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There has been concern over whether to use sodium-glucose-cotransporter-2 (SGLT-2) inhibitors in patients that use catheters due to the concern for increased urinary tract infections (UTIs). The concern is that patients who use catheters are already at an increased risk for UTIs and that SGLT-2-inhibitors may promote bacterial growth due their mechanism of action, ie. increasing glycosuria. The objective of this study was to evaluate whether using empagliflozin, a SGLT-2-inhibitor, in patients who also use catheters, increases their risks for UTIs. A retrospective chart review of electronic health records at a single-center was completed of all Veterans who received an empagliflozin prescription and were also using catheters between October 1, 2015 and September 30, 2022. Veterans were included if they were using catheters for at least 2 months prior to starting empagliflozin and were on both therapies for at least 2 months concurrently. The primary outcome for this study is the number of UTIs occurring prior to and after beginning empagliflozin treatment. Additional secondary outcomes included change in A1c, change in body mass index (BMI), UTI-hospitalizations, and fungal infections. Of the 91 patients with concurrent empagliflozin and catheter-use, only 25 Veterans were included. There was an occurrence of.09 UTIs/month pre-empagliflozin compared to.07 post-empagliflozin (P =.61). There was an observed trend in Veterans with Type 2 Diabetes having an increased rate of UTIs. There was no statistically significant difference found in UTI rates when comparing catheters alone to concurrent catheter and empagliflozin-use. [ABSTRACT FROM AUTHOR]

Objectives: There are controversies about screening strategy and cut-off levels for gestational diabetes mellitus (GDM). Here, we aimed to identify optimal cut-off values for 50-gram oral glucose tolerance testing (OGTT) in high and low risk pregnant women. Methods: A total of 500 patients who underwent two step OGTT were divided into two groups as GDM (n=31) and controls (n=469). Moreover, patients were grouped as high (n=114) and low risk (n=386) for GDM. Having= 2 risk factors such as family history of type-2 diabetes, obesity, glucosuria, previous history of GDM, macrosomia and diabetic complications were accepted as high risk. Demographic data, OGTT results, birth characteristics were recorded and compared between groups. A cut-off value for 50-gram OGTT was evaluated in low and high risk groups. Results: The 50-gram OGTT value above 140 mg/dL discriminated GDM with 100% sensitivity and 92.11% specificity in all patients (AUC=0.969, P<0.001). The prevalence of GDM was 19.3% in high and 2.3% in low risk group. The 50-gram OGTT value above 140 mg/dL discriminated GDM with 100% sensitivity and 94.57% specificity in high risk patients (AUC=0.992, P<0.001). Furthermore, 50-gram OGTT value above 149 mg/dL discriminated GDM with 100% sensitivity and 93.63% specificity in low risk patients (AUC=0.976, P<0.001). Conclusions: Although screening in low risk population is a debating issue worldwide, our local guidelines still recommend screening all pregnant women. We suggest that performing 100-gram OGTT only in patients who have higher values than 149 mg/dL in 50-gram OGTT can be an alternative screening strategy in low risk group. [ABSTRACT FROM AUTHOR]

Aim: To develop evidence‐based clinical algorithms for management of common intrapartum urinary abnormalities. Population: Women with singleton, term pregnancies in active labour and immediate postnatal period, at low risk of complications. Setting: Healthcare facilities in low‐ and middle‐income countries. Search strategy: A systematic search and review were conducted on the current guidelines from WHO, NICE, ACOG and RCOG. Additional search was done on PubMed and The Cochrane Database of Systematic Reviews up to May 2020. Case scenarios: Four common intrapartum urinary abnormalities were selected: proteinuria, ketonuria, glycosuria and oliguria. Using reagent strip testing, glycosuria was defined as ≥2+ on one occasion or of ≥1+ on two or more occasions. Proteinuria was defined as ≥2+ and presence of ketone indicated ketonuria. Oliguria was defined as hourly urine output ≤30 ml. Thorough initial assessment using history, physical examination and basic investigations helped differentiate most of the underlying causes, which include diabetes mellitus, dehydration, sepsis, pre‐eclampsia, shock, anaemia, obstructed labour, underlying cardiac or renal problems. A clinical algorithm was developed for each urinary abnormality to facilitate intrapartum management and referral of complicated cases for specialised care. Conclusions: Four simple, user‐friendly and evidence‐based clinical algorithms were developed to enhance intrapartum care of commonly encountered maternal urine abnormalities. These algorithms may be used to support healthcare professionals in clinical decision‐making when handling normal and potentially complicated labour, especially in low resource countries. Evidence‐based clinical algorithms developed to guide intrapartum management of commonly encountered urinary abnormalities. An evidence‐based clinical algorithm was developed to enhance intrapartum management of commonly encountered urinary abnormalities. [ABSTRACT FROM AUTHOR]

Summary: Introduction: The COVID‐19 pandemic posed tremendous challenges for children. However, the long‐term effects of the pandemic on various aspects of physical health at a national level remain unclear. Methods: In this retrospective cohort study, we analysed data from nationwide health checkup records amongst children aged 7–15 years. The dataset comprised 3 544 146 records from 393 794 individuals who graduated from junior high school during fiscal years 2007 to 2022. Difference‐in‐differences (DID) analyses with multiple time periods were used to examine the impact of COVID‐19 on physical health outcomes. Results: Compared with the pre‐pandemic period, the COVID‐19 pandemic was associated with excess increases in obesity for boys and girls, persisting over the 3 years (+0.42%; [95% CI, 0.23–0.61]). Also, it was associated with excess increases in underweight (+0.28% [0.25–0.32]) and poor visual acuity amongst boys in the 3rd year (+1.80% [1.30–2.30]). There were excess reductions in dental caries (−1.48% [−2.01 to −0.95]), glucosuria (−0.55 [−0.88 to −0.23]) and hematuria (−0.43% [−0.73 to −0.13]) during the 3rd year of the pandemic. Conclusions: These findings underscore the multifaceted impact of the pandemic on various health indicators for school‐aged children. This information could be valuable for public health policy and paediatric healthcare planning in the post‐pandemic era. [ABSTRACT FROM AUTHOR]

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Abstract Background Therapeutic 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. Results The 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. Conclusions We 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 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. [ABSTRACT FROM AUTHOR]

Urological diseases affect all age groups and are associated with different urinary complications. Presence of pathogenic bacteria complicates the urological diseases such as chronic kidney disease (CKD), kidney stone disease (KSD), emphysematous pyelonephritis (EPN), and urological cancers (UCs) coinciding with urinary metabolic complications. The One Health concept for preventing the spread of antibiotic resistant opportunistic pathogens necessitates detailed investigation on the virulence and the antibiotic sensitivity patterns of the pathogens from the urinary tract infections (UTIs). This cross-sectional study was aimed to profile the pathogenic bacteria associated with different urological diseases that included urine samples from the patients from a tertiary care hospital. The study included 258 patients representing CKD (15.1%), KSD (28.7%), EPN (15.5%), UC (12.0%), and UTI patients without any urological diseases (28.7%) with overall 70.5% patients showing positive urine culture. Furthermore, other than UTI in patients without any urological diseases (100%), higher culture positive cases were seen in KSD (64.9%), followed by CKD (61.5%), EPN (52.5%), and UC (48.4%). Escherichia coli was the most predominant bacteria in UTI (35.1%) and EPN (66.7%). In KSD, Pseudomonas aeruginosa (41.7%), Staphylococcus aureus (18.8%), and Proteus mirabilis (14.6%) were more common. S. aureus (86.7%) was the most isolated bacteria from the UC cases. Overall rate of multidrug resistance (MDR) was 77.8%. All (100%) E. coli, K. pneumoniae, P. mirabilis, and S. aureus strains were MDR. Among the strains, strong biofilm formation was observed in 73.6%, and 66.7% strains were urease positive. Biofilm was positively correlated with MDR and urease activity. The abundance and distribution of bacteria differed among the urological diseases suggesting their association with the urine metabolite profile. Colonization of MDR pathogens in patients with urological diseases is a serious concern requiring steps to control the emergence of drug resistance and their further spread into the ecosystem. [ABSTRACT FROM AUTHOR]

This study intended to investigate the impact of long‐term tenofovir fumarate (TDF) antiviral regimen on renal function in human immunodeficiency virus (HIV)‐infected patients with low‐risk of kidney injury. The observational study involving 100 HIV‐infected patients without underlying diseases who achieved virological suppression and immunological recovery after sustained antiviral regimen of TDF+ lamivudine+ efavirenz (TLE) for 3.19 years. Renal function, including estimated glomerular filtration rate (eGFR), blood and urine β2 microglobulin, and other parameters, was assessed every 3 months over a period of 2.5 years. The eGFR showed a slight increasement from 116.0 at month 0 to 119.7 at month 30. Blood β2 microglobulin increased from 2.02 mg/L at month 0 to 2.77 mg/L at month 30. Compared to month 0, the difference in blood β2 microglobulin was statistically significant at month 6 and months 12‐30 (P <.05). The incidence of proximal renal tubular dysfunction fluctuated from 2% at month 0 to 2.5% at month 30. The urine β2 microglobulin fluctuated from 0.5 (0.3‐1.1) to 0.8 (0.5‐1.35) mg/L at months 18‐30, which was higher than 0.41 (0.18‐1.1) mg/L at month 0 (P <.05). The abnormal concentration proportion of urine β2 microglobulin fluctuated from 72.7% to 81.3% at months 18‐30, which was higher than the proportion of 57.0% at month 0. The abnormal proportion of blood β2 microglobulin, urine β2 microglobulin, and proximal renal tubular dysfunction were not correlated with eGFR (r1 = 0.119, r2 = −0.008, r3 = −0.165, P >.05). Long‐term TDF antiviral regimen in low‐risk of kidney injury HIV‐infected patients may lead to damage in the proximal renal tubules and glomeruli. Blood and urine β2 microglobulin levels may be helpful in screening for renal dysfunction. [ABSTRACT FROM AUTHOR]

Background: Therapeutic 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. Results: The 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. Conclusions: We 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. [ABSTRACT FROM AUTHOR]

The kidneys facilitate energy conservation through reabsorption of nutrients including glucose. Almost all the filtered blood glucose is reabsorbed by the kidneys. Loss of glucose in urine (glycosuria) is offset by an increase in endogenous glucose production to maintain normal energy supply in the body. How the body senses this glucose loss and consequently enhances glucose production is unclear. Using renal Slc2a2 (also known as Glut2) knockout mice, we demonstrate that elevated glycosuria activates the hypothalamic-pituitary-adrenal axis, which in turn drives endogenous glucose production. This phenotype was attenuated by selective afferent renal denervation, indicating the involvement of the afferent nerves in promoting the compensatory increase in glucose production. In addition, through plasma proteomics analyses we observed that acute phase proteins - which are usually involved in the body’s defense mechanisms against a threat – were the top candidates which were either upregulated or downregulated in renal Slc2a2 KO mice. Overall, afferent renal nerves contribute to promoting endogenous glucose production in response to elevated glycosuria and loss of glucose in urine is sensed as a biological threat in mice. These findings may be useful in improving the efficiency of drugs like SGLT2 inhibitors that are intended to treat hyperglycemia by enhancing glycosuria but are met with a compensatory increase in endogenous glucose production.

Context: Type 1 diabetes (T1D) results from the autoimmune T-cell mediated destruction of pancreatic beta cells leading to insufficient insulin secretion. At the time of diagnosis of T1D, there is residual beta cell function that declines over the subsequent months to years. Recent interventions have been approved to preserve beta cell function in evolving T1D. Objective: The aim of this review is to summarise the approaches used to assess residual beta cell function in evolving T1D, and to highlight potential future directions. Methods: Studies including subjects aged 0 to 18 years were included in this review. The following search terms were used; "(type 1 diabetes) and (partial remission)" and "(type 1 diabetes) and (honeymoon)". References of included studies were reviewed to determine if additional relevant studies were eligible. Results: There are numerous approaches to quantifying beta cell reserve in evolving T1D. These include c-peptide measurement after a mixed meal or glucagon stimuli, fasting c-peptide, the urinary c-peptide/creatinine ratio, insulin dose-adjusted haemoglobin A1c, and other clinical models to estimate beta cell function. Other biomarkers may have a role, including the proinsulin/c-peptide ratio, cytokines, and microRNA. Studies using thresholds to determine if residual beta cell function is present often differ in values used to define remission. Conclusions: As interventions are approved to preserve beta cell function, it will become increasingly necessary to quantify residual beta cell function in research and clinical contexts. In this report, we have highlighted the strengths and limitations of the current approaches. [ABSTRACT FROM AUTHOR]

When sodium-glucose cotransporter-2 (SGLT2) inhibitors were first introduced a decade ago, no one expected them to have substantial effects beyond their known glucose-lowering effects, until the emergence of evidence of their robust renal and cardiovascular benefits showing that they could attenuate progression of kidney disease, irrespective of diabetes, as well as prevent the development of acute kidney injury. Still, the precise and elaborate mechanisms underlying the major organ protection of SGLT2 inhibitors remain unclear. SGLT2 inhibitors inhibit the reabsorption of sodium and glucose in the proximal tubule of the kidney and then recovers tubuloglomerular feedback, whereby SGLT2 inhibitors reduce glomerular hyperfiltration. This simple demonstration of their beneficial effects has perplexed experts in seeking more plausible and as yet undisclosed explanations for the whole effects of SGLT2 inhibitors, including metabolism reprogramming and the modulation of hypoxia, inflammation, and oxidative stress. Given that the renal benefits of SGLT2 inhibitors in patients with kidney disease but without diabetes were comparable to those seen in patients with diabetes, it may be reasonable to keep the emphasis on their hemodynamic actions. In this context, the aim of the present review is to provide a comprehensive overview of renal hemodynamics in individuals with diabetes who are treated with SGLT2 inhibitors, with a focus on natriuresis associated with the regulation of tubuloglomerular feedback and potential aquaresis. Throughout the discussion of alterations in renal sodium and water transports, particular attention will be given to the potential enhancement of adenosine and its receptors following SGLT2 inhibition.

Background: Despite recent well-established kidney tropism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), usually presenting as acute kidney injury (AKI), there are few published cases with SARS-CoV-2-related tubulointerstitial nephritis (TIN). We report an adolescent with TIN and delayed association with uveitis (TINU syndrome), where SARS-CoV-2 spike protein was identified in kidney biopsy. Case-diagnosis/treatment: A 12-year-old girl was assessed for a mild elevation of serum creatinine detected during the evaluation of systemic manifestations including asthenia, anorexia, abdominal pain, vomiting, and weight loss. Data of incomplete proximal tubular dysfunction (hypophosphatemia and hypouricemia with inappropriate urinary losses, low molecular weight proteinuria, and glucosuria) were also associated. Symptoms had initiated after a febrile respiratory infection with no known infectious cause. After 8 weeks, the patient tested positive in PCR for SARS-CoV-2 (Omicron variant). A subsequent percutaneous kidney biopsy revealed TIN and immunofluorescence staining with confocal microscopy detected the presence of SARS-CoV-2 protein S within the kidney interstitium. Steroid therapy was started with gradual tapering. Ten months after onset of clinical manifestations, as serum creatinine remained slightly elevated and kidney ultrasound showed mild bilateral parenchymal cortical thinning, a second percutaneous kidney biopsy was performed, without demonstrating acute inflammation or chronic changes, but SARS-CoV-2 protein S within the kidney tissue was again detected. At that moment, simultaneous routine ophthalmological examination revealed an asymptomatic bilateral anterior uveitis. Conclusions: We present a patient who was found to have SARS-CoV-2 in kidney tissue several weeks following onset of TINU syndrome. Although simultaneous infection by SARS-CoV-2 could not be demonstrated at onset of symptoms, since no other etiological cause was identified, we hypothesize that SARS-CoV-2 might have been involved in triggering the patient's illness. [ABSTRACT FROM AUTHOR]

Gymnema sylvestre, commonly known as Gurmar and belonging to the family Asclepiadaceae, is widely distributed in India, Malaysia, Sri Lanka, Australia, Indonesia, Japan, Vietnam, tropical Africa, and the southwestern region of the Republic of China. The plant G. sylvestre is traditionally used as a sugar destroyer in glycosuria and other urinary diseases. The drug is also used in the composition of Ayurvedic preparations such as Ayaskri, Varunadi kasaya, Varunadighrtam, and Mahakalyanakaghrtam. The present review focuses on the reports available in various literatures. The various chemical constituents isolated include saponins, carbohydrates, anthraquinone derivatives, flavones, flavonoids, formic acid, resins, phytin, etc. The chief constituents are saponins like gymnemic acids, gymnemasaponins, gymnemasides, and gymnemagenin. Gymnema sylvestre is found in capsule, tablet, powder, and tea powder forms. A tablet containing 200-400mg of gymnemic acid is used as a supplement for diabetes and to promote healthy pancreatic function. A 100mg capsule helps maintain blood sugar levels in the normal range and reduce inflammation. Gymnema sylvestre helps to fight sugar cravings and neutralize cravings for sweets. [ABSTRACT FROM AUTHOR]

Introduction: The presence of family members who are treated in the intensive care unit makes the patient's family feel anxiety related to the fear of the death of someone they love. In dealing with this, family-centered care is used as an approach that has advantages for families, patients, and health workers. This case report aims to describe the family-centered care toward the patient and the patient's family with diabetic ketoacidosis and Multiple Organ Dysfunction Syndrome. Method: This study used a case report to describe the intervention in the case. The sample of this study was an adult patient with diabetic ketoacidosis and MODS who has a family with psychological problems in an intensive care unit. Results: Based on the assessment the patient's general condition was weak and restless, the level of consciousness under sedation with Ramsay score was 5, and the urinalysis found a ketonuria and glucosuria. The patient's family feels guilty, and worried, and always asks about the patient's condition while crying. The interventions provided by the FCC include information on the patient's condition, treatment plans, and results after the action is taken, spiritual guidance when the family visits time, and support. The output obtained was the patient's family feels calmer and satisfied more with the health services provider. Conclusions: The implementation of the FCC can decrease anxiety and healthcare care satisfaction, but the implementation can be challenged so it is necessary to develop the FCC program in the ICU which requires involvement and input from all parties. [ABSTRACT FROM AUTHOR]

Familial Renal Glucosuria (FRG) is a co‐dominantly inherited trait characterized by orthoglycaemic glucosuria. From 2003 to 2015 we have reported several cohorts validating SLC5A2 (16p11.2), encoding SGLT2 (Na+/glucose cotransporter family member 2), as the gene responsible for FRG. The aim of this work was to validate the variants identified in our extended FRG cohort of published, as well more recent unreported cases, according to the ACMG‐AMP 2015 criteria. Forty‐six variants were evaluated, including 16 novel alleles first described in this study. All are rare, ultra‐rare or absent from population databases and most are missense changes. According to the ACMG‐AMP standards, only 74% of the variants were classified as P/LP. The lack of descriptions of unrelated patients with similar variants or failing to test additional affected family members, averted a conclusion for pathogenicity in the alleles that scored VUS, highlighting the importance of both family testing and variant reporting. Finally, the cryo‐EM structure of the hSGLT2–MAP17 complex in the empagliflozin‐bound state improved the ACMG‐AMP pathogenicity score by identifying critical/functional protein domains. [ABSTRACT FROM AUTHOR]

Objective: Diabetes mellitus (DM) is known to increase urinary tract infections. Due to the frequent use of antibiotics, periodic evaluations of urinary tract infection agents and antibiotic resistance in centers are crucial. The purpose of this study was to examine the distribution of bacteria isolated as lower urinary tract infection agents and the antibiotic resistance rates of these pathogens. Methods: The records of 267 patients with a diagnosis of DM and a suspected of lower urinary tract infection who were hospitalized in the Gaziantep University Hospital Endocrinology Clinic between December 2019 and April 2022 were reviewed retrospectively. Urine and blood samples of the patients were analyzed. Results: Of these patients, 236 (88.4%) were female. The mean age of the patients was 57.6 years, and the mean Hba1c was 10.6%. While 174 (65.16%) cultures did not grow. 80 (29.96%) bacteria and 13 (4.86%) fungi were detected in urine culture results. Twelve different bacterial species were grown in the cultures. Escherichia coli was the most frequently isolated bacterium from gram-negative bacteria. Streptococcus agalactiae was the most common gram-positive bacteria. There were 249 patients with pyuria and, 18 patients without pyuria. While 66 (26%) of the patients with pyuria had bacterial growth in the culture, 14 (77.7%) of the patients without pyuria had bacterial growth. There were 176 patients with glucosuria. Bacterial growth was observed in 56 (31.8%) of these patients' pyuria was also present in 47 patients. Bacterial growth occurred in 24 (26.4%) of 91 patients without glucosuria. In gram-negative bacteria culture, ampicillin resistance was observed in 88%. Antibiotic sensitivity were positive for colistin, meropenem, and amikacin (100%, 96%, and 94%) respectively). Conclusions: Urinary tract infections are becoming more important in diabetic patients due to their frequent recurrence and increased antibiotic resistance in isolated bacteria. Cultures take at least two days to result, necessitating the initiation of empirical antibiotic therapy. We think that each center should regularly monitor the agent distribution and antibiotic resistance status in order to select the antibiotic that can be used in empirical treatment correctly. [ABSTRACT FROM AUTHOR]

Diabetic cardiomyopathy is a well-recognized clinical entity and reflects a complex relationship between metabolic substrates and myocardial function. Sodium glucose co-transporter 2 (SGLT2) inhibitors are antidiabetic agents that are found to exert multiple cardioprotective effects. Large clinical trials showed their beneficial effects on patients with heart failure, reducing the rates of rehospitalizations and improving kidney function. The aim of this review is to summarize the latest evidence in the literature regarding the multiple effects of SGLT2 inhibitors on patients across the spectrum of cardiovascular diseases. [ABSTRACT FROM AUTHOR]

IntroductionAlström syndrome is a rare recessive genetic disease caused by mutations in ALMS1, which encodes a protein that is related to cilia function and intracellular endosome trafficking. The syndrome has been linked to impaired glucose metabolism and CKD. Polymorphisms in Alms1 have likewise been linked to CKD, but little is known about the modification of the phenotype by environmental factors.MethodsTo gain further insights, the fat aussie (foz) mouse strain, a genetic murine model of Alström syndrome, was exposed to a normal chow (NC) or to a Western diet (WD, 20% fat, 34% sucrose by weight, and 0.2% cholesterol) and renal outcomes were measured.ResultsBody weight and albuminuria were higher in foz than in wild-type (WT) mice on both diets but WD significantly increased the difference. Measurement of plasma creatinine and cystatin C indicated that glomerular filtration rate was preserved in foz versus WT independent of diet. Renal markers of injury, inflammation, and fibrosis were similar in both genotypes on NC but significantly greater in foz than in WT mice on WD. A glucose tolerance test performed in foz and WT mice on WD revealed similar basal blood glucose levels and subsequent blood glucose profiles.ConclusionsWD sensitizes a murine model of Alström syndrome to kidney injury, inflammation, and fibrosis, an effect that may not be solely due to effects on glucose metabolism. Polymorphisms in Alms1 may induce CKD in part by modulating the deleterious effects of high dietary fat and sucrose on kidney outcome.

Background: Valproic acid is prescribed for epilepsy and as prophylaxis for bipolar disorder and migraine headaches. It has also been implicated as a cause of a kidney tubular injury. Methods: We undertook a review of the literature to characterize the biochemical and histopathological features of the overt kidney tubular injury and to evaluate the possible existence of a pauci-symptomatic injury. The pre-registered review (CRD42022360357) was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology. Searches were conducted in Excerpta Medica, the National Library of Medicine, and Web of Science. The gray literature was also considered. Results: For the final analysis, we retained 36 articles: 28 case reports documented 48 individuals with epilepsy on valproic acid for 7 months or more and presenting with features consistent with an overt kidney tubular injury. The following disturbances were noted: hypophosphatemia (N = 46), normoglycemic glycosuria (N = 46), total proteinuria (N = 45), metabolic acidosis (N = 36), hypouricemia (N = 27), tubular proteinuria (N = 27), hypokalemia (N = 23), and hypocalcemia (N = 8). A biopsy, obtained in six cases, disclosed altered proximal tubular cells with giant and dysmorphic mitochondria. Eight case series addressed the existence of a pauci- or even asymptomatic kidney injury. In the reported 285 subjects on valproic acid for 7 months or more, an isolated tubular proteinuria, mostly N-acetyl-β-glucosaminidase, was often noted. Conclusions: Valproic acid may induce an overt kidney tubular injury, which is associated with a proximal tubular mitochondrial toxicity. Treatment for 7 months or more is often associated with a pauci- or oligosymptomatic kidney tubular injury. [ABSTRACT FROM AUTHOR]

Aim: Although hypertensive disorders of pregnancy and gestational diabetes mellitus (DM) are risk factors for hypertension, DM, and kidney disease in later life, the association of gestational glycosuria, proteinuria, and borderline hypertension with these chronic diseases has been unclear. Methods: This cross‐sectional study was conducted between April 2017 and November 2020 at a Japanese tertiary hospital. Three variables listed in the Maternal and Child Health Handbook were analyzed: glycosuria, proteinuria, and systolic blood pressure (<130, 130–139, and ≥ 140 mmHg) during pregnancy. The incidences of DM, kidney disease, and hypertension self‐reported by mothers of pregnant women on a questionnaire were assessed with logistic regression analysis. Results: The 312 women completed the questionnaires an average of 35.8 ± 4.2 years after delivering their daughters. Risk for DM was significantly increased among women with glycosuria (adjusted odds ratio [aOR], 3.62; 95% confidence interval [CI], 1.21–10.9), and risk for kidney disease was significantly increased among women with proteinuria (aOR, 4.07; 95% CI, 1.29–12.9). Risk for hypertension was significant in women whose blood pressures were ≥ 140 mmHg (aOR, 4.26; 95% CI, 1.96–9.24), but the association between blood pressures of 130–139 mmHg and hypertension was not significant (aOR, 1.72; 95% CI, 0.95–3.11); however, a significant positive trend (p < 0.001) between increasing blood pressure and hypertension was observed. Conclusions: Gestational glycosuria, proteinuria, and increased blood pressure were associated with the development of maternal chronic diseases. These standard and inexpensive assessments may improve lifelong health management in women. [ABSTRACT FROM AUTHOR]

Objective: To report a case of rhabdomyolysis and myoglobinuria following single induction dose of propofol in a dog. Case Summary: A 5‐year‐old intact male Shih‐Tzu dog was presented for pigmenturia occurring a few hours following anesthesia for comprehensive oral health assessment and treatment. After premedication with IV diazepam (0.5 mg/kg), anesthesia was induced with IV propofol (4 mg/kg) and maintained with isoflurane vaporized in oxygen. A few hours following recovery from anesthesia, the dog developed rhabdomyolysis and myoglobinuria associated with increased serum alanine aminotransferase and C‐reactive protein concentrations, as well as mild hypokalemia and euglycemic glycosuria. Approximately 48 hours after IV fluid therapy, the dog was clinically normal, and myoglobinuria progressively resolved. New or Unique Information Provided: This is the first case description of rhabdomyolysis and myoglobinuria following a single dose of injectable propofol. [ABSTRACT FROM AUTHOR]

Urine and urine tests are the main biomarkers of urinary tract infections. Our study aims to study the urine analysis and urinary parameters of men and women in the Tetovo region with acute and chronic urinary infections. In this study, we took for research 320 urine samples in the period 2021 to 2022 from patients attacked in the clinical laboratory of Tetovo Hospital and the Albimedika biochemical laboratory. The analyzed patients were grouped from the age of 12 to 85 years. Urine analyzes were performed by collecting urine in sterile cups and using the urine microscopy method and urine strip test using the chromatographic method, where these analyzes were performed according to the European standards manual. Out of 320 patients, 220 were female and 100 male patients, we have resulted in patients with Proteinuria, leukocyturia, Epithelial Cells, Hematuria, urine pH, Granular casts, Triplet phosphate, Calcium oxalate, Glycosuria, Bacteria and mucous. The obtained results show that urine and urinary infections in man and women are the main indicators of urinary tract infections in patients with acute and chronic infections as well as asymptomatic patients who have had no clinical symptoms. [ABSTRACT FROM AUTHOR]

An 11-year-old male Cocker Spaniel was presented with acute onset of apathy, polyuria and polydipsia. Blood examination showed hypoalbuminemia and hyperglobulinemia, while electrophoresis revealed monoclonal gammopathy. Subsequent tests showed glycosuria, proteinuria, a positive serology test for Anaplasma spp. and ultrasonographical changes of the liver and spleen. Urine electrophoresis confirmed the presence of Bence-Jones protein. The dog’s condition deteriorated, and the dog had developed skin lesions on the neck and body. The owner decided to euthanize the dog and agreed to bone marrow and skin biopsy. Bone marrow cytology revealed an increased number of plasma cells and several cellular atypia. Histopathology of the skin lesions showed a round cell tumor of lymphoid or plasmacytoid origin. Subsequent immunohistology supported the diagnosis of multiple myeloma cutaneous involvement.

[Display omitted] • A steadfast, simple, and efficient approach for the non-invasive determination of glycosuria of diabetes mellitus using fluorescence spectroscopy. • Xenon arc lamp emitting light in the range from 200–950 nm was used as an excitation source for recording the fluorescent spectra from the urine samples. • A consistent fluorescence emission peak of glucose at 450 nm was found in all samples for an excitation wavelength of 370 nm. • For distinctions between healthy and infected samples, an efficient machine learning algorithms random forest (RF) and K-Nearest Neighbors (KNN) have been utilized to predict unknown classifications based on established samples. • These results proposed that for urinary glucose assessment Random Forest based model attained can be utilized as potential machine learning algorithm for diabetes discrimination. 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. [ABSTRACT FROM AUTHOR]

The concentration of glucose in plasma is held within narrow limits (4-10 mmol/l), primarily to ensure fuel supply to the brain. Kidneys play a role in glucose homeostasis in the body by ensuring that glucose is not lost in the urine. Three membrane proteins are responsible for glucose reabsorption from the glomerular filtrate in the proximal tubule: sodium-glucose cotransporters SGLT1 and SGLT2, in the apical membrane, and GLUT2, a uniporter in the basolateral membrane. 'Knockout' of these transporters in mice and men results in the excretion of filtered glucose in the urine. In humans, intravenous injection of the plant glucoside phlorizin also results in excretion of the full filtered glucose load. This outcome and the finding that, in an animal model, phlorizin reversed the symptoms of diabetes, has stimulated the development and successful introduction of SGLT2 inhibitors, gliflozins, in the treatment of type 2 diabetes mellitus. Here we summarise the current state of our knowledge about the physiology of renal glucose handling and provide background to the development of SGLT2 inhibitors for type 2 diabetes treatment.

Simple Summary: Jerky induced Fanconi syndrome is a kidney disease related to ingestion of jerky treats, mainly in dogs, resulting in excretion of sugar in the urine despite normal blood sugar. The objectives of this study were to describe disease characteristics and long-term outcome. In 30 dogs with spontaneously occurring jerky induced Fanconi syndrome, common clinical signs were increased urination and drinking, tiredness and weight loss. Less common were decreased appetite, vomiting and diarrhea. Urine analysis often revealed blood and protein in the urine and some dogs had electrolyte disturbances evident from blood samples. Full clinical recovery was achieved for 79% of the dogs in 0.3–52 weeks (median 11 weeks) while sugar in the urine was resolved in 93% of the dogs within 1–31 weeks (median 6.5 weeks). These results indicate a more favorable outcome of the disease than previously reported, though time to recovery might be long in some cases. Acquired canine proximal renal tubulopathy (Fanconi syndrome) related to excessive ingestion of jerky treats has been recognized since 2007. This study aimed to improve knowledge about the syndrome's characteristics, especially long-term outcome. By reaching out to veterinarians and dog owners, dogs suspected of jerky induced Fanconi syndrome were identified. The dog's medical records were reviewed, and owners interviewed. Data was analyzed using linear mixed models (p < 0.05 was considered statistically significant) and descriptive statistics are reported. Thirty dogs, median body weight 6.8 (range 1.2–59) kg and age 6.5 (0.5–14) years, were enrolled as suspected cases based on history of jerkey ingestion and confirmed normoglycemic/hypoglycemic glycosuria. Clinical signs included polydipsia (23/30), polyuria (21/30), lethargy (19/30), weight loss (15/30), hyporexia (11/30), vomiting (7/30), diarrhea (7/30) and no clinical signs (2/30). Para-clinical findings included azotemia (6/28), hypophosphatemia (9/25), metabolic acidosis (3/8), hypokalemia (6/20), proteinuria (13/26), aminoaciduria (4/4), hematuria (22/29) and ketonuria (7/27). Clinical signs resolved in 22/28 within 11 (0.3–52) weeks and glycosuria resolved in 28/30 within 6.5 (1–31) weeks. There were no associations between serum creatinine and urea and the amount/duration of jerky ingestion. Serum symmetric dimethylarginine concentrations were only available for a few dogs, therefore no conclusion was achieved on a possible association with duration of jerky ingestion. Apart from a larger percentage of dogs achieving complete recovery, the current findings are in agreement with previous reports. [ABSTRACT FROM AUTHOR]

Objective: To determine the frequency of suspected dysregulated renal tubular handling of filtered glucose, and its association with blood glucose levels in type 2 diabetes mellitus., Methods: The analytical, cross-sectional study was conducted from November 2022 to June 2023 at the Department of Medicine along with the Department of Pathology and Biochemistry, Pakistan Railway Hospital, Islamic International Medical College, Rawalpindi, Pakistan, and comprised diabetics aged 19-80 years. Blood and urinary glucose were assessed at the point of contact. Blood glucose 80-180mg/dl was considered glucose in range and >180mg/dl glucose above range. Hyperfunction of sodium glucose transport receptors was suspected if urinary glucose was <++ and the function of these receptors was considered normal if urinary sugar was ++ or more. Association of suspected receptors functioning and their association with blood glucose levels was determined. Data was analysed using SPSS 26., Results: Of the 159 diabetics, 91(57%) were females and 68(43%) were males. The overall mean age was 57±11 years (range: 46-68 years). Of the total, 43(27%) patients had glucose in range and 116(73%) had glucose above range. Of the diabetics with glucose above range, 54(47%) patients had hyper-functioning sodium glucose transport receptors, and 62(53%) had normal functioning sodium glucose transport receptors. Of the patients with glucose in range, 11(26%) had hyperfunctioning sodium glucose transport receptors, and 32(74%) had normal functioning sodium glucose transport receptors. There was a significant association between sodium glucose transport receptors' function and blood glucose levels (p<0.001)., Conclusion: Dysfunction of sodium glucose transport receptors affected the secretion of glucose in the urine, resulting in impaired glucose regulation in type 2 diabetes mellitus cases.

Background: Membranous nephropathy (MN) is an immune complex-mediated disease. Massive proteinuria can lead to Fanconi syndrome, clinically manifesting as renal glycosuria. The prevalence and prognosis of M-type phospholipase A2 receptor (PLA2R)-related MN with renal glycosuria remain unknown., Materials and Methods: Patients diagnosed with PLA2R-related MN with renal glycosuria were reviewed, and the control group comprised patients with MN without renal glycosuria who were randomly selected at a ratio of 1 : 3., Results: 50 patients diagnosed with PLA2R-related MN with renal glycosuria from January 2015 to January 2020 were included, with a prevalence of 2.3%. Compared with patients without renal glycosuria, those with renal glycosuria exhibited greater proteinuria, lower estimated glomerular filtration rate (eGFR), and higher use of diuretics, anticoagulants, antibiotics, traditional Chinese medicine, and tacrolimus within 3 months prior to renal biopsy (all p < 0.05). Histologically, patients with renal glycosuria exhibited more severe pathological stages, acute/chronic tubulointerstitial lesions, and tubulointerstitial inflammation (all p < 0.05). Of the 10 patients treated with rituximab (RTX), proteinuria remission was maintained in 6 (60%) patients, and urine glucose remission was achieved in 5 of these 6 patients (83.3%). Multivariate Cox regression analysis showed that renal glycosuria and age &gt; 50 years were independent risk factors for end-stage renal disease (ESRD) or a 30% reduction in the eGFR in patients with PLA2R-related MN., Conclusion: PLA2R-related MN patients with renal glycosuria presented with more severe clinicopathological manifestations and worse prognoses. Nephrotoxic drugs should be administered rationally, and RTX should be considered as a promising treatment option.

The article focuses on the concept of the stress hyperglycaemia ratio (SHR) as a measure of relative hyperglycaemia in hospitalized patients, exploring its association with mortality and its potential implications for clinical management. Topics discussed include the performance of SHR in identifying patients at risk of deterioration, discrepancies in SHR measurement across different pathologies, and the need for further research to elucidate the relationship between SHR and clinical outcomes.

Background: For effective screening in urinalysis, information on high-risk groups is needed; however, there is a lack of evidence in young adults in particular. The aim of this study was to provide information on urinalysis in young adults and to identify high-risk groups of urinalyses using multi-year data obtained from annual large-scale check-ups. Method: We used annual health check-up data collected from 2011 to 2016 at Kyoto University in Japan. Eligible participants were those aged 18–39 years who underwent annual health check-ups for four consecutive years between 2011 and 2016. We conducted descriptive analyses and calculated the risk ratios (RRs) for urinary abnormalities in the fourth year of urinalysis. Results: In total, 13,640 participants (10,877 men, 79.7%) met the eligibility criteria. The mean prevalence rates of proteinuria, haematuria and glucosuria were 1.61% (men: 1.63%; women: 1.53%), 1.48% (men: 0.53%; women: 5.22%) and 0.46% (men: 0.52%; women: 0.25%), respectively. Participants with urinary abnormalities at least once in the initial 3 years had a higher risk of urinary abnormalities in the fourth year than participants with no abnormal findings in the initial 3 years; the risk ratios (RRs) of proteinuria, haematuria and glucosuria were 3.5 (95% confidence interval (CI) = 3.2–3.7), 12.2 (95% CI = 11.7–12.7) and 42.6 (95% CI = 37.7–48.1), respectively. The RRs of all urinary abnormalities in the fourth year increased as the frequency of urinary abnormalities over the preceding 3 years increased. In haematuria, differences of the RR were observed between men and women. Conclusion: We clarified the prevalence of urinary abnormalities in young adults and high-risk groups of urinary abnormalities. Our findings support the need for multi-year annual urinalysis. [ABSTRACT FROM AUTHOR]

Abstract Aims/Introduction The relationship between renal function and urinary glucose is poorly understood in diabetes patients who are not using sodium–glucose cotransporter 2 inhibitors. This study aimed to investigate the association of urinary glucose excretion with renal function prognosis in such patients. Materials and Methods This retrospective cohort study included 1,172 patients with type 1 or 2 diabetes mellitus. Patients were recruited and data were collected between 1 January 2007 and 31 December 2011; follow‐up data were collected until 30 June 2015. The primary outcome was set as a 30% decline in estimated glomerular filtration rate relative to baseline. The relationship between this outcome and urinary glucose was investigated using Cox proportional hazards model. For analysis, patients were categorized into two groups: urinary glucose

The article "Understanding the renal threshold for glucose: Implications for diabetes management" in the African Journal of Diabetes Medicine discusses the importance of the renal threshold for glucose in diabetes care. The renal threshold is the blood glucose level at which glucose starts to appear in the urine, indicating poor blood glucose control. Factors like age, kidney function, and medications can influence this threshold. Monitoring blood glucose levels and preventing them from exceeding the renal threshold is crucial to avoid complications like kidney damage. The presence of glucose in urine can be used as a diagnostic tool, but it is more effective when combined with blood glucose monitoring. [Extracted from the article]

Abstract Background Sodium-glucose co-transporter 2 (SGLT2) inhibitors are novel hypoglycemic agents which reduce reabsorption of glucose at the renal proximal tubule, resulting in significant glycosuria and increased risk of genital mycotic infections (GMI). These infections are typically not severe as reported in large systematic reviews and meta-analyses of the medications. These reviews have also demonstrated significant cardiovascular benefits through other mechanisms of action, making them attractive options for the management of Type 2 diabetes mellitus (T2DM). We present two cases with underlying abnormalities of the urogenital tract in which the GMI were complicated and necessitated cessation of the SGLT2 inhibitor. Case presentations Both cases are patients with T2DM on empagliflozin, an SGLT2 inhibitor. The first case is a 64 year old man with Candida albicans balanitis and candidemia who was found to have an obstructing renal calculus and prostatic abscess requiring operative management. The second case describes a 72 year old man with Candida glabrata candidemia who was found to have prostatomegaly, balanitis xerotica obliterans with significant urethral stricture and bladder diverticulae. His treatment was more complex due to fluconazole resistance and concerns about urinary tract penetration of other antifungals. Both patients recovered following prolonged courses of antifungal therapy and in both cases the SGLT2 inhibitor was ceased. Conclusions Despite their cardiovascular benefits, SGLT2 inhibitors can be associated with complicated fungal infections including candidemia and patients with anatomical abnormalities of the urogenital tract may be more susceptible to these infections as demonstrated in these cases. Clinicians should be aware of their mechanism of action and associated risk of infection and prior to prescription, assessment of urogenital anatomical abnormalities should be performed to identify patients who may be at risk of complicated infection.

Background: India is currently undergoing a demographic and epidemiological transition leading to the occurrence of hypertension and type 2 diabetes, which were once considered as disease of the elderly among the adolescents. Methods: A cross-sectional study was conducted in Dharwad district, Karnataka, including 1600 students between 11–17 years age group, across both private and government schools located in both rural and urban areas; information on socio-demographic variables, physical activity, dietary habits, substance abuse, and family history of hypertension, diabetes mellitus and level of stress among participants was collected. Anthropometric measurements were taken, blood pressure was measured, general physical examination was done to look for signs of insulin resistance. Urine was examined for the presence of glucose using urine glucose strips in overweight children with ≥2 risk factors (American Diabetes Association criteria for children). Results: Prevalence of overweight/obesity was 4.6% and hypertension was 14.8%. Multivariate logistic regression done for variables found significant in univariate analysis on comparison of risk factors between overweight and normal children showed higher odds for family h/o diabetes (OR = 1.14, CI: 0.58–2.23), private school (OR = 1.5, CI: 0.75–2.96), high socio-economic status (OR = 2.0, CI: 0.95–4.30), hypertension (OR = 2.0, CI: 0.95–4.30) and acanthosis nigricans (OR = 219, CI: 71.49–672.42) among overweight and for variables found significant in univariate analysis on comparison of risk factors between hypertensives and normotensives showed higher odds for inadequate sleep (OR = 1.4, CI: 1.00–1.87), private school (OR = 1.32, CI: 0.96–1.81), high SES (OR = 1.43, CI: 0.95–2.14), psychological stress (OR = 1.97, CI: 1.42–2.73) and obesity (OR = 6.98, CI: 3.75–12.98). Conclusions: Health education on healthy diet consumption and physical activity, BMI calculation and tracking of blood pressure should be integrated into school health programs.

ABSTRACT Uropathogenic Escherichia coli (UPEC) is the principal etiology of more than half of urinary tract infections (UTI) in humans with diabetes mellitus. Epidemiological data and studies in mouse model of ascending UTI have elucidated various host factors responsible for increasing the susceptibility of diabetic hosts to UPEC-UTI. In contrast, diabetic urinary microenvironment-mediated alterations in UPEC physiology and its contributions to shaping UPEC-UTI pathogenesis in diabetes have not been examined. To address our central hypothesis that glycosuria directly induces urinary virulence of UPEC, we compared virulence characteristics and gene expression in human UPEC strains UTI89 (cystitis) and CFT073 (pyelonephritis), exposed for 2 h in vitro to urine from either male or female donors that was either plain or supplemented with glucose to mimic glycosuria. Compared to control UPEC exposed to nutrient-rich culture medium, lysogeny broth, glycosuria-exposed UPEC exhibited significant increase in biofilm formation and reduction in the hemagglutination of Guinea pig erythrocytes (a measure of type 1 piliation). In addition, the analysis of UTI89 transcriptome by RNA sequencing revealed that 2-h-long, in vitro exposure to glycosuria also significantly alters expression of virulence and metabolic genes central to urinary virulence of UPEC. Addition of galactose as an alternative carbon source affected biofilm formation and gene expression profile of UPEC to an extent similar to that observed with glucose exposure. In summary, our results provide novel insights into how glycosuria-mediated rapid changes in UPEC fitness may facilitate UTI pathogenesis in the diabetic urinary microenvironment. IMPORTANCE Uropathogenic Escherichia coli (UPEC) is an important causative agent of urinary tract infections in diabetic humans. We examined the effects of in vitro exposure to glycosuria (presence of glucose in urine) on the virulence and gene expression by UPEC. Our results show that glycosuria rapidly (in 2 h) alters UPEC gene expression, induces biofilm formation, and suppresses type 1 piliation. These results offer novel insights into the pathogenesis of UPEC in the urinary tract.

A 3-year-old boy came to our outpatient department with complaints of dark urine noticed by the mother since birth. On examination, the child had dysmorphic facies, synophrys, hypertelorism, micrognathia, prominent lashes, and difficulty in vision. The weight and height were below the third centile. Urinalysis showed glucosuria; tandem mass spectrometry and gas chromatography-mass spectrometry showed high levels of homogentisic acid and glycerol-3-phosphate. Exome sequencing revealed a missense homozygous variant in the gene encoding homogentisate 1,2-dioxygenase. A diagnosis of alkaptonuria was made and the patient was started on a low-protein diet and ascorbic acid. [ABSTRACT FROM AUTHOR]

The pervasiveness of urinary tract infections (UTIs) with their clinical manifestations in patients with diabetes mellitus has escalated amidst the past decade or so, as myriad predisposing factors contribute to its occurrence. Although the causative agent of UTI is Escherichia coli, the etiopathogenesis can be traced back to glycosuria in the renal parenchymal region. This has precipitated pyelonephritis and renal complications, including cytopathic and altered metabolism. Furthermore, impaired immunity with scarce IL-6, 8 in urine, urinary retention, and dysfunctional voiding raise susceptibility towards uropathogens, mainly E. coli. Treatment for UTI with diabetes is based on symptoms and severity, urologic abnormalities, renal function, bladder infections, and metabolic alteration. The treatment process or regimens for patients with type 2 diabetes with asymptomatic bacteriuria are very low or negligible. Adequate management with antibiotic regimens in symptomatic patients after critical diagnosis is crucial for prophylaxis and effective treatment. [ABSTRACT FROM AUTHOR]

Sodium-glucose cotransporter 2 (SGLT2) inhibitors exert hypoglycemic and diuretic effects by inhibiting the absorption of sodium and glucose from the proximal tubule. Currently available data indicate that SGLT2 inhibitors transiently enhance urinary sodium excretion and urinary volume. When combined with loop diuretics, SGLT2 inhibitors exert a synergistic natriuretic effect. The favorable diuretic profile of SGLT2 inhibitors may confer benefits to volume management in patients with heart failure but this natriuretic effect may not be the dominant mechanism for the superior long-term outcomes observed with these agents in patients with heart failure. The first part of this review explores the causes of transient natriuresis and the diuretic mechanisms of SGLT2 inhibitors. The second part provides an overview of the synergistic effects of combining SGLT2 inhibitors with loop diuretics, and the third part summarizes the mechanisms of cardiovascular protection associated with the diuretic effects of SGLT2 inhibitors. [ABSTRACT FROM AUTHOR]

Aims: Sodium glucose co‐transporter 2 inhibitors have diuretic effects in both patients with glycosuria and with natriuresis. We sought to assess the effect of luseogliflozin on estimated plasma volume (ePV) in patients with type 2 diabetes and heart failure with preserved ejection fraction (HFpEF). Methods and results: This study was a post‐hoc analysis of the MUSCAT‐HF trial (UMIN000018395), a multicentre, prospective, open‐label, randomized controlled trial that assessed the effect of 12 weeks of luseogliflozin (2.5 mg, once daily, n = 83) as compared with voglibose (0.2 mg, three times daily, n = 82) on the reduction in brain natriuretic peptide (BNP) in patients with type 2 diabetes and HFpEF. The analysis compared the change in ePV calculated by the Straus formula from baseline to Weeks 4, 12, and 24, using a mixed‐effects model for repeated measures. We also estimated the association between changes in ePV and changes in other clinical parameters, including BNP levels. Luseogliflozin significantly reduced ePV as compared to voglibose at Week 4 {adjusted mean group‐difference −6.43% [95% confidence interval (CI): −9.11 to −3.74]}, at Week 12 [−8.73% (95%CI: −11.40 to −6.05)], and at Week 24 [−11.02% (95%CI: −13.71 to −8.33)]. The effect of luseogliflozin on these parameters was mostly consistent across various patient clinical characteristics. The change in ePV at Week 12 was significantly associated with log‐transformed BNP (r = 0.197, P = 0.015) and left atrial volume index (r = 0.283, P = 0.019). Conclusions: Luseogliflozin significantly reduced ePV in patients with type 2 diabetes and HFpEF, as compared with voglibose. The reduction of intravascular volume by luseogliflozin may provide clinical benefits to patients with type 2 diabetes and HFpEF. [ABSTRACT FROM AUTHOR]

Diabetic ketoacidosis (DKA) is an acute and major complication of diabetes mellitus (DM), both type I and type II. Biochemically, DKA consists of a triad of blood sugar levels greater than 250 mg/dL, ketonemia of greater than 3 mmol/L and/or significant ketonuria, and a blood pH less than 7.3 with an increased anion gap. Currently, the sodium-glucose cotransporter-2 inhibitors (SGLT-2i) are widely used in management of type II diabetes. There have been several reports of an association between euglycemic diabetic ketoacidosis (EuDKA) and SGLT-2i agents. We present three different patients who were on SGLT-2i therapy who developed recurrent EuDKA postprocedure or sepsis. We believe that prolonged treatment (5-6 days) with intravenous (IV) insulin with glucose until resolution of glycosuria can be considered as an inexpensive marker of resolution of EuDKA. Moreover, the recommended duration for discontinuation of these drugs prior to elective procedures should be longer than 3 days. [ABSTRACT FROM AUTHOR]

Neonatal hyperglycemia is a common metabolic disorder seen in very low birth weight (VLBW) and critically ill newborns. Hyperglycemia is a recognized cause for mortality and morbidity in the neonatal period. Incidence in preterm infants is around 45%–80%. The mechanism of increased risk of hyperglycemia in preterm infants is not well understood, but different possible mechanisms have been reported. Plasma glucose values more than 180–200 mg/dl (10–11.1 mmol) are of concern as this can lead to complications. Hyperglycemia was found to predispose to severe intraventricular hemorrhage, retinopathy of prematurity, necrotizing enterocolitis, and increased mortality. It is important to recognize and manage this condition early to avoid serious complications. Multiple etiologies with different management strategies are mentioned in the literature. Here, we discuss a complete understanding on practical management of hyperglycemia and we propose a simplified practical approach for the diagnosis and management of neonatal hyperglycemia. [ABSTRACT FROM AUTHOR]

Background: Diabetic ketoacidosis (DKA) is a common consequence of electrolyte and dehydration abnormalities that affect individuals with type-1 diabetes. DKA is a major diabetic complication worldwide. Clinical details: We have presented a male patient aging 31years with abdominal pain, nausea, vomiting(nonprojectile), shortness of breath Grade IV for 1 day, altered sensorium as well as diarrhea (every day, five watery bowel movements) for 2 days.). The laboratories results showed that the person had with an anion gap of 21 with positive ketones, low bicarbonate & high blood glucose, urine glucose and high circulating blood ketones are strongly positive. Based on the laboratory findings patient has confirmed with DKA. The patient has been referred to the ICU Hehas begun with insulin drip and serum electrolytes after every four hours (potassium, sodium, phosphorus, magnesium, & chloride). Outcomes: The patient has begun with insulin drip and serum electrolytes for every four hours (potassium, sodium, phosphorus, magnesium, & chloride). After the initiation of insulin treatment, potassium levels were shifted intracellularly and serum levels were declined.Insulin stimulated the transcellular potassium transmission and patient has developed with hypokalemia. Conclusion: Pulmonary edema may develop in DKA patients for the same causes as cerebral edema. Be careful of potential fluid loss overcorrection, although it rarely occurs. DKA prevention requires more research and collaboration among inpatient and outpatient clinicians and patient education. [ABSTRACT FROM AUTHOR]

Background We assessed the glucose-lowering efficacy of adding empagliflozin versus dose escalating existing medications in patients with uncontrolled type 2 diabetes (T2D). Methods This was a 6-month retrospective case-control study in subjects with uncontrolled T2D (glycated hemoglobin [HbA1c] >7%) on conventional treatment. The study group started add-on therapy with empagliflozin (10 mg once a day) while the control group was up-titrated with existing medication, using either monotherapy or a combination of metformin, sulfonylurea, and a dipeptidyl peptidase-4 inhibitor. The primary endpoints included changes in HbA1c, fasting plasma glucose (FPG), and 2-hour postprandial glucose (PP2) levels. Secondary outcomes included changes in body composition, body mass index (BMI), and serum ketone bodies, and urinary excretion of sodium, potassium, chlorine, calcium, phosphorus, and glucose. Results After treatment, the reduction in HbA1c was significantly greater in the empagliflozin group than in controls (from 8.6%±1.6% to 7.6%±1.5% vs. 8.5%±1.1% to 8.1%±1.1%; P