Dark tea consumption is associated with a reduced risk of dysglycaemia and increased urinary glucose and sodium excretion in Chinese adults.

AIM: To examine the associations of tea consumption (both frequency and type) with (1) prediabetes and diabetes and (2) urinary glucose and sodium excretion in Chinese community-dwelling adults. MATERIALS AND METHODS: In 1923 participants (457 with diabetes, 720 with prediabetes, and 746 with normoglycaemia), the frequency (occasional, frequent, daily, or nil) and type (green, black, dark, or other) of tea consumption were assessed using a standardized questionnaire. Morning spot urinary glucose and urine glucose-to-creatinine ratios (UGCRs) were assessed as markers of urinary glucose excretion. Tanaka's equation was used to estimate 24-h urinary sodium excretion. Logistic and multivariate linear regression analyses were performed. RESULTS: Compared with non-tea drinkers, the corresponding multivariable-adjusted odds ratios (ORs) for prediabetes and diabetes were 0.63 (95% confidence interval [CI] 0.48, 0.83) and 0.58 (95% CI 0.41, 0.82) in participants drinking tea daily. However, only drinking dark tea was associated with reduced ORs for prediabetes (0.49, 95% CI 0.36, 0.66) and diabetes (0.41, 95% CI 0.28, 0.62). Dark tea consumption was associated with increased morning spot urinary glucose (0.22 mmol/L, 95% CI 0.11, 0.34 mmol/L), UGCR (0.15 mmol/mmol, 95% CI 0.05, 0.25 mmol/L) and estimated 24-h urinary sodium (7.78 mEq/day, 95% CI 2.27, 13.28 mEq/day). CONCLUSIONS: Regular tea consumption, especially dark tea, is associated with a reduced risk of dysglycaemia and increased urinary glucose and sodium excretion in Chinese community-dwelling adults.

Utilizing machine learning algorithms for precise discrimination of glycosuria in fluorescence spectroscopic data.

Fluorescence spectroscopy coupled with a random forest machine learning algorithm offers a promising non-invasive approach for diagnosing glycosuria, a condition characterized by excess sugar in the urine of diabetic patients. This study investigated the ability of this method to differentiate between diabetic and healthy control urine samples. Fluorescent spectra were captured from urine samples using a Xenon arc lamp emitting light within the 200 to 950 nm wavelength range, with consistent fluorescence emission observed at 450 nm under an excitation wavelength of 370 nm. Healthy control samples were also analyzed within the same spectral range for comparison. To distinguish spectral differences between healthy and infected samples, the random forest (RF) and K-Nearest Neighbors (KNN) machine learning algorithms have been employed. These algorithms automatically recognize spectral patterns associated with diabetes, enabling the prediction of unknown classifications based on established samples. Principal component analysis (PCA) was utilized for dimensionality reduction before feeding the data to RF and KNN for classification. The model's classification performance was evaluated using 10-fold cross-validation, resulting in the proposed RF-based model achieving accuracy of 96 %, specificity of 100 %, sensitivity of 93 %, and precision of 100 %. These results suggest that the proposed method holds promise for a more convenient and potentially more accurate method for diagnosing glycosuria in diabetic patients.

Non-diabetic urine glucose in idiopathic membranous nephropathy.

This study aims to analyze the characteristics of idiopathic membranous nephropathy (iMN) with nondiabetic urine glucose during the follow-up. We retrospectively analyzed the data of 1313 patients who were diagnosed iMN. The prevalence of nondiabetic urine glucose during follow-up was 10.89%. There were significant differences between the patients with nondiabetic urine glucose and those without urine glucose in gender, hypertension ratio, proteinuria, N-acetyl-ß-glucosaminidase, retinol binding protein, serum albumin, serum creatinine (Scr), cholesterol, triglyceride and positive anti-phospholipase A2 receptor antibody ratio, glomerular sclerosis ratio, acute and chronic tubular injury lesion at baseline. To exclude the influence of the baseline proteinuria and Scr, case control sampling of urine glucose negative patients was applied according to gender, baseline proteinuria and Scr. The proteinuria nonremission (NR) ratio was 45.83 versus 12.50% of the urine glucose positive group and case control group. Partial remission (PR) ratio of the two groups was 36.46 versus 23.96% and complete remission (CR) ratio was 19.79% versus 63.54%, respectively. Patients with urine glucose had higher risk of 50% estimated glomerular filtration rate (eGFR) reduction. Cox regression showed that urine glucose and baseline Scr were risk factors of 50% reduction of eGFR. Urine glucose remission ratio of the patients with proteinuria NR, PR, and CR was 13.33, 56.25, and 94.73% (p < 0.005). Patients who got urine glucose remission also had better renal survival. In conclusion, non-diabetic urine glucose was closely related to proteinuria. It could be applied as a tubular injury marker to predict renal function.

Lipid Accumulation Product Combined With Urine Glucose Excretion Improves the Efficiency of Diabetes Screening in Chinese Adults.

Background: To compare the efficacy of lipid accumulation product (LAP) and urine glucose excretion (UGE) in predicting diabetes and evaluate whether the combination of LAP and UGE would help to improve the efficacy of using LAP alone or UGE alone in identifying diabetes. Methods: Data from 7485 individuals without prior history of diabetes who participated in a cross-sectional survey in Jiangsu, China, were analyzed. Each participant underwent an oral glucose-tolerance test. Operating characteristic curves (ROC) and logistic regression analyses were used to evaluate the performance of LAP and UGE in identification of newly diagnosed diabetes (NDM) and prediabetes (PDM). Results: For subjects with NDM, the area under the ROC curve was 0.72 for LAP and 0.85 for UGE, whereas for PDM, these values were 0.62 and 0.61, respectively. Furthermore, LAP exhibited a comparable sensitivity with UGE in detecting NDM (76.4% vs 76.2%, p = 0.31). In predicting PDM, LAP showed a higher sensitivity than UGE (66.4% vs 42.8%, p < 0.05). The combination of LAP and UGE demonstrated a significantly higher sensitivity than that of LAP alone and UGE alone for identification of NDM (93.6%) and PDM (80.1%). Moreover, individuals with both high LAP and high UGE had significantly increased risk of NDM and PDM than those with both low LAP and low UGE. Conclusions: The combination of LAP and UGE substantially improved the efficacy of using LAP and using UGE alone in detecting diabetes, and may be a novel approach for mass screening in the general population.

Time-based investigation of urinary metabolic markers for Type 2 diabetes: Metabolomics approach for diabetes management.

Diabetes is considered one of the most important health emergencies worldwide and Egypt has 8.2 million diabetic patients according to the International Diabetes Federation report in 2017. The objective of this study was to monitor the time-course variation in the metabolic profile of diabetic rats to detect urinary metabolic biomarkers using the metabolomics approach. Type 2 diabetes was induced in male Wistar albino rats using a single intraperitoneal injection of 40 mg/kg of streptozotocin following oral administration of 10% fructose in drinking water for 3 weeks. Then, urine was collected for 24 h from rats at three time points (0, 2, and 4 weeks after confirmation of diabetes), and were analyzed by nuclear magnetic resonance (H1 -NMR), followed by multivariate data analysis. The results from H1 -NMR pointed out that d-glucose, taurine, l-carnitine, l-fucose, 1,5-anhydrosorbitol, and d-galactose levels showed consistent significant variation (p < 0.05) between the positive (diabetic) and negative (normal) controls during the whole experimental period. Also, with the disease progression, myoinositol, and l-phenylalanine levels were significantly altered (p < 0.05) after 2 weeks and this alteration was maintained till the end of the 4-week experimental period in the positive control group. From the results of the present study, it could be concluded that we cannot depend only on glucose levels for prognostic purposes since there are other metabolic disturbances in diabetes which need to be tracked for better disease prognosis.

Non-invasive detection of glucose in human urine using a color-generating copper NanoZyme.

Renal complications are long-term effect of diabetes mellitus where glucose is excreted in urine. Therefore, reliable glucose detection in urine is critical. While commercial urine strips offer a simple way to detect urine sugar, poor sensitivity and low reliability limit their use. A hybrid glucose oxidase (GOx)/horseradish peroxidase (HRP) assay remains the gold standard for pathological detection of glucose. A key restriction is poor stability of HRP and its suicidal inactivation by hydrogen peroxide, a key intermediate of the GOx-driven reaction. An alternative is to replace HRP with a robust inorganic enzyme-mimic or NanoZyme. While colloidal NanoZymes show promise in glucose sensing, they detect low concentrations of glucose, while urine has high (mM) glucose concentration. In this study, a free-standing copper NanoZyme is used for the colorimetric detection of glucose in human urine. The sensor could operate in a biologically relevant dynamic linear range of 0.5-15 mM, while showing minimal sample matrix effect such that glucose could be detected in urine without significant sample processing or dilution. This ability could be attributed to the Cu NanoZyme that for the first time showed an ability to promote the oxidation of a TMB substrate to its double oxidation diimine product rather than the charge-transfer complex product commonly observed. Additionally, the sensor could operate at a single pH without the need to use different pH conditions as used during the gold standard assay. These outcomes outline the high robustness of the NanoZyme sensing system for direct detection of glucose in human urine. Graphical abstract.

Green synthesis of platinum nanoclusters using lentinan for sensitively colorimetric detection of glucose.

The sensitive colorimetric detection of glucose using nanomaterials has been attracting considerable attention. To improve the detection sensitivity, highly stable lentinan stabilized platinum nanoclusters (Pt-LNT NCs) were prepared, in which lentinan was employed as a mild reductant and stabilizer. The size of platinum nanoclusters (Pt NCs) was only 1.20 ± 0.29 nm. Pt-LNT NCs catalyzed the oxidation of substrate 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of hydrogen peroxide (H2O2) to produce a blue oxidation product with absorption peak at 652 nm, indicating their peroxidase-like properties. Their enzymatic kinetics followed typical Michaelis-Menten theory. In addition, fluorescence experiments confirmed their ability to efficiently catalyze the decomposition of H2O2 to generate •OH, which resulted in the peroxidase-like mechanism of Pt-LNT NCs. Moreover, a colorimetric method for highly selective and sensitive detection of glucose was established by using Pt-LNT NCs and glucose oxidase. The linear range of glucose detection was 5-1000 µM and the detection limit was 1.79 µM. Finally, this method was further used for detection of glucose in human serum and human urine. The established colorimetric method may promote the development of biological detection and environmental chemistry in the future.

Clinical and genetic determinants of urinary glucose excretion in patients with diabetes mellitus.

AIMS/INTRODUCTION: Glucosuria is a representative symptom in diabetes patients with poor glycemic control and in those treated with sodium-glucose cotransporter 2 inhibitors. Renal threshold levels of glucose excretion are known to vary among individuals, but factors contributing to glucosuria are not well characterized. The present study aimed to clarify clinical and genetic determinants of glucosuria in individuals with diabetes mellitus. MATERIALS AND METHODS: The 24-h urinary glucose excretion was measured in 135 hospitalized patients on admission, with continuous measurement for five consecutive days in 75 patients. Genetic and clinical factors contributing to glucosuria were studied. As a genetic factor, SLC5A2 polymorphism was genotyped. A total of 476 participants (266 participants with type 2 diabetes and 210 healthy controls) were additionally genotyped for the association study of SLC5A2 with type 2 diabetes. A meta-analysis was carried out with the present study and previous association studies. RESULTS: Multiple regression analysis showed that the independent variables of average blood glucose (ß = 0.41, P = 1.4 × 10-7 ), estimated glomerular filtration rate (ß = 0.28, P = 6.0 × 10-5 ), sex (ß = 0.28, P = 5.7 × 10-5 ) and SLC5A2 rs9934336 polymorphism (ß = 0.17, P = 0.02) were significantly correlated with urinary glucose excretion. The frequency of the A allele of rs9934336 tended to be lower in participants with type 2 diabetes than in controls (odds ratio 0.78, 95% confidence interval 0.53-1.13, not significant), and meta-analysis showed a significant association between the A allele and type 2 diabetes (summary odds ratio for minor allele [A] 0.86, 95% confidence interval 0.78-0.94, P < 0.002). CONCLUSIONS: Blood glucose, estimated glomerular filtration rate, sex and SLC5A2 polymorphism were independent determinants of glucosuria in diabetes mellitus.

Urine glucose concentration: A useful parameter as a surrogate for glycaemia on the first day of life in canine neonates.

INTRODUCTION: Hypoglycaemia is a well-known risk factor in neonatal puppies and kittens; glycaemia control is crucial during the first days of life. Kidneys immaturity provokes the presence of physiological glycosuria during the first 2-3 weeks of life in small animals. OBJECTIVES: The aim of this study was to evaluate the potential of glycosuria as a predictor of glycaemia in neonatal puppies during the first two weeks of life. METHODS: Prospective study. Thirty-three client-owned healthy neonatal puppies admitted to the Veterinary Teaching Hospital, Autonomous University of Barcelona, were included in the study and divided into four different groups according to the day of sampling (1, 4, 7, and 11 days post-delivery). Glucose levels in blood and urine samples were evaluated and compared between groups. Correlation between glucose levels in blood and urine was also determined. RESULTS: Hypoglycaemia was diagnosed in 17.14% of the puppies and only on day 1 after delivery. A positive and significant correlation between blood and urine glucose concentration on day 1 after delivery was observed. No significant correlation between blood and urine glucose was observed on days 4, 7 and 11 after delivery. CONCLUSIONS: Urine concentration of glucose is a useful parameter to establish glycaemic status on the first day of life in canine puppies.

Clinical Parameters, Fuel Oxidation, and Glucose Kinetics in Patients With Type 2 Diabetes Treated With Dapagliflozin Plus Saxagliptin.

OBJECTIVE: To examine the mechanisms responsible for improved glycemia with combined sodium-glucose cotransporter 2 inhibitor (SGLT2i) plus dipeptidyl peptidase 4 inhibitor therapy in type 2 diabetes. RESEARCH DESIGN AND METHODS: Fifty-six patients (HbA1c 8.9 ± 0.2% [74 ± 2 mmol/mol]) were randomized to dapagliflozin (DAPA) 10 mg, DAPA/saxagliptin (SAXA) 10/5 mg, or placebo (PCB) for 16 weeks. Basal endogenous glucose production (EGP) (3-3H-glucose), urinary glucose excretion, glucose/lipid oxidation, HbA1c, and substrate/hormone levels were determined before treatment (Pre-Tx) and after treatment (Post-Tx). RESULTS: At week 16, HbA1c decrease was greater (P < 0.05) in DAPA/SAXA (-2.0 ± 0.3%) vs. DAPA (-1.4 ± 0.2%) and greater than PCB (0.2 ± 0.2%). Day 1 of drug administration, EGP (∼2.40 mg/kg/min) decreased by -0.44 ± 0.09 mg/kg/min in PCB (P < 0.05) but only by -0.21 ± 0.02 mg/kg/min in DAPA and DAPA/SAXA (P < 0.05 vs. PCB). At week 16, EGP increased to 2.67 ± 0.09 mg/kg/min (DAPA) and 2.61 ± 0.08 mg/kg/min (DAPA/SAXA), despite reductions in fasting plasma glucose by 47 and 77 mg/dL, respectively, and no changes in PCB. Baseline plasma free fatty acids rose by 40 µmol/L with DAPA but declined by -110 with PCB and -90 µmol/L with DAPA/SAXA (P < 0.05, Pre-Tx vs. Post-Tx). In DAPA, carbohydrate oxidation rates decreased from 1.1 ± 0.1 to 0.7 ± 0.1 mg/kg/min, whereas lipid oxidation rates increased from 0.6 ± 0.1 to 0.8 ± 0.1 mg/kg/min (P < 0.01). In DAPA/SAXA, the shift in carbohydrate (1.1 ± 0.1 to 0.9 ± 0.1 mg/kg/min) and lipid (0.6 ± 0.1 to 0.7 ± 0.1 mg/kg/min) oxidation was attenuated (P < 0.05). CONCLUSIONS: The addition of SAXA to DAPA resulted in superior glycemic control compared with DAPA monotherapy partly because of increased glucose utilization and oxidation. Although the decrease in insulin/glucagon ratio was prevented by SAXA, EGP paradoxical elevation persisted, indicating that other factors mediate EGP changes in response to SGLT2i-induced glucosuria.

Colorimetric detection of urine glucose using a C/CdTe QDs-GOx aerogel based on a microfluidic assay sensor.

A sensitive fluorescent microfluidic sensor based on carbon quantum dots (CQDs), cadmium telluride quantum dots (CdTe QDs) aerogel and glucose oxidase (GOx) for urinal glucose detection was fabricated via a simple method. CQDs, emitting green fluorescence (emission peak at 520 nm) and the CdTe QDs, emitting red fluorescence (emission peak at 620 nm) under 365 nm ultraviolet irradiation, were synthesized. The as-prepared CQDs, CdTe QDs and GOx (C/CdTe QD-GOx) were mixed in a certain ratio and were then introduced into the microfluidic chip to construct a three-dimensional porous aerogel sensor after freeze-drying. A ratiometric fluorescence response was realized through the quenching of the red fluorescence by H2O2 produced from the glucose/GOx reaction, while the green fluorescence intensity stays constant. A small change in the ratio of the two fluorescence intensities led to a clear change in the fluorescent colour of the sensor, which can be easily observed under a UV lamp. The microsensor displayed a serial colour change from red to green with the changes in glucose concentration. The intensity ratio between the red fluorescence and green fluorescence (R/G value) indicates the glucose concentration. In our experiments, the optimal concentration ratio of CdTe QDs and CQDs was 0.5 : 1, and the optimal response time was 5 min. The detection range of glucose concentration was from 0 mM to 13 mM, and the detection limit was 0.223 mM. We also found that this glucose sensor has excellent selectivity, specificity and stability. The as-prepared microsensor can be stably stored for 30 days under -20 °C. Such a C/CdTe QD-GOx aerogel based microfluidic assay sensor provides a new approach towards the optical and quantitative detection of glucose, which enables daily urine glucose monitoring for the diabetic patients in a convenient way.

Retrospective analysis of the clinical characteristics of adefovir dipivoxil-induced Fanconi's syndrome in the Chinese population.

WHAT IS KNOWN AND OBJECTIVE: To explore the clinical characteristics of adefovir dipivoxil-induced Fanconi's syndrome in the Chinese population and provide a reference for rational drug use in the clinic. METHODS: By searching the CNKI, Wanfang, Chinese VIP, PubMed/MEDLINE, Web of Knowledge, Ovid, Elsevier and SpringerLink databases during 1 January 2008 to 31 December 2019, 78 studies of ADV-induced Fanconi's syndrome involving a total of 110 patients were collected and analysed retrospectively. RESULTS AND DISCUSSION: Prolonged usage of adefovir dipivoxil at low doses to treat hepatitis B might cause Fanconi's syndrome as the first symptom, especially for use over 12 months.The main clinical manifestation was bone pain accompanied by hypophosphataemia, elevated alkaline phosphatase (ALP), urine glycosuria and urine protein. X-rays and bone mineral density (BMD) examinations were mainly used to characterized osteoporosis. The patients had pain relief within 1 week to 1 month, and the biochemical indicators returned to normal within from 2 to 4 months. WHAT IS NEW AND CONCLUSION: Sufficient attention is required before and during exposure to long-term ADV therapy. The clinical picture, laboratory and radiograph alterations are important clues for ADV-induced Fanconi's syndrome.

Combination Therapy With Canagliflozin Plus Liraglutide Exerts Additive Effect on Weight Loss, but Not on HbA1c, in Patients With Type 2 Diabetes.

OBJECTIVE: To examine the effect of combination therapy with canagliflozin plus liraglutide on HbA1c, endogenous glucose production (EGP), and body weight versus each therapy alone. RESEARCH DESIGN AND METHODS: Forty-five patients with poorly controlled (HbA1c 7-11%) type 2 diabetes mellitus (T2DM) on metformin with or without sulfonylurea received a 9-h measurement of EGP with [3-3H]glucose infusion, after which they were randomized to receive 1) liraglutide 1.2 mg/day (LIRA), 2) canagliflozin 100 mg/day (CANA), or 3) liraglutide 1.2 mg plus canagliflozin 100 mg (CANA/LIRA) for 16 weeks. At 16 weeks, the EGP measurement was repeated. RESULTS: The mean decrease from baseline to 16 weeks in HbA1c was -1.67 ± 0.29% (P = 0.0001), -0.89 ± 0.24% (P = 0.002), and -1.44 ± 0.39% (P = 0.004) in patients receiving CANA/LIRA, CANA, and LIRA, respectively. The decrease in body weight was -6.0 ± 0.8 kg (P < 0.0001), -3.5 ± 0.5 kg (P < 0.0001), and -1.9 ± 0.8 kg (P = 0.03), respectively. CANA monotherapy caused a 9% increase in basal rate of EGP (P < 0.05), which was accompanied by a 50% increase (P < 0.05) in plasma glucagon-to-insulin ratio. LIRA monotherapy reduced plasma glucagon concentration and inhibited EGP. In CANA/LIRA-treated patients, EGP increased by 15% (P < 0.05), even though the plasma insulin response was maintained at baseline and the CANA-induced rise in plasma glucagon concentration was blocked. CONCLUSIONS: These results demonstrate that liraglutide failed to block the increase in EGP caused by canagliflozin despite blocking the rise in plasma glucagon and preventing the decrease in plasma insulin concentration caused by canagliflozin. The failure of liraglutide to prevent the increase in EGP caused by canagliflozin explains the lack of additive effect of these two agents on HbA1c.

Increase in Endogenous Glucose Production With SGLT2 Inhibition Is Unchanged by Renal Denervation and Correlates Strongly With the Increase in Urinary Glucose Excretion.

OBJECTIVE: Sodium-glucose cotransporter 2 (SGLT2) inhibition causes an increase in endogenous glucose production (EGP). However, the mechanisms are unclear. We studied the effect of SGLT2 inhibitors on EGP in subjects with type 2 diabetes (T2D) and without diabetes (non-DM) in kidney transplant recipients with renal denervation. RESEARCH DESIGN AND METHODS: Fourteen subjects who received a renal transplant (six with T2D [A1C 7.2 ± 0.1%] and eight non-DM [A1C 5.6 ± 0.1%) underwent measurement of EGP with [3-3H]glucose infusion following dapagliflozin (DAPA) 10 mg or placebo. Plasma glucose, insulin, C-peptide, glucagon, and titrated glucose-specific activity were measured. RESULTS: Following placebo in T2D, fasting plasma glucose (FPG) (143 ± 14 to 124 ± 10 mg/dL; P = 0.02) and fasting plasma insulin (12 ± 2 to 10 ± 1.1 µU/mL; P < 0.05) decreased; plasma glucagon was unchanged, and EGP declined. After DAPA in T2D, FPG (143 ± 15 to 112 ± 9 mg/dL; P = 0.01) and fasting plasma insulin (14 ± 3 to 11 ± 2 µU/mL; P = 0.02) decreased, and plasma glucagon increased (all P < 0.05 vs. placebo). EGP was unchanged from baseline (2.21 ± 0.19 vs. 1.96 ± 0.14 mg/kg/min) in T2D (P < 0.001 vs. placebo). In non-DM following DAPA, FPG and fasting plasma insulin decreased, and plasma glucagon was unchanged. EGP was unchanged from baseline (1.85 ± 0.10 to 1.78 ± 0.10 mg/kg/min) after DAPA, whereas EGP declined significantly with placebo. When the increase in EGP production following DAPA versus placebo was plotted against the difference in urinary glucose excretion (UGE) for all patients, a strong correlation (r = 0.824; P < 0.001) was observed. CONCLUSIONS: Renal denervation in patients who received a kidney transplant failed to block the DAPA-mediated stimulation of EGP in both individuals with T2D and non-DM subjects. The DAPA-stimulated rise in EGP is strongly related to the increase in UGE, blunting the decline in FPG.

Elevation of the renal threshold for glucose is associated with insulin resistance and higher glycated hemoglobin levels.

AIMS/INTRODUCTION: The renal threshold for glucose (RTg) corresponds to a blood glucose level of ~180 mg/dL; however, in hospitals, patients are often encountered who are hyperglycemic, but urine glucose test strip-negative, who remain negative for urine glucose even at blood glucose concentrations >180 mg/dL, implying a high RTg value. In this study, we aimed to identify factors determining high RTg in Japanese patients with type 2 diabetes mellitus. MATERIALS AND METHODS: We estimated RTg (eRTg) using urinalysis data from 67 type 2 diabetes mellitus patients for whom the glucose infusion rate (GIR) was determined by hyperinsulinemic-euglycemic clamp. After allocating patients to two groups according to their baseline eRTg (<180 mg/dL or ≥180 mg/dL), we identified the factors affecting eRTg using simple and multiple linear regression analyses. RESULTS: GIR, glycated hemoglobin (HbA1c), insulin use and dyslipidemia differed significantly between the groups. In simple regression analysis, GIR, HbA1c, body muscle-to-fat ratio and insulin use were significantly correlated with eRTg; and in multiple regression analysis, GIR and HbA1c remained independent negative and positive determinants, respectively, with the contribution of GIR being substantial. In receiver operating characteristic curve analysis, when GIR <5.7 was used as the insulin resistance threshold, the cut-off value of eRTg was 189 mg/dL (P = 0.0001). Furthermore, in receiver operating characteristic analysis using eRTg ≥189 mg/dL, the cut-off value for HbA1c was 8.0% (P = 0.0006). CONCLUSIONS: High eRTg is associated with low GIR and high HbA1c, with GIR making a substantial contribution.

Pharmacokinetics and pharmacodynamics of rongliflozin, a novel selective inhibitor of sodium-glucose co-transporter-2, in people with type 2 diabetes mellitus.

AIMS: To evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of rongliflozin in a cohort of healthy Chinese people and people with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: We examined the effects of a single ascending dose (SAD) of rongliflozin (10-200 mg) in combination with food (20 mg) in 50 healthy people, and a multiple ascending dose (MAD) of rongliflozin (10-50 mg once daily for 12 days) in 36 people with T2DM. RESULTS: No serious adverse events (AEs) or discontinuations as a result of AEs (related to rongliflozin) occurred in either study. In healthy participants and those with T2DM, rongliflozin was rapidly absorbed, with a time to maximum plasma concentration of 0.63 to 1.75 hours. Systemic exposure (maximum observed serum concentration and area under the curve) to rongliflozin and its inactive major metabolites (T1444, T1454 and T1830) increased in proportion to dose. In the SAD and MAD studies, there was a dose-related increase in urinary glucose excretion (UGE) ranging from 10 to 50 mg rongliflozin. This increase in UGE was associated with dose-related decreases in serum glucose values in people with T2DM in the MAD group. In the SAD group, UGE plateaued at 50 to 200 mg. CONCLUSIONS: Rongliflozin was well tolerated in all participants. The PK and PD measurements obtained for rongliflozin demonstrate a dose-response relationship when the drug is administered at doses ranging from 10 to 50 mg in healthy people and in people with T2DM.

Effect on urine specific gravity of the addition of glucose to urine samples of dogs and cats.

OBJECTIVE: To evaluate effects of the addition of glucose to dog and cat urine on urine specific gravity (USG) and determine whether glucosuria affects assessment of renal concentrating ability. SAMPLE: Urine samples from 102 dogs and 59 cats. PROCEDURES: Urine for each species was pooled to create samples with various USGs. Glucose was added to an aliquot of each USG pool (final concentration, 2,400 mg/dL), and serial dilutions of the glucose-containing aliquot were created for each pool. The USG then was measured in all samples. The difference in USG attributable to addition of glucose was calculated by subtracting the USG of the unaltered sample from the USG of the sample after the addition of glucose. The relationship between the difference in USG and the USG of the unaltered, undiluted sample was evaluated by the use of linear regression analysis. RESULTS: Addition of glucose to urine samples increased the USG. There was a significant relationship between USG of the undiluted sample and the difference in USG when glucose was added to obtain concentrations of 300, 600, 1,200, and 2,400 mg/dL in canine urine and concentrations of 600, 1,200, and 2,400 mg/dL in feline urine. The more concentrated the urine before the addition of glucose, the less change there was in the USG. Changes in USG attributable to addition of glucose were not clinically important. CONCLUSIONS AND CLINICAL RELEVANCE: Substantial glucosuria resulted in minimal alterations in specific gravity of canine and feline urine samples. Thus, USG can be used to assess renal concentrating ability even in samples with glucosuria.

Spectral characteristics of urine specimens from healthy human volunteers analyzed using Raman chemometric urinalysis (Rametrix).

Raman chemometric urinalysis (Rametrix™) was used to analyze 235 urine specimens from healthy individuals. The purpose of this study was to establish the "range of normal" for Raman spectra of urine specimens from healthy individuals. Ultimately, spectra falling outside of this range will be correlated with kidney and urinary tract disease. Rametrix™ analysis includes direct comparisons of Raman spectra but also principal component analysis (PCA), discriminant analysis of principal components (DAPC) models, multivariate statistics, and it is available through GitHub as the Rametrix™ LITE Toolbox for MATLAB®. Results showed consistently overlapping Raman spectra of urine specimens with significantly larger variances in Raman shifts, found by PCA, corresponding to urea, creatinine, and glucose concentrations. A 2-way ANOVA test found that age of the urine specimen donor was statistically significant (p < 0.001) and donor sex (female or male identification) was less so (p = 0.0526). With DAPC models and blind leave-one-out build/test routines using the Rametrix™ PRO Toolbox (also available through GitHub), an accuracy of 71% (sensitivity = 72%; specificity = 70%) was obtained when predicting whether a urine specimen from a healthy unknown individual was from a female or male donor. Finally, from female and male donors (n = 4) who contributed first morning void urine specimens each day for 30 days, the co-occurrence of menstruation was found statistically insignificant to Rametrix™ results (p = 0.695). In addition, Rametrix™ PRO was able to link urine specimens with the individual donor with an average of 78% accuracy. Taken together, this study established the range of Raman spectra that could be expected when obtaining urine specimens from healthy individuals and analyzed by Rametrix™ and provides the methodology for linking results with donor characteristics.

Comparison of the urinary glucose excretion contributions of SGLT2 and SGLT1: A quantitative systems pharmacology analysis in healthy individuals and patients with type 2 diabetes treated with SGLT2 inhibitors.

AIM: To develop a quantitative drug-disease systems model to investigate the paradox that sodium-glucose co-transporter (SGLT)2 is responsible for >80% of proximal tubule glucose reabsorption, yet SGLT2 inhibitor treatment results in only 30% to 50% less reabsorption in patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: A physiologically based four-compartment model of renal glucose filtration, reabsorption and excretion via SGLT1 and SGLT2 was developed as a system of ordinary differential equations using R/IQRtools. SGLT2 inhibitor pharmacokinetics and pharmacodynamics were estimated from published concentration-time profiles in plasma and urine and from urinary glucose excretion (UGE) in healthy people and people with T2DM. RESULTS: The final model showed that higher renal glucose reabsorption in people with T2DM versus healthy people was associated with 54% and 28% greater transporter capacity for SGLT1 and SGLT2, respectively. Additionally, the analysis showed that UGE is highly dependent on mean plasma glucose and estimated glomerular filtration rate (eGFR) and that their consideration is critical for interpreting clinical UGE findings. CONCLUSIONS: Quantitative drug-disease system modelling revealed mechanistic differences in renal glucose reabsorption and UGE between healthy people and those with T2DM, and clearly showed that SGLT2 inhibition significantly increased glucose available to SGLT1 downstream in the tubule. Importantly, we found that the findings of lower than expected UGE with SGLT2 inhibition are explained by the shift to SGLT1, which recovered additional glucose (~30% of total).