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Microbiology Spectrum Aug 2023Many studies have suggested that gut microbiota dysbiosis may be one of the pathogenesis factors of diabetes mellitus (DM), while it is not clear whether it is involved...
Many studies have suggested that gut microbiota dysbiosis may be one of the pathogenesis factors of diabetes mellitus (DM), while it is not clear whether it is involved in the development of diabetic kidney diseases (DKD). The objective of this study was to determine bacterial taxa biomarkers during the progression of DKD by investigating bacterial compositional changes in early and late DKD. 16S rRNA gene sequencing was performed on fecal samples, including the diabetes mellitus (DM), DNa (early DKD), and DNb (late DKD) groups. Taxonomic annotation of microbial composition was performed. Samples were sequenced on the Illumina NovaSeq platform. At the genus level, we found counts of , , and were significantly elevated both in the DNa group (0.0001, 0.0007, and 0.0174, respectively) and the DNb group (0.0001, 0.0012, and 0.0003, respectively) compared with those in the DM group. Only the level of was significantly decreased in the DNa group than the DM group and in the DNb group than the DNa group. Counts of , were significantly decreased in the DNa group compared with those in the DM group (0.001 and 0.006, respectively) and in the DNb group compared with those in the DM group (0.0001 and 0.003, respectively). Levels of , and were positively correlated with an estimated glomerular filtration rate (eGFR), but negatively correlated with microalbuminuria (MAU), 24 h urinary protein quantity (24hUP), and serum creatinine (Scr). Moreover, the areas under the curve (AUCs) of and were 83.33% and 80.77%, respectively, for the DM and DNa cohorts, respectively. Notably, the largest AUC for DNa and DNb cohorts was also that of at 83.60%. Gut microbiota dysbiosis was found in the early and late stages of DKD, especially in the early stage. may be the most promising intestinal bacteria biomarker that can help distinguish different stages of DKD. It is not clear as to whether gut microbiota dysbiosis is involved in the progression of DKD. This study may be the first to explore gut microbiota compositional changes in diabetes, early-DKD, and late DKD. We identify different gut microbial characteristics during different stages of DKD. Gut microbiota dysbiosis is found in the early and late stages of DKD. may be the most promising intestinal bacteria biomarker that can help distinguish different stages of DKD, although further studies are warranted to illustrate these mechanisms.
Topics: Diabetic Nephropathies; Humans; Male; Female; Middle Aged; Gastrointestinal Microbiome; Clostridiales; Biomarkers; Diabetes Mellitus; Bacteria; Feces; Kidney Failure, Chronic
PubMed: 37341590
DOI: 10.1128/spectrum.00382-23 -
Pakistan Journal of Medical Sciences 2024To find the correlation of serum uric acid with microalbuminuria in Type-2 diabetic patients with normal creatinine.
OBJECTIVE
To find the correlation of serum uric acid with microalbuminuria in Type-2 diabetic patients with normal creatinine.
METHODS
This cross-sectional study was conducted in the Department of Diabetes, Endocrinology and Metabolic diseases, Hayatabad Medical Complex, Peshawar, Pakistan from 1 April, 2022 to 30 September, 2022. Total 160 diabetic patients between the age of 30 and 65 years were enrolled in the study. Type-2 diabetic patients with microalbuminuria between 2.5 and 30 mg/mmol were included. The demographic details of patients were recorded in the questionnaire after taking consent. Fasting Uric acid, lipid profile and glucose along with creatinine and HbA1C were estimated from patient's venous blood samples. Ratio of albumin to creatinine (ACR) in the random spot urine sample was used to detect microalbuminuria.
RESULTS
Out of 160 participants enrolled in the study there were 86 (54%) males and 74 (46%) females with the mean age of 50.15 ± 11.1 years and BMI of 20.93 kg/m. Ninety six (60%) of the patients had Type-2 DM for less than five years, while remaining 64 (40%) were more than five years diabetic. Mean serum uric acid calculated was 6.85±2.06(mg/dl), while microalbuminuria was calculated as 8.02±0.78 (mg/mmol). The Pearson correlation of serum uric acid and microalbuminuria based on sex and age was statistically significant(p<0.05).
CONCLUSION
We found that uric acid level was significantly associated with microalbuminuria in people with Type-2 diabetes with normal serum creatinine. Uric acid level can be a potential screening tool for early detection of DKD.
PubMed: 38827879
DOI: 10.12669/pjms.40.5.8208 -
Scientific Reports May 2024Sodium-glucose co-transporters type 2 inhibitors (SLGT2i) are highly effective in controlling type 2 diabetes, but reported beneficial cardiovascular effects suggest... (Randomized Controlled Trial)
Randomized Controlled Trial
Sodium-glucose co-transporters type 2 inhibitors (SLGT2i) are highly effective in controlling type 2 diabetes, but reported beneficial cardiovascular effects suggest broader actions on insulin resistance. Weight loss may be initially explained by glycosuria-induced net caloric output and secondary volumetric reduction, but its maintenance could be due to loss of visceral fat mass. Structured ultrasound (US) imaging of abdominal adipose tissue ("eco-obesity") is a recently described methodology used to measure 5 consecutive layers of abdominal fat, not assessable by DEXA or CT scan: superficial subcutaneous (SS), deep subcutaneous (DS), preperitoneal (PP), omental (Om) and right perirenal (RK). PP, Om and RK are predictors of metabolic syndrome (MS) with defined cut-off points. To assess the effect of SLGT2i on every fat depot we enrolled 29 patients with type 2 Diabetes (HbA1c 6.5-9%) and Obesity (IMC > 30 kg/m) in an open-label, randomized, phase IV trial (EudraCT: 2019-000979-16): the Omendapa trial. Diabetes was diagnosed < 12 months before randomization and all patients were treatment naïve. 14 patients were treated with metformin alone (cohort A) and 15 were treated with metformin + dapaglifozin (cohort B). Anthropometric measures and laboratory tests for glucose, lipid profile, insulin, HOMA, leptin, ultrasensitive-CRP and microalbuminuria (MAL) were done at baseline, 3rd and 6th months. At 6th month, weight loss was -5.5 ± 5.2 kg (5.7% from initial weight) in cohort A and -8.4 ± 4.4 kg (8.6%) in cohort B. Abdominal circumference showed a -2.7 ± 3.1 cm and -5.4 ± 2.5 cm reduction, respectively (p = 0.011). Both Metformin alone (-19.4 ± 20.1 mm; -21.7%) or combined with Dapaglifozin (-20.5 ± 19.4 mm; -21.8%) induced significant Om fat reduction. 13.3% of cohort A patients and 21.4% of cohort's B reached Om thickness below the cut-off for MS criteria. RK fat loss was significantly greater in cohort B group compared to cohort A, at both kidneys. Only in the Met + Dapa group, we observed correlations between Om fat with leptin/CRP/MAL and RK fat with HOMA-IR. US is a useful clinical tool to assess ectopic fat depots. Both Metformin and Dapaglifozin induce fat loss in layers involved with MS but combined treatment is particularly effective in perirenal fat layer reduction. Perirenal fat should be considered as a potential target for cardiovascular dapaglifozin beneficial effects.
Topics: Humans; Metformin; Diabetes Mellitus, Type 2; Glucosides; Female; Male; Obesity; Middle Aged; Benzhydryl Compounds; Sodium-Glucose Transporter 2 Inhibitors; Hypoglycemic Agents; Aged; Drug Therapy, Combination; Adult
PubMed: 38734755
DOI: 10.1038/s41598-024-61590-6 -
Biomedicine & Pharmacotherapy =... Dec 2023Diabetic kidney disease (DKD) is a prevalent microvascular complication of diabetes. Inhibiting the epithelial-mesenchymal transition (EMT) of proximal tubule epithelial...
OBJECTIVES
Diabetic kidney disease (DKD) is a prevalent microvascular complication of diabetes. Inhibiting the epithelial-mesenchymal transition (EMT) of proximal tubule epithelial cells (PTCs) can slow down renal fibrosis. Trigonelline (TRL), an alkaloid isolated from the fenugreek, has demonstrated therapeutic effects on diabetes and its complications. Nevertheless, the underlying mechanisms for the effects of TRL are still obscure. The present study was aimed to evaluate the treatment of TRL against DKD and explore the potential mechanisms.
METHODS
The db/db mice were used as a spontaneous model of DKD and TRL solution was administered by daily gavage for 8 weeks. Indicators associated with glucose metabolism, renal function and urinary albumin were tested. Renal fibrosis in diabetic mice was evaluated by histopathological staining. Kidney transcriptomics was performed after confirming therapeutic effects of TRL on DKD mice. Molecular biology techniques and in vitro experiments were utilized for final mechanism verification.
RESULTS
Biochemical tests revealed that TRL ameliorated renal damage and reduced microalbuminuria in DKD mice. TRL exhibited a protective effect on PTCs, effectively mitigating tubular EMT and renal fibrosis in diabetic kidneys. Transcriptomics analysis indicated that TRL may target Smad7, an inhibitor of TGF-β1 signaling, to alleviate fibrosis. Furthermore, in vitro experiments validated that silencing Smad7 abolished the therapeutic effect of TRL.
CONCLUSION
Our findings indicate that TRL can alleviate tubular epithelial-mesenchymal transition and renal fibrosis in db/db mice by upregulating Smad7 in PTCs, suggesting that TRL is a promising medicine against DKD.
Topics: Mice; Animals; Diabetic Nephropathies; Epithelial-Mesenchymal Transition; Diabetes Mellitus, Experimental; Kidney; Alkaloids; Fibrosis
PubMed: 37864898
DOI: 10.1016/j.biopha.2023.115747 -
Cureus Oct 2023Laurence-Moon-Bardet Biedl syndrome (LMBBS) is a rare autosomal recessive genetic disorder that is most frequently found in children born from consanguineous marriages....
Laurence-Moon-Bardet Biedl syndrome (LMBBS) is a rare autosomal recessive genetic disorder that is most frequently found in children born from consanguineous marriages. The most prominent clinical characteristics of this syndrome include rod and cone dystrophy, nystagmus, central obesity, polydactyly, hypogonadism in males, renal anomalies, developmental delay, ataxia, speech difficulties, and poor coordination. In this report, we describe the case of a 31-year-old male who had the classical clinical features of LMBBS like developmental delay, retinitis pigmentosa, nystagmus, obesity, hypogonadism, and central obesity, presenting with abdominal pain associated with vomiting and tenderness in the right lower quadrant. The patient was diagnosed with cholelithiasis. This case report emphasizes the atypical complication of cholelithiasis due to the underlying syndrome and the need for further research in this area.
PubMed: 38021809
DOI: 10.7759/cureus.47316 -
Diabetes, Metabolic Syndrome and... 2023Microalbuminuria (MAU) is considered the earliest sign of diabetic nephropathy among diabetes patients. In order to effectively manage diabetic nephropathy and its... (Review)
Review
BACKGROUND
Microalbuminuria (MAU) is considered the earliest sign of diabetic nephropathy among diabetes patients. In order to effectively manage diabetic nephropathy and its consequences early, detection of microalbuminuria as soon as possible, especially for diabetes patients, is critical. Therefore, the present study aimed to determine the pooled prevalence of microalbuminuria among diabetes patients in Africa.
METHODS
Electronic databases such as Google Scholar, PubMed, African Journals Online, Web of Science, Cochrane Library, EMBASE, and ResearchGate were searched for articles and grey literature. The STATA version 14 software was used to conduct the meta-analysis. I and Cochran's Q test were employed to assess the presence of heterogeneity between studies. Due to the presence of heterogeneity, a random effect model was used. The publication bias was assessed using the symmetry of the funnel plot and Egger's test statistics. Moreover, subgroup analysis, trim and fill analysis, and sensitivity analysis were also done.
RESULTS
The overall pooled prevalence of microalbuminuria among diabetes patients in Africa was 37.11% (95% CI 31.27-42.95). Substantial heterogeneity was observed between studies, with I values of 94.7%. Moreover, this meta-analysis showed that the pooled estimate of microalbuminuria among type 1 and type 2 diabetes patients was 35.34% (95% CI: 23.89-46.80, I=94.2), and 40.24% (95% CI: 32.0-48.47, I=94.9) respectively. MAU, on the other hand, was more common in people with diabetes for more than 5 years 38.73% (95% CI: 29.34-48.13) than in people with diabetes for less than 5 years 31.48% (95% CI: 18.73-44.23).
CONCLUSION
This systematic review and meta-analysis found a high prevalence of microalbuminuria among diabetes patients. As a result, early detection of microalbuminuria is critical for preventing and treating microvascular complications such as diabetic nephropathy and the onset of end-stage renal disease.
PubMed: 37457109
DOI: 10.2147/DMSO.S409483 -
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 -
Biomolecules Jul 2023Diabetic kidney disease (DKD) is one of the most debilitating complications of type 2 diabetes mellitus (T2DM), as it progresses silently to end-stage renal disease...
Diabetic kidney disease (DKD) is one of the most debilitating complications of type 2 diabetes mellitus (T2DM), as it progresses silently to end-stage renal disease (ESRD). The discovery of novel biomarkers of early DKD becomes acute, as its incidence is reaching catastrophic proportions. Our study aimed to quantify previously identified metabolites from serum and urine through untargeted ultra-high-performance liquid chromatography coupled with electrospray ionization-quadrupole-time of flight-mass spectrometry (UHPLC-QTOF-ESI+-MS) techniques, such as the following: arginine, dimethylarginine, hippuric acid, indoxyl sulfate, p-cresyl sulfate, L-acetylcarnitine, butenoylcarnitine and sorbitol. The study concept was based on the targeted analysis of selected metabolites, using the serum and urine of 20 healthy subjects and 90 T2DM patients with DKD in different stages (normoalbuminuria-uACR < 30 mg/g; microalbuminuria-uACR 30-300 mg/g; macroalbuminuria-uACR > 300 mg/g). The quantitative evaluation of metabolites was performed with pure standards, followed by the validation methods such as the limit of detection (LOD) and the limit of quantification (LOQ). The following metabolites from this study resulted as possible biomarkers of early DKD: in serum-arginine, dimethylarginine, hippuric acid, indoxyl sulfate, butenoylcarnitine and sorbitol and in urine-p-cresyl sulfate.
Topics: Humans; Diabetic Nephropathies; Diabetes Mellitus, Type 2; Indican; Gastrointestinal Microbiome; Metabolomics; Biomarkers; Arginine; Sulfates
PubMed: 37509122
DOI: 10.3390/biom13071086 -
Frontiers in Endocrinology 2023To explore the correlations between diabetic nephropathy (DN) and serum levels of glutathione peroxidase 4 (GPX4), acyl-CoA synthetase long-chain family member 4...
OBJECTIVE
To explore the correlations between diabetic nephropathy (DN) and serum levels of glutathione peroxidase 4 (GPX4), acyl-CoA synthetase long-chain family member 4 (ACSL4), iron, transferrin (Tf), and ferritin in patients with type 2 diabetes mellitus (T2DM).
METHODS
According to the urinary albumin excretion rate(UAER) or estimated glomerular filtration rate (eGFR) levels, a total of 123 patients with T2DM were separately divided into normoalbuminuria (NO), microalbuminuria (MI), macroalbuminuria (MA) groups, and G1 (eGFR ≥ 90 mL/min), G2 (eGFR ≤ 60 mL/min to < 90 mL/min), and G3 groups (eGFR< 60 mL/min), with 33 healthy participants as the control (HC). The differences in serum GPX4, ACSL4, iron, Tf, and ferritin levels between groups were compared, and the relationships between these levels were analysed. The independent correlations between UAER or DN severity and serum GPX4, ACSL4, iron, Tf, and ferritin levels were analysed by multiple linear and multinomial logistic regression, respectively.
RESULTS
To the patients with T2DM, with the increase in UAER levels, GPX4, iron, and Tf levels gradually decreased, whereas ACSL4 levels increased, meanwhile with the decrease in eGFR levels, GPX4 and Tf levels gradually decreased, whereas ACSL4 levels increased. UAER were independently and positively correlated with ACSL4 [β = 17.53, 95% confidence interval (CI; 11.94, 23.13)] and negatively correlated with GPX4 [β = -1.633, 95% CI (-2.77, -0.496)] and Tf [β = -52.94, 95% CI (-95.78, -10.11)].The NO and MI groups were considered as reference groups, respectively. The severity of DN was negatively correlated with serum GPX4 [odds ratio (OR) = 0.925 and 0.902, 0.015 and 0.001], and Tf (OR = 0.109 and 0.119, 0.043 and 0.034), and positively correlated with ACSL4 (OR = 1.952 and 1.865, both 0.001) in the MA group.
CONCLUSION
DN severity was negatively correlated with serum GPX4 and Tf levels and positively correlated with serum ACSL4 levels in patients with T2DM.
Topics: Humans; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Ferroptosis; Diabetic Nephropathies; Iron; Transferrin; Ferritins; Albuminuria
PubMed: 38189040
DOI: 10.3389/fendo.2023.1297166 -
Cureus Apr 2024Background Ischemic stroke is a major health crisis with significant consequences. Microalbuminuria, a sign of endothelial dysfunction, has been linked to adverse...
Background Ischemic stroke is a major health crisis with significant consequences. Microalbuminuria, a sign of endothelial dysfunction, has been linked to adverse outcomes in ischemic stroke. Early neurological deterioration (END) is a critical factor influencing the patient's prognosis. This study aimed to determine the prevalence of microalbuminuria, its predictive value in assessing END, and its prognostic implications in acute ischemic stroke (AIS). Methodology This study conducted at Pradyumna Bal Memorial Hospital, Kalinga Institute of Medical Sciences Bhubaneswar (November 2020-April 2022) included 114 AIS patients over 18 years who presented within 24 hours of stroke onset. Demographics, vascular risk factors, National Institutes of Health Stroke Scale (NIHSS) scores (admission and day three), modified Rankin scores (day 10), urinary albumin-to-creatinine ratios, and carotid artery Doppler studies were collected. Results The mean age of the patients was 61.87 years, with males constituting 72.8% of the population. Hypertension (50.9%) and diabetes mellitus (28.9%) were the most common comorbid conditions. The mean NIHSS stroke severity at presentation was 11.30. END occurred in 38.6% of patients. Overall, 43.9% of cases showed carotid stenosis, and the mean carotid intimal media thickness was 1.08 mm. Notably, the presence of microalbuminuria significantly increased the chances of both END (39.45 times higher risk) and worse functional outcomes (odds ratio = 19.147, p = 0.001). Conclusions Microalbuminuria emerges as a robust independent predictor of END and a poor prognosis in AIS. These findings highlight the importance of early microalbuminuria identification and intervention to reduce END risk and potentially improve outcomes in AIS patients.
PubMed: 38752035
DOI: 10.7759/cureus.58311