for patients with type 1 diabetes (T1DM) includes methods that provide glucose-regulated physiologic insulin replacement or secretion in association with glucose monitoring methods designed to predict and prevent acute extreme changes in glycemic variability. Patients with T1DM experience an average of 2 episodes of symptomatic hypoglycemia each week and at least 1 episode of severe, disabling hypoglycemia annually. Asymptomatic hypoglycemia is common, as shown in studies using continuous glucose monitoring (CGM). Episodes of hypoglycemia (symptomatic and asymptomatic) impair counterregulatory defenses against subsequent events, resulting in the inability to respond to and recover from serious hypoglycemia. This defective counterregulation is known as hypoglycemic-associated autonomic failure. When patients are prescribed a more intensive medication regimen or reinforcing lifestyle interventions, such as medical nutrition therapy and exercise therapy, providers should also assess their ability to proactively identify and manage hypoglycemia. Although self-monitoring of blood glucose regimens, such as pre- and post-meal and periodic middle-of-the-night glucose testing, can help predict the risk of developing hypoglycemia, CGM technology allows patients to receive real-time notification of impending events either through preset alarms or simply by looking at the device display. This review explores the utility of initiating CGM within the primary care setting for patients at high risk for developing hypoglycemia.
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Use of case-based reasoning to enhance intensive management of patients on insulin pump therapy.
Schwartz, Frank L; Shubrook, Jay H; Marling, Cynthia R
2008-07-01
This study was conducted to develop case-based decision support software to improve glucose control in patients with type 1 diabetes mellitus (T1DM) on insulin pump therapy. While the benefits of good glucose control are well known, achieving and maintaining good glucose control remains a difficult task. Case-based decision support software may assist by recalling past problems in glucose control and their associated therapeutic adjustments. Twenty patients with T1DM on insulin pumps were enrolled in a 6-week study. Subjects performed self-glucose monitoring and provided daily logs via the Internet, tracking insulin dosages, work, sleep, exercise, meals, stress, illness, menstrual cycles, infusion set changes, pump problems, hypoglycemic episodes, and other events. Subjects wore a continuous glucose monitoring system at weeks 1, 3, and 6. Clinical data were interpreted by physicians, who explained the relationship between life events and observed glucose patterns as well as treatment rationales to knowledge engineers. Knowledge engineers built a prototypical system that contained cases of problems in glucose control together with their associated solutions. Twelve patients completed the study. Fifty cases of clinical problems and solutions were developed and stored in a case base. The prototypical system detected 12 distinct types of clinical problems. It displayed the stored problems that are most similar to the problems detected, and offered learned solutions as decision support to the physician. This software can screen large volumes of clinical data and glucose levels from patients with T1DM, identify clinical problems, and offer solutions. It has potential application in managing all forms of diabetes.
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Baird, Harriet M; Webb, Thomas L; Martin, Jilly; Sirois, Fuschia M
2018-05-10
Self-monitoring of blood glucose helps people with type 1 diabetes to maintain glycemic control and reduce the risk of complications. However, adherence to blood glucose monitoring is often suboptimal. Like many health behaviors, self-monitoring of blood glucose involves exerting effort in the present to achieve future benefits. As such, the present research explored whether individual differences in time perspective-specifically, the extent to which people have a balanced time perspective-are associated with the frequency with which people with type 1 diabetes monitor their blood glucose and, thus, maintain glycemic control. Adults with type 1 diabetes completed measures of time perspective, feelings associated with monitoring, attitudes toward monitoring, and trait self-control. Objective data regarding the frequency with which participants monitored their blood glucose levels and their long-term glycemic control were extracted from their medical records. Hierarchical regression analyses and tests of indirect effects (N = 129) indicated that having a more balanced time perspective was associated with more frequent monitoring of blood glucose and, as a result, better glycemic control. Further analyses (N = 158) also indicated that there was an indirect relationship between balanced time perspective and monitoring of blood glucose via the feelings that participants associated with monitoring and their subsequent attitudes toward monitoring. These findings point to the importance and relevance of time perspective for understanding health-related behavior and may help to inform interventions designed to promote self-monitoring of blood glucose in people with type 1 diabetes.
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Insulin therapy in children and adolescents with type 1 diabetes.
Malik, Faisal S; Taplin, Craig E
2014-04-01
Treatment of type 1 diabetes mellitus (T1DM) requires lifelong administration of exogenous insulin. The primary goal of treatment of T1DM in children and adolescents is to maintain near-normoglycemia through intensive insulin therapy, avoid acute complications, and prevent long-term microvascular and macrovascular complications, while facilitating as close to a normal life as possible. Effective insulin therapy must, therefore, be provided on the basis of the needs, preferences, and resources of the individual and the family for optimal management of T1DM. To achieve target glycemic control, the best therapeutic option for patients with T1DM is basal-bolus therapy either with multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII). Many formulations of insulin are available to help simulate endogenous insulin secretion as closely as possible in an effort to eliminate the symptoms and complications of hyperglycemia, while minimizing the risk of hypoglycemia secondary to therapy. When using MDI, basal insulin requirements are given as an injection of long- or intermediate-acting insulin analogs, while meal-related glucose excursions are controlled with bolus injections of rapid-acting insulin analogs. Alternatively, CSII can be used, which provides a 24-h preselected but adjustable basal rate of rapid-acting insulin, along with patient-activated mealtime bolus doses, eliminating the need for periodic injections. Both MDI treatment and CSII therapy must be supported by comprehensive education that is appropriate for the individual needs of the patient and family before and after initiation. Current therapies still do not match the endogenous insulin profile of pancreatic β-cells, and all still pose risks of suboptimal control, hypoglycemia, and ketosis in children and adolescents. The safety and success of a prescribed insulin regimen is, therefore, dependent on self-monitoring of blood glucose and/or a continuous glucose monitoring system to avoid critical hypoglycemia and glucose variability. Regardless of the mode of insulin therapy, doses should be adapted on the basis of the daily pattern of blood glucose, through regular review and reassessment, and patient factors such as exercise and pubertal status. New therapy options such as sensor-augmented insulin pump therapy, which integrates CSII with a continuous glucose sensor, along with emerging therapies such as the artificial pancreas, will likely continue to improve safe insulin therapy in the near future.
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Obermaier, Karin; Schmelzeisen-Redeker, Günther; Schoemaker, Michael; Klötzer, Hans-Martin; Kirchsteiger, Harald; Eikmeier, Heino; del Re, Luigi
2013-07-01
Even though a Clinical and Laboratory Standards Institute proposal exists on the design of studies and performance criteria for continuous glucose monitoring (CGM) systems, it has not yet led to a consistent evaluation of different systems, as no consensus has been reached on the reference method to evaluate them or on acceptance levels. As a consequence, performance assessment of CGM systems tends to be inconclusive, and a comparison of the outcome of different studies is difficult. Published information and available data (as presented in this issue of Journal of Diabetes Science and Technology by Freckmann and coauthors) are used to assess the suitability of several frequently used methods [International Organization for Standardization, continuous glucose error grid analysis, mean absolute relative deviation (MARD), precision absolute relative deviation (PARD)] when assessing performance of CGM systems in terms of accuracy and precision. The combined use of MARD and PARD seems to allow for better characterization of sensor performance. The use of different quantities for calibration and evaluation, e.g., capillary blood using a blood glucose (BG) meter versus venous blood using a laboratory measurement, introduces an additional error source. Using BG values measured in more or less large intervals as the only reference leads to a significant loss of information in comparison with the continuous sensor signal and possibly to an erroneous estimation of sensor performance during swings. Both can be improved using data from two identical CGM sensors worn by the same patient in parallel. Evaluation of CGM performance studies should follow an identical study design, including sufficient swings in glycemia. At least a part of the study participants should wear two identical CGM sensors in parallel. All data available should be used for evaluation, both by MARD and PARD, a good PARD value being a precondition to trust a good MARD value. Results should be analyzed and presented separately for clinically different categories, e.g., hypoglycemia, exercise, or night and day. © 2013 Diabetes Technology Society.
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Adherence of self-monitoring of blood glucose in persons with type 1 diabetes in Sweden
Moström, Peter; Ahlén, Elsa; Imberg, Henrik; Hansson, Per-Olof; Lind, Marcus
2017-01-01
Objective The primary aim was to evaluate the extent to which persons with type 1 diabetes perform self-monitoring of blood glucose (SMBG) according to guidelines. Secondary objectives were to investigate predictors for good SMBG adherence, reasons for non-adherence, and association between SMBG frequency and hemoglobin A1c (HbA1c). Methods This was a survey-based cross-sectional study. Questionnaires were sent out to 600 random patients at five sites. Patients were included if they were diagnosed with type 1 diabetes and ≥18 years old and excluded if they were currently using continuous glucose monitoring (CGM). Analysis of data was performed separately for the three sites where the answer frequency was ≥70%. Results In total, 138 of 314 study participants, 43.9% (95% CI 38.5% to 49.4%) performed SMBG ≥4 times per day. For the three clinics where ≥70% of surveyed patients were included in the analysis, results were similar, 41.3% (95% CI 34.7% to 47.8%). Top three reported reasons for not performing more frequent SMBG were lack of time, not remembering, and self-consciousness. Frequency of SMBG was associated with HbA1c levels (p<0.0001). 30% of patients believed that ≤3 SMBG/day was recommended by healthcare providers. Conclusions Less than 50% of patients in Sweden follow guidelines of SMBG ≥4 times per day, despite glucose meters and strips being generally available at no cost. This indicates a need for further support in performing SMBG and increased availability of other tools for glucose monitoring. PMID:28611921
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Krishnan, V; Thirunavukkarasu, J
2016-03-01
Self blood glucose monitoring is an important context of self care in the management of diabetes mellitus. All the guidelines must be followed while performing self blood glucose monitoring and tracking of values is essential to facilitate the physician while titrating the drugs and /or doses of anti diabetes medication. Self titration by patients following self monitoring must be discouraged. To assess the knowledge and practice of self blood glucose monitoring among diabetes patients and extent of self titration of anti diabetes medicines among diabetes patients based on self blood glucose monitoring. This pilot, cross-sectional, observational study was conducted using a validated questionnaire among adult male and female diabetes patients performing self blood glucose monitoring at home. Diabetes patients with complications and juvenile diabetes patients were excluded. Out of 153 patients surveyed, only 37 (24.1%) (20 males, 17 females) patients were aware and have been following self blood glucose monitoring appropriately. About 116 (75.8%) (64 males, 52 females) of patients were devoid of adequate knowledge and did not practice self blood glucose monitoring in a proper way. Ninety eight (64.05%) accepted that they self titrate their anti diabetic medicines based on self monitoring. Self monitoring of blood glucose should be encouraged and patients should be taught importance of following correct steps and tracking of self monitoring by physician or diabetes educator.
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Continuous glucose monitoring and hypoglycemia unawareness in type 1 diabetes: a pilot study.
Zalzali, Mohamed; Houdelet-Guerinot, Valérie; Socquard, Eric; Thierry, Aurore; Delemer, Brigitte; Lukas-Croisier, Céline
2017-09-01
Looking for strict normoglycemia in type 1 diabetes increases the risk of hypoglycemia, exposing to hypoglycemia unawareness. It has been shown that the early correction of hypoglycemia can help recovering the perception of hypoglycemia. The purpose of this prospective study was to assess the value of sensor-augmented insulin-pump therapy to treat hypoglycemia unawareness. Eleven patients with type 1 diabetes and partial or total hypoglycemia unawareness received sensor-augmented insulin-pump therapy combined to the low blood glucose-suspend feature (Paradigm® Veo™ pump and Enlite® sensors) for three months. Eighty per cent of the patients improved their hypoglycemia unawareness with an increase in the hypoglycemia perception threshold of 31 mg/dL as evaluated by blinded continuous glucose monitoring. These results were correlated to a self-assessment quiz evaluation. Results were sustained at six months (three months after patients stopped using the system). Sensitive neuropathy, untreated hypoglycemia and the area under the curve for hypoglycemia events were associated with less chance of recovery. These devices were globally considered by the patients as simple to use, with no major disadvantages and only a single withdrawal occurred. Sensor-augmented insulin-pump therapy should be considered as a possible treatment of hypoglycemia unawareness.
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Pérez-Calatayud, Ángel Augusto; Guillén-Vidaña, Ariadna; Fraire-Félix, Irving Santiago; Anica-Malagón, Eduardo Daniel; Briones Garduño, Jesús Carlos; Carrillo-Esper, Raúl
Metabolic changes of glucose in critically ill patients increase morbidity and mortality. The appropriate level of blood glucose has not been established so far and should be adjusted for different populations. However concepts such as glucose variability and relative hypoglycemia of critically ill patients are concepts that are changing management methods and achieving closer monitoring. The purpose of this review is to present new data about the management and metabolic control of patients in critical areas. Currently glucose can no longer be regarded as an innocent element in critical patients; both hyperglycemia and hypoglycemia increase morbidity and mortality of patients. Protocols and better instruments for continuous measurement are necessary to achieve the metabolic control of our patients. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.
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Battelino, T; Conget, I; Olsen, B; Schütz-Fuhrmann, I; Hommel, E; Hoogma, R; Schierloh, U; Sulli, N; Bolinder, J
2012-12-01
The aim of this multicentre, randomised, controlled crossover study was to determine the efficacy of adding continuous glucose monitoring (CGM) to insulin pump therapy (CSII) in type 1 diabetes. Children and adults (n = 153) on CSII with HbA(1c) 7.5-9.5% (58.5-80.3 mmol/mol) were randomised to (CGM) a Sensor On or Sensor Off arm for 6 months. After 4 months' washout, participants crossed over to the other arm for 6 months. Paediatric and adult participants were separately electronically randomised through the case report form according to a predefined randomisation sequence in eight secondary and tertiary centres. The primary outcome was the difference in HbA(1c) levels between arms after 6 months. Seventy-seven participants were randomised to the On/Off sequence and 76 to the Off/On sequence; all were included in the primary analysis. The mean difference in HbA(1c) was -0.43% (-4.74 mmol/mol) in favour of the Sensor On arm (8.04% [64.34 mmol/mol] vs 8.47% [69.08 mmol/mol]; 95% CI -0.32%, -0.55% [-3.50, -6.01 mmol/mol]; p < 0.001). Following cessation of glucose sensing, HbA(1c) reverted to baseline levels. Less time was spent with sensor glucose <3.9 mmol/l during the Sensor On arm than in the Sensor Off arm (19 vs 31 min/day; p = 0.009). The mean number of daily boluses increased in the Sensor On arm (6.8 ± 2.5 vs 5.8 ± 1.9, p < 0.0001), together with the frequency of use of the temporary basal rate (0.75 ± 1.11 vs 0.26 ± 0.47, p < 0.0001) and manual insulin suspend (0.91 ± 1.25 vs 0.70 ± 0.75, p < 0.018) functions. Four vs two events of severe hypoglycaemia occurred in the Sensor On and Sensor Off arm, respectively (p = 0.40). Continuous glucose monitoring was associated with decreased HbA(1c) levels and time spent in hypoglycaemia in individuals with type 1 diabetes using CSII. More frequent self-adjustments of insulin therapy may have contributed to these effects.
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Accuracy of a Flash Glucose Monitoring System in Diabetic Dogs.
Corradini, S; Pilosio, B; Dondi, F; Linari, G; Testa, S; Brugnoli, F; Gianella, P; Pietra, M; Fracassi, F
2016-07-01
A novel flash glucose monitoring system (FGMS) (FreeStyle Libre, Abbott, UK) was recently developed for humans. It continuously measures the interstitial glucose (IG) concentrations for 14 days. To assess the clinical and analytical accuracy of the FGMS in diabetic dogs. Ten client-owned diabetic dogs on insulin treatment. Prospective and observational study. The FGMS was placed on the neck for up to 14 days. During the 1st-2nd, 6-7th, and 13-14th days from application, the IG measurements were compared with the plasma (EDTA) glucose (PG) concentrations analyzed by a reference hexokinase based method. The application and the use of the FGMS were apparently painless, easy, and well tolerated by all dogs. Mild erythema at the site of the application was found in 5/10 dogs at the end of the wearing period. A good correlation between IG and PG concentrations (rho = 0.94; P < .001) was found. The FGMS was 93, 99, and 99% accurate at low, normal, and high blood glucose concentrations. Mean ± standard deviation difference from the reference method was 2.3 ± 46.8 mg/dL. The FGMS is easy to use and is accurate for IG glucose measurement in diabetic dogs. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.
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Forlenza, Gregory P; Pyle, Laura L; Maahs, David M; Dunn, Timothy C
2017-11-01
Increased continuous glucose monitor (CGM) use presents both the benefit and burden of increased data for clinicians to rapidly analyze. The ambulatory glucose profile (AGP) is an evolving a universal software report for CGM data analysis. We utilized the Juvenile Diabetes Research Foundation-CGM dataset to evaluate the AGP across a broad spectrum of patients to show how AGP can be used clinically to assist with CGM-related decision making. We hypothesized that AGP metrics would be different across age and HbA1c strata. AGPs were generated from the JDRF-CGM trial dataset for all periods during which there were ≥10 days of CGM coverage in the 2 weeks adjacent to an HbA1c measurement yielding 1101 AGPs for 393 unique subjects. AGPs were stratified by age group (8-14, 15-24, and ≥25 years) and HbA1c (within or above target for age) and compared for between group differences in AGP metrics via two-factor ANOVA. Glycemic differences between time periods were analyzed via segmented regression analysis. Glucose exposure (average and estimated A1c) and variability (standard deviation and interquartile range) were different between the low and high HbA1c levels. Within a given HbA1c level all age groups were significantly different from each other with older patients having lower averages with less variability than younger patients. AGP analysis of the JDRF-CGM data highlights significant differences in glycemic profiles between pediatric and adult age groups and between well and less well-controlled patient populations. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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Damiano, Edward R; McKeon, Katherine; El-Khatib, Firas H; Zheng, Hui; Nathan, David M; Russell, Steven J
2014-07-01
The effectiveness and safety of continuous glucose monitors (CGMs) is dependent on their accuracy and reliability. The objective of this study was to compare 3 CGMs in adult and pediatric subjects with type 1 diabetes under closed-loop blood-glucose (BG) control. Twenty-four subjects (12 adults) with type 1 diabetes each participated in one 48-hour closed-loop BG control experiment. Venous plasma glucose (PG) measurements obtained every 15 minutes (4657 values) were paired in time with corresponding CGM glucose (CGMG) measurements obtained from 3 CGMs (FreeStyle Navigator, Abbott Diabetes Care; G4 Platinum, Dexcom; Enlite, Medtronic) worn simultaneously by each subject. The Navigator and G4 Platinum (G4) had the best overall accuracy, with an aggregate mean absolute relative difference (MARD) of all paired points of 12.3 ± 12.1% and 10.8 ± 9.9%, respectively. Both had lower MARDs of all paired points than Enlite (17.9 ± 15.8%, P < .005). Very large errors (MARD > 50%) were less common with the G4 (0.5%) than with the Enlite (4.3%, P = .0001) while the number of very large errors with the Navigator (1.4%) was intermediate between the G4 and Enlite (P = .1 and P = .06, respectively). The average MARD for experiments in adolescent subjects were lower than in adult subjects for the Navigator and G4, while there was no difference for Enlite. All 3 devices had similar reliability. A comprehensive head-to-head-to-head comparison of 3 CGMs revealed marked differences in both accuracy and precision. The Navigator and G4 were found to outperform the Enlite in these areas. © 2014 Diabetes Technology Society.
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Képénékian, Lori; Smagala, Agnieszka; Meyer, Laurent; Imhoff, Olivier; Alenabi, Farideh; Serb, Liviu; Fleury, Dominique; Dorey, François; Krummel, Thierry; Le Floch, Jean-Pierre; Chantrel, François; Kessler, Laurence
2014-10-01
Hemodialyzed patients with diabetes face an increased cardiovascular risk. Optimal glycemic control can reduce morbidity and mortality, but it is difficult to achieve because of the alternation between dialysis and non-dialysis periods. This study evaluated the contribution of continuous glucose monitoring (CGM) to the management of insulin regimen. In this pilot prospective multicenter study, we performed CGM (Navigator®, Abbott, Rungis, France) for a total of 54 hours at baseline and for a 3-month follow-up period in a group of 28 hemodialyzed patients with type 2 diabetes treated by a basal-bolus detemir plus aspart insulin regimen. Insulin therapy was adapted to the CGM values. HbA1c and CGM parameters collected over the 3-month treatment period were compared using MANOVA for repeated measures. After 3 months, HbA1c significantly decreased from 8.4 ± 1.0% (65 ± 1 mmol/mol) to 7.6 ± 1.0% (60 ± 11 mmol/mol; p < 0.01). Similarly, mean CGM glucose values significantly decreased from 9.9 ± 1.9 to 8.9 ± 2.1 mmol/L (p = 0.05). The frequency of glucose values > 10 mmol/L significantly decreased from 41.3 ± 21.9% to 30.1 ± 22.4% (p < 0.05), without a significant increase in the frequency of glucose values < 3.3 mmol/L. Insulin requirements significantly increased from 70 ± 51 IU/d to 82 ± 77 IU/d (p < 0.001), without significant changes in body weight. CGM-adapted insulin regimen improves glycemic control without increasing hypoglycemic events in hemodialyzed diabetic patients. CGM could be a useful tool for the management of insulin therapy in these patients. These results need to be confirmed by long-term studies with larger sample sizes.
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Continuous glucose monitoring and clinical trials.
Heinemann, Lutz
2009-07-01
The use of glucose sensors during clinical trials seems like a great idea at first glance. Continuous glucose monitoring (CGM) should allow the gathering of more detailed information about metabolic control, without requiring much additional effort. In principle, CGM can reduce the duration of such studies and the number of participants required. The aim of this commentary is to highlight some of the reasons why, in practice, at least some of these hopes have not been realized. It is not only that a new technology requires extensive training of the study personnel; the practical handling of the devices and the time and effort required to download and analyze the data are often grossly underestimated initially. In addition, one must select the best endpoints for describing the level of metabolic control in view of the overwhelming amount of information provided by CGM. Several measures and endpoints were proposed as (potential) parameters that would be more meaningful than the standard parameters currently used to describe glucose profiles. Unfortunately, most of these proposed parameters have not, as yet, been proven to be more meaningful. Calibration is another critical aspect of using CGM that must be addressed. How this procedure is handled in practice has a profound impact on the quality of the glucose recordings. Finally, shall the current measurement results be displayed to the study participant or not? CGM can help prevent severe hypoglycemic episodes, but this can profoundly affect the study outcome in a manner that is unrelated to basic aim of the study (e.g., comparing medications that are designed to control glycemia). Therefore, the use of CGM in clinical trials requires much more careful consideration than was initially thought. Copyright 2009 Diabetes Technology Society.
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Accuracy of a new real-time continuous glucose monitoring algorithm.
Keenan, D Barry; Cartaya, Raymond; Mastrototaro, John J
2010-01-01
Through minimally invasive sensor-based continuous glucose monitoring (CGM), individuals can manage their blood glucose (BG) levels more aggressively, thereby improving their hemoglobin A1c level, while reducing the risk of hypoglycemia. Tighter glycemic control through CGM, however, requires an accurate glucose sensor and calibration algorithm with increased performance at lower BG levels. Sensor and BG measurements for 72 adult and adolescent subjects were obtained during the course of a 26-week multicenter study evaluating the efficacy of the Paradigm REAL-Time (PRT) sensor-augmented pump system (Medtronic Diabetes, Northridge, CA) in an outpatient setting. Subjects in the study arm performed at least four daily finger stick measurements. A retrospective analysis of the data set was performed to evaluate a new calibration algorithm utilized in the Paradigm Veo insulin pump (Medtronic Diabetes) and to compare these results to performance metrics calculated for the PRT. A total of N = 7193 PRT sensor downloads for 3 days of use, as well as 90,472 temporally and nonuniformly paired data points (sensor and meter values), were evaluated, with 5841 hypoglycemic and 15,851 hyperglycemic events detected through finger stick measurements. The Veo calibration algorithm decreased the overall mean absolute relative difference by greater than 0.25 to 15.89%, with hypoglycemia sensitivity increased from 54.9% in the PRT to 82.3% in the Veo (90.5% with predictive alerts); however, hyperglycemia sensitivity was decreased only marginally from 86% in the PRT to 81.7% in the Veo. The Veo calibration algorithm, with sensor error reduced significantly in the 40- to 120-mg/dl range, improves hypoglycemia detection, while retaining accuracy at high glucose levels. 2010 Diabetes Technology Society.
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Dow, Shireen; Pritchett, Kelly L; Hawk, Susan; Herrington, Stefanie J; Gee, David L
2012-04-01
To determine the effects of two water-soluble dietary fibers, ultrahigh-viscosity hydroxypropylmethylcellulose (UHV-HPMC, nonfermentable) and psyllium fiber (fermentable), on postprandial glucose and second meal effects. In a single-blind crossover design, 12 healthy adult subjects were given standardized, premeasured breakfast and lunch meals with either 4 g of the fiber supplements or a placebo. Blood glucose was measured with a continuous blood glucose monitoring system (DexCom Seven Plus, San Diego, CA). Subjects consuming UHV-HPMC had significantly (p < 0.05) lower blood glucose area under the curve (AUC) 2 hours after breakfast than those receiving a placebo. Subjects consuming psyllium also tended to have lower glucose levels than the placebo group. Peak glucose concentration following breakfast was significantly (p < 0.01) less with UHV-HPMC when compared with the placebo. No significant differences in AUC or peak glucose concentration between treatments following the second meal (lunch) were detected, suggesting no residual effect from the fiber supplements. Supplementation with viscous water-soluble fibers may be an effective means of reducing the glycemic response of a meal in healthy adults.
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Closed-loop controlled noninvasive ultrasonic glucose sensing and insulin delivery
NASA Astrophysics Data System (ADS)
Park, Eun-Joo; Werner, Jacob; Jaiswal, Devina; Smith, Nadine Barrie
2010-03-01
To prevent complications in diabetes, the proper management of blood glucose levels is essential. Previously, ultrasonic transdermal methods using a light-weight cymbal transducer array has been studied for noninvasive methods of insulin delivery for Type-1 diabetes and glucose level monitoring. In this study, the ultrasound systems of insulin delivery and glucose sensing have been combined by a feedback controller. This study was designed to show the feasibility of the feedback controlled ultrasound system for the noninvasive glucose control. For perspective human application, in vivo experiments were performed on large animals that have a similar size to humans. Four in vivo experiments were performed using about 200 lbs pigs. The cymbal array of 3×3 pattern has been used for insulin delivery at 30 kHz with the spatial-peak temporal-peak intensity (Isptp) of 100 mW/cm2. For glucose sensing, a 2×2 array was operated at 20 kHz with Isptp = 100 mW/cm2. Based on the glucose level determined by biosensors after the ultrasound exposure, the ultrasound system for the insulin delivery was automatically operated. The glucose level of 115 mg/dl was set as a reference value for operating the insulin delivery system. For comparison, the glucose levels of blood samples collected from the ear vein were measured by a commercial glucose meter. Using the ultrasound system operated by the close-loop, feed-back controller, the glucose levels of four pigs were determined every 20 minutes and continuously controlled for 120 minutes. In comparison to the commercial glucose meter, the glucose levels determined by the biosensor were slightly higher. The results of in vivo experiments indicate the feasibility of the feedback controlled ultrasound system using the cymbal array for noninvasive glucose sensing and insulin delivery. Further studies on the extension of the glucose control will be continued for the effective method of glucose control.
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van Beers, Cornelis A J; DeVries, J Hans; Kleijer, Susanne J; Smits, Mark M; Geelhoed-Duijvestijn, Petronella H; Kramer, Mark H H; Diamant, Michaela; Snoek, Frank J; Serné, Erik H
2016-11-01
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. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Microminiature Monitor for Vital Electrolyte and Metabolite Levels of Astronauts
NASA Technical Reports Server (NTRS)
Tohda, Koji; Gratzl, Miklos
2004-01-01
Ions, such as proton (pH) and potassium, play a crucial role in body fluids to maintain proper basic functioning of cells and tissues. Metabolites, such as glucose, control the energy available to the entire human body in normal as well as stress situations, and before, during, and after meals. These molecules diffuse easily between blood in the capillaries and the interstitial fluid residing between cells and tissues. We have developed and approach to monitoring of critical ions (called electrolytes) and glucose in the interstitial fluid under the human skin. Proton and potassium levels sensed using optode technology that translates the respective ionic concentrations into variable colors of corresponding ionophore/dye/polymeric liquid membranes. Glucose is monitored indirectly, by coupling through immobilized glucose oxidase with local pH that is then detected using a similar color scheme. The monitor consists of a tiny plastic bar, 100-200 microns wide and 1-2 mm long, placed just under the skin, with color changing spots for each analyte as well as blanks. The colors are read and translated into concentration values by a CCD camera. Direct optical coupling between the in vivo sensing bar and the ex vivo detector device requires no power, and thus eliminates the need for wires or optical fibers crossing the skin. The microminiature bar penetrates the skin easily and painlessly, so that astronauts could insert it themselves. The approach is fully compatible with telemetry in space, and thus, in vivo clinical data will be available real time in the Earth based command center once the device is fully developed. The information provided can be used for collecting hitherto unavailable vital data on clinical effects of space travel. Managing clinical emergencies in space with the sensor already in place should also become much more efficient than without a continuous monitor, as is currently the case. Civilian applications may include better glucose control of patients with moderate to severe diabetes: a growing health problem in the US and World-wide.
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Health State Utilities Associated with Glucose Monitoring Devices.
Matza, Louis S; Stewart, Katie D; Davies, Evan W; Hellmund, Richard; Polonsky, William H; Kerr, David
2017-03-01
Glucose monitoring is important for patients with diabetes treated with insulin. Conventional glucose monitoring requires a blood sample, typically obtained by pricking the finger. A new sensor-based system called "flash glucose monitoring" monitors glucose levels with a sensor worn on the arm, without requiring blood samples. To estimate the utility difference between these two glucose monitoring approaches for use in cost-utility models. In time trade-off interviews, general population participants in the United Kingdom (London and Edinburgh) valued health states that were drafted and refined on the basis of literature, clinician input, and a pilot study. The health states had identical descriptions of diabetes and insulin treatment, differing only in glucose monitoring approach. A total of 209 participants completed the interviews (51.7% women; mean age = 42.1 years). Mean utilities were 0.851 ± 0.140 for conventional monitoring and 0.882 ± 0.121 for flash monitoring (significant difference between the mean utilities; t = 8.3; P < 0.0001). Of the 209 participants, 78 (37.3%) had a higher utility for flash monitoring, 2 (1.0%) had a higher utility for conventional monitoring, and 129 (61.7%) had the same utility for both health states. The flash glucose monitoring system was associated with a significantly greater utility than the conventional monitoring system. This difference may be useful in cost-utility models comparing the value of glucose monitoring devices for patients with diabetes. This study adds to the literature on treatment process utilities, suggesting that time trade-off methods may be used to quantify preferences among medical devices. Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.
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Imai, Saeko; Fukui, Michiaki; Kajiyama, Shizuo
2014-01-01
The aim of this review was to evaluate whether eating vegetables before carbohydrates could reduce the postprandial glucose, insulin, and improve long-term glycemic control in Japanese patients with type 2 diabetes. We studied the effect of eating vegetables before carbohydrates on postprandial plasma glucose, insulin, and glycemic control for 2.5 y in patients with type 2 diabetes. The postprandial glucose and insulin levels decreased significantly when the patients ate vegetables before carbohydrates compared to the reverse regimen, and the improvement of glycemic control was observed for 2.5 y. We also compared the postprandial glucose and glucose fluctuations assessed by continuous glucose monitoring system for 72-h in patients with type 2 diabetes and subjects with normal glucose tolerance when subjects ate vegetables before carbohydrates and carbohydrates before vegetables in a randomized crossover design. The glycemic excursions and incremental glucose peak were significantly lower when the subjects ate vegetables before carbohydrates compared to the reverse regimen. This evidence supports the effectiveness of eating vegetables before carbohydrates on glucose excursions in the short-term and glycemic control in the long-term in patients with type 2 diabetes. PMID:24426184
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Imai, Saeko; Fukui, Michiaki; Kajiyama, Shizuo
2014-01-01
The aim of this review was to evaluate whether eating vegetables before carbohydrates could reduce the postprandial glucose, insulin, and improve long-term glycemic control in Japanese patients with type 2 diabetes. We studied the effect of eating vegetables before carbohydrates on postprandial plasma glucose, insulin, and glycemic control for 2.5 y in patients with type 2 diabetes. The postprandial glucose and insulin levels decreased significantly when the patients ate vegetables before carbohydrates compared to the reverse regimen, and the improvement of glycemic control was observed for 2.5 y. We also compared the postprandial glucose and glucose fluctuations assessed by continuous glucose monitoring system for 72-h in patients with type 2 diabetes and subjects with normal glucose tolerance when subjects ate vegetables before carbohydrates and carbohydrates before vegetables in a randomized crossover design. The glycemic excursions and incremental glucose peak were significantly lower when the subjects ate vegetables before carbohydrates compared to the reverse regimen. This evidence supports the effectiveness of eating vegetables before carbohydrates on glucose excursions in the short-term and glycemic control in the long-term in patients with type 2 diabetes.
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Youth and parent feelings about type 1 diabetes (T1D) management technologies
USDA-ARS?s Scientific Manuscript database
Use of T1D management technologies, including insulin pumps and continuous glucose monitors, is rapidly growing. However, research has only recently begun to evaluate youth and parent feelings about and experiences with using these technologies and the relationship with health-related quality of lif...
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A multi-sensor monitoring system of human physiology and daily activities.
Doherty, Sean T; Oh, Paul
2012-04-01
To present the design and pilot test results of a continuous multi-sensor monitoring system of real-world physiological conditions and daily life (activities, travel, exercise, and food consumption), culminating in a Web-based graphical decision-support interface. The system includes a set of wearable sensors wirelessly connected to a "smartphone" with a continuously running software application that compresses and transmits the data to a central server. Sensors include a Global Positioning System (GPS) receiver, electrocardiogram (ECG), three-axis accelerometer, and continuous blood glucose monitor. A food/medicine diary and prompted recall activity diary were also used. The pilot test involved 40 type 2 diabetic patients monitored over a 72-h period. All but three subjects were successfully monitored for the full study period. Smartphones proved to be an effective hub for managing multiple streams of data but required attention to data compression and battery consumption issues. ECG, accelerometer, and blood glucose devices performed adequately as long as subjects wore them. GPS tracking for a full day was feasible, although significant efforts are needed to impute missing data. Activity detection algorithms were successful in identifying activities and trip modes but could benefit by incorporating accelerometer data. The prompted recall diary was an effective tool for augmenting algorithm results, although subjects reported some difficulties with it. The food and medicine diary was completed fully, although end times and medicine dosages were occasionally missing. The unique combination of sensors holds promise for increasing accuracy and reducing burden associated with collecting individual-level activity and physiological data under real-world conditions, but significant data processing issues remain. Such data will provide new opportunities to explore the impacts of human geography and daily lifestyle on health at a fine spatial/temporal scale.
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Jinnouchi, Hideaki; Koyama, Masayoshi; Amano, Atsushi; Takahashi, Yoshinori; Yoshida, Akira; Hieshima, Kunio; Sugiyama, Seigo; Kurinami, Noboru; Jinnouchi, Tomio; Becker, Reinhard
2015-06-01
New insulin glargine 300 U mL(-1) (Gla-300) is a basal insulin that shows more stable and prolonged pharmacokinetic and pharmacodynamic profiles than insulin glargine 100 U mL(-1) (Gla-100). This study used continuous glucose monitoring (CGM) to compare 24-h glucose profiles in a Japanese population using Gla-300 versus Gla-100. This was an exploratory 8.4-week, single-center, 2-sequence, 2-period, open-label crossover study. Japanese adults with type 1 diabetes mellitus (T1DM) treated with basal-bolus insulin, with glycated hemoglobin (HbA1c) 6.5-10.0% and median fasting self-monitored plasma glucose concentration ≤13 mmol L(-1), were randomized to Gla-300 followed by Gla-100 (subgroup 1) or vice versa (subgroup 2), with no washout period. CGM was performed on the last 3 days of the screening period and each treatment period. Primary endpoint was comparison of 24-h glucose variability (area under the curve [AUC]mean_24 h) on the second day of each CGM measurement with Gla-300 versus Gla-100. Baseline and end of treatment period values for HbA1c, fasting plasma glucose (FPG) and daily basal/mealtime insulin doses were recorded. Hypoglycemia and adverse events (AEs) were recorded. Twenty participants were randomized (10 to subgroup 1 and 10 to subgroup 2). Participants showed comparable glucose variability over 24 h (AUCmean_24 h during treatment with Gla-300 or Gla-100 (treatment ratio 0.96; 90% confidence interval 0.79, 1.16). HbA1c and FPG were generally stable across both treatment periods. There was a trend towards fewer participants experiencing ≥1 hypoglycemia event at any time (24 h) and at night (00:00-05:59 h) with Gla-300 versus Gla-100. Treatment-emergent AEs, reported by 9/20 (45%) and 4/20 (20%) participants during Gla-300 and Gla-100 treatment, respectively, were unrelated to study medication. In this cohort of Japanese people with T1DM, no between-treatment difference was observed in glucose variability with Gla-300 versus Gla-100, as measured by CGM. There was a trend for less hypoglycemia with Gla-300, particularly at night, versus Gla-100. Both treatments were well tolerated. Sanofi, Tokyo, Japan. NCT01676233, ClinicalTrials.gov.
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Wadwa, R Paul; Laffel, Lori M; Shah, Viral N; Garg, Satish K
2018-06-01
Frequent use of continuous glucose monitoring (CGM) systems is associated with improved glycemic outcomes in persons with diabetes, but the need for calibrations and sensor insertions are often barriers to adoption. In this study, we evaluated the performance of G6, a sixth-generation, factory-calibrated CGM system specified for 10-day wear. The study enrolled participants of ages 6 years and up with type 1 diabetes or insulin-treated type 2 diabetes at 11 sites in the United States. Participation involved one sensor wear period of up to 10 days. Adults wore the system on the abdomen; youth of ages 6-17 years could choose to wear it on the abdomen or upper buttocks. Clinic sessions for frequent comparison with reference blood glucose measurements took place on days 1, 4-5, 7, and/or 10. Participants of ages 13 years and up underwent purposeful supervised glucose manipulation during in-clinic sessions. During the study, participants calibrated the systems once daily. However, analysis was performed on glucose values that were derived from reprocessed raw sensor data, independently of self-monitored blood glucose values used for calibration. Reprocessing used assigned sensor codes and a factory-calibration algorithm. Performance evaluation included the proportion of CGM values that were within ±20% of reference glucose values >100 mg/dL or within ±20 mg/dL of reference glucose values ≤100 mg/dL (%20/20), the analogous %15/15, and the mean absolute relative difference (MARD, expressed as a percentage) between temporally matched CGM and reference values. Data from 262 study participants (21,569 matched CGM reference pairs) were analyzed. The overall %15/15, %20/20, and MARD were 82.4%, 92.3%, and 10.0%, respectively. Matched pairs from 134 adults and 128 youth of ages 6-17 years were similar with respect to %20/20 (92.4% and 91.9%) and MARD (9.9% and 10.1%). Overall %20/20 values on days 1 and 10 of sensor wear were 88.6% and 90.6%, respectively. The system's "Urgent Low Soon" (predictive of hypoglycemia within 20 min) hypoglycemia alert was correctly provided 84% of the time within 30 min before impending biochemical hypoglycemia (<70 mg/dL). The 10-day sensor survival rate was 87%. The new factory-calibrated G6 real-time CGM system provides accurate readings for 10 days and removes several clinical barriers to broader CGM adoption.
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Technology to Reduce Hypoglycemia
Yeoh, Ester; Choudhary, Pratik
2015-01-01
Hypoglycemia is a major barrier toward achieving glycemic targets and is associated with significant morbidity (both psychological and physical) and mortality. This article reviews technological strategies, from simple to more advanced technologies, which may help prevent or mitigate exposure to hypoglycemia. More efficient insulin delivery systems, bolus advisor calculators, data downloads providing information on glucose trends, continuous glucose monitoring with alarms warning of hypoglycemia, predictive algorithms, and finally closed loop insulin delivery systems are reviewed. The building blocks to correct use and interpretation of this range of available technology require patient education and appropriate patient selection. PMID:25883167
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2010-05-01
that believed the delay is ≤10–15 min, 50% believed that insulin can cause changes in the blood (i.e., plasma)-to-ISF glucose gradient. Also, 50% still...by the R01HL88448-1 grant, which seeks to establish safe pediatric euglycemia after cardiac surgery in neonates using continuous glucose monitoring...2062–7. 9. Burge MR, Castillo KR, Schade DS. Meal composition is a determinant of lispro-induced hypoglycemia in IDDM. Diabetes Care. 1997;20(2):152–5
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2004-09-01
identification of the lettered features. 2.2 BFIT Sampling Chip The BFIT sampling chip is a flexible patch-like chip with a multilayer polymeric metal...PPy) and glucose oxidase (GOD). The BFIT fabrication process uses SU8 as a principal structural material consisting of five steps (Figure 2). This...process is a subset of an earlier technology developed for the polymer material PDMS.11,12,13,14,15 The first step was the deposition of a Teflon
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Use of rapid sampling microdialysis for intraoperative monitoring of bowel ischemia.
Deeba, S; Corcoles, E P; Hanna, G B; Hanna, B G; Pareskevas, P; Aziz, O; Boutelle, M G; Darzi, A
2008-09-01
Intestinal ischemia is a major cause of anastomotic leak and death and remains a clinical challenge as the physician relies on several nonspecific signs, biologic markers, and radiologic studies to make the diagnosis. This study used rapid sampling online microdialysis to evaluate the biochemical changes occurring in a segment of human bowel during and after resection, and assessed for the feasibility and reproducibility of this technique in monitoring intestinal ischemia. A custom made, rapid sampling online microdialysis analyzer was used to monitor the changes in the bowel wall of specimens being resected intraoperatively. Two patients were recruited for the pilot study to optimize the analyzer and seven patients undergoing colonic resections were recruited for the data collection and analysis. The concentration of glucose in the extracellular bowel wall fluid decreased transiently after division of individual feeding arteries followed by a rebound increase in the concentration back to baseline concentrations. After completion of resection, glucose concentrations continued to decrease while lactate concentrations increased constantly. Rapid sampling microdialysis was feasible in the clinical environment. These results suggest that tissue responds to ischemic insult by mobilizing glucose stores which later decrease again, whereas lactate concentrations constantly increased.
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Ward, W. Kenneth
2007-01-01
Amperometric sensors for continuous glucose monitoring could prevent acute and chronic complications of diabetes, but research is needed to improve accuracy and stability. In designing sensors, interference from non-glucose analytes can be minimized by use of filtration membranes or electron transfer mediators that allow polarization at low potentials. If oxygen is required for the enzymatic reaction with glucose, then the outer permselective membrane must have substantial oxygen permeability. For this reason, during development of permselective membranes, permeability studies (such as performed by Tipnis and colleagues in this issue) can be used to measure transport of glucose and oxygen and optimize membrane structure. Tipnis and colleagues present a novel biosensor based with separate layers for glucose-oxygen permselectivity, enzymatic conversion, and avoidance of interference. They also address sensor stability, in part by comparing sensor function during ascending vs descending glucose levels. By measuring the difference, they were able to minimize this aspect of instability (hysterisis), which assisted them in selecting a promising permselective membrane based on iron and humic acid. PMID:19888407
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Ward, W Kenneth
2007-03-01
Amperometric sensors for continuous glucose monitoring could prevent acute and chronic complications of diabetes, but research is needed to improve accuracy and stability. In designing sensors, interference from non-glucose analytes can be minimized by use of filtration membranes or electron transfer mediators that allow polarization at low potentials. If oxygen is required for the enzymatic reaction with glucose, then the outer permselective membrane must have substantial oxygen permeability. For this reason, during development of permselective membranes, permeability studies (such as performed by Tipnis and colleagues in this issue) can be used to measure transport of glucose and oxygen and optimize membrane structure. Tipnis and colleagues present a novel biosensor based with separate layers for glucose-oxygen permselectivity, enzymatic conversion, and avoidance of interference. They also address sensor stability, in part by comparing sensor function during ascending vs descending glucose levels. By measuring the difference, they were able to minimize this aspect of instability (hysterisis), which assisted them in selecting a promising permselective membrane based on iron and humic acid.
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Zhang, Yifei; Zhao, Zhiyun; Wang, Shujie; Zhu, Wei; Jiang, Yiran; Sun, Shouyue; Chen, Chen; Wang, Kai; Mu, Liangshan; Cao, Jinyi; Zhou, Yingxia; Gu, Weiqiong; Hong, Jie; Wang, Weiqing; Ning, Guang
2017-10-01
The effect on glucose variability in patients with intensive insulin therapy has not been fully understood. This observational study investigated the different glucose variability and hypoglycaemia patterns in type 2 diabetes patients treated with continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI) with or without metformin administration. During hospitalization, a total of 501 patients with poor glycaemic control and in initial treatment with either CSII alone (n = 187), CSII + Metformin (n = 81), MDI alone (n = 146), or MDI + Metformin (n = 87) were involved in the final analysis. Data obtained from continuous glucose monitoring were used to assess blood glucose fluctuation and nocturnal hypoglycaemia. Among the 4 groups, no difference was found in mean blood glucose levels. Results in parameters reflecting glucose fluctuation: continuous overlapping net glycaemic action in CSII + Metformin and mean amplitude of glycaemic excursions in MDI + Metformin were significantly lower than those in either CSII alone or MDI alone, respectively, even after adjustment (P = .031 and .006). Frequency of nocturnal hypoglycaemia was significantly decreased in CSII + Metformin as compared with CSII alone (0.6% vs 1.8%) and in MDI + Metformin as compared with MDI alone (1.6% vs 2.3%), with the highest frequency observed in MDI alone and the lowest in CSII + Metformin (all between group P < .001). Consistent results were obtained in between-group comparisons for hypoglycaemia duration. Subgroup analysis matched with baseline body mass index, and glycated haemoglobin and fasting blood glucose further confirmed these findings. Metformin added to initial CSII or MDI therapy is associated with a reduction in both glucose fluctuation and nocturnal hypoglycaemic risk in patients with type 2 diabetes. Copyright © 2017 John Wiley & Sons, Ltd.
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Fully integrated biochip platforms for advanced healthcare.
Carrara, Sandro; Ghoreishizadeh, Sara; Olivo, Jacopo; Taurino, Irene; Baj-Rossi, Camilla; Cavallini, Andrea; de Beeck, Maaike Op; Dehollain, Catherine; Burleson, Wayne; Moussy, Francis Gabriel; Guiseppi-Elie, Anthony; De Micheli, Giovanni
2012-01-01
Recent advances in microelectronics and biosensors are enabling developments of innovative biochips for advanced healthcare by providing fully integrated platforms for continuous monitoring of a large set of human disease biomarkers. Continuous monitoring of several human metabolites can be addressed by using fully integrated and minimally invasive devices located in the sub-cutis, typically in the peritoneal region. This extends the techniques of continuous monitoring of glucose currently being pursued with diabetic patients. However, several issues have to be considered in order to succeed in developing fully integrated and minimally invasive implantable devices. These innovative devices require a high-degree of integration, minimal invasive surgery, long-term biocompatibility, security and privacy in data transmission, high reliability, high reproducibility, high specificity, low detection limit and high sensitivity. Recent advances in the field have already proposed possible solutions for several of these issues. The aim of the present paper is to present a broad spectrum of recent results and to propose future directions of development in order to obtain fully implantable systems for the continuous monitoring of the human metabolism in advanced healthcare applications.
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Fully Integrated Biochip Platforms for Advanced Healthcare
Carrara, Sandro; Ghoreishizadeh, Sara; Olivo, Jacopo; Taurino, Irene; Baj-Rossi, Camilla; Cavallini, Andrea; de Beeck, Maaike Op; Dehollain, Catherine; Burleson, Wayne; Moussy, Francis Gabriel; Guiseppi-Elie, Anthony; De Micheli, Giovanni
2012-01-01
Recent advances in microelectronics and biosensors are enabling developments of innovative biochips for advanced healthcare by providing fully integrated platforms for continuous monitoring of a large set of human disease biomarkers. Continuous monitoring of several human metabolites can be addressed by using fully integrated and minimally invasive devices located in the sub-cutis, typically in the peritoneal region. This extends the techniques of continuous monitoring of glucose currently being pursued with diabetic patients. However, several issues have to be considered in order to succeed in developing fully integrated and minimally invasive implantable devices. These innovative devices require a high-degree of integration, minimal invasive surgery, long-term biocompatibility, security and privacy in data transmission, high reliability, high reproducibility, high specificity, low detection limit and high sensitivity. Recent advances in the field have already proposed possible solutions for several of these issues. The aim of the present paper is to present a broad spectrum of recent results and to propose future directions of development in order to obtain fully implantable systems for the continuous monitoring of the human metabolism in advanced healthcare applications. PMID:23112644
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Zueger, Thomas; Diem, Peter; Mougiakakou, Stavroula; Stettler, Christoph
2012-07-01
Data on the influence of calibration on accuracy of continuous glucose monitoring (CGM) are scarce. The aim of the present study was to investigate whether the time point of calibration has an influence on sensor accuracy and whether this effect differs according to glycemic level. Two CGM sensors were inserted simultaneously in the abdomen on either side of 20 individuals with type 1 diabetes. One sensor was calibrated predominantly using preprandial glucose (calibration(PRE)). The other sensor was calibrated predominantly using postprandial glucose (calibration(POST)). At minimum three additional glucose values per day were obtained for analysis of accuracy. Sensor readings were divided into four categories according to the glycemic range of the reference values (low, ≤4 mmol/L; euglycemic, 4.1-7 mmol/L; hyperglycemic I, 7.1-14 mmol/L; and hyperglycemic II, >14 mmol/L). The overall mean±SEM absolute relative difference (MARD) between capillary reference values and sensor readings was 18.3±0.8% for calibration(PRE) and 21.9±1.2% for calibration(POST) (P<0.001). MARD according to glycemic range was 47.4±6.5% (low), 17.4±1.3% (euglycemic), 15.0±0.8% (hyperglycemic I), and 17.7±1.9% (hyperglycemic II) for calibration(PRE) and 67.5±9.5% (low), 24.2±1.8% (euglycemic), 15.5±0.9% (hyperglycemic I), and 15.3±1.9% (hyperglycemic II) for calibration(POST). In the low and euglycemic ranges MARD was significantly lower in calibration(PRE) compared with calibration(POST) (P=0.007 and P<0.001, respectively). Sensor calibration predominantly based on preprandial glucose resulted in a significantly higher overall sensor accuracy compared with a predominantly postprandial calibration. The difference was most pronounced in the hypo- and euglycemic reference range, whereas both calibration patterns were comparable in the hyperglycemic range.
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Soto, Robert J; Schoenfisch, Mark H
2015-06-17
The utility of continuous glucose monitoring devices remains limited by an obstinate foreign body response (FBR) that degrades the analytical performance of the in vivo sensor. A number of novel materials that resist or delay the FBR have been proposed as outer, tissue-contacting glucose sensor membranes as a strategy to improve sensor accuracy. Traditionally, researchers have examined the ability of a material to minimize the host response by assessing adsorbed cell morphology and tissue histology. However, these techniques do not adequately predict in vivo glucose sensor function, necessitating sensor performance evaluation in a relevant animal model prior to human testing. Herein, the effects of critical experimental parameters, including the animal model and data processing methods, on the reliability and usefulness of preclinical sensor performance data are considered. © 2015 Diabetes Technology Society.
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Lomasney, Anna R; Yi, Lian; Roper, Michael G
2013-08-20
A method was developed that allowed simultaneous monitoring of the acute secretory dynamics of insulin and islet amyloid polypeptide (IAPP) from islets of Langerhans using a microfluidic system with two-color detection. A flow-switching feature enabled changes in the perfusion media within 5 s, allowing rapid exchange of the glucose concentrations delivered to groups of islets. The perfusate was continuously sampled by electroosmotic flow and mixed online with Cy5-labeled insulin, fluorescein isothiocyanate (FITC)-labeled IAPP, anti-insulin, and anti-IAPP antibodies in an 8.15 cm mixing channel maintained at 37 °C. The immunoassay mixture was injected for 0.3 s onto a 1.5 cm separation channel at 11.75 s intervals and immunoassay reagents detected using 488 and 635 nm lasers with two independent photomultiplier tubes for detection of the FITC and Cy5 signal. RSD of the bound-to-free immunoassay ratios ranged from 2 to 7% with LODs of 20 nM for insulin and 1 nM for IAPP. Simultaneous secretion profiles of the two peptides were monitored from groups of 4-10 islets during multiple step changes in glucose concentration. Insulin and IAPP were secreted in an approximately 10:1 ratio and displayed similar responses to step changes from 3 to 11 or 20 mM glucose. The ability to monitor the secretory dynamics of multiple peptides from islets of Langerhans in a highly automated fashion is expected to be a useful tool for investigating hormonal regulation of glucose homeostasis.
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Lewis, Kevin R; McCrone, Susan; Deiriggi, Pamela; Bendre, Sachin
2017-01-01
The purpose of this study was to determine the effect of continuous glucose monitoring (CGM) on glycemic control in children, adolescents, and young adults ages 7-21 years with poorly controlled diabetes HbA1c 9.0% or more (74 mmol/mol IFCC). The primary outcome was improvement in HbA1c. The secondary outcome included self-reported hypoglycemia. This 12-week study used a prospective, one-group, pre- and posttest pre-experimental design with a convenience sample. The study used the Medtronic Guardian CGM with Enlite Sensor. Thirty-three subjects enrolled in the study. The mean age of the participants was 15.57 years, range was 11-20 years, 47.6% were male, and 52.4% were female. Twenty-one (63.6%) completed the final study visit. There was a clinically and statistically significant reduction of 1.46 (SD = 1.6711) (p = .001) in HbA1c at 12 weeks. Fifteen of the 21 participants (71.4%) had an HbA1c reduction of greater than 0.5%. The CGM monitor was worn a mean of 4.262 days a week. None of the subjects reported significant hypoglycemia while wearing the monitor. CGM was effective in improving glycemic control in this population with poorly controlled diabetes. © 2016, Wiley Periodicals, Inc.
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Heinemann, Lutz; Boecker, Dirk
2011-01-01
Today, lancing fingertips or alternative sites for obtaining a blood sample for self-monitoring of blood glucose (SMBG) is a standard procedure for most patients with diabetes. The need for frequent lancing and associated discomfort and pain can be seen as a key hurdle for patients to comply with SMBG regimens. This article provides an overview of the status quo and future of lancing, focusing on key areas for future developments driven by customer and market needs. We also review technical issues and provide a background for possible improvements. The act of puncturing the skin with a lancet to obtain a blood sample seems to remain the standard procedure for the foreseeable future, because alternate ways of providing a blood sample have not demonstrated overall superiority (e.g., with laser technology). Other methods, which avoid lancing entirely, have also not gained broad market acceptance (e.g., minimally invasive continuous glucose monitoring) or not shown technical viability (e.g., noninvasive glucose monitoring). In relation to blood glucose (BG) meters and test strips, lancing has been a “stepchild” with regards to commercial attention and development efforts. Nevertheless, significant technological improvements have been made in this field to address key customer needs, including better performance (regarding pain, wound healing, and long-term sensitivity), reduced cost, and higher integration with other components of BG monitoring (e.g., integration of the lancing device with the glucose monitor). From a technical perspective, it is apparent that highly comfortable lancing can be accomplished; however, this still requires fairly advanced and complex devices. New developments are necessary to achieve this level of sophistication and performance with less intricate and costly system designs. Manufacturers' motivation to pursue these developments is compromised by the fact that they might not recoup their development cost on commercial advanced lancing systems through direct profits, but only through its positive influence on adherence and increased more profitable sensor utilization. We believe that two main driving forces will continue to push the evolution of lancing and sampling technology: (1) the need for maximum lancing comfort and (2) the advent of fully integrated systems, realizing a device in which all steps for SMBG are incorporated, thus providing a “one-step” experience. Rendering lancing a “nonissue” will eliminate a key barrier to adherence with appropriate SMBG regimens. Providing sophisticated lancing devices that allow the highest level of comfort and/or seamless blood sampling is key to improving user acceptance. This may have a greater impact on metabolic control than many of the new and expensive antidiabetic drugs. PMID:21880240
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Metabolic Biofouling of Glucose Sensors in Vivo: Role of Tissue Microhemorrhages
Klueh, Ulrike; Liu, Zenghe; Feldman, Ben; Henning, Timothy P; Cho, Brian; Ouyang, Tianmei; Kreutzer, Don
2011-01-01
Objective: Based on our in vitro study that demonstrated the adverse effects of blood clots on glucose sensor function, we hypothesized that in vivo local tissue hemorrhages, induced as a consequence of sensor implantation or sensor movement post-implantation, are responsible for unreliable readings or an unexplained loss of functionality shortly after implantation. Research Design and Methods: To investigate this issue, we utilized real-time continuous monitoring of blood glucose levels in a mouse model. Direct injection of blood at the tissue site of sensor implantation was utilized to mimic sensor-induced local tissue hemorrhages. Results: It was found that blood injections, proximal to the sensor, consistently caused lowered sensor glucose readings, designated temporary signal reduction, in vivo in our mouse model, while injections of plasma or saline did not have this effect. Conclusion: These results support our hypothesis that tissue hemorrhage and resulting blood clots near the sensor can result in lowered local blood glucose concentrations due to metabolism of glucose by the clot. The lowered local blood glucose concentration led to low glucose readings from the still functioning sensor that did not reflect the systemic glucose level. PMID:21722574
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Effects of non-nutritive (artificial vs natural) sweeteners on 24-h glucose profiles.
Tey, S L; Salleh, N B; Henry, C J; Forde, C G
2017-09-01
Replacing nutritive sweetener with non-nutritive sweeteners (NNS) has the potential to improve glycaemic control. The objective of this study was to investigate the effects of consuming artificial NNS (that is, aspartame), natural NNS (that is, monk fruit and stevia), and sucrose-sweetened beverages on 24-h glucose profiles. Ten healthy males took part in this randomised, crossover study with the following four treatments: aspartame-, monk fruit-, stevia-, and sucrose- (65 g) sweetened beverages. Participants were asked to consume the test beverage as a preload mid-morning. Medtronic iPro2 continuous glucose monitoring system was used to measure mean 24-h glucose, incremental area under the curve (iAUC) and total area under the curve (AUC) for glucose, and 24-h glycaemic variability. Overall no significant differences were found in mean 24-h glucose, iAUC and total AUC for glucose, and 24-h glycaemic variability between the four test beverages. Twenty-four-hour glucose profiles did not differ between beverages sweetened with non-nutritive (artificial vs natural) and nutritive sweeteners. The simple exchange of a single serving of sucrose-sweetened beverage with NNS over a day appears to have minimal effect on 24-h glucose profiles in healthy males.
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Implantable biosensors: analysis of fluorescent light propagation through skin
NASA Astrophysics Data System (ADS)
O'Neal, D. P.; McShane, Michael J.; Pishko, Michael V.; Cote, Gerard L.
2001-06-01
Progress towards a painless and hygienic glucose monitoring procedure for diabetics continues as the growth of diabetes mellitus reaches epidemic proportions in the American population. Utilizing an implantable fluorescence based glucose assay, the minimally invasive approach presented here has previously shown promise towards this goal in terms of glucose specificity and quantification for in vitro environments. However, in realistic physiological circumstances the depth of the implant can vary and optical properties of skin can change due to normal physiological conditions. Additionally, naturally occurring auto-fluorescence can obscure the sensor signal. An important concern under these conditions is that variations of fluorescent intensity due to these or other causes might be mistaken for glucose concentration fluctuations. New data shows that fluorescence-based glucose assays can be probed and interpreted in terms of glucose concentrations through pig skin at depths of up to 700 mm when immobilized in a bio-compatible polymer. When a combination of two fluorophores are employed as demonstrated here, reasonable changes in skin thickness and the confounding effects of the variations inherent in skin can be overcome for this glucose sensing application.
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Kaplan, Walid; Afandi, Bachar; Al Hassani, Noura; Hadi, Suha; Zoubeidi, Taoufik
2017-12-01
To assess the impact of fasting on interstitial glucose (IG) in adolescents with type 1 DM (T1DM) by using continuous glucose monitoring (CGM). A minimum of 2.5 days CGM was done on adolescents with T1DM during fasting in Ramadan and in the month before or after Ramadan to compare the differences in mean IG, and in the durations of hypoglycemia (<70 mg/dL), hyperglycemia (200-299 mg/dL), and severe hyperglycemia (≥300 mg/dL). Fourteen adolescents were studied, age 15 ± 4 years, duration of diabetes 6 ± 4 years, and HbA1C 8.6 ± 1.1% (70.3 mmol/mol). There was no difference in the mean IG (190 ± 39 and 180 ± 37, p= 0.4), or in the durations of hypoglycemia (5.14 ± 5% and 7.03 ± 4.9%, p=0.3), hyperglycemia (25.35 ± 11.3% and 24.24 ± 10.1% (P=0.7)), and severe hyperglycemia (13.21 ± 13.4% and 10.96 ± 10.6%, P=0.6), between Ramadan and, non-Ramadan, respectively. Adolescents with T1DM have the same wide fluctuation in IG during fasting in Ramadan as they do outside Ramadan. Insulin regimen adjustment should be targeting both extremes of glucose abnormality. Copyright © 2017 Elsevier B.V. All rights reserved.
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Use of an Intravascular Fluorescent Continuous Glucose Sensor in ICU Patients.
Strasma, Paul J; Finfer, Simon; Flower, Oliver; Hipszer, Brian; Kosiborod, Mikhail; Macken, Lewis; Sechterberger, Marjolein; van der Voort, Peter H J; DeVries, J Hans; Joseph, Jeffrey I
2015-07-01
Hyperglycemia and hypoglycemia are associated with adverse clinical outcomes in intensive care patients. In product development studies at 4 ICUs, the safety and performance of an intravascular continuous glucose monitoring (IV-CGM) system was evaluated in 70 postsurgical patients. The GluCath System (GluMetrics, Inc) used a quenched chemical fluorescence mechanism to optically measure blood glucose when deployed via a radial artery catheter or directly into a peripheral vein. Periodic ultrasound assessed blood flow and thrombus formation. Patient glucose levels were managed according to the standard of care and existing protocols at each site. Reference blood samples were acquired hourly and compared against prospectively calibrated sensor results. In all, 63 arterial sensors and 9 venous sensors were deployed in 70 patients. Arterial sensors did not interfere with invasive blood pressure monitoring, sampling or other aspects of patient care. A majority of venous sensors (66%) exhibited thrombus on ultrasound. In all, 89.4% (1383/1547) of arterial and 72.2% (182/252) of venous measurements met ISO15197:2003 criteria (within 20%), and 72.7% (1124/1547) of arterial and 56.3% (142/252) of venous measurements met CLSI POCT 12-A3 criteria (within 12.5%). The aggregate mean absolute relative difference (MARD) between the sensors and the reference was 9.6% for arterial and 14.2% for venous sensors. The GluCath System exhibited acceptable accuracy when deployed in a radial artery for up to 48 hours in ICU patients after elective cardiac surgery. Accuracy of venous deployment was substantially lower with significant rates of intravascular thrombus observed using ultrasound. © 2015 Diabetes Technology Society.
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Koyanagawa, Naohide; Miyoshi, Hideaki; Ono, Kota; Nakamura, Akinobu; Cho, Kyu Yong; Yamamoto, Kohei; Takano, Yoshinari; Dan-Noura, Midori; Atsumi, Tatsuya
2016-08-31
The dipeptidyl peptidase-4 inhibitors vildagliptin and sitagliptin are effective in treating patients with type 2 diabetes mellitus. Patients receiving standard doses of sitagliptin plus insulin may require increased doses of sitagliptin or switching to vildagliptin to improve blood glucose control. This study compared the effects of increasing sitagliptin and switching to vildagliptin in type 2 diabetes patients receiving standard doses of sitagliptin plus insulin. This prospective, randomized, parallel-group comparison trial enrolled 33 type 2 diabetes patients receiving 50 mg sitagliptin once daily plus insulin. Seventeen patients were randomized to 50 mg vildagliptin twice daily, and 16 to 100 mg sitagliptin once daily, and evaluated by continuous glucose monitoring at baseline and after 8 weeks. The primary end-point was the change in mean amplitude of glycemic excursions (MAGE). MAGE decreased from baseline in both the vildagliptin (-13.4 ± 35.7 mg/dL) and sitagliptin (-8.4 ± 24.3 mg/dL) groups, but neither within- nor between-group changes were statistically significant. Similarly, the areas under the curve for blood glucose levels ≥180 mg/dL and <70 mg/dL tended to improve in both groups, but these differences were not statistically significant. In contrast, HbA1c was significantly reduced only in the vildagliptin group, from 7.1 ± 0.6% at baseline to 6.8 ± 0.6% at 8 weeks (p=0.006). Increasing sitagliptin dose and switching to vildagliptin had limited effects in improving MAGE in type 2 diabetic patients treated with standard doses of sitagliptin.
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Jensen, Morten Hasselstrøm; Christensen, Toke Folke; Tarnow, Lise; Seto, Edmund; Dencker Johansen, Mette; Hejlesen, Ole Kristian
2013-07-01
Hypoglycemia is a potentially fatal condition. Continuous glucose monitoring (CGM) has the potential to detect hypoglycemia in real time and thereby reduce time in hypoglycemia and avoid any further decline in blood glucose level. However, CGM is inaccurate and shows a substantial number of cases in which the hypoglycemic event is not detected by the CGM. The aim of this study was to develop a pattern classification model to optimize real-time hypoglycemia detection. Features such as time since last insulin injection and linear regression, kurtosis, and skewness of the CGM signal in different time intervals were extracted from data of 10 male subjects experiencing 17 insulin-induced hypoglycemic events in an experimental setting. Nondiscriminative features were eliminated with SEPCOR and forward selection. The feature combinations were used in a Support Vector Machine model and the performance assessed by sample-based sensitivity and specificity and event-based sensitivity and number of false-positives. The best model was composed by using seven features and was able to detect 17 of 17 hypoglycemic events with one false-positive compared with 12 of 17 hypoglycemic events with zero false-positives for the CGM alone. Lead-time was 14 min and 0 min for the model and the CGM alone, respectively. This optimized real-time hypoglycemia detection provides a unique approach for the diabetes patient to reduce time in hypoglycemia and learn about patterns in glucose excursions. Although these results are promising, the model needs to be validated on CGM data from patients with spontaneous hypoglycemic events.
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Continuous Glucose Monitoring in Newborn Infants
Thomas, Felicity; Signal, Mathew; Harris, Deborah L.; Weston, Philip J.; Harding, Jane E.; Shaw, Geoffrey M.
2014-01-01
Neonatal hypoglycemia is common and can cause serious brain injury. Continuous glucose monitoring (CGM) could improve hypoglycemia detection, while reducing blood glucose (BG) measurements. Calibration algorithms use BG measurements to convert sensor signals into CGM data. Thus, inaccuracies in calibration BG measurements directly affect CGM values and any metrics calculated from them. The aim was to quantify the effect of timing delays and calibration BG measurement errors on hypoglycemia metrics in newborn infants. Data from 155 babies were used. Two timing and 3 BG meter error models (Abbott Optium Xceed, Roche Accu-Chek Inform II, Nova Statstrip) were created using empirical data. Monte-Carlo methods were employed, and each simulation was run 1000 times. Each set of patient data in each simulation had randomly selected timing and/or measurement error added to BG measurements before CGM data were calibrated. The number of hypoglycemic events, duration of hypoglycemia, and hypoglycemic index were then calculated using the CGM data and compared to baseline values. Timing error alone had little effect on hypoglycemia metrics, but measurement error caused substantial variation. Abbott results underreported the number of hypoglycemic events by up to 8 and Roche overreported by up to 4 where the original number reported was 2. Nova results were closest to baseline. Similar trends were observed in the other hypoglycemia metrics. Errors in blood glucose concentration measurements used for calibration of CGM devices can have a clinically important impact on detection of hypoglycemia. If CGM devices are going to be used for assessing hypoglycemia it is important to understand of the impact of these errors on CGM data. PMID:24876618
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Prabhudesai, Sumant; Kanjani, Amruta; Bhagat, Isha; Ravikumar, Karnam G; Ramachandran, Bala
2015-11-01
The aim of this prospective, observational study was to determine the accuracy of a real-time continuous glucose monitoring system (CGMS) in children with septic shock. Children aged 30 days to 18 years admitted to the Pediatric Intensive Care Unit with septic shock were included. A real-time CGMS sensor was used to obtain interstitial glucose readings. CGMS readings were compared statistically with simultaneous laboratory blood glucose (BG). Nineteen children were included, and 235 pairs of BG-CGMS readings were obtained. BG and CGMS had a correlation coefficient of 0.61 (P < 0.001) and a median relative absolute difference of 17.29%. On Clarke's error grid analysis, 222 (94.5%) readings were in the clinically acceptable zones (A and B). When BG was < 70, 70-180, and > 180 mg/dL, 44%, 100%, and 76.9% readings were in zones A and B, respectively (P < 0.001). The accuracy of CGMS was not affected by the presence of edema, acidosis, vasopressors, steroids, or renal replacement therapy. On receiver operating characteristics curve analysis, a CGMS reading <97 mg/dL predicted hypoglycemia (sensitivity 85.2%, specificity 75%, area under the curve [AUC] =0.85). A reading > 141 mg/dL predicted hyperglycemia (sensitivity 84.6%, specificity 89.6%, AUC = 0.87). CGMS provides a fairly, accurate estimate of BG in children with septic shock. It is unaffected by a variety of clinical variables. The accuracy over extremes of blood sugar may be a concern. We recommend larger studies to evaluate its use for the early detection of hypoglycemia and hyperglycemia.
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Chaugule, Shraddha; Graham, Claudia
2017-11-01
To evaluate the cost-effectiveness of real-time continuous glucose monitoring (CGM) compared to self-monitoring of blood glucose (SMBG) alone in people with type 1 diabetes (T1DM) using multiple daily injections (MDI) from the Canadian societal perspective. The IMS CORE Diabetes Model (v.9.0) was used to assess the long-term (50 years) cost-effectiveness of real-time CGM (G5 Mobile CGM System; Dexcom, Inc., San Diego, CA) compared with SMBG alone for a cohort of adults with poorly-controlled T1DM. Treatment effects and baseline characteristics of patients were derived from the DIAMOND randomized controlled clinical trial; all other assumptions and costs were sourced from published research. The accuracy and clinical effectiveness of G5 Mobile CGM is the same as the G4 Platinum CGM used in the DIAMOND randomized clinical trial. Base case assumptions included (a) baseline HbA1c of 8.6%, (b) change in HbA1c of -1.0% for CGM users vs -0.4% for SMBG users, and (c) disutilities of -0.0142 for non-severe hypoglycemic events (NSHEs) and severe hypoglycemic events (SHEs) not requiring medical intervention, and -0.047 for SHEs requiring medical resources. Treatment costs and outcomes were discounted at 1.5% per year. The incremental cost-effectiveness ratio for the base case G5 Mobile CGM vs SMBG was $33,789 CAD/quality-adjusted life-year (QALY). Sensitivity analyses showed that base case results were most sensitive to changes in percentage reduction in hypoglycemic events and disutilities associated with hypoglycemic events. The base case results were minimally impacted by changes in baseline HbA1c level, incorporation of indirect costs, changes in the discount rate, and baseline utility of patients. The results of this analysis demonstrate that G5 Mobile CGM is cost-effective within the population of adults with T1DM using MDI, assuming a Canadian willingness-to-pay threshold of $50,000 CAD per QALY.
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Real-time continuous glucose monitoring systems in the classroom/school environment.
Benassi, Kari; Drobny, Jessica; Aye, Tandy
2013-05-01
Children with type 1 diabetes (T1D) spend 4-7 h/day in school with very little supervision of their diabetes management. Therefore, families have become more dependent on technology, such as use of real-time continuous glucose monitoring (RT-CGM), to provide increased supervision of their diabetes management. We sought to assess the impact of RT-CGM use in the classroom/school environment. Children with T1D using RT-CGM, their parents, and teachers completed a questionnaire about RT-CGM in the classroom/school environment. The RT-CGM was tolerated well in the classroom/school environment. Seventy percent of parents, 75% of students, and 51% of teachers found RT-CGM useful in the classroom/school environment. The students found the device to be more disruptive than did their parents and teachers. However, all three groups agreed that RT-CGM increased their comfort with diabetes management at school. Our study suggests that RT-CGM is useful and not disruptive in the classroom/school environment. The development of education materials for teachers could further increase its acceptance in the classroom/school environment.
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Assessing sensor accuracy for non-adjunct use of continuous glucose monitoring.
Kovatchev, Boris P; Patek, Stephen D; Ortiz, Edward Andrew; Breton, Marc D
2015-03-01
The level of continuous glucose monitoring (CGM) accuracy needed for insulin dosing using sensor values (i.e., the level of accuracy permitting non-adjunct CGM use) is a topic of ongoing debate. Assessment of this level in clinical experiments is virtually impossible because the magnitude of CGM errors cannot be manipulated and related prospectively to clinical outcomes. A combination of archival data (parallel CGM, insulin pump, self-monitoring of blood glucose [SMBG] records, and meals for 56 pump users with type 1 diabetes) and in silico experiments was used to "replay" real-life treatment scenarios and relate sensor error to glycemic outcomes. Nominal blood glucose (BG) traces were extracted using a mathematical model, yielding 2,082 BG segments each initiated by insulin bolus and confirmed by SMBG. These segments were replayed at seven sensor accuracy levels (mean absolute relative differences [MARDs] of 3-22%) testing six scenarios: insulin dosing using sensor values, threshold, and predictive alarms, each without or with considering CGM trend arrows. In all six scenarios, the occurrence of hypoglycemia (frequency of BG levels ≤50 mg/dL and BG levels ≤39 mg/dL) increased with sensor error, displaying an abrupt slope change at MARD =10%. Similarly, hyperglycemia (frequency of BG levels ≥250 mg/dL and BG levels ≥400 mg/dL) increased and displayed an abrupt slope change at MARD=10%. When added to insulin dosing decisions, information from CGM trend arrows, threshold, and predictive alarms resulted in improvement in average glycemia by 1.86, 8.17, and 8.88 mg/dL, respectively. Using CGM for insulin dosing decisions is feasible below a certain level of sensor error, estimated in silico at MARD=10%. In our experiments, further accuracy improvement did not contribute substantively to better glycemic outcomes.
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Assessing Sensor Accuracy for Non-Adjunct Use of Continuous Glucose Monitoring
Patek, Stephen D.; Ortiz, Edward Andrew; Breton, Marc D.
2015-01-01
Abstract Background: The level of continuous glucose monitoring (CGM) accuracy needed for insulin dosing using sensor values (i.e., the level of accuracy permitting non-adjunct CGM use) is a topic of ongoing debate. Assessment of this level in clinical experiments is virtually impossible because the magnitude of CGM errors cannot be manipulated and related prospectively to clinical outcomes. Materials and Methods: A combination of archival data (parallel CGM, insulin pump, self-monitoring of blood glucose [SMBG] records, and meals for 56 pump users with type 1 diabetes) and in silico experiments was used to “replay” real-life treatment scenarios and relate sensor error to glycemic outcomes. Nominal blood glucose (BG) traces were extracted using a mathematical model, yielding 2,082 BG segments each initiated by insulin bolus and confirmed by SMBG. These segments were replayed at seven sensor accuracy levels (mean absolute relative differences [MARDs] of 3–22%) testing six scenarios: insulin dosing using sensor values, threshold, and predictive alarms, each without or with considering CGM trend arrows. Results: In all six scenarios, the occurrence of hypoglycemia (frequency of BG levels ≤50 mg/dL and BG levels ≤39 mg/dL) increased with sensor error, displaying an abrupt slope change at MARD =10%. Similarly, hyperglycemia (frequency of BG levels ≥250 mg/dL and BG levels ≥400 mg/dL) increased and displayed an abrupt slope change at MARD=10%. When added to insulin dosing decisions, information from CGM trend arrows, threshold, and predictive alarms resulted in improvement in average glycemia by 1.86, 8.17, and 8.88 mg/dL, respectively. Conclusions: Using CGM for insulin dosing decisions is feasible below a certain level of sensor error, estimated in silico at MARD=10%. In our experiments, further accuracy improvement did not contribute substantively to better glycemic outcomes. PMID:25436913
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Liu, Yong; Wang, Limin; Pang, Richard; Mo, Nanxun; Hu, Yan; Deng, Qian; Hu, Zhaohui
2015-05-01
The aim of this paper is to describe the designing and implementation of a web-based plasma glucose measurement quality monitoring system to assess the analytical quality of plasma glucose measurements in multicenter population study and provide evidence for the future studies. In the chronic non-communicable disease and related factor surveillance in China, a web based quality monitoring system for plasma glucose measurement was established to conduct evaluation on plasma glucose monitoring quality and effectiveness in 302 surveillance centers, including quality control data entry, transmission and feedback. The majority of the surveillance centers met the quality requirements and passed the evaluation of reproducibility and precision of plasma glucose measurement, only a few centers required intensive training and re-assessment. In order to ensure the completeness and reliability of plasma glucose measurement in the surveillance centers, the establishment of web-based plasma glucose measurement quality control system can facilitate the identification of the qualified surveillance centers and evaluation of plasma glucose measurement quality in different regions. Communication and training are important in ensuring plasma glucose measurement quality. It is necessary to further improve this web-based plasma glucose measurement quality monitoring system in the future to reduce the method specific plasma glucose measurement bias.
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Yates, Christopher J; Fourlanos, Spiros; Colman, Peter G; Cohney, Solomon J
2014-03-01
Prednisolone is a major risk factor for hyperglycaemia and new-onset diabetes after transplantation. Uncontrolled observational data suggest that divided dosing may reduce requirements for hypoglycaemic agents. This study aims to compare the glycaemic effects of divided twice daily (BD) and once daily (QD) prednisolone. Twenty-two kidney transplant recipients without diabetes were randomized to BD or QD prednisolone. Three weeks post-transplant, a continuous glucose monitor (iPro2(®) Medtronic) was applied for 5 days with subjects continuing their initial prednisolone regimen (Days 1-2) before crossover to the alternative regimen. Mean glucose, peak glucose, nadir glucose, exposure to hyperglycaemia (glucose ≥7.8 mmol/L) and glycaemic variability were assessed. The mean ± standard deviation (SD) age of subjects was 50 ± 10 years and 77% were male. Median (interquartile range) daily prednisolone dose was 25 (20, 25) mg. BD prednisolone was associated with decreased mean glucose (mean 7.9 ± 1.7 versus 8.1 ± 2.3 mmol/L, P < 0.001), peak glucose [median 10.4 (9.5, 11.4) versus 11.4 (10.3, 13.4) mmol/L, P< 0.001] and exposure to hyperglycaemia [median 25.5 (14.6, 30.3) versus 40.4 (33.2, 51.2) mmol/L/h, P = 0.003]. Median glucose peaked between 14:55-15.05 h with BD and 15:25-15:30 h with QD. Median glycaemic variability scores were decreased with BD: SD (1.1 versus 1.9, P < 0.001), mean amplitude of glycaemic excursion (1.5 versus 2.2, P = 0.001), continuous overlapping net glycaemic action-1 (CONGA-1; 1.0 versus 1.2, P = 0.039), CONGA-2 (1.2 versus 1.4, P = 0.008) and J-index (25 versus 31, P = 0.003). Split prednisolone dosing reduces glycaemic variability and hyperglycaemia early post-kidney transplant.
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NASA Astrophysics Data System (ADS)
Tanaka, Y.; Tajima, T.; Seyama, M.
2018-02-01
We propose a differential photoacoustic spectroscopy (PAS), wherein two wavelengths of light with the same absorbance are selected, and differential signal is linearized by one of the two signals for a non-invasive blood glucose monitoring. PAS has the possibility to overcome the strong optical scattering in tissue, but there are still remaining issues: the water background and instability due to the variation in acoustic resonance conditions. A change in sample solution temperature is one of the causes of the variation in acoustic resonance conditions. Therefore, in this study, we investigated the sensitivity against glucose concentration under the condition where the temperature of the sample water solution ranges 30 to 40 °C. The glucose concentration change is simulated by shifting the wavelength of irradiated laser light, which can effectively change optical absorption. The temperature also affects optical absorption and the acoustic resonance condition (acoustic velocity). A distributed-feedback (DFB) laser, tunable wavelength laser (TWL) and an acoustic sensor were used to obtain the differential PAS signal. The wavelength of the DFB laser was 1.382 μm, and that of TWL was switched from 1.600 to 1.610 μm to simulate the glucose concentration change. Optical absorption by glucose occurs at around 1.600 μm. The sensitivities against temperature are almost the same: 1.9 and 1.8 %/°C for 1.600 and 1.610 μm. That is, the glucose dependence across the whole temperature range remains constant. This implies that temperature correction is available.
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Park, Hyun Sang; Cho, Hune; Kim, Hwa Sun
2015-04-01
The objectives of this research were to develop and evaluate a cell phone application based on the standard protocol for personal health devices and the standard information model for personal health records to support effective blood glucose management and standardized service for patients with diabetes. An application was developed for Android 4.0.3. In addition, an IEEE 11073 Manager, Medical Device Encoding Rule, and Bluetooth Health Device Profile Connector were developed for standardized health communication with a glucometer, and a Continuity of Care Document (CCD) Composer and CCD Parser were developed for CCD document exchange. The developed application was evaluated by five healthcare professionals and 87 users through a questionnaire comprising the following variables: usage intention, effort expectancy, social influence, facilitating condition, perceived risk, and voluntariness. As a result of the evaluation of usability, it was confirmed that the developed application is useful for blood glucose self-monitoring by diabetic patients. In particular, the healthcare professionals stated their own views that the application is useful to observe the trends in blood glucose change through the automatic function which records a blood glucose level measured using Bluetooth function, and the function which checks accumulated records of blood glucose levels. Also, a result of the evaluation of usage intention was 3.52 ± 0.42 out of 5 points. The application developed by our research team was confirmed by the verification of healthcare professionals that accurate feedback can be provided to healthcare professionals during the management of diabetic patients or education for glucose management.
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Park, Hyun Sang; Cho, Hune
2015-01-01
Objectives The objectives of this research were to develop and evaluate a cell phone application based on the standard protocol for personal health devices and the standard information model for personal health records to support effective blood glucose management and standardized service for patients with diabetes. Methods An application was developed for Android 4.0.3. In addition, an IEEE 11073 Manager, Medical Device Encoding Rule, and Bluetooth Health Device Profile Connector were developed for standardized health communication with a glucometer, and a Continuity of Care Document (CCD) Composer and CCD Parser were developed for CCD document exchange. The developed application was evaluated by five healthcare professionals and 87 users through a questionnaire comprising the following variables: usage intention, effort expectancy, social influence, facilitating condition, perceived risk, and voluntariness. Results As a result of the evaluation of usability, it was confirmed that the developed application is useful for blood glucose self-monitoring by diabetic patients. In particular, the healthcare professionals stated their own views that the application is useful to observe the trends in blood glucose change through the automatic function which records a blood glucose level measured using Bluetooth function, and the function which checks accumulated records of blood glucose levels. Also, a result of the evaluation of usage intention was 3.52 ± 0.42 out of 5 points. Conclusions The application developed by our research team was confirmed by the verification of healthcare professionals that accurate feedback can be provided to healthcare professionals during the management of diabetic patients or education for glucose management. PMID:25995960
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Effect of dietary protein on post-prandial glucose in patients with type 1 diabetes.
Borie-Swinburne, C; Sola-Gazagnes, A; Gonfroy-Leymarie, C; Boillot, J; Boitard, C; Larger, E
2013-12-01
In flexible insulin therapy, determination of the prandial insulin dose only takes into account the carbohydrate content of the evening meal, and not the protein content. Protein can, however, contribute to gluconeogenesis. We compared the glycaemic effect of a standard evening meal with that of a test evening meal enriched in protein. The present study was conducted in 28 C-peptide negative patients with type 1 diabetes. Two evening meals that were similar in content, except that one was enriched by the addition of 300 g of 0%-fat fromage frais, were taken on two consecutive days. Insulin doses were maintained exactly the same before both evening meals. Patients were monitored with a continuous glucose-monitoring device. Patients ate similar quantities at both evening meals, except for protein (21.5 g more at the test evening meal). The preprandial insulin dose was 0.96 (0.4) U per 10 g carbohydrates. After correction for differences of interstitial glucose at the start of the evening meals, both interstitial and capillary glucose levels were similar after both evening meals, except for the late-post-prandial interstitial glucose level. We found no effect of dietary protein on post-prandial-, overnight- or late-night glucose levels in patients with type 1 diabetes. This confirms that dietary proteins need not be included in the calculation of prandial insulin dose. © 2013 The Authors Journal of Human Nutrition and Dietetics © 2013 The British Dietetic Association Ltd.
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Bertachi, Arthur; Quirós, Carmen; Giménez, Marga; Conget, Ignacio; Bondia, Jorge
2018-01-01
Continuous glucose monitoring (CGM) plays an important role in treatment decisions for patients with type 1 diabetes under conventional or closed-loop therapy. Physical activity represents a great challenge for diabetes management as well as for CGM systems. In this work, the accuracy of CGM in the context of exercise is addressed. Six adults performed aerobic and anaerobic exercise sessions and used two Medtronic Paradigm Enlite-2 sensors under closed-loop therapy. CGM readings were compared with plasma glucose during different periods: one hour before exercise, during exercise, and four hours after the end of exercise. In aerobic sessions, the median absolute relative difference (MARD) increased from 9.5% before the beginning of exercise to 16.5% during exercise (p < 0.001), and then decreased to 9.3% in the first hour after the end of exercise (p < 0.001). For the anaerobic sessions, the MARD before exercise was 15.5% and increased without statistical significance to 16.8% during exercise realisation (p = 0.993), and then decreased to 12.7% in the first hour after the cessation of anaerobic activities (p = 0.095). Results indicate that CGM might present lower accuracy during aerobic exercise, but return to regular operation a few hours after exercise cessation. No significant impact for anaerobic exercise was found. PMID:29522429
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Biagi, Lyvia; Bertachi, Arthur; Quirós, Carmen; Giménez, Marga; Conget, Ignacio; Bondia, Jorge; Vehí, Josep
2018-03-09
Continuous glucose monitoring (CGM) plays an important role in treatment decisions for patients with type 1 diabetes under conventional or closed-loop therapy. Physical activity represents a great challenge for diabetes management as well as for CGM systems. In this work, the accuracy of CGM in the context of exercise is addressed. Six adults performed aerobic and anaerobic exercise sessions and used two Medtronic Paradigm Enlite-2 sensors under closed-loop therapy. CGM readings were compared with plasma glucose during different periods: one hour before exercise, during exercise, and four hours after the end of exercise. In aerobic sessions, the median absolute relative difference (MARD) increased from 9.5% before the beginning of exercise to 16.5% during exercise ( p < 0.001), and then decreased to 9.3% in the first hour after the end of exercise ( p < 0.001). For the anaerobic sessions, the MARD before exercise was 15.5% and increased without statistical significance to 16.8% during exercise realisation ( p = 0.993), and then decreased to 12.7% in the first hour after the cessation of anaerobic activities ( p = 0.095). Results indicate that CGM might present lower accuracy during aerobic exercise, but return to regular operation a few hours after exercise cessation. No significant impact for anaerobic exercise was found.
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Pemberton, R M; Xu, J; Pittson, R; Drago, G A; Griffiths, J; Jackson, S K; Hart, J P
2011-01-15
Microband biosensors, screen-printed from a water-based carbon ink containing cobalt phthalocyanine redox mediator and glucose oxidase (GOD) enzyme, were used to monitor glucose levels continuously in buffer and culture medium. Five biosensors were operated amperometrically (E(app) of +0.4V), in a 12-well tissue culture plate system at 37°C, using a multipotentiostat. After 24 h, a linear calibration plot was obtained from steady-state current responses for glucose concentrations up to 10 mM (dynamic range 30 mM). Within the linear region, a correlation coefficient (R(2)) of 0.981 was obtained between biosensor and spectrophotometric assays. Over 24 h, an estimated 0.15% (89 nmol) of the starting glucose concentration (24 mM) was consumed by the microbiosensor. The sensitivity of the biosensor response in full culture medium was stable between pHs 7.3 and 8.4. Amperometric responses for HepG2 monolayer cultures decreased with time in inverse proportionality to cell number (for 0 to 10(6) cell/ml), as glucose was being metabolised. HepG2 3D cultures (spheroids) were also shown to metabolise glucose, at a rate which was independent of spheroid age (between 6 and 15 days). Spheroids were used to assay the effect of a typical hepatotoxin, paracetamol. At 1 mM paracetamol, glucose uptake was inhibited by 95% after 6 h in culture; at 500 μM, around 15% inhibition was observed after 16 h. This microband biosensor culture system could form the basis for an in vitro toxicity testing system. Copyright © 2010 Elsevier B.V. All rights reserved.
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Little, Stuart A; Speight, Jane; Leelarathna, Lalantha; Walkinshaw, Emma; Tan, Horng Kai; Bowes, Anita; Lubina-Solomon, Alexandra; Chadwick, Thomas J; Stocken, Deborah D; Brennand, Catherine; Marshall, Sally M; Wood, Ruth; Kerr, David; Flanagan, Daniel; Heller, Simon R; Evans, Mark L; Shaw, James A M
2018-04-16
Severe hypoglycemia is a feared complication of type 1 diabetes; yet, few trials have targeted prevention using optimized self-management (educational, therapeutic, and technological support). We aimed to investigate whether improved awareness and reduced severe hypoglycemia, achieved during an intensive randomized clinical trial (RCT), were sustained after return to routine care. Ninety-six adults with type 1 diabetes (29 ± 12 years' duration) and impaired awareness of hypoglycemia at five U.K. tertiary referral diabetes centers were recruited into a 24-week 2 × 2 factorial RCT (HypoCOMPaSS). Participants were randomized to pump (continuous subcutaneous insulin infusion [CSII]) or multiple daily injections (MDIs) and real-time continuous glucose monitoring (RT-CGM) or self-monitoring of blood glucose (SMBG), with equal education/attention to all groups. At 24 weeks, participants returned to routine care with follow-up until 24 months, including free choice of MDI/CSII; RT-CGM vs. SMBG comparison continued to 24 months. Primary outcome was mean difference (baseline to 24 months [between groups]) in hypoglycemia awareness. Improvement in hypoglycemia awareness was sustained (Gold score at baseline 5.1 ± 1.1 vs. 24 months 3.7 ± 1.9; P < 0.0001). Severe hypoglycemia rate was reduced from 8.9 ± 12.8 episodes/person-year over the 12 months prestudy to 0.4 ± 0.8 over 24 months ( P < 0.0001). HbA 1c improved (baseline 8.2 ± 3.2% [66 ± 12 mmol/mol] vs. 24 months 7.7 ± 3.1% [61 ± 10 mmol/mol]; P = 0.003). Improvement in treatment satisfaction and reduced fear of hypoglycemia were sustained. There were no significant differences between interventions at 24 months. Optimized insulin replacement and glucose monitoring underpinned by hypoglycemia-focused structured education should be provided to all with type 1 diabetes complicated by impaired awareness of hypoglycemia. © 2018 by the American Diabetes Association.
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Glucose-responsive insulin delivery for type 1 diabetes: The artificial pancreas story.
Bally, Lia; Thabit, Hood; Hovorka, Roman
2018-06-15
Insulin replacement therapy is integral to the management of type 1 diabetes, which is characterised by absolute insulin deficiency. Optimal glycaemic control, as assessed by glycated haemoglobin, and avoidance of hyper- and hypoglycaemic excursions have been shown to prevent diabetes-related complications. Insulin pump use has increased considerably over the past decade with beneficial effects on glycaemic control, quality of life and treatment satisfaction. The advent and progress of ambulatory glucose sensor technology has enabled continuous glucose monitoring based on real-time glucose levels to be integrated with insulin therapy. Low glucose and predictive low glucose suspend systems are currently used in clinical practice to mitigate against hypoglycaemia, and provide the first step towards feedback glucose control. The more advanced technology approach, an artificial pancreas or a closed-loop system, gradually increases and decreases insulin delivery in a glucose-responsive fashion to mitigate against hyper- and hypoglycaemia. Randomised outpatient clinical trials over the past 5 years have demonstrated the feasibility, safety and efficacy of the approach, and the recent FDA approval of the first single hormone closed-loop system establishes a new standard of care for people with type 1 diabetes. Copyright © 2017 Elsevier B.V. All rights reserved.
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Lias, Courtney; Vigersky, Robert; Clarke, William; Parkes, Joan Lee; Sacks, David B.; Kirkman, M. Sue; Kovatchev, Boris
2014-01-01
Introduction: Currently used error grids for assessing clinical accuracy of blood glucose monitors are based on out-of-date medical practices. Error grids have not been widely embraced by regulatory agencies for clearance of monitors, but this type of tool could be useful for surveillance of the performance of cleared products. Diabetes Technology Society together with representatives from the Food and Drug Administration, the American Diabetes Association, the Endocrine Society, and the Association for the Advancement of Medical Instrumentation, and representatives of academia, industry, and government, have developed a new error grid, called the surveillance error grid (SEG) as a tool to assess the degree of clinical risk from inaccurate blood glucose (BG) monitors. Methods: A total of 206 diabetes clinicians were surveyed about the clinical risk of errors of measured BG levels by a monitor. The impact of such errors on 4 patient scenarios was surveyed. Each monitor/reference data pair was scored and color-coded on a graph per its average risk rating. Using modeled data representative of the accuracy of contemporary meters, the relationships between clinical risk and monitor error were calculated for the Clarke error grid (CEG), Parkes error grid (PEG), and SEG. Results: SEG action boundaries were consistent across scenarios, regardless of whether the patient was type 1 or type 2 or using insulin or not. No significant differences were noted between responses of adult/pediatric or 4 types of clinicians. Although small specific differences in risk boundaries between US and non-US clinicians were noted, the panel felt they did not justify separate grids for these 2 types of clinicians. The data points of the SEG were classified in 15 zones according to their assigned level of risk, which allowed for comparisons with the classic CEG and PEG. Modeled glucose monitor data with realistic self-monitoring of blood glucose errors derived from meter testing experiments plotted on the SEG when compared to the data plotted on the CEG and PEG produced risk estimates that were more granular and reflective of a continuously increasing risk scale. Discussion: The SEG is a modern metric for clinical risk assessments of BG monitor errors that assigns a unique risk score to each monitor data point when compared to a reference value. The SEG allows the clinical accuracy of a BG monitor to be portrayed in many ways, including as the percentages of data points falling into custom-defined risk zones. For modeled data the SEG, compared with the CEG and PEG, allows greater precision for quantifying risk, especially when the risks are low. This tool will be useful to allow regulators and manufacturers to monitor and evaluate glucose monitor performance in their surveillance programs. PMID:25562886
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Klonoff, David C; Lias, Courtney; Vigersky, Robert; Clarke, William; Parkes, Joan Lee; Sacks, David B; Kirkman, M Sue; Kovatchev, Boris
2014-07-01
Currently used error grids for assessing clinical accuracy of blood glucose monitors are based on out-of-date medical practices. Error grids have not been widely embraced by regulatory agencies for clearance of monitors, but this type of tool could be useful for surveillance of the performance of cleared products. Diabetes Technology Society together with representatives from the Food and Drug Administration, the American Diabetes Association, the Endocrine Society, and the Association for the Advancement of Medical Instrumentation, and representatives of academia, industry, and government, have developed a new error grid, called the surveillance error grid (SEG) as a tool to assess the degree of clinical risk from inaccurate blood glucose (BG) monitors. A total of 206 diabetes clinicians were surveyed about the clinical risk of errors of measured BG levels by a monitor. The impact of such errors on 4 patient scenarios was surveyed. Each monitor/reference data pair was scored and color-coded on a graph per its average risk rating. Using modeled data representative of the accuracy of contemporary meters, the relationships between clinical risk and monitor error were calculated for the Clarke error grid (CEG), Parkes error grid (PEG), and SEG. SEG action boundaries were consistent across scenarios, regardless of whether the patient was type 1 or type 2 or using insulin or not. No significant differences were noted between responses of adult/pediatric or 4 types of clinicians. Although small specific differences in risk boundaries between US and non-US clinicians were noted, the panel felt they did not justify separate grids for these 2 types of clinicians. The data points of the SEG were classified in 15 zones according to their assigned level of risk, which allowed for comparisons with the classic CEG and PEG. Modeled glucose monitor data with realistic self-monitoring of blood glucose errors derived from meter testing experiments plotted on the SEG when compared to the data plotted on the CEG and PEG produced risk estimates that were more granular and reflective of a continuously increasing risk scale. The SEG is a modern metric for clinical risk assessments of BG monitor errors that assigns a unique risk score to each monitor data point when compared to a reference value. The SEG allows the clinical accuracy of a BG monitor to be portrayed in many ways, including as the percentages of data points falling into custom-defined risk zones. For modeled data the SEG, compared with the CEG and PEG, allows greater precision for quantifying risk, especially when the risks are low. This tool will be useful to allow regulators and manufacturers to monitor and evaluate glucose monitor performance in their surveillance programs. © 2014 Diabetes Technology Society.
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Blood glucose monitoring: an overview.
Whitmore, Catherine
Glucose monitoring is done to obtain information on blood glucose levels to ensure a therapeutic regimen; the aim is to maintain consistent glucose levels and avoid hypoglycaemia and hyperglycaemia. Self-management is central to diabetes control. Diabetes is individual, so self-monitoring of blood glucose (SMBG) targets and frequency of testing must be decided to meet each patient's needs. Nurses have key roles in education and advocacy. They can educate patients on what affects glucose levels, why they need to carry out SMBG, and how to interpret and act on the results. Nurses also match glucose monitoring meters to patients' needs by considering ease of use, technical features and lifestyle. Access to testing supplies is sometimes restricted through blanket policies and nurses have an advocacy role here in challenging inappropriate restrictions.
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A Review of Emerging Technologies for the Management of Diabetes Mellitus.
Zarkogianni, Konstantia; Litsa, Eleni; Mitsis, Konstantinos; Wu, Po-Yen; Kaddi, Chanchala D; Cheng, Chih-Wen; Wang, May D; Nikita, Konstantina S
2015-12-01
High prevalence of diabetes mellitus (DM) along with the poor health outcomes and the escalated costs of treatment and care poses the need to focus on prevention, early detection and improved management of the disease. The aim of this paper is to present and discuss the latest accomplishments in sensors for glucose and lifestyle monitoring along with clinical decision support systems (CDSSs) facilitating self-disease management and supporting healthcare professionals in decision making. A critical literature review analysis is conducted focusing on advances in: 1) sensors for physiological and lifestyle monitoring, 2) models and molecular biomarkers for predicting the onset and assessing the progress of DM, and 3) modeling and control methods for regulating glucose levels. Glucose and lifestyle sensing technologies are continuously evolving with current research focusing on the development of noninvasive sensors for accurate glucose monitoring. A wide range of modeling, classification, clustering, and control approaches have been deployed for the development of the CDSS for diabetes management. Sophisticated multiscale, multilevel modeling frameworks taking into account information from behavioral down to molecular level are necessary to reveal correlations and patterns indicating the onset and evolution of DM. Integration of data originating from sensor-based systems and electronic health records combined with smart data analytics methods and powerful user centered approaches enable the shift toward preventive, predictive, personalized, and participatory diabetes care. The potential of sensing and predictive modeling approaches toward improving diabetes management is highlighted and related challenges are identified.
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A Review of Emerging Technologies for the Management of Diabetes Mellitus
Zarkogianni, Konstantia; Litsa, Eleni; Mitsis, Konstantinos; Wu, Po-Yen; Kaddi, Chanchala D.; Cheng, Chih-Wen; Wang, May D.; Nikita, Konstantina S.
2016-01-01
Objective High prevalence of diabetes mellitus (DM) along with the poor health outcomes and the escalated costs of treatment and care poses the need to focus on prevention, early detection and improved management of the disease. The aim of this paper is to present and discuss the latest accomplishments in sensors for glucose and lifestyle monitoring along with clinical decision support systems (CDSSs) facilitating self-disease management and supporting healthcare professionals in decision making. Methods A critical literature review analysis is conducted focusing on advances in: 1) sensors for physiological and lifestyle monitoring, 2) models and molecular biomarkers for predicting the onset and assessing the progress of DM, and 3) modeling and control methods for regulating glucose levels. Results Glucose and lifestyle sensing technologies are continuously evolving with current research focusing on the development of noninvasive sensors for accurate glucose monitoring. A wide range of modeling, classification, clustering, and control approaches have been deployed for the development of the CDSS for diabetes management. Sophisticated multiscale, multilevel modeling frameworks taking into account information from behavioral down to molecular level are necessary to reveal correlations and patterns indicating the onset and evolution of DM. Conclusion Integration of data originating from sensor-based systems and electronic health records combined with smart data analytics methods and powerful user centered approaches enable the shift toward preventive, predictive, personalized, and participatory diabetes care. Significance The potential of sensing and predictive modeling approaches toward improving diabetes management is highlighted and related challenges are identified. PMID:26292334
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Technology to Reduce Hypoglycemia.
Yeoh, Ester; Choudhary, Pratik
2015-07-01
Hypoglycemia is a major barrier toward achieving glycemic targets and is associated with significant morbidity (both psychological and physical) and mortality. This article reviews technological strategies, from simple to more advanced technologies, which may help prevent or mitigate exposure to hypoglycemia. More efficient insulin delivery systems, bolus advisor calculators, data downloads providing information on glucose trends, continuous glucose monitoring with alarms warning of hypoglycemia, predictive algorithms, and finally closed loop insulin delivery systems are reviewed. The building blocks to correct use and interpretation of this range of available technology require patient education and appropriate patient selection. © 2015 Diabetes Technology Society.
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Steroid injection for shoulder pain causes prolonged increased glucose level in type 1 diabetics
Povlsen, Bo; Povlsen, Sebastian D
2014-01-01
Shoulder pain is very common in diabetic patients and often treated with steroid injections, with subsequent increases in blood glucose levels or the need for additional insulin being questioned. We report a case of significant and prolonged elevation of blood glucose levels and resultant insulin requirement in a type 1 diabetic man after a single 40 mg injection of triamcinolone for shoulder pain. Within 48 h, the shoulder pain as assessed by a visual analogue scale (0–10) was reduced to zero, but the elevated insulin requirements continued for 4 weeks after the injection. This finding suggests that steroid injections for shoulder pain in diabetics may not always be as safe as previously thought. We propose that medical practitioners advise their patients to monitor their glucose levels more carefully after such injections and that caution is exercised when considering administrating these injections to those who have poorly controlled blood glucose levels preinjection to avoid ketoacidosis. PMID:25199186
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Steroid injection for shoulder pain causes prolonged increased glucose level in type 1 diabetics.
Povlsen, Bo; Povlsen, Sebastian D
2014-09-08
Shoulder pain is very common in diabetic patients and often treated with steroid injections, with subsequent increases in blood glucose levels or the need for additional insulin being questioned. We report a case of significant and prolonged elevation of blood glucose levels and resultant insulin requirement in a type 1 diabetic man after a single 40 mg injection of triamcinolone for shoulder pain. Within 48 h, the shoulder pain as assessed by a visual analogue scale (0-10) was reduced to zero, but the elevated insulin requirements continued for 4 weeks after the injection. This finding suggests that steroid injections for shoulder pain in diabetics may not always be as safe as previously thought. We propose that medical practitioners advise their patients to monitor their glucose levels more carefully after such injections and that caution is exercised when considering administrating these injections to those who have poorly controlled blood glucose levels preinjection to avoid ketoacidosis. 2014 BMJ Publishing Group Ltd.
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Bay, Christiane; Kristensen, Peter Lommer; Pedersen-Bjergaard, Ulrik; Tarnow, Lise; Thorsteinsson, Birger
2013-05-01
A reliable method to detect biochemical nocturnal hypoglycemia is highly needed, especially in patients with recurrent severe hypoglycemia. We evaluated reliability of nocturnal continuous glucose monitoring (CGM) in patients with type 1 diabetes at high risk of severe hypoglycemia. Seventy-two type 1 diabetes patients with recurrent severe hypoglycemia (two or more events within the last year) participated for 4 nights in blinded CGM recordings (Guardian(®) REAL-Time CGMS and Sof-Sensor(®); Medtronic MiniMed, Northridge, CA). Blood was drawn hourly from 23:00 to 07:00 h for plasma glucose (PG) measurements (gold standard). Valid data were obtained in 217 nights. The sensitivity of CGM was 65% (95% confidence interval, 53-77%) below 4 mmol/L, 40% (24-56%) below 3 mmol/L, and 17% (0-47%) below 2.2 mmol/L. PG and CGM readings correlated in the total measurement range (Spearman's ρ=0.82; P<0.001). In the normo- and hyperglycemic ranges CGM underestimated PG by 1.1 mmol/L (0.9-1.2 mmol/L) (P<0.001); in contrast, in the hypoglycemic range (PG<4 mmol/L) CGM overestimated PG levels by 1.0 mmol/L (P<0.001). The mean absolute relative differences in the hypo- (≤3.9 mmol/L), normo- (4-9.9 mmol/L), and hyperglycemic (≥10 mmol/L) ranges were 45% (37-53%), 23% (22-25%), and 20% (19-21%), respectively. Continuous glucose error grid analysis indicated a clinical accuracy of 56%, 99%, and 93% in the hypo-, normo-, and hyperglycemic ranges, respectively. The accuracy in the hypoglycemic range of nocturnal CGM data using Sof-Sensor is suboptimal in type 1 diabetes patients at high risk of severe hypoglycemia. To ensure clinical useful sensitivity in detection of nocturnal hypoglycemic episodes, an alarm threshold should not be lower than 4 mmol/L.
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2012-01-01
Background No previous studies have compared the DPP-4 inhibitors vildagliptin and sitagliptin in terms of blood glucose levels using continuous glucose monitoring (CGM) and cardiovascular parameters. Methods Twenty patients with type 2 diabetes mellitus were randomly allocated to groups who received vildagliptin then sitagliptin, or vice versa. Patients were hospitalized at 1 month after starting each drug, and CGM was used to determine: 1) mean (± standard deviation) 24-hour blood glucose level, 2) mean amplitude of glycemic excursions (MAGE), 3) fasting blood glucose level, 4) highest postprandial blood glucose level and time, 5) increase in blood glucose level after each meal, 6) area under the curve (AUC) for blood glucose level ≥180 mg/dL within 3 hours after each meal, and 7) area over the curve (AOC) for daily blood glucose level <70 mg/dL. Plasma glycosylated hemoglobin (HbA1c), glycoalbumin (GA), 1,5-anhydroglucitol (1,5AG), immunoreactive insulin (IRI), C-peptide immunoreactivity (CPR), brain natriuretic peptide (BNP), and plasminogen activator inhibitor-1 (PAI-1) levels, and urinary CPR levels, were measured. Results The mean 24-hour blood glucose level was significantly lower in patients taking vildagliptin than sitagliptin (142.1 ± 35.5 vs. 153.2 ± 37.0 mg/dL; p = 0.012). In patients taking vildagliptin, MAGE was significantly lower (110.5 ± 33.5 vs. 129.4 ± 45.1 mg/dL; p = 0.040), the highest blood glucose level after supper was significantly lower (206.1 ± 40.2 vs. 223.2 ± 43.5 mg/dL; p = 0.015), the AUC (≥180 mg/dL) within 3 h was significantly lower after breakfast (484.3 vs. 897.9 mg/min/dL; p = 0.025), and urinary CPR level was significantly higher (97.0 ± 41.6 vs. 85.2 ± 39.9 μg/day; p = 0.008) than in patients taking sitagliptin. There were no significant differences in plasma HbA1c, GA, 1,5AG, IRI, CPR, BNP, or PAI-1 levels between patients taking vildagliptin and sitagliptin. Conclusions CGM showed that mean 24-h blood glucose, MAGE, highest blood glucose level after supper, and hyperglycemia after breakfast were significantly lower in patients with type 2 diabetes mellitus taking vildagliptin than those taking sitagliptin. There were no significant differences in BNP and PAI-1 levels between patients taking vildagliptin and sitagliptin. Trial registration UMIN000007687 PMID:22867630
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Lasting monitoring of immune state in patients with coronary atherosclerosis
NASA Astrophysics Data System (ADS)
Malinova, Lidia I.; Denisova, Tatyana P.; Tuchin, Valery V.
2007-02-01
Immune state monitoring is an expensive, invasive and sometimes difficult necessity in patients with different disorders. Immune reaction dynamics study in patients with coronary atherosclerosis provides one of the leading components to complication development, clinical course prognosis and treatment and rehabilitation tactics. We've chosen intravenous glucose injection as metabolic irritant in the following four groups of patients: men with proved coronary atherosclerosis (CA), non insulin dependent diabetes mellitus (NIDDM), men hereditary burden by CA and NIDDM and practically healthy persons with longlivers in generation. Immune state parameters such as quantity of leukocytes and lymphocytes, circulating immune complexes levels, serum immunoglobulin levels, HLA antigen markers were studied at 0, 30 and 60 minutes during glucose loading. To obtain continues time function of studied parameters received data were approximated by polynomials of high degree with after going first derivatives. Time functions analyze elucidate principally different dynamics studied parameters in all chosen groups of patients, which couldn't be obtained from discontinuous data compare. Leukocyte and lymphocyte levels dynamics correlated HLA antigen markers in all studied groups. Analytical estimation of immune state in patients with coronary atherosclerosis shows the functional "margin of safety" of immune system state under glucose disturbance. Proposed method of analytical estimation also can be used in immune system monitoring in other groups of patients.
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NASA Astrophysics Data System (ADS)
Grafen, M.; Nalpantidis, K.; Ostendorf, A.; Ihrig, D.; Heise, H. M.
2016-03-01
Blood glucose monitoring systems are important point-of-care devices for the hospital and personalised diabetes technology. FTIR-spectrometers have been successfully employed for the development of continuous bed-side monitoring systems in combination with micro-dialysis. For implementation in miniaturised portable systems, external-cavity quantum cascade lasers (EC-QCL) are suited. An ultra-broadly tunable pulsed EC-QCL system, covering a spectral range from 1920 to 780 cm-1, has been characterised with regard to the spectral emission profiles and wavenumber scale accuracy. The measurement of glucose in aqueous solution is presented and problems with signal linearity using Peltier-cooled MCT-detectors are discussed. The use of larger optical sample pathlengths for attenuating the laser power in transmission measurements has recently been suggested and implemented, but implications for broad mid-infrared measurements have now been investigated. The utilization of discrete wavenumber variables as an alternative for sweep-tune measurements has also been studied and sparse multivariate calibration models intended for clinical chemistry applications are described for glucose and lactate.
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Dhakal, Rajendra; Kim, E S; Jo, Yong-Hwa; Kim, Sung-Soo; Kim, Nam-Young
2017-03-01
We present a concept for the characterization of micro-fabricated based resonator incorporating air-bridge metal-insulator-semiconductor (MIS) capacitor to continuously monitor an individual's state of glucose levels based on frequency variation. The investigation revealed that, the micro-resonator based on MIS capacitor holds considerable promise for implementation and recognition as a glucose sensor for human serum. The discrepancy in complex permittivity as a result of enhanced capacitor was achieved for the detection and determination of random glucose concentration levels using a unique variation of capacitor that indeed results in an adequate variation of the resonance frequency. Moreover, the design and development of micro-resonator with enhanced MIS capacitor generate a resolution of 112.38 × 10 -3 pF/mg/dl, minimum detectable glucose level of 7.45mg/dl, and a limit of quantification of 22.58mg/dl. Additionally, this unique approach offers long-term reliability for mediator-free glucose sensing with a relative standard deviation of less than 0.5%. Copyright © 2017 IPEM. Published by Elsevier Ltd. All rights reserved.
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Dynamical glucometry: Use of multiscale entropy analysis in diabetes
NASA Astrophysics Data System (ADS)
Costa, Madalena D.; Henriques, Teresa; Munshi, Medha N.; Segal, Alissa R.; Goldberger, Ary L.
2014-09-01
Diabetes mellitus (DM) is one of the world's most prevalent medical conditions. Contemporary management focuses on lowering mean blood glucose values toward a normal range, but largely ignores the dynamics of glucose fluctuations. We probed analyte time series obtained from continuous glucose monitor (CGM) sensors. We show that the fluctuations in CGM values sampled every 5 min are not uncorrelated noise. Next, using multiscale entropy analysis, we quantified the complexity of the temporal structure of the CGM time series from a group of elderly subjects with type 2 DM and age-matched controls. We further probed the structure of these CGM time series using detrended fluctuation analysis. Our findings indicate that the dynamics of glucose fluctuations from control subjects are more complex than those of subjects with type 2 DM over time scales ranging from about 5 min to 5 h. These findings support consideration of a new framework, dynamical glucometry, to guide mechanistic research and to help assess and compare therapeutic interventions, which should enhance complexity of glucose fluctuations and not just lower mean and variance of blood glucose levels.
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Sildorf, S M; Hertel, N T; Thomsen, J; Fredheim, S; Hastrup, H; Pipper, C; Hertz, B; Svensson, J
2016-04-01
To examine trends in diabetes treatment in Danish children and adolescents with Type 1 diabetes mellitus, comparing treatment intensity with metabolic outcomes in the population, and to describe the challenges of population-based registries in a clinical setting with rapidly changing treatment methods. This observational study is based on the Danish national population registry of childhood diabetes, which includes 99% of children diagnosed with Type 1 diabetes before the age of 15 years. We included 4527 people diagnosed between 2000 and 2012. Self-monitored blood glucose measurements, insulin injections/boluses, treatment method and metabolic control quantifications were analysed and adjusted for the effects of gender and ethnicity, the combined effect of age, visit year and duration, and for the random effects of individual and hospital settings. Treatment was intensified via an increasing number of self-monitored blood glucose measurements and injections/boluses. More than six injections/boluses and an increased number of self-monitored blood glucose measurements were significantly associated with lower metabolic control. No reduction, however, in the overall mean HbA1c concentration was observed between 2005 [66 mmol/mol (8.2%)] and 2012 [65 mmol/mol (8.1%)]. Changed registration practices in 2009 introduced artificial jumps in data. Intensifying treatment alone does not lead to improved metabolic control in the overall population despite the appearance of lower HbA1c in individuals with a greater number of self-monitored blood glucose measurements and injections/boluses. The contradictory results reflect difficulties in using observational studies to predict results of intervention in the individual. Data collected from population-based registries need to be adjusted continuously to reflect changes in care. © 2015 Diabetes UK.
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Yoshimatsu, Yu; Ishizaka, Tomomichi; Chiba, Katsuyoshi; Mori, Kazuhiko
2018-05-10
Drug-induced cardiac electrophysiological abnormalities accompanied by hypoglycemia or hyperglycemia increase the risk for life-threatening arrhythmia. To assess the drug-induced cardiotoxic potential associated with extraordinary blood glucose (GLU) levels, the effect of gatifloxacin (GFLX) which was frequently associated with GLU abnormality and QT/QTc prolongations in the clinic on blood GLU and electrocardiogram (ECG) parameters was investigated in cynomolgus monkeys (n=4) given GFLX orally in an ascending dose regimen (10, 30, 60 and 100 mg/kg). Simultaneous and sequential GLU and ECG monitoring with a continuous GLU monitoring system and Holter ECG, respectively, were conducted for 24 h under free-moving conditions. Consequently, GFLX at 30 and 60 mg/kg dose-dependently induced a transient decrease in GLU without any ECG abnormality 2-4 h postdose. Highest dose of 100 mg/kg caused severe hypoglycemia with a mean GLU of <30 mg/dL, accompanied by remarkable QT/QTc prolongations by 20-30% in all animals. In contrast, hyperglycemia without QT/QTc prolongations was noted 24 h after dosing in one animal. A close correlation between GLU and QTc values was observed in animals treated with 100 mg/kg, suggesting that GFLX-induced hypoglycemia enhanced QT/QTc prolongations. Furthermore, the 24-h sequential GLU monitoring data clearly distinguished between GFLX-induced GLU abnormality and physiological GLU changes influenced by feeding throughout the day. In conclusion, the combined assessment of continuous GLU and ECG monitoring is valuable in predicting the drug-induced cardio-electrophysiological risk associated with both GLU and ECG abnormalities.
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Mougiakakou, Stavroula G; Bartsocas, Christos S; Bozas, Evangelos; Chaniotakis, Nikos; Iliopoulou, Dimitra; Kouris, Ioannis; Pavlopoulos, Sotiris; Prountzou, Aikaterini; Skevofilakas, Marios; Tsoukalis, Alexandre; Varotsis, Kostas; Vazeou, Andrianni; Zarkogianni, Konstantia; Nikita, Konstantina S
2010-05-01
SMARTDIAB is a platform designed to support the monitoring, management, and treatment of patients with type 1 diabetes mellitus (T1DM), by combining state-of-the-art approaches in the fields of database (DB) technologies, communications, simulation algorithms, and data mining. SMARTDIAB consists mainly of two units: 1) the patient unit (PU); and 2) the patient management unit (PMU), which communicate with each other for data exchange. The PMU can be accessed by the PU through the internet using devices, such as PCs/laptops with direct internet access or mobile phones via a Wi-Fi/General Packet Radio Service access network. The PU consists of an insulin pump for subcutaneous insulin infusion to the patient and a continuous glucose measurement system. The aforementioned devices running a user-friendly application gather patient's related information and transmit it to the PMU. The PMU consists of a diabetes data management system (DDMS), a decision support system (DSS) that provides risk assessment for long-term diabetes complications, and an insulin infusion advisory system (IIAS), which reside on a Web server. The DDMS can be accessed from both medical personnel and patients, with appropriate security access rights and front-end interfaces. The DDMS, apart from being used for data storage/retrieval, provides also advanced tools for the intelligent processing of the patient's data, supporting the physician in decision making, regarding the patient's treatment. The IIAS is used to close the loop between the insulin pump and the continuous glucose monitoring system, by providing the pump with the appropriate insulin infusion rate in order to keep the patient's glucose levels within predefined limits. The pilot version of the SMARTDIAB has already been implemented, while the platform's evaluation in clinical environment is being in progress.
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The Cost-Effectiveness of Real-Time Continuous Glucose Monitoring (RT-CGM) in Type 2 Diabetes.
Fonda, Stephanie J; Graham, Claudia; Munakata, Julie; Powers, Julia M; Price, David; Vigersky, Robert A
2016-07-01
This analysis models the cost-effectiveness of real-time continuous glucose monitoring (RT-CGM) using evidence from a randomized controlled trial (RCT) that demonstrated RT-CGM reduced A1C, for up to 9 months after using the technology, among patients with type 2 diabetes not on prandial insulin. RT-CGM was offered short-term and intermittently as a self-care tool to inform patients' behavior. The analyses projected lifetime clinical and economic outcomes for RT-CGM versus self-monitoring of blood glucose by fingerstick only. The base-case analysis was consistent with the RCT (RT-CGM for 2 weeks on/1 week off over 3 months). A scenario analysis simulated outcomes of an RT-CGM "refresher" after the active intervention of the RCT. Analyses used the IMS CORE Diabetes Model and were conducted from a US third-party payer perspective, including direct costs obtained from published sources and inflated to 2011 US dollars. Costs and health outcomes were discounted at 3% per annum. Life expectancy (LE) and quality-adjusted life expectancy (QALE) from RT-CGM were 0.10 and 0.07, with a cost of $653/patient over a lifetime. Incremental LE and QALE from a "refresher" were 0.14 and 0.10, with a cost of $1312/patient over a lifetime, and incremental cost-effectiveness ratios were $9319 and $13 030 per LY and QALY gained. RT-CGM, as a self-care tool, is a cost-effective disease management option in the US for people with type 2 diabetes not on prandial insulin. Repeated use of RT-CGM may result in additional cost-effectiveness. © 2016 Diabetes Technology Society.
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Farabi, Sarah S; Carley, David W; Smith, Donald; Quinn, Lauretta
2015-09-01
We measured the effects of a single bout of exercise on diurnal and nocturnal oxidative stress and glycaemic variability in obese subjects with type 2 diabetes mellitus or impaired glucose tolerance versus obese healthy controls. Subjects (in random order) performed either a single 30-min bout of moderate-intensity exercise or remained sedentary for 30 min at two separate visits. To quantify glycaemic variability, standard deviation of glucose (measured by continuous glucose monitoring system) and continuous overlapping net glycaemic action of 1-h intervals (CONGA-1) were calculated for three 12-h intervals during each visit. Oxidative stress was measured by 15-isoprostane F(2t) levels in urine collections for matching 12-h intervals. Exercise reduced daytime glycaemic variability (ΔCONGA-1 = -12.62 ± 5.31 mg/dL, p = 0.04) and urinary isoprostanes (ΔCONGA-1 = -0.26 ± 0.12 ng/mg, p = 0.04) in the type 2 diabetes mellitus/impaired glucose tolerance group. Daytime exercise-induced change in urinary 15-isoprostane F(2t) was significantly correlated with both daytime standard deviation (r = 0.68, p = 0.03) and with subsequent overnight standard deviation (r = 0.73, p = 0.027) in the type 2 diabetes mellitus/impaired glucose tolerance group. Exercise significantly impacts the relationship between diurnal oxidative stress and nocturnal glycaemic variability in individuals with type 2 diabetes mellitus/impaired glucose tolerance. © The Author(s) 2015.
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Weegman, Bradley P.; Nash, Peter; Carlson, Alexandra L.; Voltzke, Kristin J.; Geng, Zhaohui; Jahani, Marjan; Becker, Benjamin B.; Papas, Klearchos K.; Firpo, Meri T.
2013-01-01
Cellular therapies are emerging as a standard approach for the treatment of several diseases. However, realizing the promise of cellular therapies across the full range of treatable disorders will require large-scale, controlled, reproducible culture methods. Bioreactor systems offer the scale-up and monitoring needed, but standard stirred bioreactor cultures do not allow for the real-time regulation of key nutrients in the medium. In this study, β-TC6 insulinoma cells were aggregated and cultured for 3 weeks as a model of manufacturing a mammalian cell product. Cell expansion rates and medium nutrient levels were compared in static, stirred suspension bioreactors (SSB), and continuously fed (CF) SSB. While SSB cultures facilitated increased culture volumes, no increase in cell yields were observed, partly due to limitations in key nutrients, which were consumed by the cultures between feedings, such as glucose. Even when glucose levels were increased to prevent depletion between feedings, dramatic fluctuations in glucose levels were observed. Continuous feeding eliminated fluctuations and improved cell expansion when compared with both static and SSB culture methods. Further improvements in growth rates were observed after adjusting the feed rate based on calculated nutrient depletion, which maintained physiological glucose levels for the duration of the expansion. Adjusting the feed rate in a continuous medium replacement system can maintain the consistent nutrient levels required for the large-scale application of many cell products. Continuously fed bioreactor systems combined with nutrient regulation can be used to improve the yield and reproducibility of mammalian cells for biological products and cellular therapies and will facilitate the translation of cell culture from the research lab to clinical applications. PMID:24204645
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Comparison of 5 reflectance meters for capillary blood glucose determination.
Kolopp, M; Louis, J; Pointel, J P; Kohler, F; Drouin, P; Debry, G
1983-03-01
Manufacturing quality, accuracy and users opinion (i.e. medical and nurses staff and patients) were compared among five Destrostix reading reflectance-meters for home-blood-glucose-monitoring. Two machines (dextrometer and glucometer) equipped with microprocessors, integrated circuits and good quality wiring are best made. Reflectance-meter capillary blood glucose measurements were found to be accurate enough for home-blood-glucose-monitoring, compared to a reference method. However, two machines from the same brand were different in blood glucose accuracy. Glucocheck had poorest results. Users prefer small sized, battery powered machines. Glucometer appears to be best suited to home-blood-glucose-monitoring.
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Monitoring of tissue optical properties using OCT: application for blood glucose analysis
NASA Astrophysics Data System (ADS)
Larin, Kirill V.; Eledrisi, Mohsen S.; Ashitkov, Taras V.; Motamedi, Massoud; Esenaliev, Rinat O.
2002-07-01
Noninvasive monitoring of tissue optical properties in real time could significantly improve diagnostics and management of various diseases. Recently we proposed to use high- resolution Optical Coherence Tomography (OCT) technique for measurement of tissue scattering coefficient at the depth of up to 1mm. Our pilot studies performed in vitro and in vivo demonstrated that measurement of tissue scattering with this technique can potentially be applied for noninvasive monitoring of blood glucose concentration. High resolution and coherent photon detection of the OCT technique allowed detection of glucose-induced changes in the scattering coefficient. In this paper we report results of in vivo studies performed in dog, New Zealand rabbits, and first human subjects. OCT system with the wavelength of 1300 nm was used in our experiments. OCT signal slope was measured and compared with actual blood glucose concentration. Bolus glucose injections and glucose clamping administrations were used in animal studies. OCT signals were recorded form human subjects during oral glucose tolerance test. Results obtained form both animal and human studies show good correlation between slope of the OCT signals and actual blood glucose concentration measured using standard glucometesr. Sensitivity and accuracy of blood glucose concentrations monitoring with the OCT is discussed. Obtained result suggest that OCT is a promising technique for noninvasive monitoring of tissue analytes including glucose.
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Mouthguard biosensor with telemetry system for monitoring of saliva glucose: A novel cavitas sensor.
Arakawa, Takahiro; Kuroki, Yusuke; Nitta, Hiroki; Chouhan, Prem; Toma, Koji; Sawada, Shin-Ichi; Takeuchi, Shuhei; Sekita, Toshiaki; Akiyoshi, Kazunari; Minakuchi, Shunsuke; Mitsubayashi, Kohji
2016-10-15
We develop detachable "Cavitas sensors" to apply to the human oral cavity for non-invasive monitoring of saliva glucose. A salivary biosensor incorporating Pt and Ag/AgCl electrodes on a mouthguard support with an enzyme membrane is developed and tested. Electrodes are formed on the polyethylene terephthalate glycol (PETG) surface of the mouthguard. The Pt working electrode is coated with a glucose oxidase (GOD) membrane. The biosensor seamlessly is integrated with a glucose sensor and a wireless measurement system. When investigating in-vitro performance, the biosensor exhibits a robust relationship between output current and glucose concentration. In artificial saliva composed of salts and proteins, the glucose sensor is capable of highly sensitive detection over a range of 5-1000µmol/L of glucose, which encompasses the range of glucose concentrations found in human saliva. We demonstrate the ability of the sensor and wireless communication module to monitor saliva glucose in a phantom jaw imitating the structure of the human oral cavity. Stable and long-term real-time monitoring (exceeding 5h) with the telemetry system is achieved. The mouthguard biosensor will be useful as a novel method for real-time non-invasive saliva glucose monitoring for better management of dental patients. Copyright © 2015 Elsevier B.V. All rights reserved.
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Oskarsson, Per; Antuna, Ramiro; Geelhoed-Duijvestijn, Petronella; Krӧger, Jens; Weitgasser, Raimund; Bolinder, Jan
2018-03-01
Evidence for the effectiveness of interstitial glucose monitoring in individuals with type 1 diabetes using multiple daily injection (MDI) therapy is limited. In this pre-specified subgroup analysis of the Novel Glucose-Sensing Technology and Hypoglycemia in Type 1 Diabetes: a Multicentre, Non-masked, Randomised Controlled Trial' (IMPACT), we assessed the impact of flash glucose technology on hypoglycaemia compared with capillary glucose monitoring. This multicentre, prospective, non-masked, RCT enrolled adults from 23 European diabetes centres. Individuals were eligible to participate if they had well-controlled type 1 diabetes (diagnosed for ≥5 years), HbA 1c ≤ 58 mmol/mol [7.5%], were using MDI therapy and on their current insulin regimen for ≥3 months, reported self-monitoring of blood glucose on a regular basis (equivalent to ≥3 times/day) for ≥2 months and were deemed technically capable of using flash glucose technology. Individuals were excluded if they were diagnosed with hypoglycaemia unawareness, had diabetic ketoacidosis or myocardial infarction in the preceding 6 months, had a known allergy to medical-grade adhesives, used continuous glucose monitoring (CGM) within the previous 4 months or were currently using CGM or sensor-augmented pump therapy, were pregnant or planning pregnancy or were receiving steroid therapy for any disorders. Following 2 weeks of blinded (to participants and investigator) sensor wear by all participants, participants with sensor data for more than 50% of the blinded wear period (or ≥650 individual sensor results) were randomly assigned, in a 1:1 ratio by a central interactive web response system (IWRS) using the biased-coin minimisation method, to flash sensor-based glucose monitoring (intervention group) or self-monitoring of capillary blood glucose (control group). The control group had two further 14 day blinded sensor-wear periods at the 3 and 6 month time points. Participants, investigators and staff were not masked to group allocation. The primary outcome was the change in time in hypoglycaemia (<3.9 mmol/l) between baseline and 6 months in the full analysis set. Between 4 September 2014 and 12 February 2015, 167 participants using MDI were enrolled. After screening and the baseline phase, participants were randomised to intervention (n = 82) and control groups (n = 81). One woman from each group was excluded owing to pregnancy; the full analysis set included 161 randomised participants. At 6 months, mean time in hypoglycaemia was reduced by 46.0%, from 3.44 h/day to 1.86 h/day in the intervention group (baseline adjusted mean change, -1.65 h/day), and from 3.73 h/day to 3.66 h/day in the control group (baseline adjusted mean change, 0.00 h/day), with a between-group difference of -1.65 (95% CI -2.21, -1.09; p < 0.0001). For participants in the intervention group, the mean ± SD daily sensor scanning frequency was 14.7 ± 10.7 (median 12.3) and the mean number of self-monitored blood glucose tests performed per day reduced from 5.5 ± 2.0 (median 5.4) at baseline to 0.5 ± 1.0 (median 0.1). The baseline frequency of self-monitored blood glucose tests by control participants was maintained (from 5.6 ± 1.9 [median 5.2] to 5.5 ± 2.6 [median 5.1] per day). Treatment satisfaction and perception of hypo/hyperglycaemia were improved compared with control. No device-related hypoglycaemia or safety-related issues were reported. Nine serious adverse events were reported for eight participants (four in each group), none related to the device. Eight adverse events for six of the participants in the intervention group were also reported, which were related to sensor insertion/wear; four of these participants withdrew because of the adverse event. Use of flash glucose technology in type 1 diabetes controlled with MDI therapy significantly reduced time in hypoglycaemia without deterioration of HbA 1c , and improved treatment satisfaction. ClinicalTrials.gov NCT02232698 FUNDING: Abbott Diabetes Care, Witney, UK.
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Lieberman, Harris R; Falco, Christina M; Slade, Steven S
2002-07-01
The brain requires a continuous supply of glucose to function adequately. During aerobic exercise, peripheral glucose requirements increase and carbohydrate supplementation improves physical performance. The brain's utilization of glucose also increases during aerobic exercise. However, the effects of energy supplementation on cognitive function during sustained aerobic exercise are not well characterized. The effects of energy supplementation, as liquid carbohydrate, on cognitive function during sustained aerobic activity were examined. A double-blind, placebo-controlled, between-subjects design was used. Young, healthy men (n = 143) were randomly assigned to 1 of 3 treatment groups. The groups received either a 6% (by vol) carbohydrate (35.1 kJ/kg), 12% (by vol) carbohydrate (70.2 kJ/kg), or placebo beverage in 6 isovolumic doses, and all groups consumed 2 meals (3200 kJ). Over the 10-h study, the subjects performed physically demanding tasks, including a 19.3-km road march and two 4.8-km runs, interspersed with rest and other activities. Wrist-worn vigilance monitors, which emitted auditory stimuli (20/h) to which the subjects responded as rapidly as possible, and a standardized self-report mood questionnaire were used to assess cognitive function. Vigilance consistently improved with supplemental carbohydrates in a dose-related manner; the 12% carbohydrate group performed the best and the placebo group the worst (P < 0.001). Mood-questionnaire results corroborated the results from the monitors; the subjects who received carbohydrates reported less confusion (P = 0.040) and greater vigor (P = 0.025) than did those who received the placebo. Supplemental carbohydrate beverages enhance vigilance and mood during sustained physical activity and interspersed rest. In addition, ambulatory monitoring devices can continuously assess the effects of nutritional factors on cognition as individuals conduct their daily activities or participate in experiments.
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Hypoglycemia in Type 2 Diabetes--More Common Than You Think: A Continuous Glucose Monitoring Study.
Gehlaut, Richa Redhu; Dogbey, Godwin Y; Schwartz, Frank L; Marling, Cynthia R; Shubrook, Jay H
2015-04-27
Hypoglycemia is often the limiting factor for intensive glucose control in diabetes management, however its actual prevalence in type 2 diabetes (T2DM) is not well documented. A total of 108 patients with T2DM wore a continuous glucose monitoring system (CGMS) for 5 days. Rates and patterns of hypoglycemia and glycemic variability (GV) were calculated. Patient and medication factors were correlated with rates, timing, and severity of hypoglycemia. Of the patients, 49.1% had at least 1 hypoglycemic episode (mean 1.74 episodes/patient/ 5 days of CGMS) and 75% of those patients experienced at least 1 asymptomatic hypoglycemic episode. There was no significant difference in the frequency of daytime versus nocturnal hypoglycemia. Hypoglycemia was more frequent in individuals on insulin (alone or in combination) (P = .02) and those on oral hypoglycemic agents (P < .001) compared to noninsulin secretagogues. CGMS analysis resulted in treatment modifications in 64% of the patients. T2DM patients on insulin exhibited higher glycemic variability (GV) scores (2.3 ± 0.6) as compared to those on oral medications (1.8 ± 0.7, P = .017). CGMS can provide rich data that show glucose excursions in diabetes patients throughout the day. Consequently, unwarranted onset of hypo- and hyperglycemic events can be detected, intervened, and prevented by using CGMS. Hypoglycemia was frequently unrecognized by the patients in this study (75%), which increases their potential risk of significant adverse events. Incorporation of CGMS into the routine management of T2DM would increase the detection and self-awareness of hypoglycemia resulting in safer and potentially better overall control. © 2015 Diabetes Technology Society.
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Zhou, Tony; Dickson, Jennifer L; Geoffrey Chase, J
2018-01-01
Continuous glucose monitoring (CGM) devices have been effective in managing diabetes and offer potential benefits for use in the intensive care unit (ICU). Use of CGM devices in the ICU has been limited, primarily due to the higher point accuracy errors over currently used traditional intermittent blood glucose (BG) measures. General models of CGM errors, including drift and random errors, are lacking, but would enable better design of protocols to utilize these devices. This article presents an autoregressive (AR) based modeling method that separately characterizes the drift and random noise of the GlySure CGM sensor (GlySure Limited, Oxfordshire, UK). Clinical sensor data (n = 33) and reference measurements were used to generate 2 AR models to describe sensor drift and noise. These models were used to generate 100 Monte Carlo simulations based on reference blood glucose measurements. These were then compared to the original CGM clinical data using mean absolute relative difference (MARD) and a Trend Compass. The point accuracy MARD was very similar between simulated and clinical data (9.6% vs 9.9%). A Trend Compass was used to assess trend accuracy, and found simulated and clinical sensor profiles were similar (simulated trend index 11.4° vs clinical trend index 10.9°). The model and method accurately represents cohort sensor behavior over patients, providing a general modeling approach to any such sensor by separately characterizing each type of error that can arise in the data. Overall, it enables better protocol design based on accurate expected CGM sensor behavior, as well as enabling the analysis of what level of each type of sensor error would be necessary to obtain desired glycemic control safety and performance with a given protocol.
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Thomas, Felicity; Signal, Mathew; Harris, Deborah L; Weston, Philip J; Harding, Jane E; Shaw, Geoffrey M; Chase, J Geoffrey
2014-05-01
Neonatal hypoglycemia is common and can cause serious brain injury. Continuous glucose monitoring (CGM) could improve hypoglycemia detection, while reducing blood glucose (BG) measurements. Calibration algorithms use BG measurements to convert sensor signals into CGM data. Thus, inaccuracies in calibration BG measurements directly affect CGM values and any metrics calculated from them. The aim was to quantify the effect of timing delays and calibration BG measurement errors on hypoglycemia metrics in newborn infants. Data from 155 babies were used. Two timing and 3 BG meter error models (Abbott Optium Xceed, Roche Accu-Chek Inform II, Nova Statstrip) were created using empirical data. Monte-Carlo methods were employed, and each simulation was run 1000 times. Each set of patient data in each simulation had randomly selected timing and/or measurement error added to BG measurements before CGM data were calibrated. The number of hypoglycemic events, duration of hypoglycemia, and hypoglycemic index were then calculated using the CGM data and compared to baseline values. Timing error alone had little effect on hypoglycemia metrics, but measurement error caused substantial variation. Abbott results underreported the number of hypoglycemic events by up to 8 and Roche overreported by up to 4 where the original number reported was 2. Nova results were closest to baseline. Similar trends were observed in the other hypoglycemia metrics. Errors in blood glucose concentration measurements used for calibration of CGM devices can have a clinically important impact on detection of hypoglycemia. If CGM devices are going to be used for assessing hypoglycemia it is important to understand of the impact of these errors on CGM data. © 2014 Diabetes Technology Society.
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Hu, Yun; Zhang, Dan-Feng; Dai, Lu; Li, Zheng; Li, Hui-Qin; Li, Feng-Fei; Liu, Bing-Li; Sun, Xiao-Juan; Ye, Lei; He, Ke; Ma, Jian-Hua
2018-05-03
Considering the insulin sensitivity may increase by exercise particularly in patients with type 2 diabetes (T2D), glycemic variation during exercise needs to be studied when the patients are treated with insulin. This study aimed to explore the influence factors of the efficacy and safety of aerobic exercise in patients with T2D treated with Continuous Subcutaneous Insulin Infusion (CSII). A total of 267 patients with T2D, treated with CSII, were included. Glycemic variations were assessed by continuous glucose monitoring (CGM). Patients were asked to complete 30 min aerobic exercise for at least one time during CGM. The patients were divided into effective and ineffective group by incremental glucose area under curve from 0 to 60 min after exercise (AUC 0-60 min ). The patients completed a total of 776 times of aerobic exercises. Blood glucose decreased fastest in the first 60 min of exercise. Pre-exercise blood glucose (PEBG) was negatively correlated with AUC 0-60 min (standardized β = -0.386, P < 0.001) and incremental AUC of blood glucose ≤ 4.4 mmol/L (standardized β = -0.078, P = 0.034), and was significantly higher in effective group than in ineffective group (P < 0.001). The Δglucose AUC 0-60 min during post-dinner was significantly higher than that during pre-lunch, post-lunch and pre-dinner (P < 0.05 for all). PEBG is positively correlated with efficacy of aerobic exercise. Aerobic exercise will not worsen hyperglycemia when the PEBG > 16.7 mmol/L. Post-dinner exercise decreases the blood glucose better than other periods of the day. ChiCTR-ONC-17010400, www.chictr.org.cn. Copyright © 2018 Elsevier B.V. All rights reserved.
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Neural network based glucose - insulin metabolism models for children with Type 1 diabetes.
Mougiakakou, Stavroula G; Prountzou, Aikaterini; Iliopoulou, Dimitra; Nikita, Konstantina S; Vazeou, Andriani; Bartsocas, Christos S
2006-01-01
In this paper two models for the simulation of glucose-insulin metabolism of children with Type 1 diabetes are presented. The models are based on the combined use of Compartmental Models (CMs) and artificial Neural Networks (NNs). Data from children with Type 1 diabetes, stored in a database, have been used as input to the models. The data are taken from four children with Type 1 diabetes and contain information about glucose levels taken from continuous glucose monitoring system, insulin intake and food intake, along with corresponding time. The influences of taken insulin on plasma insulin concentration, as well as the effect of food intake on glucose input into the blood from the gut, are estimated from the CMs. The outputs of CMs, along with previous glucose measurements, are fed to a NN, which provides short-term prediction of glucose values. For comparative reasons two different NN architectures have been tested: a Feed-Forward NN (FFNN) trained with the back-propagation algorithm with adaptive learning rate and momentum, and a Recurrent NN (RNN), trained with the Real Time Recurrent Learning (RTRL) algorithm. The results indicate that the best prediction performance can be achieved by the use of RNN.
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In vivo interstitial glucose characterization and monitoring in the skin by ATR-FTIR spectroscopy
NASA Astrophysics Data System (ADS)
Skrebova Eikje, Natalja
2011-03-01
Successful development of real-time non-invasive glucose monitoring would represent a major advancement not only in the treatment and management of patients with diabetes mellitus and carbohydrate metabolism disorders, but also for understanding in those biochemical, metabolic and (patho-)physiological processes of glucose at the molecular level in vivo. Here, ATR-FTIR spectroscopy technique has been challenged not only for in vivo measurement of interstitial glucose levels, but also for their non-invasive molecular qualitative and quantitative comparative characterization in the skin tissue. The results, based on calculated mean values of determined 5 glucose-specific peaks in the glucose-related 1000-1160 cm-1 region, showed intra- and inter-subject differences in interstitial glucose activity levels with their changes at different times and doses of OGTT, while raising questions about the relationships between interstitial and blood glucose levels. In conclusion, the introduction of ATR-FTIR spectroscopy technique has opened up an access to the interstitial fluid space in the skin tissue for interstitial glucose characterization and monitoring in vivo. Though interstitial versus blood glucose monitoring has different characteristics, it can be argued that accurate and precise measurements of interstitial glucose levels may be more important clinically.
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Different methods and settings for glucose monitoring for gestational diabetes during pregnancy.
Raman, Puvaneswary; Shepherd, Emily; Dowswell, Therese; Middleton, Philippa; Crowther, Caroline A
2017-10-29
Incidence of gestational diabetes mellitus (GDM) is increasing worldwide. Blood glucose monitoring plays a crucial part in maintaining glycaemic control in women with GDM and is generally recommended by healthcare professionals. There are several different methods for monitoring blood glucose which can be carried out in different settings (e.g. at home versus in hospital). The objective of this review is to compare the effects of different methods and settings for glucose monitoring for women with GDM on maternal and fetal, neonatal, child and adult outcomes, and use and costs of health care. We searched the Cochrane Pregnancy and Childbirth Group Trials Register (30 September 2016) and reference lists of retrieved studies. Randomised controlled trials (RCTs) or quasi-randomised controlled trials (qRCTs) comparing different methods (such as timings and frequencies) or settings, or both, for blood glucose monitoring for women with GDM. Two authors independently assessed study eligibility, risk of bias, and extracted data. Data were checked for accuracy.We assessed the quality of the evidence for the main comparisons using GRADE, for:- primary outcomes for mothers: that is, hypertensive disorders of pregnancy; caesarean section; type 2 diabetes; and- primary outcomes for children: that is, large-for-gestational age; perinatal mortality; death or serious morbidity composite; childhood/adulthood neurosensory disability;- secondary outcomes for mothers: that is, induction of labour; perineal trauma; postnatal depression; postnatal weight retention or return to pre-pregnancy weight; and- secondary outcomes for children: that is, neonatal hypoglycaemia; childhood/adulthood adiposity; childhood/adulthood type 2 diabetes. We included 11 RCTs (10 RCTs; one qRCT) that randomised 1272 women with GDM in upper-middle or high-income countries; we considered these to be at a moderate to high risk of bias. We assessed the RCTs under five comparisons. For outcomes assessed using GRADE, we downgraded for study design limitations, imprecision and inconsistency. Three trials received some support from commercial partners who provided glucose meters or financial support, or both. Main comparisons Telemedicine versus standard care for glucose monitoring (five RCTs): we observed no clear differences between the telemedicine and standard care groups for the mother, for:- pre-eclampsia or pregnancy-induced hypertension (risk ratio (RR) 1.49, 95% confidence interval (CI) 0.69 to 3.20; 275 participants; four RCTs; very low quality evidence);- caesarean section (average RR 1.05, 95% CI 0.72 to 1.53; 478 participants; 5 RCTs; very low quality evidence); and- induction of labour (RR 1.06, 95% CI 0.63 to 1.77; 47 participants; 1 RCT; very low quality evidence);or for the child, for:- large-for-gestational age (RR 1.41, 95% CI 0.76 to 2.64; 228 participants; 3 RCTs; very low quality evidence);- death or serious morbidity composite (RR 1.06, 95% CI 0.68 to 1.66; 57 participants; 1 RCT; very low quality evidence); and- neonatal hypoglycaemia (RR 1.14, 95% CI 0.48 to 2.72; 198 participants; 3 RCTs; very low quality evidence).There were no perinatal deaths in two RCTs (131 participants; very low quality evidence). Self-monitoring versus periodic glucose monitoring (two RCTs): we observed no clear differences between the self-monitoring and periodic glucose monitoring groups for the mother, for:- pre-eclampsia (RR 0.17, 95% CI 0.01 to 3.49; 58 participants; 1 RCT; very low quality evidence); and- caesarean section (average RR 1.18, 95% CI 0.61 to 2.27; 400 participants; 2 RCTs; low quality evidence);or for the child, for:- perinatal mortality (RR 1.54, 95% CI 0.21 to 11.24; 400 participants; 2 RCTs; very low quality evidence);- large-for-gestational age (RR 0.82, 95% CI 0.50 to 1.37; 400 participants; 2 RCTs; low quality evidence); and- neonatal hypoglycaemia (RR 0.64, 95% CI 0.39 to 1.06; 391 participants; 2 RCTs; low quality evidence). Continuous glucose monitoring system (CGMS) versus self-monitoring of glucose (two RCTs): we observed no clear differences between the CGMS and self-monitoring groups for the mother, for:- caesarean section (RR 0.91, 95% CI 0.68 to 1.20; 179 participants; 2 RCTs; very low quality evidence);or for the child, for:- large-for-gestational age (RR 0.67, 95% CI 0.43 to 1.05; 106 participants; 1 RCT; very low quality evidence) and- neonatal hypoglycaemia (RR 0.79, 95% CI 0.35 to 1.78; 179 participants; 2 RCTs; very low quality evidence).There were no perinatal deaths in the two RCTs (179 participants; very low quality evidence). Other comparisons Modem versus telephone transmission for glucose monitoring (one RCT): none of the review's primary outcomes were reported in this trial Postprandial versus preprandial glucose monitoring (one RCT): we observed no clear differences between the postprandial and preprandial glucose monitoring groups for the mother, for:- pre-eclampsia (RR 1.00, 95% CI 0.15 to 6.68; 66 participants; 1 RCT);- caesarean section (RR 0.62, 95% CI 0.29 to 1.29; 66 participants; 1 RCT); and- perineal trauma (RR 0.38, 95% CI 0.11 to 1.29; 66 participants; 1 RCT);or for the child, for:- neonatal hypoglycaemia (RR 0.14, 95% CI 0.02 to 1.10; 66 participants; 1 RCT).There were fewer large-for-gestational-age infants born to mothers in the postprandial compared with the preprandial glucose monitoring group (RR 0.29, 95% CI 0.11 to 0.78; 66 participants; 1 RCT). Evidence from 11 RCTs assessing different methods or settings for glucose monitoring for GDM suggests no clear differences for the primary outcomes or other secondary outcomes assessed in this review.However, current evidence is limited by the small number of RCTs for the comparisons assessed, small sample sizes, and the variable methodological quality of the RCTs. More evidence is needed to assess the effects of different methods and settings for glucose monitoring for GDM on outcomes for mothers and their children, including use and costs of health care. Future RCTs may consider collecting and reporting on the standard outcomes suggested in this review.
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Hwang, Joon Ho; Sohn, Yong-Hak; Chang, Seong-Sil; Kim, Seung Yeon
2015-08-01
We evaluated three blood glucose self-monitoring for measuring whole blood glucose levels in preterm and low-birth-weight infants. Between December 1, 2012 and March 31, 2013, 230 blood samples were collected from 50 newborns, who weighed, ≤2,300 g or were ≤36 weeks old, in the the neonatal intensive care unit of Eulji University Hospital. Three blood glucose self-monitoring (A: Precision Pcx, Abbott; B: One-Touch Verio, Johnson & Johnson; C: LifeScan SureStep Flexx, Johnson & Johnson) were used for the blood glucose measurements. The results were compared to those obtained using laboratory equipment (D: Advia chemical analyzer, Siemens Healthcare Diagnostics Inc.). The correlation coefficients between laboratory equipment and the three blood glucose self-monitoring (A, B, and C) were found to be 0.888, 0.884, and 0.900, respectively. For glucose levels≤60 mg/dL, the correlation coefficients were 0.674, 0.687, and 0.679, respectively. For glucose levels>60 mg/dL, the correlation coefficients were 0.822, 0.819, and 0.839, respectively. All correlation coefficients were statistically significant. And the values from the blood glucose self-monitoring were not significantly different from the value of the laboratory equipment , after correcting for each device's average value (P>0.05). When using laboratory equipment (blood glucose ≤60 mg/dL), each device had a sensitivity of 0.458, 0.604, and 0.688 and a specificity of 0.995, 0.989, and 0.989, respectively. Significant difference is not found between three blood glucose self-monitoring and laboratory equipment. But correlation between the measured values from blood glucose self-monitoring and laboratory equipment is lower in preterm or low-birth-weight infants than adults.
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Continuous Glucose Monitoring: A Review of Successes, Challenges, and Opportunities.
Rodbard, David
2016-02-01
Continuous glucose monitoring (CGM) provides information unattainable by intermittent capillary blood glucose, including instantaneous real-time display of glucose level and rate of change of glucose, alerts and alarms for actual or impending hypo- and hyperglycemia, "24/7" coverage, and the ability to characterize glycemic variability. Progressively more accurate and precise, reasonably unobtrusive, small, comfortable, user-friendly devices connect to the Internet to share information and are sine qua non for a closed-loop artificial pancreas. CGM can inform, educate, motivate, and alert people with diabetes. CGM is medically indicated for patients with frequent, severe, or nocturnal hypoglycemia, especially in the presence of hypoglycemia unawareness. Surprisingly, despite tremendous advances, utilization of CGM has remained fairly limited to date. Barriers to use have included the following: (1) lack of Food and Drug Administration approval, to date, for insulin dosing ("nonadjuvant use") in the United States and for use in hospital and intensive care unit settings; (2) cost and variable reimbursement; (3) need for recalibrations; (4) periodic replacement of sensors; (5) day-to-day variability in glycemic patterns, which can limit the predictability of findings based on retrospective, masked "professional" use; (6) time, implicit costs, and inconvenience for uploading of data for retrospective analysis; (7) lack of fair and reasonable reimbursement for physician time; (8) inexperience and lack of training of physicians and other healthcare professionals regarding interpretation of CGM results; (9) lack of standardization of software methods for analysis of CGM data; and (10) need for professional medical organizations to develop and disseminate additional clinical practice guidelines regarding the role of CGM. Ongoing advances in technology and clinical research have addressed several of these barriers. Use of CGM in conjunction with an insulin pump with automated suspension of insulin infusion in response to actual observed or predicted hypoglycemia, as well as progressive refinement of closed-loop systems, is expected to dramatically enhance the clinical utility and utilization of CGM.
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Continuous Glucose Monitoring: A Review of Successes, Challenges, and Opportunities
2016-01-01
Abstract Continuous glucose monitoring (CGM) provides information unattainable by intermittent capillary blood glucose, including instantaneous real-time display of glucose level and rate of change of glucose, alerts and alarms for actual or impending hypo- and hyperglycemia, “24/7” coverage, and the ability to characterize glycemic variability. Progressively more accurate and precise, reasonably unobtrusive, small, comfortable, user-friendly devices connect to the Internet to share information and are sine qua non for a closed-loop artificial pancreas. CGM can inform, educate, motivate, and alert people with diabetes. CGM is medically indicated for patients with frequent, severe, or nocturnal hypoglycemia, especially in the presence of hypoglycemia unawareness. Surprisingly, despite tremendous advances, utilization of CGM has remained fairly limited to date. Barriers to use have included the following: (1) lack of Food and Drug Administration approval, to date, for insulin dosing (“nonadjuvant use”) in the United States and for use in hospital and intensive care unit settings; (2) cost and variable reimbursement; (3) need for recalibrations; (4) periodic replacement of sensors; (5) day-to-day variability in glycemic patterns, which can limit the predictability of findings based on retrospective, masked “professional” use; (6) time, implicit costs, and inconvenience for uploading of data for retrospective analysis; (7) lack of fair and reasonable reimbursement for physician time; (8) inexperience and lack of training of physicians and other healthcare professionals regarding interpretation of CGM results; (9) lack of standardization of software methods for analysis of CGM data; and (10) need for professional medical organizations to develop and disseminate additional clinical practice guidelines regarding the role of CGM. Ongoing advances in technology and clinical research have addressed several of these barriers. Use of CGM in conjunction with an insulin pump with automated suspension of insulin infusion in response to actual observed or predicted hypoglycemia, as well as progressive refinement of closed-loop systems, is expected to dramatically enhance the clinical utility and utilization of CGM. PMID:26784127
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Evaluating the accuracy and large inaccuracy of two continuous glucose monitoring systems.
Leelarathna, Lalantha; Nodale, Marianna; Allen, Janet M; Elleri, Daniela; Kumareswaran, Kavita; Haidar, Ahmad; Caldwell, Karen; Wilinska, Malgorzata E; Acerini, Carlo L; Evans, Mark L; Murphy, Helen R; Dunger, David B; Hovorka, Roman
2013-02-01
This study evaluated the accuracy and large inaccuracy of the Freestyle Navigator (FSN) (Abbott Diabetes Care, Alameda, CA) and Dexcom SEVEN PLUS (DSP) (Dexcom, Inc., San Diego, CA) continuous glucose monitoring (CGM) systems during closed-loop studies. Paired CGM and plasma glucose values (7,182 data pairs) were collected, every 15-60 min, from 32 adults (36.2±9.3 years) and 20 adolescents (15.3±1.5 years) with type 1 diabetes who participated in closed-loop studies. Levels 1, 2, and 3 of large sensor error with increasing severity were defined according to absolute relative deviation greater than or equal to ±40%, ±50%, and ±60% at a reference glucose level of ≥6 mmol/L or absolute deviation greater than or equal to ±2.4 mmol/L,±3.0 mmol/L, and ±3.6 mmol/L at a reference glucose level of <6 mmol/L. Median absolute relative deviation was 9.9% for FSN and 12.6% for DSP. Proportions of data points in Zones A and B of Clarke error grid analysis were similar (96.4% for FSN vs. 97.8% for DSP). Large sensor over-reading, which increases risk of insulin over-delivery and hypoglycemia, occurred two- to threefold more frequently with DSP than FSN (once every 2.5, 4.6, and 10.7 days of FSN use vs. 1.2, 2.0, and 3.7 days of DSP use for Level 1-3 errors, respectively). At levels 2 and 3, large sensor errors lasting 1 h or longer were absent with FSN but persisted with DSP. FSN and DSP differ substantially in the frequency and duration of large inaccuracy despite only modest differences in conventional measures of numerical and clinical accuracy. Further evaluations are required to confirm that FSN is more suitable for integration into closed-loop delivery systems.
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Thabit, Hood; Leelarathna, Lalantha; Wilinska, Malgorzata E; Elleri, Daniella; Allen, Janet M; Lubina-Solomon, Alexandra; Walkinshaw, Emma; Stadler, Marietta; Choudhary, Pratik; Mader, Julia K; Dellweg, Sibylle; Benesch, Carsten; Pieber, Thomas R; Arnolds, Sabine; Heller, Simon R; Amiel, Stephanie A; Dunger, David; Evans, Mark L; Hovorka, Roman
2015-11-01
Closed-loop (CL) systems modulate insulin delivery based on glucose levels measured by a continuous glucose monitor (CGM). Accuracy of the CGM affects CL performance and safety. We evaluated the accuracy of the Freestyle Navigator(®) II CGM (Abbott Diabetes Care, Alameda, CA) during three unsupervised, randomized, open-label, crossover home CL studies. Paired CGM and capillary glucose values (10,597 pairs) were collected from 57 participants with type 1 diabetes (41 adults [mean±SD age, 39±12 years; mean±SD hemoglobin A1c, 7.9±0.8%] recruited at five centers and 16 adolescents [mean±SD age, 15.6±3.6 years; mean±SD hemoglobin A1c, 8.1±0.8%] recruited at two centers). Numerical accuracy was assessed by absolute relative difference (ARD) and International Organization for Standardization (ISO) 15197:2013 15/15% limits, and clinical accuracy was assessed by Clarke error grid analysis. Total duration of sensor use was 2,002 days (48,052 h). Overall sensor accuracy for the capillary glucose range (1.1-27.8 mmol/L) showed mean±SD and median (interquartile range) ARD of 14.2±15.5% and 10.0% (4.5%, 18.4%), respectively. Lowest mean ARD was observed in the hyperglycemic range (9.8±8.8%). Over 95% of pairs were in combined Clarke error grid Zones A and B (A, 80.1%, B, 16.2%). Overall, 70.0% of the sensor readings satisfied ISO criteria. Mean ARD was consistent (12.3%; 95% of the values fall within ±3.7%) and not different between participants (P=0.06) within the euglycemic and hyperglycemic range, when CL is actively modulating insulin delivery. Consistent accuracy of the CGM within the euglycemic-hyperglycemic range using the Freestyle Navigator II was observed and supports its use in home CL studies. Our results may contribute toward establishing normative CGM performance criteria for unsupervised home use of CL.
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Peyser, Thomas A; Nakamura, Katherine; Price, David; Bohnett, Lucas C; Hirsch, Irl B; Balo, Andrew
2015-08-01
Accuracy of continuous glucose monitoring (CGM) devices in hypoglycemia has been a widely reported shortcoming of this technology. We report the accuracy in hypoglycemia of a new version of the Dexcom (San Diego, CA) G4 Platinum CGM system (software 505) and present results regarding the optimum setting of CGM hypoglycemic alerts. CGM values were compared with YSI analyzer (YSI Life Sciences, Yellow Springs, OH) measurements every 15 min. We reviewed the accuracy of the CGM system in the hypoglycemic range using standard metrics. We analyzed the time required for the CGM system to detect biochemical hypoglycemia (70 mg/dL) compared with the YSI with alert settings at 70 mg/dL and 80 mg/dL. We also analyzed the time between the YSI value crossing 55 mg/dL, defined as the threshold for cognitive impairment due to hypoglycemia, and when the CGM system alerted for hypoglycemia. The mean absolute difference for a glucose level of less than 70 mg/dL was 6 mg/dL. Ninety-six percent of CGM values were within 20 mg/dL of the YSI values between 40 and 80 mg/dL. When the CGM hypoglycemic alert was set at 80 mg/dL, the device provided an alert for biochemical hypoglycemia within 10 min in 95% of instances and at least a 10-min advance warning before the cognitive impairment threshold in 91% of instances in the study. Use of an 80 mg/dL threshold setting for hypoglycemic alerts on the G4 Platinum (software 505) may provide patients with timely warning of hypoglycemia before the onset of cognitive impairment, enabling them to treat themselves for hypoglycemia with fast-acting carbohydrates and prevent neuroglycopenia associated with very low glucose levels.
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Roze, Stéphane; Smith-Palmer, Jayne; Valentine, William J; Cook, Mark; Jethwa, Manisha; de Portu, Simona; Pickup, John C
2016-01-01
Continuous subcutaneous insulin infusion (CSII) is an important treatment option for type 1 diabetes patients unable to achieve adequate glycemic control with multiple daily injections (MDI). Combining CSII with continuous glucose monitoring (CGM) in sensor-augmented pump therapy (SAP) with a low glucose-suspend (LGS) feature may further improve glycemic control and reduce the frequency of hypoglycemia. A cost-effectiveness analysis of SAP + LGS vs. CSII plus self-monitoring of blood glucose (SMBG) was performed to determine the health economic benefits of SAP + LGS in type 1 diabetes patients using CSII in the U.K. Cost-effectiveness analysis was performed using the CORE diabetes model. Treatment effects were sourced from the literature, where SAP + LGS was associated with a projected HbA1c reduction of -1.49% vs. -0.62% for CSII, and a reduced frequency of severe hypoglycemia. The time horizon was that of patient lifetimes; future costs and clinical outcomes were discounted at 3.5% and 1.5% per annum, respectively. Projected outcomes showed that SAP + LGS was associated with higher mean quality-adjusted life expectancy (17.9 vs. 14.9 quality-adjusted life years [QALYs], SAP + LGS vs. CSII), and higher life expectancy (23.8 vs. 21.9 years), but higher mean lifetime direct costs (GBP 125,559 vs. GBP 88,991), leading to an incremental cost-effectiveness ratio (ICER) of GBP 12,233 per QALY gained for SAP + LGS vs. CSII. Findings of the base-case analysis remained robust in sensitivity analyses. For UK-based type 1 diabetes patients with poor glycemic control, the use of SAP + LGS is likely to be cost-effective compared with CSII plus SMBG.
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Cappon, Giacomo; Marturano, Francesca; Vettoretti, Martina; Facchinetti, Andrea; Sparacino, Giovanni
2018-05-01
The standard formula (SF) used in bolus calculators (BCs) determines meal insulin bolus using "static" measurement of blood glucose concentration (BG) obtained by self-monitoring of blood glucose (SMBG) fingerprick device. Some methods have been proposed to improve efficacy of SF using "dynamic" information provided by continuous glucose monitoring (CGM), and, in particular, glucose rate of change (ROC). This article compares, in silico and in an ideal framework limiting the exposition to possibly confounding factors (such as CGM noise), the performance of three popular techniques devised for such a scope, that is, the methods of Buckingham et al (BU), Scheiner (SC), and Pettus and Edelman (PE). Using the UVa/Padova Type 1 diabetes simulator we generated data of 100 virtual subjects in noise-free, single-meal scenarios having different preprandial BG and ROC values. Meal insulin bolus was computed using SF, BU, SC, and PE. Performance was assessed with the blood glucose risk index (BGRI) on the 9 hours after meal. On average, BU, SC, and PE improve BGRI compared to SF. When BG is rapidly decreasing, PE obtains the best performance. In the other ROC scenarios, none of the considered methods prevails in all the preprandial BG conditions tested. Our study showed that, at least in the considered ideal framework, none of the methods to correct SF according to ROC is globally better than the others. Critical analysis of the results also suggests that further investigations are needed to develop more effective formulas to account for ROC information in BCs.
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Is management of hyperglycaemia in acute phase stroke still a dilemma?
Savopoulos, C; Kaiafa, G; Kanellos, I; Fountouki, A; Theofanidis, D; Hatzitolios, A I
2017-05-01
Close monitoring of blood glucose levels during the immediate post-acute stroke phase is of great clinical value, as there is evidence that the risk of neurological deterioration is associated with both hyper- and hypoglycaemia. The aim of this review paper is to summarise the evidence on post-stroke blood glucose management and its impact on clinical outcomes, during the early post-acute stage. Post-stroke hyperglycaemia has been associated with increased cerebral oedema, haemorrhagic transformation, lower likelihood of recanalisation and deteriorating neurological state. Thus, hyperglycaemia during an acute stroke may result in poorer clinical outcomes, infarct progression, poor functional recovery and increased mortality rates. Although hypoglycaemia may also lead to poorer outcomes via further brain injury, it can be readily reversed by glucose administration. In most patients, the goal of regular treatment is euglycaemia and for acute-stroke patients, a reasonable approach is to target control of glucose level at 100-150 mg/dL. Both hypoglycaemia and hyperglycaemia may lead to further brain injury and clinical deterioration; that is the reason these conditions should be avoided after stroke. Yet, when correcting hyperglycaemia, great care should be taken not to switch the patient into hypoglycaemia, and subsequently aggressive insulin administration treatment should be avoided. Early identification and prompt management of hyperglycaemia, especially in acute ischaemic stroke, is recommended. Although the appropriate level of blood glucose during acute stroke is still debated, a reasonable approach is to keep the patient in a mildly hyperglycaemic state, rather than risking hypoglycaemia, using continuous glucose monitoring.
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Carrara, Marcia Aparecida; Batista, Márcia Regina; Saruhashi, Tiago Ribeiro; Felisberto, Antonio Machado; Guilhermetti, Marcio; Bazotte, Roberto Barbosa
2012-06-06
The contribution of insulin resistance (IR) and glucose tolerance to the maintenance of blood glucose levels in non diabetic pregnant Wistar rats (PWR) was investigated. PWR were submitted to conventional insulin tolerance test (ITT) and glucose tolerance test (GTT) using blood sample collected 0, 10 and 60 min after intraperitoneal insulin (1 U/kg) or oral (gavage) glucose (1g/kg) administration. Moreover, ITT, GTT and the kinetics of glucose concentration changes in the fed and fasted states were evaluated with a real-time continuous glucose monitoring system (RT-CGMS) technique. Furthermore, the contribution of the liver glucose production was investigated. Conventional ITT and GTT at 0, 7, 14 and 20 days of pregnancy revealed increased IR and glucose tolerance after 20 days of pregnancy. Thus, this period of pregnancy was used to investigate the kinetics of glucose changes with the RT-CGMS technique. PWR (day 20) exhibited a lower (p<0.05) glucose concentration in the fed state. In addition, we observed IR and increased glucose tolerance in the fed state (PWR-day 20 vs. day 0). Furthermore, our data from glycogenolysis and gluconeogenesis suggested that the liver glucose production did not contribute to these changes in insulin sensitivity and/or glucose tolerance during late pregnancy. In contrast to the general view that IR is a pathological process associated with gestational diabetes, a certain degree of IR may represent an important physiological mechanism for blood glucose maintenance during fasting. Copyright © 2012 Elsevier Inc. All rights reserved.
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Spectroscopic approach for dynamic bioanalyte tracking with minimal concentration information
NASA Astrophysics Data System (ADS)
Spegazzini, Nicolas; Barman, Ishan; Dingari, Narahara Chari; Pandey, Rishikesh; Soares, Jaqueline S.; Ozaki, Yukihiro; Dasari, Ramachandra Rao
2014-11-01
Vibrational spectroscopy has emerged as a promising tool for non-invasive, multiplexed measurement of blood constituents - an outstanding problem in biophotonics. Here, we propose a novel analytical framework that enables spectroscopy-based longitudinal tracking of chemical concentration without necessitating extensive a priori concentration information. The principal idea is to employ a concentration space transformation acquired from the spectral information, where these estimates are used together with the concentration profiles generated from the system kinetic model. Using blood glucose monitoring by Raman spectroscopy as an illustrative example, we demonstrate the efficacy of the proposed approach as compared to conventional calibration methods. Specifically, our approach exhibits a 35% reduction in error over partial least squares regression when applied to a dataset acquired from human subjects undergoing glucose tolerance tests. This method offers a new route at screening gestational diabetes and opens doors for continuous process monitoring without sample perturbation at intermediate time points.
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Helton, Kristen L; Ratner, Buddy D; Wisniewski, Natalie A
2011-01-01
This article is the second part of a two-part review in which we explore the biomechanics of the sensor–tissue interface as an important aspect of continuous glucose sensor biocompatibility. Part I, featured in this issue of Journal of Diabetes Science and Technology, describes a theoretical framework of how biomechanical factors such as motion and pressure (typically micromotion and micropressure) affect tissue physiology around a sensor and in turn, impact sensor performance. Here in Part II, a literature review is presented that summarizes examples of motion or pressure affecting sensor performance. Data are presented that show how both acute and chronic forces can impact continuous glucose monitor signals. Also presented are potential strategies for countering the ill effects of motion and pressure on glucose sensors. Improved engineering and optimized chemical biocompatibility have advanced sensor design and function, but we believe that mechanical biocompatibility, a rarely considered factor, must also be optimized in order to achieve an accurate, long-term, implantable sensor. PMID:21722579
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Kim, Jongoh; Kim, Se Min; Nguyen, Ha Cam Thuy; Redondo, Maria Jose
2012-01-01
Treatment of pediatric diabetes can be challenging. Strict glucose control can be accompanied by hypoglycemia and weight gain. Recently, there have been many developments in insulin preparations and delivery methods which make insulin levels more close to a physiologic pattern. Newly developed rapid/long acting analogues and delivery devices such as continuous subcutaneous insulin infusion (CSII, insulin pump) may reduce hypoglycemia and improve glycemic control. CSII combined with continuous glucose monitoring can achieve even better glycemic control. The closed-loop system is rapidly evolving and an artificial pancreas will be available in the near future. It is now recognized that several hormones other than insulin such as glucagon, amylin, and incretins contribute to glucose homeostasis. The role of co-adjuncts such as metformin, amylin analogues, and incretin based therapy is now emerging. Immunotherapy in a high risk population or patients in the early phase of type 1 diabetes may prevent further destruction of pancreatic β cells. Copyright © 2011 Elsevier Ltd. All rights reserved.
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Sharifi, Amin; Varsavsky, Andrea; Ulloa, Johanna; Horsburgh, Jodie C; McAuley, Sybil A; Krishnamurthy, Balasubramanian; Jenkins, Alicia J; Colman, Peter G; Ward, Glenn M; MacIsaac, Richard J; Shah, Rajiv; O'Neal, David N
2016-05-01
Current electrochemical glucose sensors use a single electrode. Multiple electrodes (redundancy) may enhance sensor performance. We evaluated an electrochemical redundant sensor (ERS) incorporating two working electrodes (WE1 and WE2) onto a single subcutaneous insertion platform with a processing algorithm providing a single real-time continuous glucose measure. Twenty-three adults with type 1 diabetes each wore two ERSs concurrently for 168 hours. Post-insertion a frequent sampling test (FST) was performed with ERS benchmarked against a glucose meter (Bayer Contour Link). Day 4 and 7 FSTs were performed with a standard meal and venous blood collected for reference glucose measurements (YSI and meter). Between visits, ERS was worn with capillary blood glucose testing ≥8 times/day. Sensor glucose data were processed prospectively. Mean absolute relative deviation (MARD) for ERS day 1-7 (3,297 paired points with glucose meter) was (mean [SD]) 10.1 [11.5]% versus 11.4 [11.9]% for WE1 and 12.0 [11.9]% for WE2; P < .0001. ERS Clarke A and A+B were 90.2% and 99.8%, respectively. ERS day 4 plus day 7 MARD (1,237 pairs with YSI) was 9.4 [9.5]% versus 9.6 [9.7]% for WE1 and 9.9 [9.7]% for WE2; P = ns. ERS day 1-7 precision absolute relative deviation (PARD) was 9.9 [3.6]% versus 11.5 [6.2]% for WE1 and 10.1 [4.4]% for WE2; P = ns. ERS sensor display time was 97.8 [6.0]% versus 91.0 [22.3]% for WE1 and 94.1 [14.3]% for WE2; P < .05. Electrochemical redundancy enhances glucose sensor accuracy and display time compared with each individual sensing element alone. ERS performance compares favorably with 'best-in-class' of non-redundant sensors. © 2015 Diabetes Technology Society.
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Sakaguchi, Kazuhiko; Hirota, Yushi; Hashimoto, Naoko; Ogawa, Wataru; Sato, Toshiyuki; Okada, Seiki; Hagino, Kei; Asakura, Yoshihiro; Kikkawa, Yasuo; Kojima, Junko; Maekawa, Yasunori; Nakajima, Hiromu
2012-06-01
Recent studies have highlighted the importance of managing postprandial hyperglycemia, but adequate monitoring of postprandial glucose remains difficult because of wide variations in levels. We have therefore developed a minimally invasive system to monitor postprandial glucose area under the curve (AUC). This system involves no blood sampling and uses interstitial fluid glucose (IG) AUC (IG-AUC) as a surrogate marker of postprandial glucose. This study aimed to evaluate the usefulness of this system by comparing data with the findings of oral glucose tolerance tests (OGTTs) in subjects with and without diabetes. The glucose AUC monitoring system was validated by OGTTs in 37 subjects with and 10 subjects without diabetes. A plastic microneedle array was stamped on the forearm to extract IG. A hydrogel patch was then placed on the pretreated area to accumulate IG. Glucose and sodium ion concentrations in the hydrogel were measured to calculate IG-AUC at 2-h postload glucose. Plasma glucose (PG) levels were measured every 30 min to calculate reference PG-AUC. IG-AUC correlated strongly with reference PG-AUC (r=0.93) over a wide range. The level of correlation between IG-AUC and maximum PG level was also high (r=0.86). The painless nature of the technique was confirmed by the response of patients to questionnaires. The glucose AUC monitoring system using IG provided good estimates of reference PG-AUC and maximum PG level during OGTTs in subjects with and without diabetes. This system provides easy-to-use monitoring of glucose AUC, which is a good indicator of postprandial glucose.
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Choleau, C; Klein, J C; Reach, G; Aussedat, B; Demaria-Pesce, V; Wilson, G S; Gifford, R; Ward, W K
2002-08-01
The calibration of a continuous glucose monitoring system, i.e. the transformation of the signal I(t) generated by the glucose sensor at time (t) into an estimation of glucose concentration G(t), represents a key issue. The two-point calibration procedure consists of the determination of a sensor sensitivity S and of a background current I(o) by plotting two values of the sensor signal versus the concomitant blood glucose concentrations. The estimation of G(t) is subsequently given by G(t) = (I(t)-I(o))/S. A glucose sensor was implanted in the subcutaneous tissue of nine type 1 diabetic patients during 3 (n = 2) and 7 days (n = 7). For each individual trial, S and I(o) were determined by taking into account the values of two sets of sensor output and blood glucose concentration distant by at least 1 h, the procedure being repeated for each consecutive set of values. S and I(o) were found to be negatively correlated, the value of I(o) being sometimes negative. Theoretical analysis demonstrates that this phenomenon can be explained by the effect of measurement uncertainties on the determination of capillary glucose concentration and of sensor output.
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NASA Astrophysics Data System (ADS)
Rushambwa, Munyaradzi C.; Gezimati, Mavis; Jeeva, J. B.
2017-11-01
Novel advancements in systems miniaturization, electronics in health care and communication technologies are enabling the integration of both patients and doctors involvement in health care system. A Wearable Wireless Body Area Network (WWBAN) provides continuous, unobtrusive ambulatory, ubiquitous health monitoring, and provide real time patient’s status to the physician without any constraint on their normal daily life activities. In this project we developed a wearable wireless body area network system that continuously monitor the health of the elderly and the disabled and provide them with independent, safe and secure living. The WWBAN system monitors the following parameters; blood oxygen saturation using a pulse oximeter sensor (SpO2), heart rate (HR) pulse sensor, Temperature, hydration, glucose level and fall detection. When the wearable system is put on, the sensor values are processed and analysed. If any of the monitored parameter values falls below or exceeds the normal range, there is trigger of remote alert by which an SMS is send to a doctor or physician via GSM module and network. The developed system offers flexibility and mobility to the user; it is a real time system and has significance in revolutionizing health care system by enabling non-invasive, inexpensive, continuous health monitoring.
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Ekberg, Neda Rajamand; Brismar, Kerstin; Malmstedt, Jonas; Hedblad, Mari-Anne; Adamson, Ulf; Ungerstedt, Urban; Wisniewski, Natalie
2010-01-01
Objective The very presence of an implanted sensor (a foreign body) causes changes in the adjacent tissue that may alter the analytes being sensed. The objective of this study was to investigate changes in glucose availability and local tissue metabolism at the sensor–tissue interface in patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Method Microdialysis was used to model implanted sensors. Capillary glucose and subcutaneous (sc) microdialysate analytes were monitored in five T1DM and five T2DM patients. Analytes included glucose, glycolysis metabolites (lactate, pyruvate), a lipolysis metabolite (glycerol), and a protein degradation byproduct (urea). On eight consecutive days, four measurements were taken during a period of steady state blood glucose. Results Microdialysate glucose and microdialysate-to-blood-glucose ratio increased over the first several days in all patients. Although glucose recovery eventually stabilized, the lactate levels continued to rise. These trends were explained by local inflammatory and microvascular changes observed in histological analysis of biopsy samples. Urea concentrations mirrored glucose trends. Urea is neither produced nor consumed in sc tissue, and so the initially increasing urea trend is explained by increased local capillary presence during the inflammatory process. Pyruvate in T2DM microdialysate was significantly higher than in T1DM, an observation that is possibly explained by mitochondrial dysfunction in T2DM. Glycerol in T2DM microdialysate (but not in T1DM) was higher than in healthy volunteers, which is likely explained by sc insulin resistance (insulin is a potent antilipolytic hormone). Urea was also higher in microdialysate of patients with diabetes mellitus compared to healthy volunteers. Urea is a byproduct of protein degradation, which is known to be inhibited by insulin. Therefore, insulin deficiency or resistance may explain the higher urea levels. To our knowledge, this is the first histological evaluation of a human tissue biopsy containing an implanted glucose monitoring device. Conclusions Monitoring metabolic changes at a material–tissue interface combined with biopsy histology helped to formulate an understanding of physiological changes adjacent to implanted glucose sensors. Microdialysate glucose trends were similar over 1-week in T1DM and T2DM; however, differences in other analytes indicated wound healing and metabolic activities in the two patient groups differ. We propose explanations for the specific observed differences based on differential insulin insufficiency/resistance and mitochondrial dysfunction in T1DM versus T2DM. PMID:20920426
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Ekberg, Neda Rajamand; Brismar, Kerstin; Malmstedt, Jonas; Hedblad, Mari-Anne; Adamson, Ulf; Ungerstedt, Urban; Wisniewski, Natalie
2010-09-01
The very presence of an implanted sensor (a foreign body) causes changes in the adjacent tissue that may alter the analytes being sensed. The objective of this study was to investigate changes in glucose availability and local tissue metabolism at the sensor-tissue interface in patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Microdialysis was used to model implanted sensors. Capillary glucose and subcutaneous (sc) microdialysate analytes were monitored in five T1DM and five T2DM patients. Analytes included glucose, glycolysis metabolites (lactate, pyruvate), a lipolysis metabolite (glycerol), and a protein degradation byproduct (urea). On eight consecutive days, four measurements were taken during a period of steady state blood glucose. Microdialysate glucose and microdialysate-to-blood-glucose ratio increased over the first several days in all patients. Although glucose recovery eventually stabilized, the lactate levels continued to rise. These trends were explained by local inflammatory and microvascular changes observed in histological analysis of biopsy samples. Urea concentrations mirrored glucose trends. Urea is neither produced nor consumed in sc tissue, and so the initially increasing urea trend is explained by increased local capillary presence during the inflammatory process. Pyruvate in T2DM microdialysate was significantly higher than in T1DM, an observation that is possibly explained by mitochondrial dysfunction in T2DM. Glycerol in T2DM microdialysate (but not in T1DM) was higher than in healthy volunteers, which is likely explained by sc insulin resistance (insulin is a potent antilipolytic hormone). Urea was also higher in microdialysate of patients with diabetes mellitus compared to healthy volunteers. Urea is a byproduct of protein degradation, which is known to be inhibited by insulin. Therefore, insulin deficiency or resistance may explain the higher urea levels. To our knowledge, this is the first histological evaluation of a human tissue biopsy containing an implanted glucose monitoring device. Monitoring metabolic changes at a material-tissue interface combined with biopsy histology helped to formulate an understanding of physiological changes adjacent to implanted glucose sensors. Microdialysate glucose trends were similar over 1-week in T1DM and T2DM; however, differences in other analytes indicated wound healing and metabolic activities in the two patient groups differ. We propose explanations for the specific observed differences based on differential insulin insufficiency/resistance and mitochondrial dysfunction in T1DM versus T2DM. © 2010 Diabetes Technology Society.
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Ulf, Samuelsson; Ragnar, Hanas; Arne, Whiss Per; Johnny, Ludvigsson
2008-08-01
HbA1c levels are influenced by the glycemic control of previous 2-3 months. Sometimes patients have surprisingly low HbA1c in spite of many correctly measured high blood glucose values, which is difficult to explain. As glucose sensors give an objective picture based on glucose readings several times per minute over 24 hours, we used the area under the curve (AUC) of such subcutaneous glucose profiles to evaluate their relationship with HbA1c. Thirty-two patients were randomized into two study arms, one open and the other blinded. Both arms had 8 pump users and 8 patients with multiple daily injections (MDI). After three months the two arms crossed over. Both study arms wore a continuous glucose monitoring system (CGMS) for 3 days every 2 weeks. HbA1c was determined before and after each 3-month study period. There was no relationship between HbA1c and s.c. glucose AUC or between HbA1c and the number of peaks >15.0 mmol/L when all CGMS profiles during the 6 months were taken together. Children on MDI showed a positive relationship between HbA1c and AUC (P<0.01) as well as the number of peaks (P<0.01). Children with a negative relationship between HbA1c and AUC generally had fewer fluctuations in blood glucose values, whereas children with a positive relationship had wide fluctuations. between s.c. glucose AUC and HbA1c, the results indicate that wide blood glucose fluctuations may be related to high HbA1c values. Therefore, complications and therapeutic interventions should aim at reducing such fluctuations. Although there was no relationship between s.c. glucose AUC and HbA1c, the results indicate that wide blood glucose fluctuations may be related to high HbA1c values. Therefore, complications and therapeutic interventions should aim at reducing such fluctuations.
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Continuous glucose monitoring microsensor with a nanoscale conducting matrix and redox mediator
NASA Astrophysics Data System (ADS)
Pesantez, Daniel
The major limiting factor in kidney clinical transplantation is the shortage of transplantable organs. The current inability to distinguish viability from non-viability on a prospective basis represents a major obstacle in any attempt to expand organ donor criteria. Consequently, a way to measure and monitor a relevant analyte to assess kidney viability is needed. For the first time, the initial development and characterization of a metabolic microsensor to assess kidney viability is presented. The rate of glucose consumption appears to serve as an indicator of kidney metabolism that may distinguish reversible from irreversible kidney damage. The proposed MetaSense (Metabolic Sensor) microdevice would replace periodic laboratory diagnosis tests with a continuous monitor that provides real-time data on organ viability. Amperometry, a technique that correlates an electrical signal with analyte concentration, is used as a method to detect glucose concentrations. A novel two-electrode electrochemical sensing cell design is presented. It uses a modified metallic working electrode (WE) and a bare metallic reference electrode (RE) that acts as a pseudo-reference/counter electrode as well. The proposed microsensor has the potential to be used as a minimally invasive sensor for its reduced number of probes and very small dimensions achieved by micromachining and lithography. In order to improve selectivity of the microdevice, two electron transfer mechanisms or generations were explored. A first generation microsensor uses molecular oxygen as the electron acceptor in the enzymatic reaction and oxidizes hydrogen peroxide (H2O2) to get the electrical signal. The microsensor's modified WE with conductive polymer polypyrrole (PPy) and corresponding enzyme glucose oxidase (GOx) immobilized into its matrix, constitutes the electrochemical detection mechanism. Photoluminescence spectroscopic analysis confirmed and quantified enzyme immobilized concentrations within the matrix. In vitro testing for glucose shows increasing current with increasing analyte concentration. Testing the glucose microsensor with known concentrations of glucose over a period of 48 hours demonstrated both the potential durability and sensitivity of the device. Unknown/blind in vitro glucose experiments showed the reproducibility and accuracy of the microsensor to detect various glucose levels. Thinner polymer matrix films lead to better sensing performance during in vitro tests (0.6nA/mM lower limit sensitivity and 0.2nA/mM upper limit sensitivity). In vitro experiments using electroactive ascorbic acid (AA) and uric acid (UA) showed the selectivity of the sensor for glucose. In an effort to reduce the sensor's oxidation potential (0.7V) and noise, a second generation electron transfer approach was developed by incorporating into a modified Platinum WE with a nanoscale PPy and GOx matrix, a redox mediator. Ferrocene (Fc) was selected as the artificial electron carrier, substituting molecular oxygen in the enzymatic reaction. The incorporation of Fc into the polymer matrix is done by a simple electrochemical synthesis. Modifications in the microsensor design, materials and fabrication process are presented. Experiments with the new sensor generation resulted in higher sensitivity values (22.8nA/mM lower limit sensitivity and 12.5nA/mM upper limit sensitivity) for glucose and noise was further eliminated by operating the sensor at a lower oxidation potential (0.3V). The final experimental work consisted of preliminary ex vivo tests with the MetaSense microdevice on bovine kidney samples, which showed a qualitatively correlation between glucose consumption trend profile during preservation and viability histology outcome.
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Yatabe, Tomoaki; Nakamura, Ryu; Kitagawa, Hiroyuki; Munekage, Masaya; Hanazaki, Kazuhiro
2016-03-01
A 57-year-old woman was diagnosed with type I glycogen storage disease in her twenties. She had undergone hepatectomy under general anesthesia with epidural anesthesia. Fifty minutes after the induction of anesthesia, a 20-gauge venous catheter was inserted in the patient's right hand, and an artificial pancreas (STG-55, Nikkiso Co., Tokyo, Japan) was connected for continuous glucose monitoring and automatic glucose control. Insulin was infused when the blood glucose level reached 120 mg/dL or higher, and glucose was infused when the level fell to 100 mg/dL or lower. After the Pringle maneuver, the blood glucose level increased, and insulin was administered automatically via an artificial pancreas. Hypoglycemia did not occur during the operation. After total parenteral nutrition was started in the intensive care unit (ICU), the blood glucose level increased, and the artificial pancreas controlled the blood glucose level through automatic insulin administration. Thirty-four hours after admission to the ICU, the artificial pancreas was removed because the blood sampling failed. After the removal of the artificial pancreas, blood glucose level was measured every 2 h until extubation. During the ICU stay, hypoglycemia never occurred, with the average blood glucose level being 144 mg/dL. In conclusion, the use of an artificial pancreas for perioperative blood glucose management in a patient with glycogen storage disease had the beneficial effect of enabling the management of blood glucose levels without hypoglycemia.
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[Technological innovations in the treatment of type 1 diabetes in pediatrics].
Tubiana-Rufi, Nadia
2016-01-01
Insulin pumps, continuous glucose monitoring sensors and algorithms for managing the doses of insulin necessary to control blood sugar levels within target values: more and more research is being carried out into "closed loop" systems. The artificial pancreas is today at the stage of clinical trials in adults and children. Copyright © 2015 Elsevier Masson SAS. All rights reserved.