Neonatal diabetes mellitus is a rare cause of persistent hyperglycemia in early infancy and is usually monogenic. We describe a male preterm neonate born at 34 weeks' gestation with intrauterine growth restriction who developed severe hyperglycemia from the first days of life. Plasma glucose reached a maximum of 570 mg/dL with persistent glycosuria, negative urine ketones, and a normal acid-base profile. C-peptide was profoundly suppressed (0.01 ng/mL), supporting marked endogenous insulin deficiency. Following optimization of glucose administration, intravenous short-acting regular human insulin was initiated with hourly glucose monitoring and complicated by early asymptomatic hypoglycemia requiring rapid correction and insulin dose reduction. As enteral feeds started, treatment was switched to micro-dosed subcutaneous short-acting regular human insulin with the use of a freshly prepared dilution and a pre-feed threshold strategy. Insulin requirements progressively decreased, and therapy was discontinued by three months of age with maintenance of normoglycemia and normal glycated hemoglobin (HbA1c). Growth and neurodevelopment were normal through two years of follow-up. This case highlights the importance of keeping neonatal diabetes in mind for preterm, growth-restricted infants with persistent severe hyperglycemia requiring insulin after exclusion of secondary causes, and also to master the details of practical safety considerations for insulin use in early life.

Cardiovascular-kidney-metabolic (CKM) syndrome is a recently defined clinical entity that encompasses cardiovascular disease (CVD), chronic kidney disease (CKD) and metabolic disorders. It has emerged as a growing public health concern that adversely affects the quality of life and imposes a substantial burden on human health. Sodium-glucose cotransporter 2 inhibitor (SGLT-2i) is a novel class of oral hypoglycemic agent with novel insulin-independent mechanism. In the last decade, published studies highlight its substantial effects on renal and cardiovascular outcomes. SGLT-2i is recommended for patients with stages 2-4 CKM syndrome, particularly those with CKD or diabetes to delay disease progression, and improve long-term clinical outcomes. This review comprehensively summarizes the current clinical evidence and elucidates the underlying mechanisms of SGLT-2i in CKM syndrome. Glycosuria and natriuresis, the primary effects of SGLT2 inhibition, play a pivotal role in improving glycemic control, reducing body weight, and lowering blood pressure. These initial effects trigger a cascade of downstream mechanisms: hemodynamic optimization via interstitial fluid reduction, enhanced cardiac efficiency through ketogenesis, and attenuation of inflammation and oxidative stress. Additional systemic benefits include increased fatty acid utilization, reduced hyperuricemia and stimulated erythropoiesis, thereby generating a network of interrelated therapeutic benefits in CKM syndrome. The pleiotropic effects of SGLT-2i position it as a highly promising therapeutic strategy for CKM syndrome. A deeper understanding of underlying mechanisms will better inform the application of SGLT-2i for this newly defined condition and guide optimal treatment strategies.

Sodium-glucose cotransporter 2 inhibitors increase urinary glucose excretion, theoretically predisposing to urinary tract infection, yet clinical trials have not shown higher rates of severe infection. In this issue of Kidney International, Sendtner et al. provide a plausible mechanistic framework for this paradox. Combining human cohort data with experimental pyelonephritis, they demonstrate that sodium-glucose cotransporter 2 inhibition with empagliflozin is associated with reduced C1q expression, preserved antibacterial defenses, and altered inflammatory signaling. These findings suggest that sodium-glucose cotransporter 2 inhibition with empagliflozin may influence kidney antibacterial defenses without increasing infection risk.

Reliable detection of urinary glucose is crucial for the early diagnosis of renal tubular dysfunctions, including normoglycemic glycosuria (NG), a condition characterized by glucose excretion despite normal blood glucose levels. Conventional urinary dipsticks lack the sensitivity required to quantify the low glucose concentrations typical of NG. Here, we present a rapid in situ synthesis of bioinspired enzyme-copper nanoflowers directly on a paper substrate. This foundational innovation, which achieves a hierarchical morphology in under 10 minutes, is integrated into a microfluidic dipstick (μDip) to create a platform for point-of-care diagnosis. The resulting bioinspired nanostructures exhibit superior catalytic activity and stability. When deployed in the μDip system comprising a 3D-printed body and a smartphone-based interface, the sensor enables ultrasensitive detection of urinary glucose across the clinically relevant range for NG (0-0.75 mM) with a detection limit of 0.017 mM, more than a 160-fold improvement over conventional strips. This facile, low-cost platform, which satisfies the ASSURED criteria for point-of-care diagnostics, offers a promising tool for decentralized screening and early renal health assessment.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors were initially developed as glucose-lowering agents for type 2 diabetes mellitus (T2DM) by reducing proximal tubular glucose reabsorption and promoting glucosuria. Subsequent cardiovascular and renal outcome trials established that these agents provide clinically meaningful benefits that extend beyond glycemic control, including reductions in heart failure (HF) events and slowing of chronic kidney disease (CKD) progression in patients with and without diabetes. We conducted a narrative literature review using PubMed and Google Scholar to identify English-language studies published between January 2019 and December 2025 evaluating SGLT2 inhibitors (empagliflozin, dapagliflozin, canagliflozin, ertugliflozin) across cardiovascular and renal outcomes. Eligible evidence included randomized controlled trials, large observational studies, systematic reviews/meta-analyses, guidelines, post‑hoc exploratory analyses, secondary analyses, and mechanistic/preclinical studies. Mechanistic data support benefits through natriuresis and osmotic diuresis with favorable ventricular loading, restoration of tubuloglomerular feedback and reduced intraglomerular pressure, improved myocardial energetics, and attenuation of oxidative stress and inflammation. Clinically, SGLT2 inhibitors consistently reduce HF hospitalizations and composite cardiorenal endpoints in diabetic and non-diabetic populations across CKD stages studied and heart conditions, with a generally favorable safety profile; genital mycotic infections are most common, while diabetic ketoacidosis and volume depletion are uncommon with appropriate patient selection and counselling. Evidence gaps remain for stage 5 CKD and dialysis populations and for defining outcomes in lower-risk post-myocardial infarction cohorts. Overall, current data support SGLT2 inhibitors as foundational therapy for eligible patients with HF and/or CKD irrespective of diabetes status.

We report a case of a 48-year-old man newly diagnosed with type 2 diabetes mellitus (T2DM), presenting with a critically elevated HbA1c of 10.3%, who achieved near-normal glycaemic control (HbA1c 6.0%) through a structured, three-month lifestyle intervention without initiation of any antidiabetic pharmacotherapy. The intervention entailed aerobic and resistance exercise, nutritional counselling, weekly coaching, and continuous activity monitoring. Notably, body weight remained constant (∼98.4 kg; BMI:31.8 kg/m2), while significant improvements occurred in body composition: -3.2 kg fat mass, -1.2 L visceral fat, +1.5 kg skeletal muscle, and -5 cm waist circumference. This case underscores the potential for non-pharmacological remission in patients with high baseline glycaemic dysregulation and supports early implementation of structured lifestyle programmes in clinical practice despite significantly elevated HbA1c.

Empagliflozin is a sodium-glucose cotransporter-2 inhibitor used for treating humans with heart failure, among other conditions. This drug could have applications in veterinary cardiology, but whether empagliflozin has biological effects in dogs when administered at dosages approximating human therapeutic dosages is unknown. This study investigated whether empagliflozin (target dosage, 0.3 mg/kg) could produce significant increases in urinary glucose concentrations and measurable plasma drug concentrations, without increasing serum β-hydroxybutyrate (β-HA) concentrations in dogs. Six healthy, privately-owned dogs weighing 22-36 kg were studied prospectively. Urinary glucose, serum β-HA, and plasma empagliflozin concentrations were measured 0 h, 6 h, 12 h, 24 h, 48 h, and 72 h after single-dose oral administration of 10 mg empagliflozin. The dosage administered was 0.28-0.45 mg/kg. Mean urinary glucose concentration peaked at 24 h (8,041 mg/dL) before returning to baseline (< 40 mg/dL) at 72 h (p < 0.001). Serum β-HA concentrations remained within the reference interval for dogs (< 2.1 mg/dL). Plasma drug concentrations at 24 h were 13 times greater than the reported human in vitro IC50. The half-life was 4.4-6 h. Oral empagliflozin 0.28-0.45 mg/kg produced glucosuria and measurable plasma drug concentrations in healthy dogs, without ketonemia, after a single dose.