Urine Glucose Concentrations Research Articles

Familial Renal Glucosuria and Potential Pharmacogenetic Impact on SGLT2 Inhibitors.

Renal glucosuria is a rare inheritable trait caused by loss-of-function variants in the gene that encodes SGLT2 (i.e., SLC5A2). The genetics of renal glucosuria is poorly understood and even less is known on how loss-of-function variants in SLC5A2 may affect response to SGLT2 inhibitors, a new class of medication gaining popularity to treat diabetes by artificially inducing glucosuria. We used two biobanks that link genomic with electronic health record data to study the genetics of renal glucosuria. This included 245,394 participants enrolled in the All of Us (AoU) Research Program and 11,011 enrolled in Marshfield Clinic's Personalized Research Project (PMRP). Association studies in AoU and PMRP identified 10 variants that reached an experiment-wise Bonferroni threshold in either cohort, nine were novel. PMRP was further used as a recruitment source for a prospective SGLT2 pharmacogenetic trial. During a glucose tolerance test, the trial measured urine glucose concentrations in 15 SLC5A2 variant-positive individuals and 15 matched wild types with and without an SGLT2 inhibitor. This trial demonstrated that carriers of SLC5A2 risk variants may be more sensitive to SGLT2 inhibitors compared to wild types (P=0.075). Based on population data, 2% of an ethnically diverse population carry rare variants in SLC5A2 and are at risk for renal glucosuria. As a result, 2% of individuals being treated with SGLT2 inhibitors may respond differently to this new class of medication compared to the general population suggesting a larger investigation into SLC5A2 variants and SGLT2 inhibitors is needed.

Optimization of Optical Biosensor Based on 1D Photonic Crystals with Metaheuristic Algorithms for Measuring Glucose Concentration

We aim to simulate an optimal optical biosensor based on one-dimensional crystal photonics, for measuring blood and urine glucose concentration. By optimizing the sensor structure through metaheuristic optimization algorithms, sensitivity was increased. To measure blood and urine glucose concentration, these materials are used as a defect layer in one-dimensional crystal photonics, consisting of three materials: magnesium fluoride (MgF2), borosilicate glass (BK7), and orphan iodide (LiI) with refractive indices of 37/1, 1/5, and 1/99. By changing the concentration of glucose, the refractive index of the defect layer changes, changing the optical properties of the defect layer in the photonic crystal and the spectrum of transmitted and reflected light. According to the amount of light absorption by glucose, a wavelength range of 900–2200 nm (near infrared) was used as the input light. The transfer matrix method was used to calculate multi-layer systems. This method is based on the definition of two matrices, the boundary matrix and the diffusion matrix, which can be used to directly apply the boundary conditions. By plotting the spectrum passing through the crystal using the transfer matrix method and determining the location of the peak in the spectrum, the sensitivity of the sensor was calculated for different concentrations of glucose in blood and urine. The sensitivity obtained before optimization was 530 nm RIU−1, while after optimization it reached 842 nm RIU−1.

Urine glucose concentration detection biosensor using one-dimensional photonic crystals with periodical and Fibonacci sequences based on Tamm plasmon resonance

This paper presents the design of biosensors utilizing one-dimensional photonic crystals with periodical and Fibonacci sequences for measuring glucose concentration in urine, aimed at facilitating continuous blood glucose monitoring for diabetic patients. Exploiting Tamm plasmon resonance within a photonic band gap in the medium wave infrared band, the biosensor comprises a configuration with a one-dimensional photonic crystal and an Ag layer deposited on an infrared prism, with a urine sample layer in between. Utilizing the transfer matrix method, the reflection spectra for electromagnetic waves are calculated. The wavelength position of the Tamm plasmon resonant dip is influenced by variations in glucose concentration within the urine sample. This is attributed to the distinct refractive indices exhibited by urine samples with different glucose concentrations. Optimizing biosensor performance under various incident angles involves adjusting the Ag layer and urine sample thicknesses while maintaining excellent linear characteristics. The optimal performance of the biosensor with Fibonacci sequence one-dimensional photonic crystal is significantly superior, with a sensitivity of 113,000 nm RIU−1, a figure of merit of 2.05 × 105 RIU−1, and a detection limit of 4.84 × 10−7 RIU. The combination of high performance and a straightforward structure makes the proposed biosensors for detecting urine glucose concentrations promising in biomedical diagnostics.

SGLT2 Inhibitors Correct Fluid Overload in Adult Kidney Transplant Recipients-A Prospective Observational Study.

In this longitudinal observational study, we measured urinary glucose concentration, body composition and volume status (bioimpedance spectroscopy) and plasma renin and aldosterone concentrations in n = 22 kidney transplant recipients (KTRs) initiating on SGLT2I at baseline (BL), and after 1week and 1, 3, and 6months. Estimated glomerular filtration rate (eGFR) decreased by -2mL/min/1.73m2 (IQR -10-0) after 1week and remained stable thereafter. Urinary glucose concentration was 10 (3-24) g/g creatinine after 1week and correlated with eGFR (r2 = 0.273; p = 0.057). SGLT2I did not affect HbA1c, fasting blood glucose, body weight, fat or lean mass. SGLT2I decreased fluid overload dependent on baseline overhydration (OH, r2 = 0.54, p = 0.0003) without occurrence of dehydration. Plasma aldosterone increased at day 7, while plasma renin did not change significantly. In conclusion, SGLT2I corrected fluid overload in patients with elevated overhydration at baseline, while in euvolemic KTRs fluid status remained stable without reduction of body water below the reference range, thus promoting the safety of SGLT2I therapy in patients following kidney transplantation. Glucosuria, together with effects of SGLT2I on blood glucose control and body weight, is attenuated in KTRs dependent on eGFR.

Effect of Carnosine on Oxidative Damage to the Kidneys in Experinental Diabetes Mellitus

The article presents the results of a study into the effect of carnosine on oxidative damage to the kidneys in experimental diabetes mellitus. The experiment was carried out using two groups of Wistar rats: control (n=8) and experimental (n=11). In both groups, streptozotocin-induced diabetes mellitus was simulated for eight weeks. Experimental animals were intragastrically injected with carnosine (15 mg/kg) from weeks 4 to 8. The concentration of glucose, protein and creatinine excretion in urine were determined. At the end of eight weeks, the kidneys were removed from the rats to determine the indicators of oxidative stress severity (concentration of thiobarbiturate-reactive products, total antioxidant activity, activity of catalase, superoxide dismutase, glutathione peroxidase) and to conduct morphometry of the size of the renal glomeruli, the area of the vascular bed, capillaries and mesangium in the glomeruli, the number of podocytes. A comparison with the control showed the use of carnosine led to a 1.5-fold decrease in the concentration of thiobarbiturate-reactive products (p<0.001), a 2.2-fold increase in the total antioxidant activity (p<0.001), and a 1.2-fold increase in catalase activity (p=0.039). The area of the renal glomeruli and the mesangium in this group decreased by 1.6 times (p<0.001 and p=0.04, respectively). The total area of blood flow increased by 2.4 times (p<0.001), the area of one capillary, and the number of podocytes in the glomerulus increased by 1.9 times (p<0.001 and p=0.001). A 3.5-fold decrease in protein concentration in urine was also noted (p=0.007). Therefore, inhibition of the formation of advanced glycation end products by carnosine in experimental diabetes mellitus attenuates oxidative damage to the kidneys. This is evidenced by a decrease in proteinuria, an increase in the number of podocytes, a decrease in the area of the renal glomeruli, and an improvement in the condition of the glomerular vascular system.

Effect of sodium-glucose cotransporter 2 inhibitor canagliflozin on interstitial glucose concentration in insulin-treated diabetic dogs.

The utility of sodium-glucose cotransporter 2 inhibitors (SGLT2i) has not been reported in insulin-treated diabetic dogs. Canagliflozin, a PO-administered SGLT2i, decreases interstitial glucose concentration (IG) in insulin-treated diabetic dogs. Five insulin-treated diabetic dogs. Uncontrolled open label longitudinal study. Canagliflozin (2-4 mg/kg/day PO) was added to an unchanged insulin dose for 7 days. Fractional excretion of glucose was calculated by dividing the product of urine glucose and serum creatinine concentrations by the product of serum glucose and urine creatinine concentrations. Hypoglycemia was defined as IG <60 mg/dL. Median IG in 2869 measurements obtained while dogs were treated with insulin and canagliflozin was 87 mg/dL (range, 40-500 mg/dL) and was significantly lower than median IG in 1426 measurements obtained while dogs were treated with insulin alone (212 mg/dL; range, 41-500 mg/dL; P < .001). Median fractional excretion of glucose when dogs were treated with insulin and canagliflozin was 1.1% (range, 0.9%-2.0%), significantly higher than when dogs were treated with insulin alone (0.3%; range, 0.01%-1.0%; P = .04). The frequency of hypoglycemia was higher in dogs treated with insulin and canagliflozin (544 of 2869 IG measurements, 19%) compared with the frequency of hypoglycemia in dogs treated with insulin alone (52 of 1426 IG measurements, 4%; P < .001). Canagliflozin may have a role in improving glycemic control in insulin-treated diabetic dogs, but the dose of insulin should be decreased when adding canagliflozin to insulin treatment.

Assays for Qualitative and Quantitative Assessment of Mouse Urine Glucose Concentrations

Assays for Qualitative and Quantitative Assessment of Mouse Urine Glucose Concentrations

Assays for Qualitative and Quantitative Assessment of Mouse Urine Glucose Concentrations

Assays for Qualitative and Quantitative Assessment of Mouse Urine Glucose Concentrations

Protein Recognition Based on Temperature-Stimulated Multiparameter Response Virtual Array Sensing Strategy.

In the field of array sensing, researchers are committed to miniaturizing array sensing systems while ensuring the acquisition of multiple sensing information. Here, a new strategy called "stimulus responsive array sensing" was presented to obtain virtual multiple sensing without constructing multiple physical sensing units. Based on bioluminescence resonance energy transfer, where luciferase acts as the donor and temperature stimulus response polymers act as the receptors, by using only one sensing unit to output multiple stimulus responsive sensing signals in temperature dimension, an equivalent array sensing could be achieved. This strategy can distinguish and quantify a variety of proteins. More importantly, glucose responsive monomers were doped in polymers; thus, more virtual sensing units can be further increased to obtain more sensing signals, greatly increasing the accuracy of protein recognition, and it can also be used to differentiate several compositions of protein under different glucose concentrations in urine caused by different renal diseases. The results show the potential of the "stimulus responsive array sensing" for analyzing molecular compositions in complex biological systems and show a new tack in array sensing.

Biochemical test as an efficient system to improve safety in parenteral nutrition for premature infants

ObjectiveThe biochemical test validation process of parenteral nutrition bags is described to verify the correct composition of critical compounds before its administration, as well as its impact on safety after two years since its implantation in a population of premature infants. MethodFor the validation of the technique, 35 samples of parenteral nutrition without lipids were processed by the emergency laboratory, following the routine procedures used to measure the concentrations of glucose and electrolytes in plasma and urine. To analyze its impact on safety, pre-implantation and post-implantation risk analysis was carried out using failure mode, effects and criticality analysis (FMECA). Likewise, all out-of-range results and their potential repercussions on patient safety were evaluated. ResultsRegression analysis showed no systematic measurement error for glucose, calcium and potassium; however, there is a constant systematic error for sodium and magnesium, thus both were discarded for routine analysis. Failure mode, effects and criticality analysis results showed a decrease in the risk of the process of 11% for the biochemical test. We tested 1,734 parenteral nutritions from 218 premature neonates; 58 (3.3%) results were out of the acceptance range, and 7 were considered to be potentially dangerous compounding errors. ConclusionsThe biochemical test of glucose and electrolytes is an efficient and reproducible method that prevents possible compounding errors from reaching the patient.

Utilization of hydralazine as a reactive matrix for enhanced detection and on-MALDI-target derivatization of saccharides

Saccharides are a sort of ubiquitous and vital molecules within the whole life. However, the application of saccharides analysis with matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) is restricted by their low ionization efficiency and the instability of the sialic acid fraction. Derivatization strategy based on nonreductive amination provides a good solution, however, this is often time consuming and may result in sample loss due to removal of excessive derivatization reagents. Herein, hydralazine (HZN) was utilized as a reactive matrix for labeling reducing saccharides directly on MALDI target which eliminated tedious sample preparation and avoided sample loss. After optimization, effective and reproducible on-MALDI-target derivatization of neutral and acidic saccharides was achieved in both positive and negative modes. Compared with 2,5-dihydroxybenzoic acid (DHB) and 9-aminoacridine (9-AA), HZN improved the detection sensitivity of reducing saccharides and provided more abundant fragment ions in MS/MS analysis. Moreover, 26 kinds of neutral glycans and 5 kinds of sialic glycans were identified from ovalbumin (OVA) and bovine fetuin, respectively. Combined with the statistical models, this strategy could be used to distinguish and predict samples of 6 brands of beer, and discriminate 2 kinds of beer fermentation modes. In addition, HZN was applied for quantitative analysis of glucose in urine samples, and the obtained urine glucose concentrations of diabetic patients were consistent with the clinical test results, showing the potential of qualitative and quantitative analysis of reducing saccharides in complex samples.

A nonenzymic microfiber optic-biosensor modified phenylboric acid for sensitively and specifically detecting low glucose concentration

A microfiber interferometer coated with sensitive films formed by amide bond between 3-Carboxy-4-fluorophenylboronic acid (FPBA) and polydopamine (PDA) for the detection of trace glucose concentration is designed and demonstrated. Due to a huge evanescent field, this microfiber interferometer has a very sensitive response to the refractive index (RI) of the surrounding environment, which has excellent sensing performance including RI sensitivity response of 1825.83 nm/RIU and low temperature response of −0.04 nm/°C. Due to the good film-forming performance of PDA, whose the amino group coupled with the carboxyl molecule on FPBA to form an amide bond, PDA/FPBA can be attached to the microfiber interferometer for detecting different concentrations of glucose. The concentration range of glucose detection is 0.1–20 mM with a sensitivity of 1.71 nm/mM and a limit of detection of 12.6 ppm. Finally, the sensor is tested in actual samples of human urine to detect different concentrations of glucose and proved to be responsive and reproducible in urine. We can estimate the concentration of glucose in urine by wavelength shift. The sensor has the advantages of simple manufacture, low cost, high sensitivity, and specific recognition glucose in urine. In addition, the success of this sensor shows that the combination of ultrafine fiber and organic chemical materials has broad prospects in the field of optical detection.

Fast, Multiple-Use Optical Biosensor for Point-of-Care Glucose Detection with Mobile Devices Based on Bienzyme Cascade Supported on Polyamide 6 Microparticles.

Non-invasive glucose determination provides major advantages in health monitoring and protection. It enables widespread point-of-care testing, which is affordable, sensitive, specific, rapid and equipment-free. This work reports on the development and analytical performance of a colorimetric biosensor in detecting glucose in human urine. Highly porous polyamide microparticles were synthesized as the support for the glucose oxidase (GOx) and horseradish peroxidase (HRP) dyad, which was immobilized randomly or consecutively-first HRP and then GOx. The latter system was superior, as GH@PA-C showed much higher activity than the random system, and it was used to prepare the biosensor, along with the 3,3',5,5'-tetramethylbenzidine chromogen. When in contact with urine, the biosensor displayed a strict linear correlation between the color difference and the glucose concentration in urine in the range of 0.01-3.0 mM, as established by the CIELab image processing algorithm and UV-VIS measurements. The biosensor acted in 20 s and had a detection limit of 30.7 µM in urine, high operational activity at pH = 4-8 and unchanged detection performance after 30 days of storage. Its unique feature is the possibility of multiple consecutive uses without the serious deterioration of the recovery and dispersion values. These characteristics can open the way for new routines in non-invasive personal diabetes detection.

Evaluation of the Antioxidant, Antihyperglycemic and Hypolipidemic Potential of &lt;i&gt;Alstonia scholaris&lt;/i&gt; Leaves Extracts in Streptozotocin-Induced Diabetic Rats

The evergreen tree Alstonia scholaris (L) R. Br. (Family: Apocynaceae) is native to Australasia, southern China and the tropics of Asia. Despite its importance as a medicinal plant, little is known about its potential role in complementing standard methods of treating diabetes and its associated consequences. Therefore, the present study scientifically investigated extracts from the leaves of A. scholaris for their antioxidant (in vitro), anti-diabetic, and hypolipidemic effects in rats with type 2 diabetes mellitus. Male Wistar rats were administered streptozotocin (45 mg/kg, i.p.) and fed a high-fat diet to induce type 2 diabetes mellitus. They were treated with 400 mg/kg of an ethyl acetate (EAEAS) and ethanolic (EAAS) extract of A. scholaris leaves after complications persisted. Typical drugs were metformin (200 mg/kg) and canagliflozin (10 mg/kg). In the end, blood was drawn to determine various biochemical parameters such as fasting blood sugar, lipid profile and markers of heart, liver and kidney damage. In addition, the rat’s weight, urinary glucose concentration, urine volume, blood pressure, Electrocardiogram (ECG), and antioxidant potential of EEAS were measured. The pancreas, heart, kidneys, and liver were all subjected to histopathological analysis. A wide range of biochemical and physiological markers, including blood and urine glucose, lipid profile, markers of heart, kidney and liver damage, antioxidant levels and blood pressure, showed significant improvement in response to EEAS. Histopathology illustrates the reverse modulation in heart, kidney, and liver tissue compared to disease control. Based on the data obtained, the EAEAS achieved is far inferior to that required to treat diabetes mellitus. In summary, this present study demonstrates that EEAS (400 mg/kg) can lower blood sugar levels, fight free radicals, and lower bad cholesterol levels in rats with diabetes and complications. Further investigations can be undertaken to explore its mechanism of action at the molecular level.

One-dimensional photonic crystal-based biosensor for the detection of glucose concentration in human urine

A biosensor structure based on a ternary photonic crystal (TPC) containing a defect is designed and simulated. This proposed biosensor detects the concentration of glucose in human urine. Based on the transfer matrix method, we theoretically studied the transmission spectra through the TPC presuming blood samples with different refractive indices (RIs) infiltrated into the defect layer of the proposed structures. By varying the concentration of glucose in the urine, the RI of the urine is changed, which in turn changes the sensor’s output response; both transmission response and resonance wavelength are affected. We evaluated average sensitivity (S) for the number of periods at different values N for optimization purposes. Our results show that the biosensor has performance parameters for a period value N = 6. Indeed, a value of 1033 nm of full width at half maximum photonic bandgap can be observed with a S of 965 nm / RIU. The quality factor is 1892.542 and the figure of merit is 756.86 RIU − 1. The proposed biosensor can be a miniaturized structure with extreme sensitivity in the concentration of glucose detection models

Nano-Materials-Based Printed Glucose Sensor for Use in Incontinence Products for Health-Care Applications

Our recent development of a wireless humidity sensor system embedded in incontinence products enables new sensor applications to diagnose and supervise geriatric diseases (i.e., age-related diabetes mellitus type II). The measurement of glucose in urine, so-called glucosuria, is an early indicator for an incipient diabetes mellitus disease, whose symptoms are often age-related but misjudged. In this paper, an incontinence glucose sensor is printed with biocompatible ink and Prussian blue as an electron mediator on foil and functionalized with immobilized glucose oxidase. Inkjet printing of multiple layers of Nafion prevents large interference substances from diffusing into the measuring electrode and allows precise adjustment of the linear working range, which is significantly different from blood glucose measurement. Performance tests show the potential to detect minimum glucose values and store the sensor over a prolonged period at room temperature. The printed glucose sensor can be embedded into the absorber material of incontinence products, where capillary forces transport the urine analyte to the detection area. An attached readout module with an integrated potentiostat measures the glucose concentration in urine, which is transmitted wirelessly with incontinence events and stored in a cloud service for further analysis by medical staff and care workers.

Detection of glucose concentrations in urine based on coupling of Tamm–Fano resonance in photonic crystals

Detection of glucose concentrations in urine based on coupling of Tamm–Fano resonance in photonic crystals

One-dimensional optical Bragg grating sensor for the detection of urine glucose concentration

One-dimensional optical Bragg grating sensor for the detection of urine glucose concentration

Monitoring glucose levels in urine using FTIR spectroscopy combined with univariate and multivariate statistical methods

The development of novel platforms for non-invasive continuous glucose monitoring applied in the screening and monitoring of diabetes is crucial to improve diabetes surveillance systems. Attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy of urine can be an alternative as a sustainable, label-free, fast, non-invasive, and highly sensitive analysis to detect changes in urine promoted by diabetes and insulin treatment. In this study, we used ATR-FTIR to evaluate the urinary components of non-diabetic (ND), diabetic (D), and diabetic insulin-treated (D + I) rats. As expected, insulin treatment was capable to revert changes in glycemia, 24-h urine collection volume, urine creatinine, urea, and glucose excretion promoted by diabetes. Several differences in the urine spectra of ND, D, and D + I were observed, with urea, creatinine, and glucose analytes being related to these changes. Principal components analysis (PCA) scores plots allowed for the discrimination of ND and D + I from D with an accuracy of ∼ 99 %. The PCA loadings associated with PC1 confirmed the importance of urea and glucose vibrational modes for this discrimination. Univariate analysis of second derivative spectra showed a high correlation (r: 0.865, p < 0.0001) between the height of 1074 cm-1 vibrational mode with urinary glucose concentration. In order to estimate the amount of glucose present in the infrared spectra from urine, multivariate curve resolution-alternating least square (MCR-ALS) was applied and a higher predicted concentration of glucose in the urine was observed with a correlation of 78.9 % compared to urinary glucose concentration assessed using enzyme assays. In summary, ATR-FTIR combined with univariate and multivariate chemometric analyses provides an innovative, non-invasive, and sustainable approach to diabetes surveillance.

A Potential Treatment Strategy for the Treatment of Diabetic Kidney Disease in Streptozotocin-induced Diabetic Rats: Leptadenia Hastata Extract

Background: Kidney disorders are serious outcomes of diabetes, resulting in renal ailments. This study seeks to provide an alternative treatment for the disorder through the use of medicinal plants that offer renal protection and ameliorate the deleterious effect of diabetes. Methods: Thirty rats were divided into six groups of five and hyperglycemia was induced by intraperitoneal injection of 50 mg/kg streptozotocin. The rats with a fasting blood glucose level exceeding 250 mg/dl were selected. The L. hastata leaf extract was administered orally and a daily insulin injection was given intramuscularly into the left thigh for 28 days. Rats were then sacrificed and the urine was collected for urinalysis. The kidneys were harvested and examined histologically. The micrographs obtained were subjected to morphometric analyses to evaluate several parameters. Results: The extract-treated groups showed preservation of the cytoarchitecture of the renal tubules and glomeruli as compared to the diabetic control group, which showed distortion of the glomeruli and atrophied renal tubules. The rats that received the extract showed a significantly increased glomerular perimeters and areas (P&lt;0.01). The cellularity was significantly increased (P&lt;0.001); however, the glomerular basement membranes were significantly thicker in these groups compared to the controls (P&lt;0.001). Both the extract-treated and insulin-treated rats showed reduced urine glucose concentrations. Urobilirubinogen, protein, and ketone levels were elevated in the diabetic controls compared to the extract-treated rats. Conclusion: Administration of the L. hastata extract led to renal protection by preserving the cytoarchitecture of the glomeruli and renal tubules, restoring the kidneys’ function.