Urinary Glucose Research Articles

Smartphone-based colorimetric detection platform using color correction algorithms to reduce external interference

Smartphone-based digital image colorimetry is a powerful, fast, low-cost approach to detecting target analytes. However, lighting conditions and camera parameters easily affect the detection results, significantly curtailing its applicability in multiple scenarios. In this study, an Android-based mobile application (SMP-CC) is developed, which offers a comprehensive package that includes image acquisition, color correction, and colorimetric analysis functions. Using a custom color card, a built-in algorithm in SMP-CC can minimize the color difference between the standard color block image captured by different smartphones under different lighting conditions and the standard value by an LS171 colorimeter less than 4.36. The algorithm significantly eliminates the impacts of external lighting conditions and differences in cell phone models. Furthermore, the feasibility of SMP-CC was verified by successful colorimetric detection of urine pH, glucose, and protein, demonstrating its potential in smartphone-based digital image colorimetry.

SGLT-2 Inhibitors: Focus on Dapagliflozin.

Dapagliflozin (trade name FARXIGA) is a sodium-glucose cotransporter-2 (SGLT-2) inhibitor that has transcended its initial antidiabetic application to demonstrate benefits in cardiac and renal diseases. It was first approved by the food and department administration for type 2 diabetes in 2014. Since then, it has gained food and department administration approval for chronic kidney disease in 2021, heart failure with reduced ejection fraction in 2020, and heart failure with preserved ejection fraction in 2023. Thus, dapagliflozin plays a pivotal role in improving patient outcomes. By competitive binding to renal SGLT-2 cotransporters, dapagliflozin effectively prevents glucose and sodium reabsorption, leading to glucosuria. Its pharmacokinetic profile involves minimal cytochrome P450-induced metabolism, rapid absorption with an 18-hour duration of action, and stable effects. Clinical trials have revealed dapagliflozin's efficacy in glycemic control without the risk of hypoglycemia, making it an advantageous choice for patients insufficiently managed on other antidiabetic drugs. Comparative analysis with other SGLT-2 inhibitors suggests dapagliflozin's potential superiority in preventing heart failure. Compared to empagliflozin, it has more extended effects, contributing to stable sodium diuresis, reduced blood pressure fluctuations, and potentially lower cardiovascular disease risks. However, it leads to less urinary glucose excretion compared with canagliflozin. Dapagliflozin has specific contraindications, such as type 1 diabetes and end-stage chronic kidney disease. Adverse effects include an increased risk of genital infections, urinary tract infections, and Fournier's gangrene. A nuanced understanding of dapagliflozin's benefits and limitations is imperative for informed clinical decision-making in the management of diabetes and its complications.

Refined protocol for newly onset identification in non-obese diabetic mice: an animal-friendly, cost-effective, and efficient alternative

BackgroundTherapeutic interventions for diabetes are most effective when administered in the newly onset phase, yet determining the exact onset moment can be elusive in practice. Spontaneous autoimmune diabetes among NOD mice appears randomly between 12 and 32 weeks of age with an incidence range from 60 to 90%. Furthermore, the disease often progresses rapidly to severe diabetes within days, resulting in a very short window of newly onset phase, that poses significant challenge in early diagnosis. Conventionally, extensive blood glucose (BG) testing is typically required on large cohorts throughout several months to conduct prospective survey. We incorporated ultrasensitive urine glucose (UG) testing into an ordinary BG survey process, initially aiming to elucidate the lag period required for excessive glucose leaking from blood to urine during diabetes progression in the mouse model.ResultsThe observations unexpectedly revealed that small amounts of glucose detected in the urine often coincide with, sometimes even a couple days prior than elevated BG is diagnosed. Accordingly, we conducted the UG-based survey protocol in another cohort that was validated to accurately identified every individual near onset, who could then be confirmed by following few BG tests to fulfill the consecutive BG + criteria. This approach required fewer than 95 BG tests, compared to over 700 tests with traditional BG survey, to diagnose all the 37–38 diabetic mice out of total 60. The average BG level at diagnosis was slightly below 350 mg/dl, lower than the approximately 400 mg/dl observed with conventional BG monitoring.ConclusionsWe demonstrated a near perfect correlation between BG + and ultrasensitive UG + results in prospective survey with no lag period detected under twice weekly of testing frequency. This led to the refined protocol based on surveying with noninvasive UG testing, allowing for the early identification of newly onset diabetic mice with only a few BG tests required per mouse. This protocol significantly reduces the need for extensive blood sampling, lancet usage, labor, and animal distress, aligning with the 3Rs principle. It presents a convenient, accurate, and animal-friendly alternative for early diabetes diagnosis, facilitating research on diagnosis, pathogenesis, prevention, and treatment.

The effect of renal function on the pharmacokinetics and pharmacodynamics of enavogliflozin, a potent and selective sodium-glucose cotransporter-2 inhibitor, in type 2 diabetes.

To explore the effect of renal function on the pharmacokinetic (PK) and pharmacodynamic (PD) profile and safety of enavogliflozin, a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, in patients with type 2 diabetes mellitus (T2DM). An open-label, two-part clinical trial was conducted in T2DM patients, stratified by renal function: Group 1, normal renal function; Group 2, mild renal impairment (RI); Group 3, moderate RI; and Group 4, severe RI. In Part A, Groups 2 and 4 received enavogliflozin 0.5 mg once. In Part B, Groups 1 and 3 received enavogliflozin 0.5 mg once daily for 7 days. Serial blood and timed urine samples were collected to analyse the PK and PD characteristics of enavogliflozin. Pearson's correlation coefficients were calculated to assess the correlations between PK or PD parameters and creatinine clearance (CrCL). A total of 21 patients completed the study as planned. The area under the curve (AUC) for enavogliflozin was not significantly correlated with CrCL, although the maximum concentration slightly decreased as renal function decreased. By contrast, daily urinary glucose excretion (UGE) was positively correlated with CrCL after both single- (r = 0.7866, p < 0.0001) and multiple-dose administration (r = 0.6606, p = 0.0438). Systemic exposure to oral enavogliflozin 0.5 mg was similar among the patients with T2DM regardless of their renal function levels. However, the glucosuric effect of enavogliflozin decreased with RI. Considering the UGE observed and approved therapeutic use of other SGLT2 inhibitors, the efficacy of enavogliflozin with regard to glycaemic control could be explored in patients with mild and moderate RI (estimated glomerular filtration rate ≥30 or ≥45 mL/min/1.73 m2) in a subsequent larger study.

Clinical spectrum, over 12-year follow-up and experience of SGLT2 inhibitors treatment on patients with glycogen storage disease type Ib: a single-center retrospective study

BackgroundGlycogen storage disease type Ib (GSD Ib) is a rare disorder characterized by impaired glucose homeostasis caused by mutations in the SLC37A4 gene. It is a severe inherited metabolic disease associated with hypoglycemia, hyperlipidemia, lactic acidosis, hepatomegaly, and neutropenia. Traditional treatment consists of feeding raw cornstarch which can help to adjust energy metabolism but has no positive effect on neutropenia, which is fatal for these patients. Recently, the pathophysiologic mechanism of the neutrophil dysfunction and neutropenia in GSD Ib has been found, and the treatment with the SGLT2 inhibitor empaglifozin is now well established. In 2020, SGLT2 inhibitor empagliflozin started to be used as a promising efficient remover of 1,5AG6P in neutrophil of GSD Ib patients worldwide. However, it is necessary to consider long-term utility and safety of a novel treatment.ResultsIn this study, we retrospectively examined the clinical manifestations, biochemical examination results, genotypes, long-term outcomes and follow-up of thirty-five GSD Ib children who visited our department since 2009. Fourteen patients among them underwent empagliflozin treatment since 2020. This study is the largest cohort of pediatric GSD Ib patients in China as well as the largest cohort of pediatric GSD Ib patients treated with empagliflozin in a single center to date. The study also discussed the experience of long-term management on pediatric GSD Ib patients.ConclusionEmpagliflozin treatment for pediatric GSD Ib patients is efficient and safe. Increase of urine glucose is a signal for pharmaceutical effect, however attention to urinary infection and hypoglycemia is suggested.

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&lt;0.001), a 2.2-fold increase in the total antioxidant activity (p&lt;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&lt;0.001 and p=0.04, respectively). The total area of blood flow increased by 2.4 times (p&lt;0.001), the area of one capillary, and the number of podocytes in the glomerulus increased by 1.9 times (p&lt;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.

Mathematical Models of the Effect of Glucagon on Glycemia in Individuals With Type 2 Diabetes Treated With Dapagliflozin.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors lower blood glucose levels by promoting urinary glucose excretion, but their overall effects on hormonal and metabolic status remain unclear. We here investigated the roles of insulin and glucagon in the regulation of glycemia in individuals treated with an SGLT2 inhibitor using mathematical model analysis. Hyperinsulinemic-euglycemic clamp and oral glucose tolerance tests were performed in 68 individuals with type 2 diabetes treated with the SGLT2 inhibitor dapagliflozin. Data previously obtained from such tests in 120 subjects with various levels of glucose tolerance and not treated with an SGLT2 inhibitor were examined as a control. Mathematical models of the feedback loops connecting glucose and insulin (GI model) or glucose, insulin, and glucagon (GIG model) were generated. Analysis with the GI model revealed that the disposition index/clearance, which is defined as the product of insulin sensitivity and insulin secretion divided by the square of insulin clearance and represents the glucose-handling ability of insulin, was significantly correlated with glycemia in subjects not taking an SGLT2 inhibitor but not in those taking dapagliflozin. Analysis with the GIG model revealed that a metric defined as the product of glucagon sensitivity and glucagon secretion divided by glucagon clearance (designated production index/clearance) was significantly correlated with blood glucose level in subjects treated with dapagliflozin. Treatment with an SGLT2 inhibitor alters the relation between insulin effect and blood glucose concentration, and glucagon effect may account for variation in glycemia among individuals treated with such drugs.

Dual-Probe SERS Nanosensor: A Promising Approach for Sensitive and Ratiometric Detection of Glucose in Clinical Settings.

Diabetes is a major global health concern, with millions of annual deaths. Monitoring glucose levels is vital for clinical management, and urine samples offer a noninvasive alternative to blood samples. Optical techniques for urine glucose sensing have gained notable traction due to their cost-effectiveness and portability. Among these methods, surface-enhanced Raman spectroscopy (SERS) has attracted considerable attention thanks to its remarkable sensitivity and multiplexing capabilities. However, challenges remain in achieving reliable quantification through SERS. In this study, an alternative approach is proposed to enhance quantification involving the use of dual probes. Each probe is encoded with unique SERS signatures strategically positioned in the biologically silent region. One probe indicates the glucose presence, while the other acts as an internal reference for calibration. This setup enables ratiometric analysis of the SERS signal, directly correlating it with the glucose concentration. The fabrication of the sensor relies on the prefunctionalization of Fe sheets using an aryl diazonium salt bearing a -C≡CH group (internal reference), followed by the immobilization of Ag nanoparticles modified with an aryl diazonium salt bearing a -B(OH)2 group (for glucose capture). A secondary probe bearing a -B(OH)2 group on one side and a -C≡N group on the other side enables the ratiometric analysis by forming a sandwich-like structure in the presence of glucose (glucose indicator). Validation studies in aqueous solutions and artificial urine demonstrated the high spectral stability and the potential of this dual-probe nanosensor for sensitive glucose monitoring in clinical settings.

Bimetal Thin Film, Semiconductors, and 2D Nanomaterials in SPR Biosensors: An Approach to Enhanced Urine Glucose Sensing.

This work introduces a systematic approach for the development of Kretschmann configuration-based biosensors designed for non-invasive urine glucose detection. The methodology encompasses the utilization of various semiconductors, including Silicon (Si), Germanium (Ge), Gallium Nitride (GaN), Aluminum Nitride (AlN), and Indium Nitride (InN), in combination with a bimetallic layer (comprising Au and Ag films of equal thickness) to enhance the biosensor sensitivity. Additionally, 2D nanomaterials, such as Black Phosphorus and Graphene, are integrated into the semiconductor layers to enhance performance further. These configurations are meticulously optimized through the application of the transfer matrix method (TMM), and the sensing parameters are assessed using the angular modulation method. Among the semiconductors, AlN and GaN exhibit superior results. On these substrates, Graphene and Black phosphorous (BP) layers are applied, resulting in four final structures (thicknesses in nm): BK7/Au(26)/Ag(26)/Si(6)/BP(0.53)/Biosample, BK7/Au(26)/Ag(26)/AlN(14)/BP(0.53)/Biosample, BK7/Au(26)/Ag(26)/GaN(12)/BP(0.53)/Biosample, and BK7/Au(26)/Ag(26)/GaN(12)/Graphene(0.34)/Biosample. These biosensors achieve Sensitivity(° /RIU) and Figure of Merit (FoM) (1/RIU) of 380, 360, 440, 400, and 58.5, 90, 90.65, and 82.4, respectively. Subsequently, these high-performing sensors undergo testing with actual urine glucose samples. Among them, two biosensors, BK7/Au(26)/Ag(26)/AlN(14)/BP (0.53)/Biosample and BK7/Au(26)/Ag(26)/GaN(14)/Graphene(0.34)/Biosample, exhibit outstanding performance, with sensitivities (° /RIU) and FoM (1/RIU) of 394.44 & 294.44, and 112.6 & 92.01 respectively. A comparison is also made with relevant previously published work, revealing improved performance in glucose detection.

Nascent shifts in renal cellular metabolism, structure, and function due to chronic empagliflozin in prediabetic mice.

Sodium-glucose cotransporter, type 2 inhibitors (SGLT2i) are emerging as the gold standard for treatment of type 2 diabetes (T2D) with renal protective benefits independent of glucose lowering. We took a high-level approach to evaluate the effects of the SGLT2i, empagliflozin (EMPA) on renal metabolism and function in a prediabetic model of metabolic syndrome. Male and female 12-wk-old TallyHo (TH) mice, and their closest genetic lean strain (Swiss-Webster, SW) were treated with a high-milk-fat diet (HMFD) plus/minus EMPA (@0.01%) for 12-wk. Kidney weights and glomerular filtration rate were slightly increased by EMPA in the TH mice. Glomerular feature analysis by unsupervised clustering revealed sexually dimorphic clustering, and one unique cluster relating to EMPA. Periodic acid Schiff (PAS) positive areas, reflecting basement membranes and mesangium were slightly reduced by EMPA. Phasor-fluorescent life-time imaging (FLIM) of free-to-protein bound NADH in cortex showed a marginally greater reliance on oxidative phosphorylation with EMPA. Overall, net urine sodium, glucose, and albumin were slightly increased by EMPA. In TH, EMPA reduced the sodium phosphate cotransporter, type 2 (NaPi-2), but increased sodium hydrogen exchanger, type 3 (NHE3). These changes were absent or blunted in SW. EMPA led to changes in urine exosomal microRNA profile including, in females, enhanced levels of miRs 27a-3p, 190a-5p, and 196b-5p. Network analysis revealed "cancer pathways" and "FOXO signaling" as the major regulated pathways. Overall, EMPA treatment to prediabetic mice with limited renal disease resulted in modifications in renal metabolism, structure, and transport, which may preclude and underlie protection against kidney disease with developing T2D.NEW & NOTEWORTHY Renal protection afforded by sodium glucose transporter, type 2 inhibitors (SGLT2i), e.g., empagliflozin (EMPA) involves complex intertwined mechanisms. Using a novel mouse model of obesity with insulin resistance, the TallyHo/Jng (TH) mouse on a high-milk-fat diet (HMFD), we found subtle changes in metabolism including altered regulation of sodium transporters that line the renal tubule. New potential epigenetic determinants of metabolic changes relating to FOXO and cancer signaling pathways were elucidated from an altered urine exosomal microRNA signature.

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.

Ag-carbon dots with peroxidase-like activity for colorimetric and SERS dual mode detection of glucose and glutathione

Currently, nanozymes have made important research progress in the fields of catalysis, biosensing and tumor therapy, but most of nanozymes sensing systems are single-mode detection, which are easily affected by environment and operation, so it is crucial to construct nanozymes sensing system with dual-signal detection to obtain a more stable and reliable performance. In this paper, Ag-carbon dots (Ag-CDs) bifunctional nanomaterials were synthesized using carbon dots as reducing agent and protective agent by a facile and green one-step method. A simple and sensitive colorimetric-SERS dual-mode sensing platform was constructed for the detection of glucose and glutathione(GSH) in body fluids by taking advantage of good peroxidase-like and SERS activities of Ag-CDs. Ag-CDs catalyzes H2O2 to hydroxyl radicals(•OH), which oxidized TMB to form ox-TMB blue solution with characteristic absorption peak at 652 nm and Raman characteristic peak at 1607 cm−1. Ag-CDs sensing method exhibited high performance for glucose and GSH with detection limits for colorimetric and SERS as low as 11.30 μM and 3.54 μM, 0.38 μM and 0.24 μM respectively (S/N = 3). In addition, Ag-CDs have good stability and uniformity, ensuring long-term applicability of catalytic system. This colorimetric-SERS dual-mode sensing platform can be used for the determination of glucose and GSH in saliva and urine, and has the advantages of simple, low cost, rapid, and high accuracy, which has a potential application prospect in biosensor and medical research.

Dosing Time-Dependent Difference in the Suppressive Effect of Empagliflozin on the Development of Mechanical Pain Hypersensitivity in Diabetic Mice.

A problem for patients with diabetes is the rise of complications, such as peripheral neuropathy, nephropathy, and retinopathy. Among them, peripheral neuropathy, characterized by numbness and/or hypersensitivity to pain in the extremities, is likely to develop in the early stages of diabetes. Empagliflozin (EMPA), a sodium-glucose cotransporter-2 inhibitor, exerts hypoglycemic effects by preventing glucose reabsorption in proximal tubular cells. EMPA can improve cardiovascular and renal outcomes in diabetic patients, but its suppressive effect on the development of diabetic neuropathy remains unclear. In this study, we demonstrated that optimizing the dosing schedule of EMPA suppressed the development of pain hypersensitivity in streptozotocin (STZ)-induced diabetic model mice maintained under standardized light/dark cycle conditions. A single intraperitoneal administration of STZ to mice induced hyperglycemia accompanied by pain hypersensitivity. Although EMPA did not exert anti-hypersensitivity effect on STZ-induced diabetic mice after the establishment of neuropathic pain, the development of pain hypersensitivity in the diabetic mice was significantly suppressed by daily oral administration of EMPA at the beginning of the dark phase. On the other hand, the suppressive effect was not observed when EMPA was administered at the beginning of the light phase. The hypoglycemic effect of EMPA and its stimulatory effect on urinary glucose excretion were also enhanced by the administration of the drug at the beginning of the dark phase. Nocturnal mice consumed their food mainly during the dark phase. Our results support the notion that morning administration of EMPA may be effective in suppressing the development of peripheral neuropathy in diabetic patients. SIGNIFICANCE STATEMENT: Empagliflozin, a sodium-glucose cotransporter-2 inhibitor suppressed the development of neuropathic pain hypersensitivity in streptozotocin-induced diabetic model mice in a dosing time-dependent manner.

Prolonged renal function impairment in infants born during the peri-viable period: A retrospective longitudinal cohort study

BackgroundThe number of infants born during the peri-viable period who survive has been increasing. AimTo clarify renal function in infants from the time of birth during the peri-viable period until their due date. Study designThis retrospective cohort study was conducted at a single center. SubjectsWe reviewed the data of infants born at ≤28 weeks of gestation between 2018 and 2022 at our hospital. The infants were divided into the following groups: born at 22–24 weeks vs. 25–28 weeks (appropriate-for-gestational age [AGA] infants), and AGA infants vs. small-for-gestational age (SGA) infants (born at 22–28 weeks). Outcome measuresWe compared the perinatal data and renal function of the infants from birth until their due date. ResultsEighty-one infants were included. Their serum creatinine, fractional excretion of sodium, and urine glucose levels were high or positive soon after birth but gradually improved. The urine albumin level was significantly higher among AGA infants born at 22–24 weeks, even at term equivalent age, than among those born at 25–28 weeks. ConclusionsPersistent renal insufficiency was observed even around the term equivalent age in peri-viable infants. Follow-up data collected after the neonatal period should be investigated in these infants.

A Possible Therapeutic Application of the Selective Inhibitor of Urate Transporter 1, Dotinurad, for Metabolic Syndrome, Chronic Kidney Disease, and Cardiovascular Disease.

The reabsorption of uric acid (UA) is mainly mediated by urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9) in the kidneys. Dotinurad inhibits URAT1 but does not inhibit other UA transporters, such as GLUT9, ATP-binding cassette transporter G2 (ABCG2), and organic anion transporter 1/3 (OAT1/3). We found that dotinurad ameliorated the metabolic parameters and renal function in hyperuricemic patients. We consider the significance of the highly selective inhibition of URAT1 by dotinurad for metabolic syndrome, chronic kidney disease (CKD), and cardiovascular disease (CVD). The selective inhibition of URAT1 by dotinurad increases urinary UA in the proximal tubules, and this un-reabsorbed UA may compete with urinary glucose for GLUT9, reducing glucose reabsorption. The inhibition by dotinurad of UA entry via URAT1 into the liver and adipose tissues increased energy expenditure and decreased lipid synthesis and inflammation in rats. Such effects may improve metabolic parameters. CKD patients accumulate uremic toxins, including indoxyl sulfate (IS), in the body. ABCG2 regulates the renal and intestinal excretion of IS, which strongly affects CKD. OAT1/3 inhibitors suppress IS uptake into the kidneys, thereby increasing plasma IS, which produces oxidative stress and induces vascular endothelial dysfunction in CKD patients. The highly selective inhibition of URAT1 by dotinurad may be beneficial for metabolic syndrome, CKD, and CVD.

PREVENTION OF TYPE 2 DIABETES MELLITUS

Prevention of type 2 diabetes mellitus and complications is an urgent problem in modern medicine. In patients with a body mass index (BMI) above 25 kg/m2, indicators of markers of carbohydrate metabolism (serum glucose -fasting and postprandial glycemia, glycosylated hemoglobin and urine glucose) and lipid metabolism -total cholesterol (TC), triglycerides (TG), lipidogram (low-density lipoprotein cholesterol -LDL cholesterol, atherogenic index -AI is significantly higher, and high-density lipoprotein cholesterol -HDL cholesterol is significantly lower than in patients with normal body mass index (BMI) and abdominal index (AI). Asignificant positive relationship between age, abdominal index, BMI, AI, glucose level in blood serum. Assessment of markers of carbohydrate and lipid metabolism should be included in the list of mandatory examinations of patients over the age of 30 years, and be strictly individual. There is a relationship between the progression of carbohydrate metabolism disorders and changes in lipid parameters metabolism in the examined women.The population should be widely informed about the development of type 2 diabetes mellitus and the progression of complications.

Effects of Empagliflozin-Induced Glycosuria on Weight Gain, Food Intake and Metabolic Indicators in Mice Fed a High-Fat Diet.

Sodium glucose-linked transporter 2 (SGLT2) inhibitors promote glucose, and therefore calorie, excretion in the urine. Patients taking SGLT2 inhibitors typically experience mild weight loss, but the amount of weight loss falls short of what is expected based on caloric loss. Understanding the mechanisms responsible for this weight loss discrepancy is imperative, as strategies to improve weight loss could markedly improve type 2 diabetes management and overall metabolic health. Two mouse models of diet-induced obesity were administered the SGLT2 inhibitor empagliflozin in the food for 3 months. Urine glucose excretion, body weight, food intake and activity levels were monitored. In addition, serum hormone measurements were taken, and gene expression analyses were conducted. In both mouse models, mice receiving empagliflozin gained the same amount of body weight as their diet-matched controls despite marked glucose loss in the urine. No changes in food intake, serum ghrelin concentrations or activity levels were observed, but serum levels of fibroblast growth factor 21 (FGF21) decreased after treatment. A decrease in the levels of deiodinase 2 (Dio2) was also observed in the white adipose tissue, a primary target tissue of FGF21. These findings suggest that compensatory metabolic adaptations, other than increased food intake or decreased physical activity, occur in response to SGLT2 inhibitor-induced glycosuria that combats weight loss, and that reductions in FGF21, along with subsequent reductions in peripheral Dio2, may play a role.

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

Mechanistic Modeling of Empagliflozin: Predicting Pharmacokinetics, Urinary Glucose Excretion, and Investigating Compensatory Role of SGLT1 in Renal Glucose Reabsorption.

The aim of this study was to use a combination of physiologically based pharmacokinetic (PBPK) modeling and urinary glucose excretion (UGE) modeling to predict the time profiles of pharmacokinetics (PK) and UGE for the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin (EMP). Additionally, the study aims to explore the compensatory effect of SGLT1 in renal glucose reabsorption (RGR) when SGLT2 is inhibited. The PBPK-UGE model was developed using physicochemical and biochemical properties, renal physiological parameters, binding kinetics, glucose, and Na+ reabsorption kinetics by SGLT1/2. For area under the plasma concentration-time curve, maximum plasma concentration, and cumulative EMP excretion in urine, the predicted values fell within a range of 0.5-2.0 when compared to observed data. Additionally, the simulated UGE data also matched well with the clinical data, further validating the accuracy of the model. According to the simulations, SGLT1 and SGLT2 contributed approximately 13% and 87%, respectively, to RGR in the absence of EMP. However, in the presence of EMP at doses of 2.5 and 10 mg, the contribution of SGLT1 to RGR significantly increased to approximately 76%-82% and 89%-93%, respectively, in patients with type 2 diabetes mellitus. Furthermore, the model supported the understanding that the compensatory effect of SGLT1 is the underlying mechanism behind the moderate inhibition observed in total RGR. The PBPK-UGE model has the capability to accurately predict the PK and UGE time profiles in humans. Furthermore, it provides a comprehensive analysis of the specific contributions of SGLT1 and SGLT2 to RGR in the presence or absence of EMP.