Concept: Glucose meter
A chemiluminescence (CL) amplification platform based on HCC/Lucigenin&GOx (HLG) film was developed. Hollow structural calcium carbonate (HCC) particles were used as alternative materials for carrying both enzyme and CL reagent. The model enzyme (GOx), immobilized in confined space of HCC particles, exhibited an improved biocatalysis. The Michaelis constant (Km) and the enzymatic rate constant (kcat) were determined to be 0.209 μM and 2.21 s(-1), respectively, which are much better than those of either free GOx in aqueous solution or the GOx immobilized on common nanomaterials. Based on the HLG platform, CL signal was effectively amplified and visualized after adding trace glucose, which could be attributed to the HCC particles' high biocompatibility, large specific surface area, attractive interfacial properties and efficient interaction with analyses. The visual CL bioplatform showed an excellent performance with high selectivity, wide linear range and low detection limit for sensing trace glucose. Because it eliminates the need of complicated assembly procedure and enables visualization by the naked eye, the sensitive and selective CL bioplatform would provide wide potential applications in disease diagnosis and food safety.
Background The threshold-suspend feature of sensor-augmented insulin pumps is designed to minimize the risk of hypoglycemia by interrupting insulin delivery at a preset sensor glucose value. We evaluated sensor-augmented insulin-pump therapy with and without the threshold-suspend feature in patients with nocturnal hypoglycemia. Methods We randomly assigned patients with type 1 diabetes and documented nocturnal hypoglycemia to receive sensor-augmented insulin-pump therapy with or without the threshold-suspend feature for 3 months. The primary safety outcome was the change in the glycated hemoglobin level. The primary efficacy outcome was the area under the curve (AUC) for nocturnal hypoglycemic events. Two-hour threshold-suspend events were analyzed with respect to subsequent sensor glucose values. Results A total of 247 patients were randomly assigned to receive sensor-augmented insulin-pump therapy with the threshold-suspend feature (threshold-suspend group, 121 patients) or standard sensor-augmented insulin-pump therapy (control group, 126 patients). The changes in glycated hemoglobin values were similar in the two groups. The mean AUC for nocturnal hypoglycemic events was 37.5% lower in the threshold-suspend group than in the control group (980±1200 mg per deciliter [54.4±66.6 mmol per liter]×minutes vs. 1568±1995 mg per deciliter [87.0±110.7 mmol per liter]×minutes, P<0.001). Nocturnal hypoglycemic events occurred 31.8% less frequently in the threshold-suspend group than in the control group (1.5±1.0 vs. 2.2±1.3 per patient-week, P<0.001). The percentages of nocturnal sensor glucose values of less than 50 mg per deciliter (2.8 mmol per liter), 50 to less than 60 mg per deciliter (3.3 mmol per liter), and 60 to less than 70 mg per deciliter (3.9 mmol per liter) were significantly reduced in the threshold-suspend group (P<0.001 for each range). After 1438 instances at night in which the pump was stopped for 2 hours, the mean sensor glucose value was 92.6±40.7 mg per deciliter (5.1±2.3 mmol per liter). Four patients (all in the control group) had a severe hypoglycemic event; no patients had diabetic ketoacidosis. Conclusions This study showed that over a 3-month period the use of sensor-augmented insulin-pump therapy with the threshold-suspend feature reduced nocturnal hypoglycemia, without increasing glycated hemoglobin values. (Funded by Medtronic MiniMed; ASPIRE ClinicalTrials.gov number, NCT01497938 .).
The delivery of therapeutic peptides for diabetes therapy is compromised by short half-lives of drugs with the consequent need for multiple daily injections that reduce patient compliance and increase treatment cost. In this study, we demonstrate a smart exendin-4 (Ex4) delivery device based on microneedle (MN)-array patches integrated with dual mineralized particles separately containing Ex4 and glucose oxidase (GOx). The dual mineralized particle-based system can specifically release Ex4 while immobilizing GOx as a result of the differential response to the microenvironment induced by biological stimuli. In this manner, the system enables glucose-responsive and closed-loop release to significantly improve Ex4 therapeutic performance. Moreover, integration of mineralized particles can enhance the mechanical strength of alginate-based MN by crosslinking to facilitate skin penetration, thus supporting painless and non-invasive transdermal administration. We believe this smart glucose-responsive Ex4 delivery holds great promise for type 2 diabetes therapy by providing safe, long-term, and on-demand Ex4 therapy.
We present a proof-of-concept demonstration of an all-printed temporary tattoo-based glucose sensor for noninvasive glycemic monitoring. The sensor represents the first example of an easy-to-wear flexible tattoo-based epidermal diagnostic device combining reverse iontophoretic extraction of interstitial glucose and an enzyme-based amperometric biosensor. In-vitro studies reveal the tattoo sensor’s linear response toward physiologically relevant glucose levels with negligible interferences from common coexisting electroactive species. The iontophoretic-biosensing tattoo platform is reduced to practice by applying the device on human subjects and monitoring variations in glycemic levels due to food consumption. Correlation of the sensor response with that of a commercial glucose meter underscores the promise of the tattoo sensor to detect glucose levels in a noninvasive fashion. Control on-body experiments demonstrate the importance of the reverse iontophoresis operation and validate the sensor specificity. This preliminary investigation indicates that the tattoo-based iontophoresis-sensor platform holds considerable promise for efficient diabetes management and can be extended toward noninvasive monitoring of other physiologically relevant analytes present in the interstitial fluid.
Fabrication of an enzyme amperometric biosensor for glucose via electropolymerization of pyrrole in the presence of glucose oxidase onto a hydrogel coated platinum electrode is hereby established as a viable biotransducer fabrication method. Platinum micro- (ϕ=25μm) and macro- (ϕ=100μm) electrodes were electrochemically activated and chemically modified with 3-aminopropyl-trimethoxysilane (APTMS), functionalized with acryloyl(polyethyleneglycol)-N-hydroxysuccinamide (ACRL-PEG-NHS), dipped into a polyHEMA based hydrogel cocktail and UV cross-linked. Electropolymerization of Py in the presence of GOx produced glucose responsive biotransducers that showed; (i) a 4-fold reduction in sensitivity compared with directly electropolymerized PPy films, (ii) an electropolymerization charge density dependence of biotransducer sensitivity and enzyme activity that was maximal at 1.0mC/cm(2) with an apparent K(M) of 33mM, (iii) interference screening of ascorbic acid and (iv) a temporal increase in sensitivity with storage over a 17 days period. This method has the ability to precisely and quantitatively add enzyme catalytic bioactivity to metal or semiconductor biointerfaces for applications in biosensors, bioelectronics and bionics.
Abstract Blood and urine oxalate determinations have been limited to the laboratory setting because of complex sample storage and processing methods as well as the need for color spectrophotometry and ion chromatography. We hypothesized that glucometer test strips, impregnated with glucose oxidase and dyes that measure secondary hydrogen peroxide production, could be infused with oxalate oxidase and produce enhanced color changes in the presence of oxalate. By increasing the amount of sodium oxalate in fresh blood, we found that glucometer-measured oxalate increased on a linear scale. In addition, oxalate levels in synthetic urine could be measured using a visual scale, suggesting that strip dwell time or oxalate/oxalate oxidase concentrations could be manipulated to enhance optimal sensitivity. Although further testing is necessary, this simple, first-generation oxometer may eventually allow point of care testing in the home or office, empowering patients with oxalate-based medical conditions and giving healthcare providers real-time oxalate feedback.
Glucose Meters with Built-In Automated Bolus Calculator: Gadget or Real Value for Insulin-Treated Diabetic Patients?
- Diabetes therapy : research, treatment and education of diabetes and related disorders
- Published over 6 years ago
Self-monitoring of blood glucose is now widely recognized as efficacious to enhance and facilitate diabetes management. More than just a means of recording and storing data, some blood glucose meters (BGMs) are now designed with an embedded automated bolus calculator (ABC) with the goal to propose patients recommendations about insulin dosage. The growing literature in this field tends to claim that these new smart BGMs make patient’s life easier and decision making safer. The main purpose of this review is to verify whether BGMs with a built-in ABC indeed improve the willingness and the ability of insulin-treated patients to make adequate therapeutic decisions and positively impact the metabolic control and the quality of life of ABC users. It appears that, as long as the education provided by caregivers remains a top priority, BGMs with a built-in ABC (more than just electronic gadgets) can be regarded as bringing real value to insulin-treated patients with diabetes.
A novel glucose biosensor, based on the modification of well-aligned polypyrrole nanowires array (PPyNWA) with Pt nanoparticles (PtNPs) and subsequent surface adsorption of glucose oxidase (GOx), is described. The distinct differences in the electrochemical properties of PPyNWA-GOx, PPyNWA-PtNPs, and PPyNWA-PtNPs-GOx electrodes were revealed by cyclic voltammetry. In particular, the results obtained for PPyNWA-PtNPs-GOx biosensor showed evidence of direct electron transfer due mainly to modification with PtNPs. Optimum fabrication of the PPyNWA-PtNPs-GOx biosensor for both potentiometric and amperometric detection of glucose were achieved with 0.2M pyrrole, applied current density of 0.1mAcm(-2), polymerization time of 600s, cyclic deposition of PtNPs from -200mV to 200mV, scan rate of 50mVs(-1), and 20 cycles. A sensitivity of 40.5mV/decade and a linear range of 10μM to 1000μM (R(2)=0.9936) were achieved for potentiometric detection, while for amperometric detection a sensitivity of 34.7μAcm(-2)mM(-1) at an applied potential of 700mV and a linear range of 0.1-9mM (R(2)=0.9977) were achieved. In terms of achievable detection limit, potentiometric detection achieved 5.6μM of glucose, while amperometric detection achieved 27.7μM.
Abstract Background: Systems for self-monitoring of blood glucose (SMBG) have to provide accurate and reproducible blood glucose (BG) values in order to ensure adequate therapeutic decisions by people with diabetes. Materials and Methods: Twelve SMBG systems were compared in a standardized manner under controlled laboratory conditions: nine systems were available on the German market and were purchased from a local pharmacy, and three systems were obtained from the manufacturer (two systems were available on the U.S. market, and one system was not yet introduced to the German market). System accuracy was evaluated following DIN EN ISO (International Organization for Standardization) 15197:2003. In addition, measurement reproducibility was assessed following a modified TNO (Netherlands Organization for Applied Scientific Research) procedure. Comparison measurements were performed with either the glucose oxidase method (YSI 2300 STAT Plus™ glucose analyzer; YSI Life Sciences, Yellow Springs, OH) or the hexokinase method (cobas(®) c111; Roche Diagnostics GmbH, Mannheim, Germany) according to the manufacturer’s measurement procedure. Results: The 12 evaluated systems showed between 71.5% and 100% of the measurement results within the required system accuracy limits. Ten systems fulfilled with the evaluated test strip lot minimum accuracy requirements specified by DIN EN ISO 15197:2003. In addition, accuracy limits of the recently published revision ISO 15197:2013 were applied and showed between 54.5% and 100% of the systems' measurement results within the required accuracy limits. Regarding measurement reproducibility, each of the 12 tested systems met the applied performance criteria. Conclusions: In summary, 83% of the systems fulfilled with the evaluated test strip lot minimum system accuracy requirements of DIN EN ISO 15197:2003. Each of the tested systems showed acceptable measurement reproducibility. In order to ensure sufficient measurement quality of each distributed test strip lot, regular evaluations are required.
Objective: To understand how patients use continuous glucose monitoring (CGM) data in their diabetes management.Methods: We surveyed patients who regularly used CGM (>6 days per week), using 70 questions, many scenario-based. The survey had 6 sections: patient characteristics, general CGM use, hypoglycemia prevention and management, hyperglycemia prevention and management, insulin dosing adjustments (both for incidental hyperglycemia not at meals and at mealtimes), and real-time use versus retrospective analysis.Results: The survey was completed by 222 patients with type 1 diabetes. In response to a glucose of 220mg/dL, the average correction dose adjustment based on rate of change arrows varied dramatically. Specifically, when the CGM device showed 2 arrows up (glucose increasing >3mg/dL/min) respondents stated they would increase their correction bolus, on average, by 140% (range 0-600%). Conversely, 2 arrows down (glucose decreasing >3mg/dL/min) caused respondents to reduce their dose by 42%, with 24% omitting their dose entirely. Furthermore, 59% of respondents stated they would delay a meal in response to rapidly rising glucose; whereas, 60% would wait until after a meal to bolus in response to falling glucose levels. With a glucose value of 120 mg/dL and a falling glucose trend, 70% of respondents would prophylactically consume carbohydrates to avoid hypoglycemia.Conclusion: CGM users utilize CGM data to alter multiple aspects of their diabetes care including insulin dose timing, dose adjustments, and in hypoglycemia prevention. The insulin adjustments are much larger than common recommendations. Additional studies are needed to determine appropriate insulin adjustments based on glucose trend data.