RÉSUMÉ
Given the substantial burden of chronic kidney disease associated with type 2 diabetes, an aggressive approach to treatment is required. Despite the benefits of guideline-directed therapy, there remains a high residual risk of continuing progression of chronic kidney disease and of cardiovascular events. Historically, a linear approach to pharmacologic management of chronic kidney disease has been used, in which drugs are added, then adjusted, optimized, or stopped in a stepwise manner based on their efficacy, toxicity, effects on a patient's quality of life, and cost. However, there are disadvantages to this approach, which may result in missing a window of opportunity to slow chronic kidney disease progression. Instead, a pillar approach has been proposed to enable earlier treatment that simultaneously targets multiple pathways involved in disease progression. Combination therapy in patients with chronic kidney disease associated with type 2 diabetes is being investigated in several clinical trials. In this article, we discuss current treatment options for patients with chronic kidney disease associated with type 2 diabetes and provide a rationale for tailored combinations of therapies with complementary mechanisms of action to optimize therapy using a pillar-based treatment strategy. [This article includes a plain language summary as an additional file].
Sujet(s)
Maladies cardiovasculaires , Diabète de type 2 , Association de médicaments , Insuffisance rénale chronique , Humains , Diabète de type 2/complications , Diabète de type 2/traitement médicamenteux , Insuffisance rénale chronique/complications , Insuffisance rénale chronique/traitement médicamenteux , Maladies cardiovasculaires/prévention et contrôle , Maladies cardiovasculaires/étiologie , Hypoglycémiants/usage thérapeutique , Néphropathies diabétiques/traitement médicamenteuxRÉSUMÉ
Objectives: To explore the therapeutic effects of M2 macrophages in diabetic nephropathy (DN) and their mechanism.Methods: We infused M2 macrophages stimulated with IL-4 into 10-week-old db/db mice once a week for 4 weeks through the tail vein as M2 group. Then we investigated the role of M2 macrophages in alleviating the infammation of DN and explored the mechanism.Results: M2 macrophages hindered the progression of DN, reduced the levels of IL-1ß (DN group was 34%, M2 group was 13%, p < 0.01) and MCP-1 (DN group was 49%, M2 group was 16%, p < 0.01) in the glomeruli. It was also proven that M2 macrophages alleviate mesangial cell injury caused by a high glucose environment. M2 macrophage tracking showed that the infused M2 macrophages migrated to the kidney, and the number of M2 macrophages in the kidney reached a maximum on day 3. Moreover, the ratio of M2 to M1 macrophages was 2.3 in the M2 infusion group, while 0.4 in the DN group (p < 0.01). Mechanistically, M2 macrophages downregulated Janus kinase (JAK) 2 and signal transducer and activator of transcription (STAT) 3 in mesangial cells.Conclusions: Multiple infusions of M2 macrophages significantly alleviated inflammation in the kidney and hindered the progression of DN at least partially by abrogating the M1/M2 homeostasis disturbances and suppressing the JAK2/STAT3 pathway in glomerular mesangial cells. M2 macrophage infusion may be a new therapeutic strategy for DN treatment.
Sujet(s)
Néphropathies diabétiques , Kinase Janus-2 , Macrophages , Facteur de transcription STAT-3 , Transduction du signal , Animaux , Kinase Janus-2/métabolisme , Néphropathies diabétiques/métabolisme , Facteur de transcription STAT-3/métabolisme , Souris , Macrophages/métabolisme , Mâle , Cellules mésangiales/métabolisme , Modèles animaux de maladie humaine , Glomérule rénal/anatomopathologie , Glomérule rénal/métabolisme , Chimiokine CCL2/métabolisme , Souris de lignée C57BL , Interleukine-1 bêta/métabolismeRÉSUMÉ
Over recent years, the prevalence of diabetes has been on the rise, paralleling improvements in living standards. Diabetic nephropathy (DN), a prevalent complication of diabetes, has also exhibited a growing incidence. While some clinical studies and reviews have hinted at a link between diabetic nephropathy and gut microbiota (GM), the nature of this connection, specifically its causative nature, remains uncertain. Investigating the causal relationship between diabetic nephropathy and gut microbiota holds the promise of aiding in disease screening and identifying novel biomarkers. In this study, we employed a two-sample Mendelian randomization analysis. Our dataset encompassed 4,111 DN patients from the GWAS database, juxtaposed with 308,539 members forming a control group. The aim was to pinpoint specific categories within the vast spectrum of the 211 known gut microbiota types that may have a direct causal relationship with diabetic nephropathy. Rigorous measures, including extensive heterogeneity and sensitivity analyses, were implemented to mitigate the influence of confounding variables on our experimental outcomes. Ultimately, our comprehensive analysis revealed 15 distinct categories of gut microbiota that exhibit a causal association with diabetic nephropathy. In summary, the phyla Bacteroidota and Verrucomicrobiae, the families Peptostreptococcaceae and Veillonellaceae, the genus Akkermansia, and the species Catenibacterium, Lachnoclostridium, Parasutterella, along with the orders Bacteroidales and Verrucomicrobiales, and the class Bacteroidetes were identified as correlates of increased risk for DN. Conversely, the family Victivallaceae, the species Eubacterium coprostanoligenes, and the Clostridium sensu stricto 1 group were found to be associated with a protective effect against the development of DN.These findings not only provide valuable insights but also open up novel avenues for clinical research, offering fresh directions for potential treatments.
Sujet(s)
Néphropathies diabétiques , Microbiome gastro-intestinal , Séquençage du génome entier , Humains , Néphropathies diabétiques/microbiologie , Microbiome gastro-intestinal/génétique , Analyse de randomisation mendélienne , Étude d'association pangénomiqueRÉSUMÉ
OBJECTIVE: Previous observational studies have indicated associations between various immune cells and diabetic nephropathy (DN). However, the causality remains unclear. We aimed to further evaluate the causal association between immune cells and DN using bidirectional two-sample Mendelian randomization (MR) analysis. METHOD: The DN data were retrieved from the IEU OpenGWAS Project database, while the data for 731 immune cells were sourced from GWAS summary statistics by Orru Ì et al. The investigation into the causal relationship between immune cells and DN employed the inverse variance weighted (IVW), weighted median (WME), and MR-Egger methods. The stability and reliability of the findings underwent evaluation through Cochran's Q test, MR-Egger intercept's P-value, MR-PRESSO, and Leave-One-Out (LOO) method. RESULT: The IVW estimates suggested a positive causal effect of CD25 on IgD-CD38dim B cell, CD25 on naive-mature B cell, CD127 on granulocyte, SSC-A on HLA DR + Natural Killer, HLA DR on plasmacytoid Dendritic Cell, and HLA DR on Dendritic Cell on DN. Conversely, the abundance of Myeloid Dendritic Cell, CD62L- Dendritic Cell %Dendritic Cell, CD86+ myeloid Dendritic Cell %Dendritic Cell, CD14- CD16-, CX3CR1 on CD14- CD16-, and SSC-A on CD4+ T cell had negative causal effects on DN. However, after correcting the P value for significant causality results using the FDR method, it was concluded that only Myeloid Dendritic Cells had a causal relationship with DN (FDR-p = 0.041), while the other immune cells showed no significant association with DN, so their relationship was suggestive. The results were stable with no observed horizontal pleiotropy and heterogeneity. Reverse MR analysis indicated no causal relationship between DN and the increased risk of positively identified immune cells. CONCLUSION: This study provides an initial insight into the genetic perspective of the causal relationship between immune cells and DN. It establishes a crucial theoretical foundation for future endeavors in precision medicine and individualized treatment.
Sujet(s)
Néphropathies diabétiques , Analyse de randomisation mendélienne , Humains , Néphropathies diabétiques/génétique , Néphropathies diabétiques/immunologie , Étude d'association pangénomique , Cellules dendritiques/immunologie , Reproductibilité des résultats , Lymphocytes B/immunologie , Facteurs de risqueRÉSUMÉ
MicroRNAs (miRNAs) are 18-25 nucleotides long, single-stranded, non-coding RNA molecules that regulate gene expression. They play a crucial role in maintaining normal cellular functions and homeostasis in organisms. Studies have shown that miR-124-3p is highly expressed in brain tissue and plays a significant role in nervous system development. It is also described as a tumor suppressor, regulating biological processes like cancer cell proliferation, apoptosis, migration, and invasion by controlling multiple downstream target genes. miR-124-3p has been found to be involved in the progression of various kidney diseases, including diabetic kidney disease, calcium oxalate kidney stones, acute kidney injury, lupus nephritis, and renal interstitial fibrosis. It mediates these processes through mechanisms like oxidative stress, inflammation, autophagy, and ferroptosis. To lay the foundation for future therapeutic strategies, this research group reviewed recent studies on the functional roles of miR-124-3p in renal diseases and the regulation of its downstream target genes. Additionally, the feasibility, limitations, and potential application of miR-124-3p as a diagnostic biomarker and therapeutic target were thoroughly investigated.
Sujet(s)
Maladies du rein , microARN , microARN/métabolisme , microARN/génétique , Humains , Maladies du rein/génétique , Maladies du rein/métabolisme , Néphropathies diabétiques/métabolisme , Néphropathies diabétiques/génétique , Atteinte rénale aigüe/génétique , Atteinte rénale aigüe/métabolisme , Animaux , Stress oxydatif , Glomérulonéphrite lupique/génétique , Glomérulonéphrite lupique/métabolisme , Calculs rénaux/génétique , Calculs rénaux/métabolismeRÉSUMÉ
Previously, no randomized controlled trials investigated the renoprotective effects of glucagon-like peptide-1 receptor agonists (GLP-1RA) as the primary endpoint in patients with diabetes and chronic kidney disease. In the FLOW trial, Perkovic et al. showed that once-weekly semaglutide reduced kidney failure, kidney-related death, and cardiovascular death by 24% as compared with placebo in patients with type 2 diabetes at high risk of renal progression.1.
Sujet(s)
Diabète de type 2 , Récepteur du peptide-1 similaire au glucagon , Peptides glucagon-like , Insuffisance rénale chronique , Humains , Diabète de type 2/traitement médicamenteux , Récepteur du peptide-1 similaire au glucagon/agonistes , Insuffisance rénale chronique/traitement médicamenteux , Peptides glucagon-like/usage thérapeutique , Peptides glucagon-like/pharmacologie , Peptides glucagon-like/administration et posologie , Hypoglycémiants/usage thérapeutique , Hypoglycémiants/pharmacologie , Néphropathies diabétiques/traitement médicamenteuxRÉSUMÉ
The inhibition of the autophagolysosomal pathway mediated by transcription factor EB (TFEB) inactivation in proximal tubular epithelial cells (TECs) is a key mechanism of TEC injury in diabetic kidney disease (DKD). Acetylation is a novel mechanism that regulates TFEB activity. However, there are currently no studies on whether the adjustment of the acetylation level of TFEB can reduce the damage of diabetic TECs. In this study, we investigated the effect of Trichostatin A (TSA), a typical deacetylase inhibitor, on TFEB activity and damage to TECs in both in vivo and in vitro models of DKD. Here, we show that TSA treatment can alleviate the pathological damage of glomeruli and renal tubules and delay the DKD progression in db/db mice, which is associated with the increased expression of TFEB and its downstream genes. In vitro studies further confirmed that TSA treatment can upregulate the acetylation level of TFEB, promote its nuclear translocation, and activate the expression of its downstream genes, thereby reducing the apoptosis level of TECs. TFEB deletion or HDAC6 knockdown in TECs can counteract the activation effect of TSA on autophagolysosomal pathway. We also found that TFEB enhances the transcription of Tfeb through binding to its promoter and promotes its own expression. Our results, thus, provide a novel therapeutic mechanism for DKD that the alleviation of TEC damage by activating the autophagic lysosomal pathway through upregulating TFEB acetylation can, thus, delay DKD progression.
Sujet(s)
Facteurs de transcription à motifs basiques hélice-boucle-hélice et à glissière à leucines , Néphropathies diabétiques , Cellules épithéliales , Inhibiteurs de désacétylase d'histone , Acides hydroxamiques , Tubules contournés proximaux , Animaux , Facteurs de transcription à motifs basiques hélice-boucle-hélice et à glissière à leucines/métabolisme , Facteurs de transcription à motifs basiques hélice-boucle-hélice et à glissière à leucines/génétique , Néphropathies diabétiques/métabolisme , Souris , Acétylation , Cellules épithéliales/métabolisme , Cellules épithéliales/effets des médicaments et des substances chimiques , Tubules contournés proximaux/métabolisme , Tubules contournés proximaux/anatomopathologie , Acides hydroxamiques/pharmacologie , Inhibiteurs de désacétylase d'histone/pharmacologie , Mâle , Souris de lignée C57BL , Autophagie/effets des médicaments et des substances chimiques , Apoptose/effets des médicaments et des substances chimiquesRÉSUMÉ
Objective: This study aimed to evaluate the efficacy and safety of polyethylene glycol loxenatide (PEG-Loxe) compared to those of dapagliflozin in patients with mild-to-moderate diabetic kidney disease (DKD), a prevalent microvascular complication of type 2 diabetes mellitus (T2DM). The study is set against the backdrop of increasing global diabetes incidence and the need for effective DKD management. Methods: This study constituted a single-center, randomized, open-label, clinical trial. The trial included patients with mild-to-moderate DKD and suboptimal glycemic control. Eligible participants were randomly allocated to one of the two groups for treatment with either PEG-Loxe or dapagliflozin. The primary endpoint was the change in UACR from baseline at 24 weeks. Results: Overall, 106 patients were randomized and 80 patients completed the study. Following 24 weeks of treatment, the PEG-Loxe group exhibited a mean percent change in baseline UACR of -29.3% (95% confidence interval [CI]: -34.8, -23.7), compared to that of -31.8% in the dapagliflozin group (95% CI: -34.8, -23.7). Both PEG-Loxe and dapagliflozin showed similar efficacy in reducing UACR, with no significant difference between the groups (p = 0.336). The HbA1c levels decreased by -1.30% (95% CI: -1.43, -1.18) in the PEG-Loxe group and by -1.29% (95% CI: -1.42, -1.17) in the dapagliflozin group (p = 0.905). The TG levels decreased by -0.56 mmol/L (95% CI: -0.71, -0.42) in the PEG-Loxe group and -0.33 mmol/L (95% CI: -0.48, -0.19) in the dapagliflozin group (p = 0.023). Differences in TC, HDL-C, LDL-C, SBP, and DBP levels between the groups were not statistically significant (all p > 0.05). Safety profiles were consistent with previous findings, with gastrointestinal adverse events being more common in the PEG-Loxe group. Conclusions: PEG-Loxe is as effective as dapagliflozin in improving urine protein levels in patients with mild-to-moderate DKD and offers superior benefits in improving lipid profiles. These findings support the use of PEG-Loxe in DKD management, contributing to evidence-based treatment options. Clinical Trial Registration: www.chictr.org.cn, identifier ChiCTR2300070919.
Sujet(s)
Composés benzhydryliques , Diabète de type 2 , Néphropathies diabétiques , Glucosides , Polyéthylène glycols , Humains , Diabète de type 2/traitement médicamenteux , Diabète de type 2/complications , Mâle , Femelle , Adulte d'âge moyen , Néphropathies diabétiques/traitement médicamenteux , Polyéthylène glycols/usage thérapeutique , Polyéthylène glycols/effets indésirables , Polyéthylène glycols/administration et posologie , Glucosides/usage thérapeutique , Glucosides/effets indésirables , Glucosides/administration et posologie , Composés benzhydryliques/usage thérapeutique , Composés benzhydryliques/effets indésirables , Sujet âgé , Hypoglycémiants/usage thérapeutique , Hypoglycémiants/effets indésirables , Résultat thérapeutique , Hémoglobine glyquée/analyse , Glycémie/effets des médicaments et des substances chimiques , Glycémie/analyse , AdulteRÉSUMÉ
BACKGROUND: This cohort study aimed to explore the relationship between hydration status and the risk of diabetic kidney disease (DKD) as well as all-cause death in DKD patients. METHODS: Weighted univariable and multivariable logistic regression models were used to explore the association between hydration status and DKD risk in diabetic population while weighted univariable and multivariable Cox regression models were used to identify the association between hydration status and all-cause mortality in DKD patients. Kaplan-Meier curve was plotted to present the survival probability of patients with different hydration status. Estimates were presented as odds ratio (OR), and hazard ratio (HR) with 95% confidence interval (CI). RESULTS: The mean follow-up time was 79.74 (±1.89) months. There were 2041 participants with DKD, and 2889 participants without. At the end of the follow-up, 965 participants were alive. The risk of DKD was increased as the increase of osmolarity level (OR = 1.07, 95%CI: 1.05-1.08). The elevated risk of DKD was observed in patients with impending dehydration (OR = 1.49, 95%CI: 1.19-1.85) or current dehydration (OR = 2.69, 95%CI: 2.09-3.46). The association between increased osmolarty level and elevated risk of all-cause mortality in DKD patients was statistically different (HR = 1.02, 95%CI: 1.01-1.03). Current dehydration was correlated with increased all-cause mortality risk in DKD patients (HR = 1.27, 95%CI: 1.01-1.61). Compared to DKD patients with normal hydration, the survival probability of DKD patients with current dehydration was significant lower (p < 0.001). CONCLUSION: Increased osmolarity level was associated with increased risk of DKD and elevated risk of all-cause mortality in DKD patients.
Sujet(s)
Déshydratation , Néphropathies diabétiques , Humains , Mâle , Femelle , Adulte d'âge moyen , Néphropathies diabétiques/mortalité , Néphropathies diabétiques/complications , Sujet âgé , Déshydratation/complications , Déshydratation/mortalité , Facteurs de risque , Estimation de Kaplan-Meier , Modèles des risques proportionnels , Cause de décès , Modèles logistiques , Concentration osmolaireRÉSUMÉ
PURPOSE: To assess the effect of Amorphophallus campanulatus tuber (Ac) extract in the protection of diabetic nephropathy in streptozotocin (STZ) induced diabetic nephropathy (DN) rat model. METHODS: Diabetes was induced with STZ (60 mg/kg, i.p.), and DN was confirmed after six weeks of STZ administration with the estimation of kidney function test. Further rats were treated with Ac 250 and 500 mg/kg p.o. for next four week. Oxidative stress and level of inflammatory cytokines were estimated in the kidney tissue of DN rats. Histopathology of kidney tissue was performed using hematoxylin and eosin staining. RESULTS: There was improvement in the body weight of Ac treated groups than DN group of rats. Blood glucose level was observed to be reduced in Ac treated groups than DN group on 42nd and 70th day of protocol. Treatment with Ac ameliorated the altered level of kidney function tests (creatinine and BUN), enzymes of liver function (aspartate aminotransferase and alanine aminotransferase), and lipid profile in the serum of DN rats. Oxidative stress parameters (malondialdehyde and reactive oxygen species enhances and reduction in the level of glutathione and superoxide dismutase) and inflammatory cytokines such as interleukin-6, tumour necrosis factor-α, and monocyte chemoattractant protein-1 reduces in the tissue of Ac treated group than DN group. Treatment with Ac also attenuates the altered histopathological changes in the kidney tissue of DN rats. CONCLUSIONS: The report suggests that Ac protects renal injury in DN rats by regulating inflammatory cytokines and oxidative stress.
Sujet(s)
Diabète expérimental , Néphropathies diabétiques , Stress oxydatif , Extraits de plantes , Facteur de nécrose tumorale alpha , Animaux , Stress oxydatif/effets des médicaments et des substances chimiques , Néphropathies diabétiques/traitement médicamenteux , Néphropathies diabétiques/prévention et contrôle , Extraits de plantes/pharmacologie , Extraits de plantes/usage thérapeutique , Diabète expérimental/complications , Diabète expérimental/traitement médicamenteux , Mâle , Streptozocine , Rats , Rat Wistar , Rein/effets des médicaments et des substances chimiques , Rein/anatomopathologie , Glycémie/effets des médicaments et des substances chimiques , Glycémie/analyse , Modèles animaux de maladie humaine , Reproductibilité des résultats , Tubercules/composition chimiqueRÉSUMÉ
Visceral adiposity index (VAI) is a reliable indicator of visceral adiposity. However, no stu-dies have evaluated the association between VAI and DKD in US adults with diabetes. Theref-ore, this study aimed to explore the relationship between them and whether VAI is a good pr-edictor of DKD in US adults with diabetes. Our cross-sectional study included 2508 participan-ts with diabetes who were eligible for the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018. Univariate and multivariate logistic regression were used to an-alyze the association between VAI level and DKD. Three models were used to control for pot-ential confounding factors, and subgroup analysis was performed for further verification. A tot-al of 2508 diabetic patients were enrolled, of whom 945 (37.68%) were diagnosed with DKD. Overall, the VAI was 3.36 ± 0.18 in the DKD group and 2.76 ± 0.11 in the control group. VAI was positively correlated with DKD (OR = 1.050, 95% CI 1.049, 1.050) after fully adjusting for co-nfounding factors. Compared with participants in the lowest tertile of VAI, participants in the highest tertile of VAI had a significantly increased risk of DKD by 35.9% (OR = 1.359, 95% CI 1.355, 1.362). Through subgroup analysis, we found that VAI was positively correlated with the occurrence of DKD in all age subgroups, male(OR = 1.043, 95% CI 1.010, 1.080), participants wit-hout cardiovascular disease(OR = 1.038, 95% CI 1.011, 1.069), hypertension (OR = 1.054, 95% CI 1.021, 1.090), unmarried participants (OR = 1.153, 95% CI 1.036, 1.294), PIR < 1.30(OR = 1.049, 95% CI 1.010, 1.094), PIR ⧠3 (OR = 1.085, 95% CI 1.021, 1.160), BMI ⧠30 kg/m2 (OR = 1.050, 95% CI 1.016, 1.091), former smokers (OR = 1.060, 95% CI 1.011, 1.117), never exercised (OR = 1.033, 95% CI 1.004, 1.067), non-Hispanic white population (OR = 1.055, 95% CI 1.010, 1.106) and non-Hipanic black population (OR = 1.129, 95% CI 1.033, 1.258). Our results suggest that elevated VAI levels are closely associated with the development of DKD in diabetic patients. VAI may be a simpl-e and cost-effective index to predict the occurrence of DKD. This needs to be verified in furt-her prospective investigations.
Sujet(s)
Néphropathies diabétiques , Graisse intra-abdominale , Humains , Mâle , Femelle , États-Unis/épidémiologie , Adulte d'âge moyen , Études transversales , Adulte , Néphropathies diabétiques/épidémiologie , Incidence , Obésité abdominale/épidémiologie , Obésité abdominale/complications , Enquêtes nutritionnelles , Adiposité , Facteurs de risque , Sujet âgé , Diabète/épidémiologieRÉSUMÉ
Diabetic nephropathy, characterized by inflammation and oxidative stress, poses a management challenge. This study investigates the effect of Polygonum hyrcanicum extract on diabetic nephropathy in alloxan-induced diabetic mice. In this experimental animal study, the P. hyrcanicum extract was prepared using continuous macerations. Thirty male Albino mice, divided into five groups, were induced with alloxan-induced diabetes. They received intraperitoneal injections of the plant extract (100 and 200 mg/kg) and metformin (300 mg/kg) for four weeks. Kidney and blood samples were collected to assess protein carbonyl, glutathione, lipid peroxidation, TNF-α and IL-6 levels. The amount of total flavonoid and phenolic content in the hydroalcoholic extract of P. hyrcanicum were 7.5 ± 0.3 mg of quercetin and 88.2 ± 1.3 mg gallic acid per gram of extract respectively. The antioxidant activity level of the hydroalcoholic extract was determined to be 1.78 ± 0.51 mM equivalent per gram of extract. Alloxan administration resulted in a significant reduction in glutathione levels and a significant increase in protein carbonyl, lipid peroxidation, TNF-α, and IL-6 levels. Hydroalcoholic extract of P. hyrcanicum effectively reduced oxidative stress markers and inflammatory cytokines (TNF-α, IL-6), indicating its potential in mitigating diabetic nephropathy. However, no significant difference in efficacy was observed between the 100 mg/kg and 200 mg/kg doses in terms of reducing these toxicities.
Sujet(s)
Antioxydants , Diabète expérimental , Néphropathies diabétiques , Stress oxydatif , Extraits de plantes , Polygonum , Animaux , Stress oxydatif/effets des médicaments et des substances chimiques , Extraits de plantes/pharmacologie , Extraits de plantes/composition chimique , Diabète expérimental/traitement médicamenteux , Diabète expérimental/métabolisme , Néphropathies diabétiques/traitement médicamenteux , Néphropathies diabétiques/métabolisme , Souris , Mâle , Antioxydants/pharmacologie , Polygonum/composition chimique , Alloxane , Peroxydation lipidique/effets des médicaments et des substances chimiques , Facteur de nécrose tumorale alpha/métabolisme , Glutathion/métabolisme , Rein/effets des médicaments et des substances chimiques , Rein/métabolisme , Rein/anatomopathologie , Interleukine-6/métabolisme , Interleukine-6/sangRÉSUMÉ
The landscape of diabetes management has changed, such that the goal of pharmacotherapy extends beyond glucose-lowering to prioritize risk reduction of cardiovascular disease and diabetic kidney disease. Two newer classes of medications, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2-Is), have become first line therapies for many patients with type 2 diabetes to reduce cardiovascular and renal complications of type 2 diabetes. This review article will describe the mechanism of action, evidence for cardiovascular and kidney outcomes, contraindications, adverse effects, and risk mitigation strategies for the GLP-1 RA and SGLT2-I drug classes. In addition, we will provide a practical approach for primary care clinicians to prescribe, adjust, and combine these medication classes, while considering patient preference, tolerability, comorbidities, cost, and availability.
Sujet(s)
Maladies cardiovasculaires , Diabète de type 2 , Néphropathies diabétiques , Récepteur du peptide-1 similaire au glucagon , Hypoglycémiants , Inhibiteurs du cotransporteur sodium-glucose de type 2 , Humains , Inhibiteurs du cotransporteur sodium-glucose de type 2/usage thérapeutique , Diabète de type 2/traitement médicamenteux , Diabète de type 2/complications , Maladies cardiovasculaires/prévention et contrôle , Maladies cardiovasculaires/étiologie , Récepteur du peptide-1 similaire au glucagon/agonistes , Néphropathies diabétiques/prévention et contrôle , Néphropathies diabétiques/traitement médicamenteux , Hypoglycémiants/usage thérapeutique , Glycémie/effets des médicaments et des substances chimiquesRÉSUMÉ
Glomerular hyperfiltration(GHF), as an early manifestation of prediabetes and diabetic kidney disease, occurs mainly by the mechanism of glomerular-tubular feedback and hemodynamic alterations, and the risk of hyperfiltration can be elevated in younger patients, shorter duration of the disease, poor glycemic control, and high-protein, low-salt diet. Currently, there is no recognized standard for the definition of GHF, GHF lacks typical clinical manifestations, imaging diagnostic criteria are unclear, and GHF-related laboratory markers need to be further studied. Hyperfiltration, if not diagnosed and intervened in time, can accelerate the damage of nephron and the rate of nephropathy progression, and increase the risk of complications and death. Sodium-glucose cotransporter 2 inhibitor(SGLT2i), glucagon-like peptide-1 receptor agonist(GLP-1RA)and so on can effectively reverse the hyperfiltration state. Clinical attention should be paid to the diagnosis of diabetic hyperfiltration and the prevention of its poor prognosis.
Sujet(s)
Néphropathies diabétiques , Humains , Pronostic , Débit de filtration glomérulaireRÉSUMÉ
Objective: To investigate the efficacy and safety of Shengjiang powder as a treatment for DKD. Methods: A comprehensive search was performed in eight databases from their inception to December 30, 2023, to identify relevant RCTs. The inclusion criteria were diagnosis of DKD and intervention including TCM that contained Shengjiang powder. Two researchers independently conducted literature screening and data extraction, utilizing the Rob2 tool and GRADE to assess the quality of the RCTs. Meta-analysis was carried out using RevMan 5.4.1 and Stata 15.0. Results: As a result of the search, 23 RCTs comprising 1,682 patients. The interventions resulted in significant reductions in all the assessed indicators: 24-h urinary protein, UAER, mALB, BUN, Scr, FBG, 2hPG, HbA1c, total cholesterol, and Triglycerides. Together the results showed that Shengjiang powder, in conjunction with conventional therapy, is an effective treatment of DKD. Subgroup analyses, considering duration, stage, blood glucose control levels, baseline blood glucose levels, and baseline Scr levels indicated that shorter duration treatment had a greater effect on UAER, 2hPG, and HbA1c. Additionally, Shengjiang powder was more effective in reducing 24-h urinary protein, Scr, and 2hPG in stage IV patients compared to corresponding values at other stages. However, with respect to FBG, the treatment was more effective in stage II/III. Shengjiang powder also, reduced Scr levels significantly in patients with higher baseline Scr and reduced urinary protein excretion with stricter blood glucose control. The interventions had additional lipid-regulating effects in cases with looser blood glucose control and led to a remarkable reduction in BUN and Scr levels in patients with FBG > 11.1 mmol/L. Conclusion: Shengjiang powder may supplement conventional therapy, thus benefiting DKD patients in terms of reducing urinary protein, stabilizing kidney function, and improving blood glucose and lipid metabolism. Considering the significant heterogeneity among studies and limited quality of some reports, our conclusions need to be further verified through analyses utilizing larger, multi-center samples of higher quality. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42024490795.
Sujet(s)
Néphropathies diabétiques , Médicaments issus de plantes chinoises , Humains , Glycémie/analyse , Néphropathies diabétiques/traitement médicamenteux , Médicaments issus de plantes chinoises/usage thérapeutique , Médicaments issus de plantes chinoises/administration et posologie , Médicaments issus de plantes chinoises/effets indésirables , Médecine traditionnelle chinoise/méthodes , Poudres , Essais contrôlés randomisés comme sujet , Résultat thérapeutiqueRÉSUMÉ
Chronic kidney disease (CKD) is a microvascular complication that frequently affects numerous patients diagnosed with diabetes. For the diagnosis of CKD, the guidelines recommend the identification of the urinary albumin/creatinine ratio and the determination of serum creatinine, based on which the estimated rate of glomerular filtration (eGFR) is calculated. Serum creatinine is routinely measured in clinical practice and reported as creatinine-based estimated glomerular filtration rate (eGFRcr). It has enormous importance in numerous clinical decisions, including the detection and management of CKD, the interpretation of symptoms potentially related to this pathology and the determination of drug dosage. The equations based on cystatin C involve smaller differences between race groups compared to GFR estimates based solely on creatinine. The cystatin C-based estimated glomerular filtration rate (eGFRcys) or its combination with creatinine (eGFRcr-cys) are suggested as confirmatory tests in cases where creatinine is known to be less precise or where a more valid GFR estimate is necessary for medical decisions. Serum creatinine is influenced by numerous factors: age, gender, race, muscle mass, high-protein diet, including protein supplements, and the use of medications that decrease tubular creatinine excretion (H2 blockers, trimethoprim, fenofibrate, ritonavir, and other HIV drugs). The low levels of creatinine stemming from a vegetarian diet, limb amputation, and conditions associated with sarcopenia such as cirrhosis, malnutrition, and malignancies may lead to inaccurately lower eGFRcr values. Therefore, determining the GFR based on serum creatinine is not very precise. This review aims to identify a new perspective in monitoring renal function, considering the disadvantages of determining the GFR based exclusively on serum creatinine.
Sujet(s)
Créatinine , Cystatine C , Débit de filtration glomérulaire , Insuffisance rénale chronique , Humains , Cystatine C/sang , Insuffisance rénale chronique/sang , Insuffisance rénale chronique/diagnostic , Créatinine/sang , Marqueurs biologiques/sang , Diabète/sang , Néphropathies diabétiques/diagnostic , Néphropathies diabétiques/sang , Néphropathies diabétiques/étiologieRÉSUMÉ
BACKGROUND: Previous studies examined the association of Helicobacter pylori infection (H. pylori) with complications of diabetes, but the results have been inconsistent. The aim of this study of patients with type-2 diabetes (T2D) was to determine the association of H. pylori infection with the major complications of diabetes. METHODS: This single-center retrospective study examined patients with T2D who received H. pylori testing between January 2016 and December 2021. Logistic regression analyses were used to evaluate the association of H. pylori infection with four major complications of diabetes. RESULTS: We examined 960 patients with T2D, and 481 of them (50.1%) were positive for H. pylori. H. pylori infection was significantly associated with diabetic nephropathy (odds ratio [OR] = 1.462; 95% confidence interval [CI]: 1.006,2.126; P = 0.046). In addition, the co-occurrence of H. pylori positivity with hypertension (OR = 4.451; 95% CI: 2.351,8.427; P < 0.001), with glycated hemoglobin A1c (HbA1c) of at least 8% (OR = 2.925; 95% CI: 1.544,5.541; P = 0.001), and with diabetes duration of at least 9 years (OR = 3.305; 95% CI:1.823,5.993; P < 0.001) further increased the risk of diabetic nephropathy. There was no evidence of an association of H. pylori infection with retinopathy, neuropathy, or peripheral vascular disease. CONCLUSIONS: Our study of T2D patients indicated that those with H. pylori infections had an increased risk of nephropathy, and this risk was greater in patients who also had hypertension, an HbA1c level of 8% or more, and diabetes duration of 9 years or more.
Sujet(s)
Diabète de type 2 , Néphropathies diabétiques , Infections à Helicobacter , Helicobacter pylori , Humains , Infections à Helicobacter/complications , Études rétrospectives , Mâle , Femelle , Adulte d'âge moyen , Diabète de type 2/complications , Diabète de type 2/épidémiologie , Helicobacter pylori/isolement et purification , Néphropathies diabétiques/épidémiologie , Néphropathies diabétiques/étiologie , Néphropathies diabétiques/complications , Sujet âgé , Complications du diabète/microbiologie , Complications du diabète/épidémiologie , Hémoglobine glyquée/analyse , Hémoglobine glyquée/métabolisme , Études de suivi , Pronostic , AdulteRÉSUMÉ
Diabetes mellitus is a major public health concern, often leading to undiagnosed micro- and macrovascular complications, even in patients with controlled blood glucose levels. Recent evidence suggests that empagliflozin and metformin have renoprotective effects in addition to their hypoglycemic action. This study investigated the potential protective effect of empagliflozin and metformin on diabetic renal complications. Forty-two adult male Sprague Dawley rats were randomized into six groups: normal control, diabetic control, metformin (250 mg/kg), empagliflozin (10 mg/kg), and combination therapy groups. Type 2 diabetes was induced in rats by a single intraperitoneal injection of streptozotocin (40 mg/kg) following two weeks of 10% fructose solution in their drinking water. Blood glucose, creatinine, urea nitrogen, inflammatory markers (IL-6, TNF-α), and renal tissue caspase-3 were assessed after eight weeks. Blood glucose, urea, creatinine, serum IL-6, TNF-α, and tissue caspase-3 were significantly decreased in the treatment groups compared to the diabetic group. The histopathological findings revealed that treatment with empagliflozin and/or metformin improved the damage in the renal tissue caused by diabetes-induced nephropathy. Moreover, co-administration of empagliflozin and metformin resulted in even better outcomes. Our data revealed that empagliflozin and metformin could improve renal function and decrease inflammation and apoptosis in diabetic animals, delaying the progression of diabetic nephropathy. Combined treatment with metformin and empagliflozin proved to have an additive protective action on renal tissue.
Sujet(s)
Composés benzhydryliques , Diabète expérimental , Néphropathies diabétiques , Glucosides , Metformine , Rat Sprague-Dawley , Metformine/pharmacologie , Metformine/usage thérapeutique , Composés benzhydryliques/pharmacologie , Composés benzhydryliques/usage thérapeutique , Animaux , Glucosides/pharmacologie , Glucosides/usage thérapeutique , Glucosides/administration et posologie , Mâle , Rats , Néphropathies diabétiques/traitement médicamenteux , Diabète expérimental/complications , Diabète expérimental/traitement médicamenteux , Hypoglycémiants/pharmacologie , Hypoglycémiants/usage thérapeutique , Diabète de type 2/complications , Diabète de type 2/traitement médicamenteux , Association de médicaments , Glycémie , Rein/effets des médicaments et des substances chimiques , Rein/anatomopathologieRÉSUMÉ
Objective: The oxidative balance score (OBS) is a comprehensive concept that includes 20 oxidative stressors and can be used to assess individual pro-oxidant versus antioxidant exposure, and the aim of the present study was to investigate the association between OBS and the risk of diabetic kidney disease (DKD), low estimated glomerular filtration rate (low-eGFR) and albuminuria in patients with diabetes mellitus (DM). Methods: This cross-sectional study included nationally representative consecutive National Health and Nutrition Examination Survey DM patients aged 18 years and older from 2003-2018. The continuous variable OBS was converted into categorical variables by quartiles, and weighted multiple logistic regression analyses and restricted triple spline models were used to explore the relationships. We also performed subgroup analyses and interaction tests to verify the stability of the results. Results: A total of 5389 participants were included, representing 23.6 million non-institutionalized US residents. The results from both multivariate logistic regression analysis and restricted cubic spline models indicated that OBS and dietary OBS levels were negatively associated with the risk of DKD, low-eGFR, and albuminuria, without finding a significant correlation between lifestyle OBS and these clinical outcomes. Compared to the lowest OBS quartile group, the prevalence risk of DKD (OR = 0.61, 95% CI: 0.46-0.80), low-eGFR (OR = 0.46, 95% CI: 0.33-0.64) and albuminuria (OR = 0.68, 95% CI: 0.51-0.92) decreased by 39%, 54% and 32%, respectively, in the highest OBS quartile group. The results remained stable in subgroup analyses and no interaction between subgroups was found. Conclusion: Higher levels of OBS and dietary OBS were associated with a lower risk of DKD, low-eGFR, and albuminuria. These findings provided preliminary evidence for the importance of adhering to an antioxidant-rich diet and lifestyle among individuals with diabetes.
Sujet(s)
Albuminurie , Diabète de type 2 , Néphropathies diabétiques , Débit de filtration glomérulaire , Stress oxydatif , Humains , Études transversales , Mâle , Femelle , Albuminurie/épidémiologie , Néphropathies diabétiques/épidémiologie , Néphropathies diabétiques/physiopathologie , Néphropathies diabétiques/étiologie , Adulte d'âge moyen , Diabète de type 2/complications , Diabète de type 2/métabolisme , Diabète de type 2/physiopathologie , Adulte , Sujet âgé , Enquêtes nutritionnelles , Facteurs de risqueRÉSUMÉ
BACKGROUND: Western guidelines often recommend biguanides as the first-line treatment for diabetes. However, dipeptidyl peptidase-4 (DPP-4) inhibitors, alongside biguanides, are increasingly used as the first-line therapy for type 2 diabetes (T2DM) in Japan. However, there have been few studies comparing the effectiveness of biguanides and DPP-4 inhibitors with respect to diabetes-related complications and cardio-cerebrovascular events over the long term, as well as the costs associated. OBJECTIVE: We aimed to compare the outcomes of patients with T2DM who initiate treatment with a biguanide versus a DPP-4 inhibitor and the long-term costs associated. METHODS: We performed a cohort study between 2012 and 2021 using a new-user design and the Shizuoka Kokuho database. Patients were included if they were diagnosed with T2DM. The primary outcome was the incidence of cardio-cerebrovascular events or mortality from the initial month of treatment; and the secondary outcomes were the incidences of related complications (nephropathy, renal failure, retinopathy, and peripheral neuropathy) and the daily cost of the drugs used. Individuals who had experienced prior events during the preceding year were excluded, and events within 6 months of the start of the study period were censored. Propensity score matching was performed to compare between two groups. RESULTS: The matched 1:5 cohort comprised 529 and 2,116 patients who were initially treated with a biguanide or a DPP-4 inhibitor, respectively. Although there were no significant differences in the incidence of cardio-cerebrovascular events or mortality and T2DM-related complications between the two groups (p = 0.139 and p = 0.595), daily biguanide administration was significantly cheaper (mean daily cost for biguanides, 61.1 JPY; for DPP-4 inhibitors, 122.7 JPY; p<0.001). CONCLUSION: In patients with T2DM who initiate pharmacotherapy, there were no differences in the long-term incidences of cardio-cerebrovascular events or complications associated with biguanide or DPP-4 use, but the former was less costly.