Obesity is a chronic disorder resulting from a prolonged energy imbalance, with a significant contribution of genetic, metabolic, and lifestyle factors, and is recognized as one of the leading global public health challenges. It is associated with the development of numerous chronic non-communicable diseases, including type 2 diabetes mellitus and cardiovascular diseases. Chronic low-grade inflammation represents a key pathophysiological link between obesity and its comorbidities, and SGLT2 inhibitors have been shown to exert anti-inflammatory effects, providing a biological rationale for investigating their therapeutic potential in obesity management. SGLT2 inhibitors reduce glycemia via an insulin-independent mechanism and contribute to body weight loss through increased glucosuria. Although their beneficial metabolic effects are well documented in patients with T2DM, evidence regarding their efficacy in reducing body weight in patients without T2DM remains limited, and their therapeutic positioning relative to GLP-1 receptor agonists has not been comprehensively evaluated. This systematized narrative review aims to address this gap by synthesizing available preclinical and clinical evidence on the effects of SGLT2 inhibitors on body weight and metabolic parameters in obese patients with and without T2DM. Preclinical studies demonstrate reductions in visceral adipose tissue, increased fatty acid oxidation, and activation of the browning of white adipose tissue. Clinical trials confirm modest but consistent reductions in body weight, generally ranging from 2 to 4 kg, in obese patients with and without T2DM, along with improvements in glycemic control and metabolic parameters. The long-term effectiveness of SGLT2 inhibitors in body weight management is limited by compensatory hyperphagia and plateau effects. Current evidence is insufficient to support their routine use as primary anti-obesity agents. Compared to GLP-1 receptor agonists and dual incretin therapies, the magnitude of weight loss achieved with SGLT2 inhibitors remains substantially lower. Therefore, SGLT2 inhibitors are best positioned as adjunctive components of a comprehensive metabolic therapeutic strategy.

We present a case of acute Candida glabrata prostatitis complicated by secondary candidemia in a 72-year-old man with poorly controlled Type 2 diabetes mellitus and benign prostatic hyperplasia, without classical healthcare-associated risk factors for invasive candidiasis. The patient presented with fever, urinary symptoms, and markedly elevated prostate-specific antigen. Urine and blood cultures confirmed disseminated C. glabrata infection. Despite a comprehensive diagnostic workup, no alternative source of candidemia was identified, supporting primary prostatic infection with secondary hematogenous dissemination. Among the identified predisposing factors was ongoing treatment with dapagliflozin, a sodium-glucose cotransporter 2 inhibitor (SGLT2 inhibitor). While SGLT2 inhibitor use is established as a risk factor for superficial mycotic genitourinary infections, invasive fungal complications remain poorly characterized. This case suggests that the SGLT2 inhibitor-induced glucosuria, in combination with structural urinary obstruction and poorly controlled diabetes, may contribute to invasive fungal infections and highlights the need for clinical vigilance in patients with multiple converging risk factors.

Proteus mirabilis is a leading cause of complicated urinary tract infections (UTIs). Prior work showed P. mirabilis metabolizes sugars during experimental UTI, yet the role of sugar import systems in pathogenesis remains poorly defined. To investigate this, we generated a panel of 47 targeted mutants in predicted sugar transporter genes and assessed their growth in vitro and fitness in vivo. Growth screening in nutrient-rich and minimal media revealed carbon source-dependent defects in several phosphotransferase system (PTS) mutants, including ptsH and ptsI. Pooled insertion sequencing (In-seq) identified xapB, ptsH, and ptsI as in vivo fitness factors, with validation in a traditional murine co-challenge model. Functional studies showed that xapB, annotated as a xanthosine permease, did not support xanthosine or guanosine uptake in P. mirabilis, suggesting misannotation. Dissection of the PTS network revealed that a triple mutant lacking scrA, ulaC, and ptsG recapitulated the ptsH phenotype in vivo. To evaluate whether increased sugar availability exacerbates these defects, we modeled glucosuria using the SGLT2 inhibitor dapagliflozin in CBA/J mice. Dapagliflozin treatment significantly increased urinary glucose and enhanced P. mirabilis colonization. There was an inverse correlation between colonization and urinary glucose, but only in untreated mice. These findings reveal limitations in genome-based transporter annotation, establish a functional link between sugar import and P. mirabilis fitness during UTI, and demonstrate that host metabolic conditions such as glucosuria can influence the severity of infection.

Kidney diseases are a group of disorders that cause kidney damage, characterized by renal dysfunction, pathological changes in renal tissue, and abnormal components in blood or urine. A plethora of factors have been identified as causes of renal diseases, including cadmium exposure. Cadmium is an environmental pollutant, and excessive intake of cadmium in the human body can result in cadmium poisoning. Accumulating evidence has demonstrated that cadmium exposure is a contributing factor to the development of kidney diseases. The associated symptoms include damage to the renal tubules and glomeruli, proteinuria, aminuria, and glycosuria, which pose a significant threat to human health. Currently, there is no ideal method for treating cadmium-induced kidney injury. In this review, we aim to summarize the pathogenesis and mechanisms of cadmium-induced kidney diseases, the development of therapeutic drugs for cadmium poisoning, and their potential mechanisms of action. Furthermore, the application limitations of these therapeutic agents in cadmium- induced kidney injury and their potential solutions are also discussed. It is hoped that this review may provide valuable insights and guidance for researchers in related fields.

Severe hyperglycemia may remain clinically silent despite significant metabolic derangement, particularly in patients with inconsistent engagement in care. We report the case of a 50-year-old patient with type 2 diabetes mellitus enrolled in a gout clinical trial, in which protocol-driven laboratory monitoring revealed progressive, asymptomatic hyperglycemia and worsening glucosuria across multiple study visits. Fasting blood glucose increased from 250 mg/dL at baseline to 474 mg/dL at Week 24, while urine glucose exceeded 1000 mg/dL from Week 16 through Week 24. Hemoglobin A1c was 13%, and the patient had class II obesity with a body mass index of 39.7 kg/m². Despite these findings, the patient denied classic symptoms of hyperglycemia and demonstrated no evidence of acute metabolic decompensation. Evaluation of investigational product safety data did not support a drug-related cause. Further assessment identified medication nonadherence, inconsistent primary care follow-up, and socioeconomic barriers as likely contributors. Following coordination with the patient's primary care physician, insulin therapy was initiated, resulting in rapid improvement in fasting blood glucose and complete resolution of glucosuria, although fasting glucose remained elevated at Week 32. This case demonstrates that protocol-driven monitoring can uncover clinically silent metabolic deterioration and highlights the critical role of adherence and social determinants of health in diabetes outcomes. Early identification and timely intervention remain essential to preventing progression to life-threatening complications.

Cigarette smoke contains numerous toxicants, including cadmium, polycyclic aromatic hydrocarbons (PAHs), tobacco-specific nitrosamines (TSNAs), and volatile organic compounds, all of which may contribute to hepato-renal injury. This study, conducted in Buea (Southwest Region, Cameroon), aimed to assess cadmium inhalation exposure from cigarette smoking as a contributing factor to altered liver and kidney function biomarkers in apparently healthy smokers, while acknowledging that combined exposure to multiple co-toxicants may potentiate organ dysfunction. A survey was used to recruit smokers and collect data on their smoking habits. Cadmium contents in the major cigarette brands selected were used to estimate the cadmium Daily Exposure (DE), Weekly Inhalational Exposure (WIE) and the percentage contribution to the Tolerable Weekly Intake (TWI) of cadmium. Serum alanine aminotransferase (ALT) activity, urea, creatinine contents, and urinary albuminuria and glucosuria were measured in blood and urine samples from smokers and nonsmokers. The 102 smokers enrolled were categorized respectively as light (37.3%; 38/102), moderate (38.2%; 39/102), and heavy (24.5%; 25/102) smokers, smoking an average number of 4.7 ± 0.5, 9.1 ± 1.5, and 19.1 ± 3.0 cigarettes/day, respectively. Cadmium levels in cigarette brands ranged from 0.72-1.08 µg Cd per gram of tobacco removed from the cigarette. Heavy smokers exceeded the permitted cadmium No Significant Risk Level (NSRL) by up to 28-fold, contributing 4-8% to the cadmium TWI. Serum ALT activity and creatinine content were significantly higher (P < 0.05) in smokers groups compared to non-smokers. Also, moderate and heavy smokers were at a significantly higher risk (relative risk 6.90-13.32; P < 0.05) of displaying abnormal elevated serum urea content, positive albuminuria and glucosuria. Our findings demonstrate that healthy active smokers are highly exposed to cadmium (and potentially to other cigarette toxicants) and are at significantly higher risk of displaying abnormally elevated levels of biochemical markers of liver and kidney function, suggesting early signs of organ damage.

Light chain deposition disease (LCDD) is characterized by the deposition of monotypic immunoglobulin light chains in multiple organs. The kidneys are usually affected in cases of LCCD, and they typically present with mesangial nodule formation, extensive monoclonal light chain deposition, proteinuria, and renal insufficiency. We report a rare case of LCDD that presented with bone pain and proximal amyosthenia secondary to renal tubular phosphate loss. A 42-year-old woman presented with progressive pain in the waist and bilateral hips, along with increasing amyosthenia in both lower limbs that had persisted for more than a year. Upon investigation, she was diagnosed with hypophosphatemic osteomalacia (HO). She also had aminoaciduria, renal glucosuria, hypokalemia, hypouricemia, and renal tubular proteinuria with elevated serum kappa light chains. A renal biopsy revealed the presence of fibrillar deposits of kappa light chains along the glomerular basement membranes, as observed using electron microscopy and immunofluorescence. Congo red staining was negative. Based on the ‌finding of abnormal plasma cells comprising 1.1%‌ of cellular elements in a bone marrow biopsy, we made a diagnosis of monoclonal gammopathy of renal significance. The patient received chemotherapy and exhibited positive clinical and biochemical responses. This case describes a unique presentation of renal injury due to LCDD masquerading as HO. The aim of this report is to highlight that HO in adults is usually acquired and that addressing the underlying etiology can result in a successful cure.

Glycosuria, whether genetically induced or triggered by SGLT2 inhibitors, activates compensatory glucose-producing pathways that limit glucose lowering in type 2 diabetes. To define these pathways, we studied renal Glut2 knockout mice, which progressively lose Slc5a2 (encoding SGLT2) expression yet maintain normoglycemia despite marked urinary glucose loss. Metabolic profiling and isotope tracing revealed coordinated adaptations in mannose and glutamine metabolism during glycosuria. Skeletal muscle reduced glucose utilization and instead oxidized mannose, while whole-body glycolysis declined, establishing a systemic glucose-sparing state. Disruption of glutamine transport or mannose utilization caused hypoglycemia in mice treated with an SGLT2 inhibitor, demonstrating dependence on these substrates to maintain glucose homeostasis during glycosuria. Multiomic profiling revealed increased expression and chromatin accessibility of mannose and glutamine transport pathways. These findings identify a kidney-driven metabolic program that preserves systemic glucose homeostasis during glycosuria and may inform strategies to optimize the glucose lowering efficacy of SGLT2 inhibitors.

Type 2 diabetes mellitus (T2DM) is a progressive metabolic disease that necessitates individualized therapeutic strategies focusing on both glycemic control and the mitigation of comorbidities. In recent years, sodium-glucose cotransporter-2 (SGLT2) inhibitors have emerged as a cornerstone of modern treatment due to their unique renal mechanism of action. This review summarizes the metabolic mechanisms, pleiotropic effects, and clinical significance of SGLT2 inhibitors in the management of T2DM. This review provides an updated overview of the metabolic and systemic effects of SGLT2 inhibition. By promoting glycosuria, SGLT2 inhibitors induce a negative energy balance that contributes to modest weight loss, improved body composition, and beneficial alterations in lipid metabolism. Beyond their metabolic effects, accumulating preclinical evidence suggests that SGLT2 inhibitors exert anti-inflammatory and antifibrotic actions, partly through modulation of macrophage polarization and attenuation of oxidative stress. The clinical utility of SGLT2 inhibitors is highlighted through the review of major cardiovascular and renal outcome trials, which confirm significant benefits in reducing heart failure hospitalizations and slowing the progression of chronic kidney disease. Finally, we integrate these findings into the context of the latest international guidelines while addressing safety profiles, the rationale for combination therapies, and the transition toward a personalized, risk-based management approach in T2DM.

Cushing's disease (CD) is a rare endocrine disorder caused by the overproduction of adrenocorticotrophin hormone (ACTH) from a pituitary tumour, leading to excessive secretion of cortisol. The chronic exposure to cortisol leads to endocrine and cardiovascular complications that persist even after remission of hypercortisolism. CD is associated with a significant clinical burden characterised by insulin resistance, renal dysfunction and cardiovascular complications. In addition, patients frequently experience impaired health-related quality of life (HRQoL) and have an increased risk of mortality. There are currently no approved therapies targeting these complications. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are antihyperglycaemic agents that target SGLT2 transporters in the renal proximal convoluted tubules, thus leading to glycosuria and reduction of glycaemia. Initially approved as anti-diabetic agents, SGLT2i have subsequently revealed to exert a wide range of beneficial effects, namely cardiorenal protection; therefore having been recently approved as a first-line treatment for chronic kidney disease and heart failure, regardless of the presence of diabetes. While the clinical and metabolic efficacy of SGLT2i has been extensively documented in type 2 diabetes, heart failure and chronic kidney disease, their systemic effects may also be relevant in patients with CD, who exhibit cardiovascular, renal and metabolic alterations even after biochemical remission. The myriad benefits of SGLT2i align closely with the unmet clinical needs for new medical treatment for patients with CD, supporting their potential therapeutic relevance in this disease. Accordingly, we herein review the pathophysiology, clinical presentation and treatment of CD, and explore the potential therapeutic benefit of SGLT2i in this disorder.