Type 2 diabetes mellitus in adults: pathogenesis, prevention and therapy

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Окт. 2, 2024

Язык: Английский

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Chronic kidney disease

Nature Reviews Disease Primers, Год журнала: 2025, Номер 11(1)

Опубликована: Янв. 30, 2025

Язык: Английский

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Gut–X axis

iMeta, Год журнала: 2025, Номер 4(1)

Опубликована: Фев. 1, 2025

Abstract Recent advances in understanding the modulatory functions of gut and microbiota on human diseases facilitated our focused attention contribution to pathophysiological alterations many extraintestinal organs, including liver, heart, brain, lungs, kidneys, bone, skin, reproductive, endocrine systems. In this review, we applied “gut–X axis” concept describe linkages between other organs discussed latest findings related axis,” underlying mechanisms potential clinical intervention strategies.

Язык: Английский

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Albuminuria in Cardiovascular, Kidney, and Metabolic Disorders: A State-of-the-Art Review

Circulation, Год журнала: 2025, Номер 151(10), С. 716 - 732

Опубликована: Март 10, 2025

Albuminuria—increased urine albumin excretion—is associated with cardiovascular mortality among patients diabetes, hypertension, chronic kidney disease, or heart failure, as well adults few risk factors. Many authors have hypothesized that albuminuria reflects widespread endothelial dysfunction, but additional work is needed to uncover whether directly pathologic causative of disease. Urinary albumin-to-creatinine ratio an attractive, unifying biomarker cardiovascular, kidney, and metabolic conditions may be useful for identifying monitoring disease trajectory. However, develop through unique mechanisms across these distinct clinical phenotypes. This state-of-the-art review discusses the role in conditions; identifies potential pathways linking adverse outcomes; provides practical approaches screening managing cardiologists. Future research determine how broadly frequently screen albuminuria, it cost-effective treat low-grade (10–30 mg/g), equitably offer newer antiproteinuric therapies spectrum cardiovascular-kidney-metabolic diseases.

Язык: Английский

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State-of-the-art-review Mechanisms of action of SGLT2 inhibitors and clinical implications

American Journal of Hypertension, Год журнала: 2024, Номер 37(11), С. 841 - 852

Опубликована: Июль 15, 2024

Abstract BACKGROUND Inhibitors of the Na+-coupled glucose transporter SGLT2 (SGLT2i) primarily shift reabsorption large amounts from kidney’s early proximal tubule to downstream tubular segments expressing SGLT1, and non-reabsorbed is spilled into urine together with some osmotic diuresis. How can this protect kidneys heart failing as observed in individuals without type 2 diabetes? GOAL Mediation analyses identified clinical phenotypes SGLT2i associated improved kidney outcome, including a reduction plasma volume or increase hematocrit, lowering serum urate levels albuminuria. This review outlines how primary effects on explain these phenotypes. RESULTS The physiology tubule-glomerular communication provides basis for acute GFR glomerular capillary pressure, which contributes albuminuria but also long term preservation GFR, at least part by reducing cortex oxygen demand. Functional co-regulation other sodium metabolite transporters explains why initially excrete more than expected are uricosuric, thereby urate. Inhibition reduces gluco-toxicity shifting transport may simulate “systemic hypoxia”, resulting erythropoiesis, diuresis, enhances hematocrit improves blood delivery. Cardio-renal protection provided fasting-like insulin-sparing metabolic phenotype and, potentially, off-target microbiotic formation uremic toxins.

Язык: Английский

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Empagliflozin prevents heart failure through inhibition of the NHE1-NO pathway, independent of SGLT2

Basic Research in Cardiology, Год журнала: 2024, Номер 119(5), С. 751 - 772

Опубликована: Июль 24, 2024

Sodium glucose cotransporter 2 inhibitors (SGLT2i) constitute the only medication class that consistently prevents or attenuates human heart failure (HF) independent of ejection fraction. We have suggested earlier protective mechanisms SGLT2i Empagliflozin (EMPA) are mediated through reductions in sodium hydrogen exchanger 1 (NHE1)-nitric oxide (NO) pathway, SGLT2. Here, we examined role SGLT2, NHE1 and NO a murine TAC/DOCA model HF. SGLT2 knockout mice showed attenuated systolic dysfunction without having an effect on other signs EMPA protected against diastolic dysfunction, hypertrophy, fibrosis, increased Nppa/Nppb mRNA expression lung/liver edema. In addition, prevented increases oxidative stress, calcium calcium/calmodulin-dependent protein kinase II activation to equal degree WT KO animals. particular, while activity was isolated cardiomyocytes from untreated HF, treatment this. Since is not required for effects EMPA, pathway between further explored vivo with specific NHE1-inhibitor Cariporide mimicked protection by additional EMPA. On hand, inhibition NOS L-NAME deteriorated HF conclusion, data support beneficial NHE1-NO TAC/DOCA-induced inhibition.

Язык: Английский

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How can inhibition of glucose and sodium transport in the early proximal tubule protect the cardiorenal system?

Nephrology Dialysis Transplantation, Год журнала: 2024, Номер 39(10), С. 1565 - 1573

Опубликована: Март 1, 2024

What mechanisms can link the inhibition of sodium-glucose cotransporter 2 (SGLT2) in early proximal tubule to kidney and heart protection patients with without type diabetes? Due physical functional coupling SGLT2 other sodium metabolite transporters (including NHE3, URAT1), inhibitors (SGLT2i) reduce reabsorption not only glucose, inducing osmotic diuresis, but metabolites plus a larger amount than expected based on alone, thereby reducing volume retention, hypertension hyperuricemia. Metabolic adaptations SGLT2i include fasting-like response, enhanced lipolysis formation ketone bodies that serve as additional fuel for kidneys heart. Making use physiology tubulo-glomerular communication, functionally lower glomerular capillary pressure filtration rate, stress barrier, tubular exposure albumin nephrotoxic compounds, oxygen demand reabsorbing filtered load. Together reduced gluco-toxicity better distribution transport work along nephron, preserve integrity function and, thereby, rate long-term. By shifting downstream, may simulate systemic hypoxia at sensors deep cortex/outer medulla, which stimulates erythropoiesis together enhances hematocrit improves delivery all organs. The described SGLT2-dependent effects be complemented by off-target itself microbiome cardiovascular-effective uremic toxins.

Язык: Английский

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Amino acid metabolism in kidney health and disease

Nature Reviews Nephrology, Год журнала: 2024, Номер 20(12), С. 771 - 788

Опубликована: Авг. 28, 2024

Язык: Английский

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Biomarker-based prediction of sinus rhythm in atrial fibrillation patients: the EAST-AFNET 4 biomolecule study

European Heart Journal, Год журнала: 2024, Номер unknown

Опубликована: Авг. 31, 2024

Abstract Background and Aims In patients with atrial fibrillation (AF), recurrent AF sinus rhythm during follow-up are determined by interactions between cardiovascular disease processes control therapy. Predictors of attaining at not well known. Methods To quantify the interaction outcomes, 14 biomarkers reflecting AF-related in 1586 EAST-AFNET 4 biomolecule study (71 years old, 45% women) were quantified baseline. Mixed logistic regression models including clinical features constructed for each biomarker. Biomarkers interrogated early control. Outcome was 12 months. Results validated 24 months external datasets. Higher baseline concentrations three independently associated a lower chance months: angiopoietin 2 (ANGPT2) (odds ratio [OR] .76 [95% confidence interval .65–.89], P < .001), bone morphogenetic protein 10 (BMP10) (OR .83 [.71–.97], = .017), N-terminal pro-B-type natriuretic peptide (NT-proBNP) .73 [.60–.88], .001). Analysis confirmed results. Early interacted predictive potential NT-proBNP (Pinteraction .033). The effect reduced randomized to (usual care: OR .64 [.51–.80], .001; control: .90 [.69–1.18], .453). External validation that low ANGPT2, BMP10, predict follow-up. Conclusions Low identify who likely attain ability is attenuated receiving

Язык: Английский

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Empagliflozin in nondiabetic individuals with calcium and uric acid kidney stones: a randomized phase 2 trial

Nature Medicine, Год журнала: 2025, Номер unknown

Опубликована: Янв. 2, 2025

Efficacy of sodium-glucose cotransporter 2 inhibitors for kidney stone prevention in nondiabetic patients is unknown. In a double-blind, placebo-controlled, single-center, crossover phase trial, 53 adults (≥18 and <75 years) with calcium (n = 28) or uric acid (UA; n 25) stones (at least one previous event) without diabetes (HbA1c < 6.5%, no treatment) were randomized to once daily empagliflozin 25 mg followed by placebo reverse (2 weeks per treatment). Randomization analysis performed separately both types. Primary analyses conducted the protocol set. outcomes urine relative supersaturation ratios (RSRs) oxalate (CaOx), phosphate (CaP) UA—validated surrogates recurrence. Prespecified RSR reductions (≥15%) met groups formers. stones, reduced CaP (relative difference placebo, −36%; 95% confidence interval, −48% −21%; P 0.001), but not RSRs CaOx UA. UA (−30%; −44% −12%; 0.002) CaP. No serious prespecified adverse events occurred. Thus, substantially stones. ClinicalTrials.gov registration: NCT04911660 . As part SWEETSTONE authors report ability inhibitor reduce likelihood formation individuals diabetes.

Язык: Английский

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