Introduction: Sodium-glucose-linked-transporter inhibitors (SGLT2-i) have demonstrated cardiovascular and renal benefits in type 2 diabetes mellitus (T2DM), but patients aged ≥75 years remain underrepresented in major trials, creating uncertainty regarding their risk–benefit profile. Real-world data show mixed safety signals. In Malaysia, local evidence is limited despite a growing elderly diabetic population. This study evaluates the glycemic efficacy and safety of SGLT2-i in advanced elderly patients in a real-world public hospital setting. Methodology: We conducted a retrospective observational cohort study of patients aged ≥75 years with T2DM initiated on SGLT2-i in Hospital Putrajaya (2020–2024). Electronic records were reviewed for demographics, comorbidities, medications, and biochemical parameters. Outcomes at 6–12 months assessed glycemic control and safety. Adverse events and discontinuation rates were recorded. Patients with incomplete data, type 1 diabetes, active malignancy, or severe renal impairment were excluded. Results: A total of 104 patients (mean age 78.2 years; 54% female) were included with a high proportion (76.9%) classified as at high cardiovascular risk due to established macrovascular disease (57.7%) or nephropathy (53.8%). Indications for SGLT2-i initiation were glycemic control alone (69.2%) and together with cardiorenal protection (58.7%). Glycemic control remained stable (hemoglobin A1c: 7.66–7.45%; p = 0.076), with preserved renal function (estimated glomerular filtration rate: 58.65–58.11 mL/min/1.73 m²; p = 0.575). Overall safety was favorable, with 90.4% experiencing no adverse events. Minor adverse events included urinary tract infections (2.9%) and polyuria (1.9%). ASCVD-related hospitalizations occurred in 4.8% of patients, with a low discontinuation rate (7.7%). A statistically significant weight reduction was observed (baseline 66.67 kg, −1.01 kg; p = 0.005) but was not clinically significant. Proteinuria improvement was noted in 15.7% of patients. Conclusion SGLT2-i are safe and well-tolerated in elderly T2DM patients (≥75 years), with stable glycemic control, preserved renal function, and minimal adverse events, supporting their use in very elderly Asian populations.
Aged ; Diabetes Mellitus, Type 2 ; Sodium-Glucose Transporter 2 Inhibitors

Introduction: Sodium-glucose cotransporter-2 (SGLT2) inhibitors are cornerstone therapies for heart failure and diabetes, offering proven cardiorenal benefits. However, expanded use necessitates vigilance regarding adverse effects, particularly genitourinary infections. While mild cystitis is common, serious upper urinary tract infections remain rare and potentially life-threatening. We describe a case of renal abscess presenting as recurrent urinary tract infections (UTI) following SGLT2 inhibitor initiation, emphasizing the need for clinical vigilance. Case: A 69-year-old male with a significant cardiovascular history, including heart failure with reduced ejection fraction (HFrEF), hypertrophic cardiomyopathy with an implantable cardioverter-defibrillator for non-sustained ventricular tachycardia, diabetes mellitus, hypertension, and hyperlipidemia, presented with a 1-week history of right flank pain, dysuria, urinary frequency, and fever. Initial labs confirmed infection: leukocytosis (22.6 × 10³/ µL), markedly elevated CRP (200 mg/L), and bacteriuria. He was diagnosed with a UTI and started on IV Cefuroxime. This marked his third UTI admission in 5 months, following discharge just 3 weeks prior for septic shock secondary to UTI, establishing a relapsing pattern. Subsequent urine and blood cultures were unremarkable. Medication review revealed Dapagliflozin had been initiated for HFrEF 8 months ago. Following clinical improvement from each prior UTI episode, Dapagliflozin was consistently restarted. Despite an initial antibiotic response, symptoms recurred after discharge each time. The recurrent nature of his infections prompted a renal ultrasound revealing a large (5.3 × 7.5 × 7.4 cm), non-drainable, heterogeneously hypoechoic collection at the left kidney’s mid-lower pole, diagnostic of an early renal abscess. Conclusion This report highlights renal abscess as a rare and severe complication of SGLT2 inhibitor therapy. It serves as a critical reminder that recurrent or relapsing UTIs in patients on these agents should prompt immediate investigation with renal imaging to rule out deep-seated pathology rather than simple cystitis. While these drugs offer proven cardiorenal benefits, their role in promoting urological infections necessitates a cautious approach.
Abscess ; Sodium-Glucose Transporter 2 Inhibitors

OBJECTIVE: To elucidate the clinical and genetic characteristics of familial cases with Glucose transporter type 1 deficiency syndrome (Glut1DS). METHODS: A survey of family history was conducted on children (proband) with Glut1DS who had visited Peking University First Hospital between November 2008 and April 2024 by focusing on the clinical manifestations of family members. Peripheral venous blood (2 mL) was collected from the pediatric patients and their parents. Genomic DNA was extracted and sequenced subsequently. Sanger sequencing was performed to validate the identified variant sites of the SLC2A1 gene in the probands and their family members. The pathogenicity of suspected variants was analyzed according to the 2015 American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Interpretation of Sequence Variants. The clinical features, auxiliary examinations, and mutational characteristics of family members with SLC2A1 variants were analyzed. This study has been approved by the Clinical Research Ethics Committee of Peking University First Hospital (Ethics No. 2021 Research 332). RESULTS: Among 87 cases with Glut1DS, 10 families with autosomal dominate inherited cases were identified, accounting for 11.0% of the cases. Of the 11 children, 8 were boys and 3 were girls. The onset of the disease had ranged from 3 months to 120 months (median 6 months), with 4 cases of early-onset classic type, 2 cases of late-onset classic type, and 5 cases of non-classic type. Six children had seizures, and 7 exhibited movement disorders. Seven children underwent developmental assessment, of which 3 had mild developmental delay, 2 were borderline, and 2 were normal. Nine children underwent lumbar puncture. The cerebrospinal fluid glucose levels ranged from 1.45 to 2.25 mmol/L (median 1.86 mmol/L), and the cerebrospinal fluid to blood glucose ratios ranged from 0.29 to 0.44 (median 0.35). Among the 8 fathers with SLC2A1 gene variants, 4 were asymptomatic, 2 developed paroxysmal exercise-induced movement disorders (PED) in childhood and adulthood, respectively. 1 had poor memory since childhood, 1 developed migraines during adolescence, and his sister was an asymptomatic carrier. The father with childhood-onset PED had a cerebrospinal fluid test with CSF glucose of 1.85 mmol/L. Of the 3 mothers with SLC2A1 gene mutations, 1 was an asymptomatic carrier; 2 developed PED in childhood and after the age of 20, respectively. The mother who developed PED in childhood also had psychomotor developmental delay. Genetic testing results revealed that among 10 families, 8 carried missense variants, 1 carried a nonsense variant, and 1 carried a small fragment insertion leading to a frameshift variant. Among the 11 cases, SLC2A1 gene variants in 8 children were inherited from their fathers, while in 3 cases, the variants were inherited from their mothers. The pathogenicity of the genetic variants was evaluated according to the Standards and Guidelines for the Interpretation of Sequence Variants published by the ACMG. Among the 8 variants identified in the 10 families, 4 were classified as pathogenic variants, 1 as likely pathogenic, and 3 as variants of uncertain significance (VUS). Four variant sites, including c.204_205insTCTC (p.V69fs), c.412G>C (p.G138R), c.431T>G (p.V144G), and c.875A>G (p.Y292C), were not previously reported in the literature. Among these, the latter three were categorized as VUS. CONCLUSION Familial Glut1DS account for 11.0% of the cases in China, with the majority of SLC2A1 gene variants inherited from the fathers, predominantly missense mutations, and with an autosomal dominant inheritance pattern. Probands tend to have earlier onset and more severe symptoms than their parents, who often present with mild or no symptoms.
Humans ; Male ; Female ; Glucose Transporter Type 1/deficiency* ; Monosaccharide Transport Proteins/deficiency* ; Child ; Child, Preschool ; Carbohydrate Metabolism, Inborn Errors/genetics* ; Mutation ; Infant ; Pedigree ; Adolescent ; Adult

BACKGROUND: Angiotensin receptor neprilysin inhibitors (ARNIs), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers (BBs), and mineralocorticoid receptor antagonists (MRAs) are the cornerstones in treating heart failure with reduced ejection fraction (HFrEF). Sodium-glucose cotransporter 2 inhibitors (SGLT-2is) are included in HFrEF treatment guidelines. However, the effect of SGLT-2i and the five drugs on HFrEF have not yet been systematically evaluated. METHODS: PubMed, Embase, and the Cochrane Library were searched for randomized controlled trials (RCTs) from inception dates to September 23, 2022. Additional trials from previous relevant reviews and references were also included. The primary outcomes were changes in left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter/dimension (LVEDD), left ventricular end-systolic diameter/dimension (LVESD), left ventricular end-diastolic volume (LVEDV), and left ventricular end-systolic volume (LVESV), left ventricular end-systolic volume index (LVESVI), and left ventricular end-diastolic volume index (LVEDVI). Secondary outcomes were New York Heart Association (NYHA) class, 6-min walking distance (6MWD), B-type natriuretic peptide (BNP) level, and N-terminal pro-BNP (NT-proBNP) level. The effect sizes were presented as the mean difference (MD) with 95% confidence interval (CI). RESULTS: We included 68 RCTs involving 16,425 patients. Compared with placebo, ARNI + BB + MRA + SGLT-2i was the most effective combination to improve LVEF (15.63%, 95% CI: 9.91% to 21.68%). ARNI + BB + MRA + SGLT-2i (5.83%, 95% CI: 0.53% to 11.14%) and ARNI + BB + MRA (3.83%, 95% CI: 0.72% to 6.90%) were superior to the traditional golden triangle ACEI + BB + MRA in improving LVEF. ACEI + BB + MRA + SGLT-2i was better than ACEI + BB + MRA (-8.05 mL/m 2 , 95% CI: -14.88 to -1.23 mL/m 2 ) and ACEI + BB + SGLT-2i (-18.94 mL/m 2 , 95% CI: -36.97 to -0.61 mL/m 2 ) in improving LVEDVI. ACEI + BB + MRA + SGLT-2i (-3254.21 pg/mL, 95% CI: -6242.19 to -560.47 pg/mL) was superior to ARB + BB + MRA in reducing NT-proBNP. CONCLUSIONS: Adding SGLT-2i to ARNI/ACEI + BB + MRA is beneficial for reversing cardiac remodeling. The new quadruple drug "ARNI + BB + MRA + SGLT-2i" is superior to the golden triangle "ACEI + BB + MRA" in improving LVEF. REGISTRATION PROSPERO; No. CRD42022354792.
Humans ; Heart Failure/physiopathology* ; Stroke Volume/physiology* ; Angiotensin Receptor Antagonists/therapeutic use* ; Angiotensin-Converting Enzyme Inhibitors/therapeutic use* ; Sodium-Glucose Transporter 2 Inhibitors/therapeutic use* ; Randomized Controlled Trials as Topic ; Mineralocorticoid Receptor Antagonists/therapeutic use* ; Adrenergic beta-Antagonists/therapeutic use*

Glucose transporters (GLUTs) are pivotal membrane proteins that facilitate the passive transport of glucose into cells. However, their aberrant overexpression is closely linked to the Warburg effect and chemotherapy resistance of tumors. GLUTs are complex multi-pass transmembrane proteins that require detergents for extraction from the cell membrane during preparation. The persistent presence of detergents in the sample can disrupt lipid-protein interactions, potentially leading to conformational distortion and functional losses of GLUTs, severely hindering the research into their structures and transport mechanisms. To eliminate detergent interference and preserve its authentic conformation, this study employs nanodisc technology and utilizes the self-assembly of the membrane scaffold protein MSP1E3D1 and phospholipids to produce a biomimetic membrane environment, thereby overcoming the limitations of conventional methods. The C-terminal His10-tagged GLUT1 was heterologously expressed in the insect cell Sf9/Bac-to-Bac system, and the GLUT1-nanodisc complex was obtained after detergent solubilization, affinity chromatography purification via anti-His antibody resin, and self-assembly. The successfully reconstituted nanodisc complex was further purified by Ni-NTA affinity chromatography. Nanodisc reconstitution produced monodisperse GLUT1 particles that retained native secondary structure, as confirmed by far-UV circular dichroism (CD) spectroscopy and dynamic light scattering (DLS). Unlike conventional detergent micelles, which lack a true lipid bilayer, distort transmembrane-helix topology, and occlude ligand-binding sites, the nanodisc platform embeds GLUT1 in a phospholipid bilayer that preserves its authentic conformation while eliminating detergent interference. The resulting GLUT1-nanodisc complex is therefore a superior scaffold for high-resolution cryo-EM structural analysis, permitting detailed interrogation of the transporter's conformational cycle, its interactions with partner proteins, and downstream structure-guided, high-throughput drug screening.
Nanostructures/chemistry* ; Glucose Transporter Type 1/biosynthesis* ; Humans ; Animals ; Phospholipids/chemistry* ; Detergents/chemistry*

BACKGROUND

Congruent with the increasing prevalence of diabetes, a growing armamentarium of anti-diabetes medications has been introduced. Among these are sodium glucose co-transporter-2 inhibitors (SGLT2i).

SGLT2i use has been linked to an increased incidence of urogenital infections. The study aims to compare resistance patterns of urinary tract isolates among patients with diabetes who are on SGLT2i and not on SGLT2i.

Single-center retrospective cohort study. A total of 464 patients (75 on SGLT2i, 389 not on SGLT2i) with DM type 2 and urinary tract infection were included. Urine culture results were compared.

A similar pattern of urinary tract isolates was found between groups except for C. albicans being more common in the SGLT2i group. There was no significant association between the presence of resistant urinary tract pathogens and the use of SGLT2i. There was no statistically significant difference in resistance rates between groups, except for Imipenem (p = 0.015).

SGLT2i use per se does not play a pivotal role in mediating bacterial resistance in urinary tract pathogens among patients with DM type 2. We do not recommend for or against the use of specific antimicrobials based on SGLT2 inhibitor alone. Patient’s clinical profile along with urine culture test results remain key factors in patient management.

OBJECTIVES: To examine how the glucose transporter SLC2A1 influences the proliferation and migration of lung adenocarcinoma (LUAD) and explore the underlying molecular mechanisms. METHODS: We examined the differential expression of SLC2A1 between normal and LUAD tissues in the TCGA database and its prognostic implications. Immunohistochemistry was used to detect SLC2A1 protein levels in clinical samples of LUAD and adjacent tissues, and the association of SLC2A1 expression levels with clinicopathological features of the patients was analyzed. In PC9 cells with stable SLC2A1 overexpression or knockdown, the effects of SLC2A1 expression level on cell proliferation and migration were assessed using CCK-8 and Transwell assays, and the changes in expressions of ferroptosis- and autophagy-related proteins were measured; the occurrence of ferroptosis was confirmed using ROS and Fe²⁺ fluorescence staining. RESULTS: SLC2A1 expression was significantly higher in LUAD tumor tissues than in normal lung tissues (P<0.05) and was associated with worse pathological parameters and prognosis of the patients (P<0.05). In PC9 cells, SLC2A1 overexpression significantly promoted cell proliferation, invasion and migration, and SLC2A1 knockdown significanty increased cell death and inhibited cell invasion and proliferation. SLC2A1 knockdown caused obvious activation of cell ferroptosis, reduced GPX4 and xCT expressions, and increased intracellular levels of ROS and Fe²⁺. SLC2A1 knockdown also resulted in increased cell autophagy shown by increased LC3B expression, which could be reversed by treatement with 3-MA. CONCLUSIONS High SLC2A1 expression is correlated with poor prognosis of patients with LUAD, and inhibiting SLC2A1 can induce ferroptosis and autophagy of LUAD cells, suggesting the potential of SLC2A1 as a target for LUAD diagnosis and treatment.
Humans ; Ferroptosis/genetics* ; Cell Proliferation ; Adenocarcinoma of Lung/genetics* ; Lung Neoplasms/genetics* ; Cell Line, Tumor ; Cell Movement ; Glucose Transporter Type 1/genetics* ; Prognosis ; Autophagy ; Neoplasm Invasiveness ; Female ; Male

Metformin has robust glucose-lowering effects and multiple benefits beyond hypoglycemic effects. It can also be used in combination with various hypoglycemic drugs and is cost effective. In the absence of the strong indications of glucagon like peptide-1 receptor agonist (GLP-1RA) or sodium glucose cotransporter 2 inhibitor (SGLT2i) for cardiorenal protection, metformin should be used as the first-line pharmacological treatment for newly diagnosed type 2 diabetes and the basic drug for the combined treatment of hypoglycemic drugs. Metformin does not increase the risk of liver and kidney function damage, but patients with renal dysfunction should adjust the dosage of metformin based on estimated glomerular filtration rate (eGFR) levels. Moreover, the correct use of metformin does not increase the risk of lactic acidosis. Because long-term use of metformin is associated with a decrease in vitamin B₁₂ levels, patients with insufficient intake or absorption of vitamin B₁₂ should be regularly monitored and appropriately supplemented with vitamin B₁₂. In view of the new progress made in the basic and clinical research related to metformin, the consensus updating expert group updated the consensus on the basis of the Expert Consensus on the Clinical Application of Metformin (2018 Edition).
Humans ; Consensus ; Diabetes Mellitus, Type 2/complications* ; Hypoglycemic Agents ; Metformin/therapeutic use* ; Sodium-Glucose Transporter 2 Inhibitors/therapeutic use* ; Vitamins/therapeutic use* ; China

This study aims to explore the mechanism of Yanghe Decoction(YHD) against subcutaneous tumor in pulmonary metastasis from breast cancer, which is expected to lay a basis for the treatment of breast carcinoma with YHD. The chemical components of medicinals in YHD, and the targets of the components were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and SwissTargetPrediction. The disease-related targets were searched from GeneCards and Online Mendelian Inheritance in Man(OMIM). Excel was employed to screen the common targets and plot the Venn diagram. The protein-protein interaction network was constructed. R language was used for Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment. A total of 53 female SPF Bablc/6 mice were randomized into normal group(same volume of normal saline, ig), model group(same volume of normal saline, ig), and low-dose and high-dose YHD groups(YHD, ig, 30 days), with 8 mice in normal group and 15 mice in each of the other groups. Body weight and tumor size was measured every day. Curves for body weight variation and growth of tumor in situ were plotted. In the end, the subcutaneous tumor sample was collected and observed based on hematoxylin and eosin(HE) staining. The mRNA and protein levels of hypoxia inducible factor-1α(HIF-1α), pyruvate kinase M2(PKM2), lactate dehydrogenase A(LDHA), and glucose transporter type 1(GLUT1) were detected by PCR and Western blot. A total of 213 active components of YHD and 185 targets against the disease were screened out. The hypothesis that YHD may regulate glycolysis through HIF-1α signaling pathway to intervene in breast cancer was proposed. Animal experiment confirmed that the mRNA and protein levels of HIF-1α, PKM2, LDHA, and GLUT1 in the high-and low-dose YHD groups were lower than those in the model group. YHD has certain inhibitory effect on subcutaneous tumor in pulmonary metastasis from breast cancer in the early stage, which may intervene pulmonary metastasis from breast cancer by regulating glycolysis through HIF-1α signaling pathway.
Female ; Mice ; Animals ; Glucose Transporter Type 1/genetics* ; Network Pharmacology ; Animal Experimentation ; Saline Solution ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Signal Transduction ; Glycolysis ; RNA, Messenger ; Neoplasms/drug therapy* ; Molecular Docking Simulation

Humans ; Diabetes Mellitus, Type 2/drug therapy* ; Sodium-Glucose Transporter 2 Inhibitors/therapeutic use* ; Arrhythmias, Cardiac/etiology* ; Glucose ; Sodium