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Diabetology & Metabolic Syndrome Jan 2024We aimed to explore the associations between urine albumin-to-creatinine ratio (uACR) and cardia-cerebrovascular disease (CVD) in Chinese population with type 2...
AIMS
We aimed to explore the associations between urine albumin-to-creatinine ratio (uACR) and cardia-cerebrovascular disease (CVD) in Chinese population with type 2 diabetes(T2D).
METHODS
We included 8975 participants with T2D but free of prevalent CVD (including myocardial infarction, ischemic and hemorrhagic stroke) at baseline from Kailuan study who were assessed with uACR between 2014 and 2016. The participants were divided into three groups based on their baseline uACR: normal (< 3 mg/mmol), microalbuminuria (3-30 mg/mmol), and macroalbuminuria (≥ 30 mg/mmol). Cox regression models and restricted cubic spline were used to evaluate the hazard ratios (HRs) and 95% confidence intervals (CIs) of incident CVD. The area under the receiver operating characteristic curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used to see if incorporating uACR into existing models could improve performance.
RESULTS
During a median follow-up of 4.05 years, 560 participants developed first CVD event (6.24%). After adjustment for potential confounders, participants with microalbuminuria had higher risks of CVD compared with normal uACR, with HRs of 1.57(95% CI 1.04-2.37) for myocardial infarction, 1.24(95% CI 1.00-1.54) for ischemic stroke,1.62(95% CI 0.73-3.61) for hemorrhagic stroke, and 1.30(95% CI 1.07-1.57) for total CVD. The risks gradually attenuated with uACR increase, with HRs of 2.86(95% CI 1.63-5.00) for myocardial infarction, 2.46(95% CI 1.83-3.30) for ischemic stroke, 4.69(95% CI 1.72-12.78) for hemorrhagic stroke, and 2.42(95% CI 1.85-3.15) for total CVD in macroalbuminuria. The addition of uACR to established CVD risk models improved the CVD risk prediction efficacy.
CONCLUSIONS
Increasing uACR, even below the normal range, is an independent risk factor for new-onset CVD in T2D population. Furthermore, uACR could improve the risk prediction for CVD among community based T2D patients.
PubMed: 38291519
DOI: 10.1186/s13098-024-01256-5 -
Journal of Diabetes Investigation May 2024There is a large body of literature demonstrating a social gradient in health and increasing evidence of an association between social deprivation and diabetes... (Review)
Review
There is a large body of literature demonstrating a social gradient in health and increasing evidence of an association between social deprivation and diabetes complications. Diabetic kidney disease (DKD) increases mortality in people with diabetes. Socioeconomic deprivation is increasingly recognized as a modifier of risk factors for kidney disease but also an independent risk factor itself for kidney disease. This may not be truly appreciated by clinicians and warrants further attention and exploration. In this review we explore the literature to date from Europe on the relationship between social deprivation and DKD. The majority of the studies showed at least an association with microalbuminuria, an early marker of DKD, while many showed an association with overt nephropathy. This was seen across many countries in Europe using a variety of different measures of deprivation. We reviewed and considered the mechanisms by which deprivation may lead to DKD. Health related behaviors such as smoking and suboptimal control of risk factors such as hypertension, hyperglycemia and elevated body mass index (BMI) accounts for some but not all of the association. Poorer access to healthcare, health literacy, and stress are also discussed as potential mediators of the association. Addressing deprivation is difficult but starting points include targeted interventions for people living in deprived circumstances, equitable roll out of diabetes technology, and flexible outpatient clinic arrangements including virtual and community-based care.
Topics: Humans; Diabetic Nephropathies; Europe; Risk Factors; Socioeconomic Factors
PubMed: 38279774
DOI: 10.1111/jdi.14156 -
Diabetes & Metabolism Journal Mar 2024Hypertriglyceridemia and decreased high-density lipoprotein cholesterol (HDL-C) persist despite statin therapy, contributing to residual atherosclerotic cardiovascular... (Review)
Review
Hypertriglyceridemia and decreased high-density lipoprotein cholesterol (HDL-C) persist despite statin therapy, contributing to residual atherosclerotic cardiovascular disease (ASCVD) risk. Asian subjects are metabolically more susceptible to hypertriglyceridemia than other ethnicities. Fenofibrate regulates hypertriglyceridemia, raises HDL-C levels, and is a recommended treatment for dyslipidemia. However, data on fenofibrate use across different Asian regions are limited. This narrative review summarizes the efficacy and safety data of fenofibrate in Asian subjects with dyslipidemia and related comorbidities (diabetes, metabolic syndrome, diabetic retinopathy, and diabetic nephropathy). Long-term fenofibrate use resulted in fewer cardiovascular (CV) events and reduced the composite of heart failure hospitalizations or CV mortality in type 2 diabetes mellitus. Fenofibrate plays a significant role in improving irisin resistance and microalbuminuria, inhibiting inflammatory responses, and reducing retinopathy incidence. Fenofibrate plus statin combination significantly reduced composite CV events risk in patients with metabolic syndrome and demonstrated decreased triglyceride and increased HDL-C levels with an acceptable safety profile in those with high CV or ASCVD risk. Nevertheless, care is necessary with fenofibrate use due to possible hepatic and renal toxicities in vulnerable individuals. Long-term trials and real-world studies are needed to confirm the clinical benefits of fenofibrate in the heterogeneous Asian population with dyslipidemia.
Topics: Humans; Fenofibrate; Hypolipidemic Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Diabetes Mellitus, Type 2; Metabolic Syndrome; Dyslipidemias; Hypertriglyceridemia; Atherosclerosis
PubMed: 38273789
DOI: 10.4093/dmj.2023.0168 -
Frontiers in Nutrition 2023Chronic kidney disease (CKD) is often accompanied by alterations in the metabolic profile of the body, yet the causative role of these metabolic changes in the onset of...
BACKGROUND
Chronic kidney disease (CKD) is often accompanied by alterations in the metabolic profile of the body, yet the causative role of these metabolic changes in the onset of CKD remains a subject of ongoing debate. This study investigates the causative links between metabolites and CKD by leveraging the results of genomewide association study (GWAS) from 486 blood metabolites, employing bulk two-sample Mendelian randomization (MR) analyses. Building on the metabolites that exhibit a causal relationship with CKD, we delve deeper using enrichment analysis to identify the metabolic pathways that may contribute to the development and progression of CKD.
METHODS
In conducting the Mendelian randomization analysis, we treated the GWAS data for 486 metabolic traits as exposure variables while using GWAS data for estimated glomerular filtration rate based on serum creatinine (eGFRcrea), microalbuminuria, and the urinary albumin-to-creatinine ratio (UACR) sourced from the CKDGen consortium as the outcome variables. Inverse-variance weighting (IVW) analysis was used to identify metabolites with a causal relationship to outcome. Using Bonferroni correction, metabolites with more robust causal relationships are screened. Additionally, the IVW-positive results were supplemented with the weighted median, MR-Egger, weighted mode, and simple mode. Furthermore, we performed sensitivity analyses using the Cochran Q test, MR-Egger intercept test, MR-PRESSO, and leave-one-out (LOO) test. Pathway enrichment analysis was conducted using two databases, KEGG and SMPDB, for eligible metabolites.
RESULTS
During the batch Mendelian randomization (MR) analyses, upon completion of the inverse-variance weighted (IVW) approach, sensitivity analysis, and directional consistency checks, 78 metabolites were found to meet the criteria. The following four metabolites satisfy Bonferroni correction: mannose, N-acetylornithine, glycine, and bilirubin (Z, Z), and mannose is causally related to all outcomes of CKD. By pathway enrichment analysis, we identified eight metabolic pathways that contribute to CKD occurrence and progression.
CONCLUSION
Based on the present analysis, mannose met Bonferroni correction and had causal associations with CKD, eGFRcrea, microalbuminuria, and UACR. As a potential target for CKD diagnosis and treatment, mannose is believed to play an important role in the occurrence and development of CKD.
PubMed: 38260086
DOI: 10.3389/fnut.2023.1274078 -
Journal of Clinical Medicine Jan 2024Multiple studies have analyzed the possible correlations between diabetes and Alzheimer's disease. Less is known about the context of cognitive deterioration among...
Multiple studies have analyzed the possible correlations between diabetes and Alzheimer's disease. Less is known about the context of cognitive deterioration among patients with atypical Parkinsonian syndromes and glucose metabolism impairment. The aim of this study was to evaluate the association between the impaired glucose metabolism and cognitive decline among patients with progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). The study included 22 patients with PSP and CBS with disease durations varying from 3 to 6 years. The levels of glycated hemoglobin (HbA1C), fasting blood glucose, fasting C-peptide and the presence of microalbuminuria were evaluated, and oral glucose tolerance tests (OGTT) were performed. Based on the OGTT results, the glycemic variability, mean glycemia, glycemia standard deviation (SD) and coefficient of variation (%CV) were calculated. All patients underwent a three-Tesla brain magnetic resonance (MRI) examination and neuropsychological cognitive assessment with the use of standardized scales: Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE) and Frontal Assessment Battery (FAB). A statistical analysis revealed that poor control of glycemia with high glycemic variability and increased atrophy of the medial temporal lobe among patients with PSP and CBS correlated with worse cognitive performance independent of age or sex, even among patients who did not fulfill the criteria for diabetes. The study results indicate the importance of glucose metabolism control and optimal treatment in the context of cognition maintenance among patients with PSP and CBS. Due to the relatively small number of analyzed patients, the issue requires further assessment. To the best of our knowledge, this is the first study discussing the role of glycemic variability in atypical Parkinsonian syndromes.
PubMed: 38256599
DOI: 10.3390/jcm13020465 -
Bioinformation 2023The diabetic nephropathy is one of the most prevalent microvascular complications with type 2 diabetes mellitus. The most accurate and widely used marker for diabetic...
The diabetic nephropathy is one of the most prevalent microvascular complications with type 2 diabetes mellitus. The most accurate and widely used marker for diabetic nephropathy is microalbuminuria and it is also regarded as conventional method. However, it is not a sensitive or specific nephropathy biomarker. Therefore, it is of interest to evaluate the role of podocalyxin to predict early onset of nephropathy in patients with type 2 diabetes mellitus. This cross - sectional study is conducted on 150 subjects. Among these 150 T2DM patients (Group 2: T2DM with normoalbuminuria and Group 3: T2DM with microalbuminuria) and 50 were age, gender and BMI matched healthy controls (Group 1). The biochemical and experimental parameters was analyzed. T2DM patients have higher levels of urine podocalyxin. This level was significantly elevated in patients with T2DM with microalbuminuria than normoalbuminuria. Urinary podocalyxin levels and HbA1c were found to be positively correlated. Thus, urinary podocalyxin is useful as early predictable marker for nephropathy in patients with type 2 diabetes mellitus.
PubMed: 38250530
DOI: 10.6026/973206300191124 -
International Journal of Biological... 2024Proteinuria is a common and important clinical manifestation of chronic kidney disease (CKD) and an independent risk factor for the progression of kidney disease. As a...
Proteinuria is a common and important clinical manifestation of chronic kidney disease (CKD) and an independent risk factor for the progression of kidney disease. As a component of the glomerular filtration barrier (GFB), podocyte plays a key role in the pathogenesis of glomerular diseases and proteinuria. However, the pathophysiology of glomerular diseases associated with mitochondrial function is incompletely understood. Here, we identified three novel mutations in , encoding a membrane protein in mitochondria, associated with multisystem manifestations including nephrotic proteinuria and kidney injury in two Chinese patients. Conditional podocyte-specific Mtx2 knockout (Pod-Mtx2-KO) mice present a series of podocyte and glomerular abnormalities from 8 weeks to old age, including microalbuminuria, glomerular mesangial hyperplasia, fusion and effacement of foot process. MTX2 deficiency impaired podocyte functions manifested by reductions of adhesion, migration and endocytosis, which were further restored by overexpression of MTX2. Moreover, MTX2 defects led to abnormal mitochondrial structure and dysfunction, evidenced with defects of complex I and III, increased production of reactive oxygen species (ROS), and decreased protein levels of Sam50-CHCHD3-Mitofilin axis in the mitochondrial intermembrane space bridging (MIB) complex which is responsible for maintaining mitochondrial cristae morphology. Collectively, these findings reveal that the normal expression of MTX2 in glomerulus plays an important role in the adhesion, migration, endocytosis, proliferation and other physiological functions of podocytes, which may be realized by maintaining the morphological structure and function of mitochondria. Abnormal expression of MTX2 can lead to mitochondrial dysfunction and structural abnormalities by Sam50-CHCHD3-Mitofilin axis in podocyte, which further induces podocyte injury, glomerular lesions and proteinuria.
Topics: Animals; Humans; Mice; Kidney Glomerulus; Mitochondrial Diseases; Mitochondrial Proteins; Podocytes; Proteinuria; Renal Insufficiency, Chronic
PubMed: 38250156
DOI: 10.7150/ijbs.89916 -
Journal of Personalized Medicine Jan 2024An elevated platelet count may contribute to significant thrombotic events and pose a risk for diabetic microvascular complications. Albuminuria, one of the hallmarks of...
An elevated platelet count may contribute to significant thrombotic events and pose a risk for diabetic microvascular complications. Albuminuria, one of the hallmarks of diabetes, is thought to be a risk factor for endothelial dysfunction. In this study, we investigated the association between relative thrombocytosis and an increased urine albumin-to-creatinine ratio in healthy adult participants. Using multivariate analyses on data from the Korea National Health and Nutrition Examination Survey V-VI, 12,525 eligible native Koreans aged ≥ 20 were categorized into platelet count quintiles by sex. The highest platelet count quintile included younger, more obese participants with elevated white blood cell counts, poor lipid profiles, and a better estimated glomerular filtration rate. Restricted cubic spline regression analysis revealed significant associations between platelet count and fasting blood glucose, glycated hemoglobin, and urine albumin-to-creatinine ratio. Adjusted logistic regression models indicated that heightened fasting blood glucose and platelet count were linked to risk of microalbuminuria (fasting blood glucose, odds ratio = 1.026, 95%CI = 1.011-1.042; platelet count, odds ratio = 1.004, 95%CI = 1.002-1.006). Particularly, an increased platelet count was notably associated with microalbuminuria progression in subjects with impaired fasting glucose. These findings suggest that an elevated platelet count, even below diagnostic thrombocytosis levels, independently correlates with an increased risk of vascular endothelial dysfunction in patients with impaired fasting glucose.
PubMed: 38248790
DOI: 10.3390/jpm14010089 -
Medical Ultrasonography Mar 2024To explore benefits of high-frame-rate contrast-enhanced ultrasonography (H-CEUS) for early kidney injury in a rabbit model of diabetic nephropathy (DN).
AIM
To explore benefits of high-frame-rate contrast-enhanced ultrasonography (H-CEUS) for early kidney injury in a rabbit model of diabetic nephropathy (DN).
METHODS
Diabetic rabbits were induced with alloxan administration and split into 2 groups with or without urinary microalbuminuria after a fatty and sugary diet: diabetic rabbits with nephropathy (Group A) and diabetic rabbits without nephropathy (Group B). The control group (Group C) comprised healthy rabbits. Renal H-CEUS and conventional CEUS (C-CEUS) imaging were conducted. Serum creatinine (SCR), blood urea nitrogen (BUN) and urinary microalbuminuria were measured.
RESULTS
SCR and BUN levels were barely changed in Groups B and C (p>0.05), whereas Group A exhibited a rise (p<0.05). Perfusion parameters of the two CEUS modalities showed reduced peak intensity (PI) and ascending slope (AS) and elevated area under the curve (AUC) and time to peak (TTP) in Group A versus Group B (p<0.05) and Group B versus Group C (p<0.05). The arrival time (AT) and descending slope (DS) exhibited little difference among the three groups. H-CEUS had a stronger correlation of perfusion parameters with SCR and BUN than C-CEUS.
CONCLUSIONS
H-CEUS outperforms C-CEUS in diagnosing early renal damage in DN. H-CEUS perfusion parameters demonstrate temporal superiority over routine laboratory indices.
Topics: Animals; Rabbits; Diabetic Nephropathies; Contrast Media; Kidney; Urinary Tract; Ultrasonography; Diabetes Mellitus
PubMed: 38244221
DOI: 10.11152/mu-4318 -
Heliyon Jan 2024QiDiTangShen granules (QDTS), a traditional Chinese medicine (TCM) compound prescription, have remarkable efficacy in diabetic nephropathy (DN) patients, and their...
BACKGROUND
QiDiTangShen granules (QDTS), a traditional Chinese medicine (TCM) compound prescription, have remarkable efficacy in diabetic nephropathy (DN) patients, and their pharmacological mechanism needs further exploration.
METHODS
According to the active ingredients and targets of the QDTS in the TCMSP database, the network pharmacology of QDTS was investigated. The potential active ingredients were chosen based on the oral bioavailability and the drug similarity index. At the same time, targets for DN-related disease were obtained from GeneCards, OMIM, PharmGKB, TTD, and DrugBank. The TCM-component-target network and the protein-protein interaction (PPI) network were constructed with the Cytoscape and STRING platforms, respectively, and then the core targets of DN were selected with CytoNCA. GO and KEGG enrichment analysis using R software. Molecular docking to identify the core targets of QDTS for DN. In vivo, db/db mice were treated as DN models, and the urine microalbuminuria, the pathological changes in the kidney and the protein expression levels of p-PI3K, p-Akt, JUN, nephrin and synaptopodin were detected by immunohistochemistry, immunofluorescence method and Western blotting. After QDTS was used in vitro, the protein expression of mouse podocyte clone-5 (MPC5) cells was detected by immunohistochemistry, immunofluorescence and Western blot.
RESULTS
Through network pharmacology analysis, 153 potential targets for DN in QDTS were identified, 19 of which were significant. The KEGG enrichment analysis indicated that QDTS might have therapeutic effects on IL-17, TNF, AGE-RAGE, PI3K-Akt, HIF-1, and EGFR through interfering with Akt1 and JUN. The main active ingredients in QDTS are , , and . Both in vivo and in vitro studies showed that QDTS could decrease the urine microalbuminuria and renal pathology of db/db mice, and alleviate podocyte injuries through the PI3K/Akt signaling pathway.
CONCLUSION
Through network pharmacology, in vivo and in vitro experiments, QDTS has been shown to improve the urine microalbuminuria and renal pathology in DN, and to reduce podocyte damage via the PI3K/Akt pathway.
PubMed: 38223704
DOI: 10.1016/j.heliyon.2023.e23535