Changes In Glucose Concentration Research Articles

Effectiveness of a novel 1% glucose isotonic electrolyte solution for intraoperative fluid therapy in children: a randomized controlled trial.

BackgroundAn appropriate electrolyte solution is important for safe intraoperative anesthesia management in children. This trial assessed the effectiveness of a novel 1% glucose isotonic electrolyte solution in intraoperative fluid therapy in children.MethodsThis trial analyzed data from 100 patients aged older than 1 month with an ASA score of I to II who received general anesthesia. Patients were randomly assigned to receive either the novel electrolyte solution (containing glucose, sodium, potassium, chloride, and bicarbonate) or lactated Ringer’s solution intraoperatively as a maintenance fluid. Patient demographics and the results of blood gas analysis at 1, 2, and 3 hours were documented, and changes in glucose and electrolyte concentrations and the acid–base status were analyzed.ResultsDuring infusion of the novel solution, the glucose and potassium concentrations were stable. Conversely, the solution was linked to increased sodium levels but decreased bicarbonate levels, although both changes were within the physiological ranges. In addition, pH remained stable during the intraoperative period. Hypoglycemia, hyperglycemia, hyponatremia, or hypernatremia was not detected.ConclusionsThe novel 1% glucose isotonic electrolyte solution helped to maintain glucose and electrolyte concentrations and acid–base stability, and it may therefore improve children’s safety during the intraoperative period.

Changes in blood glucose and lactate concentrations with hemodialysis.

Blood glucose concentrations are recognized to vary during hemodialysis (HD), with hypoglycemia reported with glucose-free dialysates. As glucose can be converted to lactate, and conversely lactate to glucose, we wished to study factors associated with peri-dialytic changes in blood glucose. We prospectively collected data including patient profile, dialysis prescription, hemodynamic parameters, medications, dialysis adequacy and monthly blood tests for three consecutive months. All patients used a 100mg/dl glucose dialysate. Linear mixed model, general estimated equation and binary logistic regression were used for analysis. We studied 157 sessions in 55 patients, median age 67.1 (58.5-72.6) years, 67% male, 71% diabetic, 40% prescribed insulin, dialysis vintage 20.4 (10.7-57.7) months. Mean single pool Kt/Vurea and normalized protein nitrogen appearance rate (nPNA) were 1.70±0.34 and 1.01±0.30g/kg/day respectively. Hypoglycemia (<70mg/dl) occurred during 10 sessions (6.4%). 25% of non-diabetes experienced hypoglycemia. The % change in peri-dialytic blood glucose was associated with the % change in lactate (estimate of fixed effect=0.23 p<0.001) and pre-HD glucose (estimate of fixed effect=0.09, p<0.001). The fall in glucose was not associated with urea clearance, consumption of food, administration of insulin or antidiabetic medications, nPNA, body mass index, or pyridoxine concentrations. Peri-dialytic hypoglycemia cannot simply be explained by dialyzer clearance, as the corresponding fall in lactate would potentially suggest increased gluconeogenesis. Despite using a glucose containing dialysate, asymptomatic hypoglycemia occurred in 6.4% of sessions, suggesting a role for peri-dialytic blood glucose monitoring and avoiding fasting during dialysis.

Nanoparticles capable of managing hypoglycemia and preventing myocardial ischemia‐reperfusion injury

AbstractDiabetes, and its complications, is a major threat to human health. In this research, we successfully synthesized a new type of glucose‐responsive poly(3‐acrylamidophenylboronic acid‐co‐pterostilbene) (p(AAPBA‐co‐PTE) nanoparticle. The nanoparticles are round in shape with a size between 150 and 200 nm. Insulin‐loaded p(AAPBA‐co‐PTE) nanoparticles can self‐adjust according to the changes in glucose concentration in vitro to achieve effective and sustained levels of insulin. P(AAPBA‐co‐PTE) nanoparticles have good stability, and the drug loading of insulin‐loaded p(AAPBA‐co‐PTE) nanoparticles is up to 16.7%, the encapsulation efficiency is up to 82.4% and the release rate of pterostilbene in vitro is up to 81%. The p(AAPBA‐co‐PTE) nanoparticles have low toxicity toward cells, and can effectively reduce blood sugar within 24 h. After 14 days of treatment, an animal model of myocardial ischemia‐reperfusion injury (MI/RI) was established. After treatment with the insulin‐loaded p(AAPBA‐co‐PTE) nanoparticles, the rat heart function was significantly improved, and the levels of inflammatory factors were significantly reduced. P(AAPBA‐co‐PTE) nanoparticles were therefore successfully synthesized, and had good performance. P(AAPBA‐co‐PTE) nanoparticles appear to have the effect of reducing blood sugar and preventing MI/RI, and may be valuable for the development of treatments for MI/RI.

Artificial blood vessel biofuel cell for self-powered blood glucose monitoring

Biofuel cell (BFC) is a kind of bio-cell based on biological enzymes. The enzyme as a catalyst can interconvert renewable and sustainable energy into each other more rapidly, such as the biochemical energy in glucose and ethanol into electrical energy. In this work, artificial blood vessel and fuel cell are based on polyaniline/thermoplastic polyurethane (PANI/TPU) fiber membrane with an average fiber diameter of 1300 nm, a film thickness of 167 μm, and a permeability of 18.4 mm s−1. The PANI/TPU fiber membrane was prepared by electrospinning and followed in situ polymerization. The membrane has good flexibility and mechanical properties, and can be stretched up to 200%. The advantages of good hydrophilicity, biocompatibility and high porosity make it possible to efficiently load glucose oxidase and laccase. The prepared BFC can stably output a voltage of 50 mV in simulated blood, and the output electrical signal changes significantly with the change of glucose concentration, which may be used in implantable devices or blood glucose monitoring.

Effects of psychological, sensory, and metabolic energy prime manipulation on the acute endocrine stress response in fasted women

The stress response supports survival through energy mobilization. Paradoxically, a low blood glucose level dampens the endocrine stress response, and sugar consumption prior to stress restores it. Thus, energy availability may play a causal role in the endocrine stress response. Yet, it has never been tested whether sweet taste or expectations towards a drink content modulate the stress response. We investigated the potential role of sweetness, energy load and expectations towards energy load of a drink consumed prior to stress in restoring stress reactivity after fasting. N = 152 women (meanage=21.53, sdage=2.61) participated in the Trier Social Stress Test for groups in the morning after an overnight fast. Prior to stress induction, participants consumed a drink containing saccharose (sugar, n = 51), an equally sweet drink containing non-caloric sweetener (sweetener, n = 46), or water (n = 56). Additionally, participants in the sugar and sweetener group (n = 97) were informed whether or not their drink contained any calories (energy prime), which was deceptive in 50% of the cases. Eight salivary cortisol (−30, −20, −10, 0, +12, +25, +35, +45 min) and three blood glucose samples (−30, 0, +25 min) were assessed throughout the experiment. The effects of the experimental manipulations on cortisol trajectories were tested using multilevel mixed models. We found that compared with water, sugar and sweetener both significantly increased cortisol stress reactivity and with comparable intensity. However, our sensitivity analysis revealed a significant effect of sugar on cortisol trajectories compared to water and to sweetener. Drink-induced changes in blood glucose concentration were not associated with increases in cortisol. The energy prime did not affect the stress response. Overall, we could replicate the boosting effect of sugar consumption in a female sample after 8 h of fasting. The specific contribution of sweet taste and metabolic hormones to this boosting effect should be tested more rigorously in sex-balanced designs in the future.

Feasibility Evaluation of Metamaterial Microwave Sensors for Non-Invasive Blood Glucose Monitoring.

The use of microwave technology is currently under investigation for non-invasive estimation of glycemia in patients with diabetes. Due to their construction, metamaterial (MTM)-based sensors have the potential to provide higher sensitivity of the phase shift of the S21 parameter () to changes in glucose concentration compared to standard microstrip transmission line (MSTL)-based sensors. In this study, a MSTL sensor and three MTM sensors with 5, 7, and 9 MTM unit cells are exposed to liquid phantoms with different dielectric properties mimicking a change in blood glucose concentration from 0 to 14 mmol/L. Numerical models were created for the individual experiments, and the calculated S-parameters show good agreement with experimental results, expressed by the maximum relative error of 8.89% and 0.96% at a frequency of 1.99 GHz for MSTL and MTM sensor with nine unit cells, respectively. MTM sensors with an increasing number of cells show higher sensitivity of 0.62° per mmol/L and unit cell to blood glucose concentration as measured by changes in . In accordance with the numerical simulations, the MTM sensor with nine unit cells showed the highest sensitivity of the sensors proposed by us, with an average of 3.66° per mmol/L at a frequency of 1.99 GHz, compared to only 0.48° per mmol/L for the MSTL sensor. The multi-cell MTM sensor has the potential to proceed with evaluation of human blood samples.

An Electromagnetic Band Gap-Based Complementary Split Ring Resonator Loaded Patch Antenna for Glucose Level Measurement

This paper reports a novel antenna design using a complementary split-ring resonator loaded truncated patch along with electromagnetic band gap structure etching on the ground plane. It can be used for non-invasive measurement of glucose concentration in blood plasma. The size of antenna design is compact having volume ( $20\times 15\times 1.524$ ) mm3. It has a wide bandwidth of 5.2 GHz, which covers a range from 24.1 GHz to 29.3 GHz with a resonant frequency of 25.55 GHz. 3D model of the fingertip is loaded on the radiating patch which works as an RF sensor. Simulation results of reflection coefficient S11 (dB) shows a deviation in resonant frequency due to change in electrical properties of blood plasma such as dielectric constant and dielectric loss tangent. After proper calibration in laboratory, such type of changes can be utilized in the glucose concentration monitoring of diabetic patients non-invasively. In laboratory, the measurements of S11 (dB) and frequency shift with respect to different time periods are observed. The proposed antenna works as an RF sensor that is able to transmit in 5G range from 24.1 GHz to 29.3 GHz for glucose level monitoring in real-time access. The accuracy and sensitivity of the proposed antenna based RF sensor towards small variation in electrical properties of blood due to change in blood glucose concentration are also evaluated and they are found to be satisfactory.

Longitudinal FRET Imaging of Glucose and Lactate Dynamics and Response to Therapy in Breast Cancer Cells.

The reprogramming of cellular metabolism is a hallmark of cancer. The ability to noninvasively assay glucose and lactate concentrations in cancer cells would improve our understanding of the dynamic changes in metabolic activity accompanying tumor initiation, progression, and response to therapy. Unfortunately, common approaches for measuring these nutrient levels are invasive or interrupt cell growth. This study transfected FRET reporters quantifying glucose and lactate concentration into breast cancer cell lines to study nutrient dynamics and response to therapy. Two FRET reporters, one assaying glucose concentration and one assaying lactate concentration, were stably transfected into the MDA-MB-231 breast cancer cell line. Correlation between FRET measurements and ligand concentration were measured using a confocal microscope and a cell imaging plate reader. Longitudinal changes in glucose and lactate concentration were measured in response to treatment with CoCl2, cytochalasin B, and phloretin which, respectively, induce hypoxia, block glucose uptake, and block glucose and lactate transport. The FRET ratio from the glucose and lactate reporters increased with increasing concentration of the corresponding ligand (p < 0.005 and p < 0.05, respectively). The FRET ratio from both reporters was found to decrease over time for high initial concentrations of the ligand (p < 0.01). Significant differences in the FRET ratio corresponding to metabolic inhibition were found when cells were treated with glucose/lactate transporter inhibitors. FRET reporters can track intracellular glucose and lactate dynamics in cancer cells, providing insight into tumor metabolism and response to therapy over time.

Wearable Bifocal Contact Lens for Continual Glucose Monitoring Integrated with Smartphone Readers.

Commercial implantable continuous glucose monitoring devices are invasive and discomfort. Here, a minimally-invasive glucose detection system is developed to provide quantitative glucose measurements continually based on bifocal contact lenses. A glucose-sensitive phenylboronic acid derivative is immobilized in a hydrogel matrix and the surface of the hydrogel is imprinted with a Fresnel lens. The glucose-responsive hydrogel is attached to a commercial soft contact lens to be transformed into a bifocal contact lens. The contact lens showed bifocal lengths; far-field focal length originated from the contact lens' curvature, and near-field focal length resulting from the Fresnel lens. When tear glucose increased, the refractive index and groove depth of the Fresnel lens changed, shifting the near-field focal length and the light focusing efficiency. The recorded optical signals are detected at an identical distance far from the contact lens change. The bifocal contact lens allowed for detecting the tear glucose concentration within the physiological range of healthy individuals and diabetics (0.0-3.3mm). The contact lens rapidly responded to glucose concentration changes and reached 90% of equilibrium within 40min. The bifocal contact lens is a wearable diagnostic platform for continual biomarker detection at point-of-care settings.

Towards robust glucose chemical exchange saturation transfer imaging in humans at 3T: Arterial input function measurements and the effects of infusion time.

Dynamic glucose-enhanced (DGE) magnetic resonance imaging (MRI) has shown potential for tumor imaging using D-glucose as a biodegradable contrast agent. The DGE signal change is small at 3T (around 1%) and accurate detection is hampered by motion. The intravenous D-glucose injection is associated with transient side effects that can indirectly generate subject movements. In this study, the aim was to study DGE arterial input functions (AIFs) in healthy volunteers at 3T for different scanning protocols, as a step towards making the glucose chemical exchange saturation transfer (glucoCEST) protocol more robust. Two different infusion durations (1.5 and 4.0min) and saturation frequency offsets (1.2 and 2.0ppm) were used. The effect of subject motion on the DGE signal was studied by using motion estimates retrieved from standard retrospective motion correction to create pseudo-DGE maps, where the apparent DGE signal changes were entirely caused by motion. Furthermore, the DGE AIFs were compared with venous blood glucose levels. A significant difference (p = 0.03) between arterial baseline and postinfusion DGE signal was found after D-glucose infusion. The results indicate that the measured DGE AIF signal change depends on both motion and blood glucose concentration change, emphasizing the need for sufficient motion correction in glucoCEST imaging. Finally, we conclude that a longer infusion duration (e.g. 3-4 min) should preferably be used in glucoCEST experiments, because it can minimize the glucose infusion side effects without negatively affecting the DGE signal change.

In Vivo Monitoring of Glucose Using Ultrasound-Induced Resonance in Implantable Smart Hydrogel Microstructures.

A novel glucose sensor is presented using smart hydrogels as biocompatible implantable sensing elements, which eliminates the need for implanted electronics and uses an external medical-grade ultrasound transducer for readout. The readout mechanism uses resonance absorption of ultrasound waves in glucose-sensitive hydrogels. In vivo glucose concentration changes in the interstitial fluid lead to swelling or deswelling of the gels, which changes the resonance behavior. The hydrogels are designed and shaped such as to exhibit specific mechanical resonance frequencies while remaining sonolucent to other frequencies. Thus, they allow conventional and continued ultrasound imaging, while yielding a sensing signal at specific frequencies that correlate with glucose concentration. The resonance frequencies can be tuned by changing the shape and mechanical properties of the gel structures, such as to allow for multiple, colocated implanted hydrogels with different sensing characteristics or targets to be employed and read out, without interference using the same ultrasound transducer, by simply toggling frequencies. The fact that there is no need for any implantable electronics, also opens up the path toward future use of biodegradable hydrogels, thus creating a platform that allows injection of sensors that do not need to be retrieved when they reach the end of their useful lifespan.

Non-Invasive Glucose Measurement Using Sub-Terahertz Sensor, Time Domain Processing, and Neural Network

This paper reports a non-invasive sub-Terahertz glucose concentration measurement system consisting of Sensor Unit (SU) and Processing Unit (PU). The SU. uses waveguide probe sensors to obtain the S parameters of glucose samples of different concentrations. These S parameters depend on the dielectric properties of glucose samples. The frequency-dependent permittivity values of various glucose samples are theoretically estimated using the double-Debye model for sensitivity and uncertainty investigations. The glucose sample concentration is used in the range 70-145 mg/dl to mimic healthy human bodies' blood glucose levels, ranging from 70 to 140 mg/dl. The S parameters obtained through SU are converted to the time domain to obtain real-valued impulse responses, which are normalized in PU, making the input data suitable for analysis using Levenberg-Marquardt (LM) algorithm-based Back Propagation Neural Network. The proposed SU. provides a sensitivity of 2 dB for 15 mg/dl change in glucose concentration, and PU exhibits an accuracy of ±5%, which falls within the clinical range specified for non-invasive based monitoring systems for diabetes. Overall, SU provides high sensitivity towards blood glucose measurement, and PU enhances the measurement system's readability by forming a non-linear relationship between S parameters and glucose concentration values.

Acute Glucose Shift Induces the Activation of the NLRP3 Inflammasome in THP-1 Cells

We aimed to investigate the effect of acute glucose shift on the activation of the NLRP3 inflammasome, IL-1β secretion, and underlying signaling pathways in THP-1 cells. THP-1 cells were divided into four groups and exposed to the following glucose concentrations for 24 h: constant normal glucose (NG, 5.5 mM), constant high glucose (HG, 25 mM), normal to high glucose shift (NG-to-HG, 5.5 to 25 mM), and high to normal glucose shift (HG-to-NG, 25 to 5.5 mM). Cell viability, oxidative stress, and the levels of NLRP3 inflammasome components were assessed. Both directions of the acute glucose shift increased the activation of the NLRP3 inflammasome, generation of reactive oxygen species (ROS), and expression of phosphorylated p38 MAPK, JNK, and NF-κB compared with either constant NG or HG. Treatment with N-acetylcysteine, a pharmacological antioxidant, inhibited the acute glucose shift-induced generation of ROS, activation of NLRP3 inflammasome, and upregulation of MAPK-NF-κB. Further analysis using inhibitors of p38 MAPK, JNK, and NF-κB indicated that acute glucose shifts promoted IL-1β secretion by activating the signaling pathway in a ROS-MAPK-NF-κB-NLRP3 inflammasome in THP-1 cells. These findings suggested that acute changes in glucose concentration might cause monocyte inflammation, which is associated with diabetic complications.

Seasonal effect of milk yield and blood metabolites in relation to ketosis of dairy cows fed under a high ambient temperature.

Background and Aim:Metabolism and environment are closely related. Under high ambient temperature (HTa), dairy cows may have different energy metabolism during summer and winter. The present study was carried out to investigate the effect of HTa on the milk yield and blood concentration of beta-hydroxybutyrate (BHBA) and glucose at the herd level.Materials and Methods:One large dairy farm in Thailand with more than 100 crossbred Holstein cows milked each month was selected. The first experiment was performed on non-lactating cows to determine the normal daily concentrations of blood BHBA and glucose. Under the HTa condition, there was no significant change in blood BHBA and glucose concentrations. The second experiment was performed using a prospective cohort clinical design to demonstrate the seasonal effect on milk yield and blood BHBA as an indication of energy metabolism at the herd level.Results:The temperature and humidity index for the winter (78.1±0.5) and summer (83.4±0.7) periods differ significantly. The average milk yield during the winter period was 17.8% higher than during the summer period. The reduction of body condition score (BCS) during early lactation was significant in the winter cows. Both higher milk yield and lower BCS in the winter cows suggested a state of negative energy balance. However, there was no difference in blood BHBA and glucose concentrations between winter and summer cows. The effect of HTa on insulin signaling appeared to be a counterbalancing factor for the ketogenic status. Based on the present results, it would be interesting to further investigate the incidence of subclinical and clinical ketosis in a dairy farm under tropical conditions.Conclusion:The present experiment revealed that HTa during summer decreased milk yield in dairy cows fed under tropical conditions. Higher milk yield in winter caused a greater reduction of BCS and suggested a greater negative energy balance. However, there was no seasonal effect on blood BHBA and glucose concentrations.

Preemptive Midazolam Can Reduce the Glycemic Stress Response to Surgery for Type-2 Diabetics Undergoing Simple Eye Surgery

Abstract Background: Estimation of percentage of change of blood glucose concentration (BGC) at 30- and 60-min after single dose of intravenous midazolam injection and at end of surgery in relation to pre-injection concentration. Aim of Study: Estimation of percentage of changes of blood glucose concentration (BGC) at 30- and 60-min after intravenous injection of single dose of midazolam and at end of surgery in relation to pre-injection BGC. Patients and Methods: 100 type-2 diabetic patients with fasting BGC of ³200mg/dl, ASA grade II or III and assigned for cataract surgery were evaluated clinically and received midazolam injection in a dose of 0. 0 1-0. 1 mg/kg, up to a total dose of 2.5mg, over two minutes or until patient was sedated and achieved Ramsy score 2 or 3. BGC was estimated before midazolam injection and at 30-min, 60-min after injection and at end of surgery. Then, patients received peribulbar and subtenon local anesthetic infiltration was performed. Results: All surgeries were conducted uneventfully within a mean operative time of 62.6±8.8 min. BGC showed progres-sive increases during surgery reaching a maximum at 60-min after injection and declined at end of surgery, but with non-significant differences between the three estimations and the pre-injection levels. Median value of percentage of increase of BGC at 60-min was significantly higher in comparison to median values of other estimations, with significantly higher percentage of increase at end of surgery than at 30-min after injection. Conclusion: Preemptive administration of midazolam for diabetic patients could control the surgery-induced hypergly-cemic effect and thus could protect patients against postoper-ative hyperglycemic complications.

Branched-Chain Amino Acid Catabolism and Cardiopulmonary Function Following Acute Maximal Exercise Testing in Adolescents.

Background: To provide energy for cardiopulmonary function and maintenance of blood glucose, acute aerobic exercise induces lipolysis, fatty acid oxidation (FAO), glycolysis, and glycogenolysis/gluconeogenesis. These adaptations are mediated by increases in cortisol, growth hormone (GH), and catecholamines and facilitated by a decline in insulin. Branched-chain amino acids (BCAA) also undergo catabolism during intense exercise. Here, we investigated the relationship between BCAA catabolism and metrics of cardiopulmonary function in healthy, well-developed, mature adolescent athletes undergoing an acute bout of maximal aerobic exercise.Hypothesis: We hypothesized: (a) acute maximal exercise in adolescents induces lipolysis, FAO, and BCAA catabolism associated with increases in GH and cortisol and a reduction in insulin; (b) increases in GH are associated with increases in ghrelin; and (c) metrics of cardiopulmonary function (aVO2, rVO2, aVO2/HRmax) following maximal exercise correlate with increases in GH secretion, FAO, and BCAA catabolism.Methods: Blood samples before and after maximal cardiopulmonary exercise in 11 adolescent athletes were analyzed by tandem-mass spectrometry. Paired, two-tailed student's t-tests identified significant changes following exercise. Linear regression determined if pre-exercise metabolite levels, or changes in metabolite levels, were associated with aVO2, rVO2, and aVO2/HRmax. Sex and school of origin were included as covariates in all regression analyses.Results: Following exercise there were increases in GH and cortisol, and decreases in ghrelin, but no changes in glucose or insulin concentrations. Suggesting increased lipolysis and FAO, the levels of glycerol, ketones, β-hydroxybutyrate, and acetylcarnitine concentrations increased. Pyruvate, lactate, alanine, and glutamate concentrations also increased. Plasma concentrations of valine (a BCAA) declined (p = 0.002) while valine degradation byproducts increased in association with decreases in urea cycle amino acids arginine and ornithine. Metrics of cardiopulmonary function were associated with increases in propionylcarnitine (C3, p = 0.013) and Ci4-DC/C4-DC (p < 0.01), byproducts of BCAA catabolism.Conclusions: Induction of lipolysis, FAO, gluconeogenesis, and glycogenolysis provides critical substrates for cardiopulmonary function during exercise. However, none of those pathways were significantly associated with metrics of cardiopulmonary function. The associations between rVO2, and aVO2/HRmax and C3 and Ci4-DC/C4-DC suggest that the cardiopulmonary response to maximal exercise in adolescents is linked to BCAA utilization and catabolism.

Optical glucose detection using birefringent long-period fiber grating functionalized with graphene oxide

We propose an optical glucose sensor based on an enzymatic graphene oxide (GO)-functionalized π-phase-shifted long-period fiber grating (PS-LPFG) inscribed on high-birefringence fiber (HBF) by CO2 laser irradiation. To fabricate a sensitive and selective sensor head, we coated the PS-LPFG inscribed on HBF (referred to as the HB-PS-LPFG) with GO and covalently immobilized glucose oxidase (GOD) on the coated GO film. When the enzymatic GO-functionalized HB-PS-LPFG (i.e., the sensor head) is immersed in glucose solution samples, the immobilized GOD catalyzes the oxidation of glucose to gluconic acid, resulting in refractive index (RI) changes in the local sensing region of the fiber. These RI changes lead to variations in the transmission spectrum of the HB-PS-LPFG, and the glucose concentration of the sample can be quantified by measuring spectral shifts. Owing to the birefringence of HBF, the fabricated HB-PS-LPFG had polarization-dependent attenuation dips, which exhibited variations in transmission level or wavelength for both glucose concentration and temperature changes (ΔC and ΔT, respectively). From these attenuation dips, we selected two dips (designated as AD 1 and AD 3) as sensor indicators because they showed linear and independent responses to ΔC in a glucose concentration range of 5 to 25 mM and ΔT in a temperature range of 25°C to 45°C, respectively. The glucose concentration and temperature-induced sensitivities of the two indicators were calculated as ∼0.0 pm / mM and ∼86.8 pm / ° C for AD 1 and ∼20.8 pm / mM and ∼149.2 pm / ° C for AD 3, respectively, which revealed the sensor capability of simultaneous measurement. With these unique ΔC and ΔT responses of the sensor head, our sensor can detect glucose concentration in a cost-effective way, minimizing the temperature-induced measurement uncertainty.

A modified fluorescent sensor for reporting glucose concentration in the airway lumen.

We have modified the periplasmic Escherichia coli glucose/galactose binding protein (GBP) and labelled with environmentally sensitive fluorophores to further explore its potential as a sensor for the evaluation of glucose concentration in airway surface liquid (ASL). We identified E149C/A213R GBP labelled with N,N’-Dimethyl-N-(iodoacetyl)-N’-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)ethylenediamine (IANBD, emission wavelength maximum 536nm) with a Kd for D-glucose of 1.02mM and a fluorescence dynamic range of 5.8. This sensor was specific for D-glucose and exhibited fluorescence stability in experiments for several hours. The use of E149C/A213R GBP-IANBD in the ASL of airway cells grown at air-liquid-interface (ALI) detected an increase in glucose concentration 10 minutes after raising basolateral glucose from 5 to 15mM. This sensor also reported a greater change in ASL glucose concentration in response to increased basolateral glucose in H441 airway cells compared to human bronchial epithelial cells (HBEC) and there was less variability with HBEC data than that of H441 indicating that HBEC more effectively regulate glucose movement into the ASL. The sensor detected glucose in bronchoalveolar lavage fluid (BALf) from diabetic db/db mice but not normoglycaemic wildtype mice, indicating limited sensitivity of the sensor at glucose concentrations <50μM. Using nasal inhalation of the sensor and spectral unmixing to generate images, E149C/A213R GBP-IANBD fluorescence was detected in luminal regions of cryosections of the murine distal lung that was greater in db/db than wildtype mice. In conclusion, this sensor provides a useful tool for further development to measure luminal glucose concentration in models of lung/airway to explore how this may change in disease.

Metformin-hydrogel with glucose responsiveness for chronic inflammatory suppression

Diabetes-induced chronic inflammation accelerates tissue degeneration and is difficult to cure due to the persistent pathological high-glucose microenvironment. Herein, a glucose-responsive drug delivery system was constructed by conjugating phenylboronic acid on the surface of liposomes via membrane insertion and further crosslinked into a glucosamine-modified hydrogel composed of hyaluronic acid (HA) and poly(ethylene glycol) diacrylate (PEG) through borate linkages to deliver metformin, which could achieve the anti-inflammation effect under high glucose condition (Met@HA-PEG).The release kinetics results revealed that Met@HA-PEG could adjust the amount of metformin by responding to the change of glucose concentrations. It is proved that Met@HA-PEG could protect mitochondria from ROS, thereby inhibiting the activation of the NLRP3 inflammatory pathway and finally increasing the synthesis of extracellular matrix (ECM) in the nucleus pulposus cells compared to the high glucose-treated group. In vivo experiments showed that Met@HA-PEG could effectively promote tissue regeneration in the diabetes-induced intervertebral disc degeneration model rats by inhibiting high glucose-induced chronic inflammation and stimulating ECM synthesis. Overall, a drug delivery system with glucose sensitivity was designed to achieve the spatiotemporal release of metformin, the long-term anti-inflammation and promotion of ECM synthesis which ensures the smooth completion of tissue regeneration under diabetic conditions.

Changes in urinary glucose concentration and body weight in patients treated with the selective SGLT2 inhibitor luseogliflozin

AimsWe investigated the effects of the SGLT2 inhibitor luseogliflozin on blood and urinary glucose and body weight. MethodsLuseogliflozin 2.5 mg was administered once daily for 24 weeks to 30 outpatients with type 2 diabetes. Urinary glucose concentration, continuous glucose monitoring values, HbA1c, fasting glucose, and body weight were evaluated. Correlations with urinary glucose, subcutaneous/visceral fat mass, insulin, EPA/AA ratio, plasma free fatty acids, ghrelin, blood ketones, plasma 1,5-anhydro-D-glucitol were evaluated. ResultsUrinary glucose significantly increased from 11.1 ± 11.8 g at Week −4 to 84.5 ± 46.8 g at Week 24. HbA1c significantly declined from 7.88 ± 0.88% to 7.36 ± 1.13% at Week 24. Mean blood glucose significantly decreased from 149.6 ± 41.8 to 131.6 ± 31.1 mg/dL at Week 24. Subcutaneous and visceral fat mass was also significantly decreased, as were AST and ALT (P < 0.01). Blood urea nitrogen was significantly increased, and urate significantly decreased from 5.04 ± 1.07 to 4.53 ± 0.94 mg/dL. The homeostasis model assessment ratio remained significantly improved throughout the treatment period. Acyl ghrelin levels remained constant but des-acyl ghrelin increased significantly. ConclusionsLuseogliflozin monotherapy resulted in an improvement in blood glucose, a decrease in body weight, and decreased insulin resistance. Luseogliflozin appears to be an effective therapy for obese diabetics.