Diabetic Nephropathy Patients Research Articles

Gut microbiota microbial metabolites in diabetic nephropathy patients: far to go

Diabetic nephropathy (DN) is one of the main complications of diabetes and a major cause of end-stage renal disease, which has a severe impact on the quality of life of patients. Strict control of blood sugar and blood pressure, including the use of renin–angiotensin–aldosterone system inhibitors, can delay the progression of diabetic nephropathy but cannot prevent it from eventually developing into end-stage renal disease. In recent years, many studies have shown a close relationship between gut microbiota imbalance and the occurrence and development of DN. This review discusses the latest research findings on the correlation between gut microbiota and microbial metabolites in DN, including the manifestations of the gut microbiota and microbial metabolites in DN patients, the application of the gut microbiota and microbial metabolites in the diagnosis of DN, their role in disease progression, and so on, to elucidate the role of the gut microbiota and microbial metabolites in the occurrence and prevention of DN and provide a theoretical basis and methods for clinical diagnosis and treatment.

Effect of endothelial no synthase gene polymorphism on the course of diabetic nephropathy in patients with type 2 diabetes mellitus

Effect of endothelial no synthase gene polymorphism on the course of diabetic nephropathy in patients with type 2 diabetes mellitus

Significant Association of Candidate Genes (AGTR1 and TGF-Β1) Polymorphism with Diabetic Nephropathy in Diabetes Mellitus Type 2 Patients

Background/Aims: Diabetic nephropathy (DN) is one of the complications of diabetes mellitus (DM). This study aimed to investigate the association between genetic polymorphisms, specifically AGTR1 (rs5186) and TGF-β1 (rs1800470), and the risk of developing Diabetic nephropathy (DN) in type 2 diabetes mellitus patients, compared to those without DN and healthy controls. Methods: A case-control study was conducted on 165 diabetic patients (59 with diabetic nephropathy (DN) and 54 without DN (DM)), and 52 healthy controls (HC). The genotyping was done using amplification refractory mutation system method (ARMS-PCR). Age, gender, and duration of diabetes were matched across groups. Clinical parameters including FBS, RBS, HbA1C, creatinine, urea, SBP, DBP, total cholesterol, triglycerides, LDL, and BMI were assessed. Results: Diabetic patients with nephropathy exhibited significantly higher levels of clinical parameters compared to those without nephropathy and healthy controls. The risk allele of AGTR1 , C (p <0.0001), and risk allele containing genotypes AC (p <0.0001) and CC (p - 0.0010) were significantly higher in DN patients compared to DM and HC groups. Similarly, the TGF-β1 risk allele C (p - 0.0001), and corresponding genotypes TC (p - 0.0038) and CC (p - 0.0027) were significantly associated with increased risk of diabetic nephropathy compared to DM and HC groups. Conclusion: The data showed significant association of AGTR1 (rs5186) and TGF-β1 (rs1800470) polymorphism with an increased risk of diabetic nephropathy in type 2 diabetes mellitus patients. More investigation will be required to disseminate the results, while increasing the samples size and using whole genome sequencing.

Effects of dietary intervention on diabetic nephropathy: an umbrella review of systematic reviews and meta-analyses of randomized controlled trials.

To evaluate the quality of evidence, potential biases, and validity of all available studies on dietary intervention and diabetic nephropathy (DN). We conducted an umbrella review of existing meta-analyses of randomized controlled trials (RCTs) that focused on the effects of dietary intervention on DN incidence. The literature was searched via PubMed, Embase, Web of Science, and the Cochrane Database of Systematic Reviews. According to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE), evidence of each outcome was evaluated and graded as "high", "moderate", "low" or "very low" quality to draw conclusions. Additionally, we classified evidence of outcomes into 4 categories. We identified 36 meta-analyses of RCTs and 55 clinical outcomes of DN from 395 unique articles. Moderate-quality evidence suggested that probiotic supplementation could significantly improve blood urea nitrogen (BUN), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels in DN patients. Low-quality evidence indicated that probiotic supplementation significantly improved the serum creatinine concentration, urinary albumin-creatinine ratio (UACR), fasting blood glucose (FBG), HbA1c and high-density lipoprotein cholesterol (HDL-C) in DN patients. In addition, low-quality evidence suggested that a salt restriction diet could significantly improve the creatinine clearance rate (CrCl) in patients with DN. Low-quality evidence suggested that vitamin D supplementation could significantly improve the UACR in patients with DN. In addition, low-quality evidence has indicated that soy isoflavone supplementation could significantly improve BUN, FBG, total cholesterol (TC), triglyceride (TG) and LDL-C levels in patients with DN. Furthermore, low-quality evidence suggested that coenzyme Q10 supplementation could significantly improve HbA1c, TC and HDL-C in patients with DN, and dietary polyphenols also significantly improved HbA1c in patients with DN. Finally, low-quality evidence suggested that supplementation with antioxidant vitamins could significantly improve the serum creatinine concentration, systolic blood pressure, and HbA1c level in patients with DN. Given the small sample size, all significantly associated outcomes were evaluated as class IV evidence. Moderate to low amounts of evidence suggest that supplementation with probiotics, vitamin D, soy isoflavones, coenzyme Q10, dietary polyphenols, antioxidant vitamins, or salt-restricted diets may significantly improve clinical outcomes in patients with DN. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024512670.

Artificial intelligence assists identification and pathologic classification of glomerular lesions in patients with diabetic nephropathy.

Glomerular lesions are the main injuries of diabetic nephropathy (DN) and are used as a crucial index for pathologic classification. Manual quantification of these morphologic features currently used is semi-quantitative and time-consuming. Automatically quantifying glomerular morphologic features is urgently needed. A series of convolutional neural networks (CNN) were designed to identify and classify glomerular morphologic features in DN patients. Associations of these digital features with pathologic classification and prognosis were further analyzed. Our CNN-based model achieved a 0.928 F1-score for global glomerulosclerosis and 0.953 F1-score for Kimmelstiel-Wilson lesion, further obtained a dice of 0.870 for the mesangial area and F1-score beyond 0.839 for three glomerular intrinsic cells. As the pathologic classes increased, mesangial cell numbers and mesangial area increased, and podocyte numbers decreased (p for all < 0.001), while endothelial cell numbers remained stable (p = 0.431). Glomeruli with Kimmelstiel-Wilson lesion showed more severe podocyte deletion compared to those without (p < 0.001). Furthermore, CNN-based classifications showed moderate agreement with pathologists-based classification, the kappa value between the CNN model 3 and pathologists reached 0.624 (ranging from 0.529 to 0.688, p < 0.001). Notably, CNN-based classifications obtained equivalent performance to pathologists-based classifications on predicting baseline and long-term renal function. Our CNN-based model is promising in assisting the identification and pathologic classification of glomerular lesions in DN patients.

Non-diabetic nephropathy in diabetic patients: incidence, HbA1c variability and other predictive factors, and implications.

Diabetes mellitus (DM) is the leading cause of chronic kidney disease (CKD) in the population. In patients with diabetes mellitus, the incidence of non-diabetic nephropathy (NDNP) has been estimated to range from 3% to 69.5%. Personal judgment is frequently employed while deciding whether or not to do a kidney biopsy(KB) on diabetic patients. NDNP alters the prognosis and course of treatment for people with DM. In our study, we examined the incidence of NDNP concurrent with the progression of diabetes mellitus, as well as the laboratory and clinical indicators that could be utilized to forecast it. A retrospective analysis of 76 diabetic patients who underwent KB was conducted. Based on the pathological diagnoses of these patients, they were categorized as DNP (diabetic nephropathy) or NDNP. The definition of HbA1c variability was determined by calculating the mean HbA1c and the average value of the HbA1c measurements, as well as the standard deviation (SD) for each participant. NDNP was detected in 50% of 76 patients. Among patients with NDNP, 36.8% had focal segmental glomerulosclerosis (FSGS), 23.6% had membranous glomerulonephritis, and 7.8% had IgA nephritis. The NDNP group exhibited significantly higher rates of female gender, absence of diabetic retinopathy, shorter time to diagnosis of diabetes mellitus, chronic kidney disease, and proteinuria, less intensive medication for diabetes mellitus, presence of hematuria and leukociduria, immunological serological marker positivity, and non-HbA1C variability. Risk factors for predicting non-diabetic nephropathy, as determined by multivariate analysis, included female gender, the absence of diabetic retinopathy, non-HbA1c variability and a positive immunological serological test. In this study, a significant number of diabetic patients with chronic kidney disease were diagnosed with NDNP. Identifying these patients allows for treatment of the specific underlying disease. Factors such as the absence of DR, non-HbA1c variability, female gender, and immunological serological test positivity can predict NDNP and guide the clinician's decision on kidney biopsy. Further prospective studies are warranted to validate the efficacy of potential predictive factors like HbA1c variability.

Comparison of Telmisartan and Verapamil in Reducing Proteinuria in Diabetic Nephropathy Patients

Background: In diabetes, complications often extend to diabetic nephropathy, marked by proteinuria. This study investigates telmisartan and verapamil's efficacy in mitigating proteinuria. Verapamil, a calcium channel blocker, dilates vessels, while telmisartan, an angiotensin II receptor blocker, induces vasodilation. However, evidence is confined to a single foreign study, prompting this research for more comprehensive insights. Objective: To comparison of telmisartan and verapamil in reducing proteinuria in diabetic nephropathy patients. Study Design: It was a prospective comparative study. Settings: Department of Medicine, DHQ Teaching Hospital, KMU Institute of Medical Sciences, Kohat. Duration: 05-02-2022 to 05-08-2022. Methods: One hundred patients with diabetic retinopathy and meeting inclusion criteria were enrolled in the study after taking informed written consents and two equal groups were made using lottery method. Patients in group A were given trandolapril 2 mg/day + telmisartan 80 mg/day whereas patients in group B were given trandolapril 2 mg/day + verapamil 120 mg/day, for three months. Study variables were noted at baseline and at three months. SPSS version 26.0 was used for data analysis. Results: Mean age of the patients was 46.20±13.80 years. Gender distribution revealed that 52.0% were male, while 48.0% were female. The duration of the disease varied among the participants, with an overall mean of 9.20±3.73 years. Mean BMI was 27.46±3.50 kg/m². MABP was recorded as 120.16±2.84 mmHg. Proteinuria, a significant parameter in this study, was observed with a mean value of 354.37±20.26 g/day. Glomerular Filtration Rate (GFR) was measured at 56.72±2.52 mL/dk. HbA1C was found to be 8.94±0.34%. Both the groups did not possess any significant difference between them at baseline (p-value&gt;0.05). After treatment, mean proteinuria level in this study was significantly less in group A than group B with p-value=0.043. Moreover, mean change in proteinuria between before and after treatment was significantly high in group A than group B (p-value=0.000). After treatment mean GFR was less in insignificantly high in group A than group B (p-value=0.450) and likewise mean change in GFR from the baseline also had insignificant difference between the groups (p-value=0.489). Post treatment, mean HbA1c and MABP were less in group A than group B but the difference was not significant (p-value&gt;0.05). Likewise, mean change also had insignificant difference between the groups. Conclusion: In conclusion, our study comparing the effects of Trandolapril with Telmisartan versus Trandolapril with Verapamil in diabetic nephropathy patients revealed a significant reduction in proteinuria in the Telmisartan group. However, no substantial differences were noted in GFR, HbA1c, and MABP between the groups. These findings provide valuable insights into optimal therapeutic strategies for managing diabetic nephropathy.

Impact of bisphenol a on the levels of vascular calcification biomarkers in type 2 diabetes mellitus with vascular complications: A case-control study

Bisphenol A (BPA) is an endocrine disruptor present in polycarbonate plastics used in food containers and water bottles that resists insulin action and leads to type 2 diabetes mellitus (T2DM). However, there is scant research on the impact of BPA on T2DM-related vascular complications. Fetuin-A (FTA) and osteoprotegerin (OPG) are crucial markers for vascular calcification, which is the primary risk factor for developing vascular complications. This study aims to link external factor BPA levels with the vascular calcification markers FTA and OPG in diabetic subjects with and without vascular complications. Therefore, 120 study subjects were included and divided as control (n = 30), T2DM with cardiovascular diseases (CVD) (n = 30), T2DM with diabetic nephropathy (DN) (n = 30), and T2DM without vascular complications (n = 30). Serum and urinary FTA, OPG, and BPA levels were measured using an ELISA. FTA (AHSG) and OPG (TNFRSF11B) gene expression were analyzed using qPCR. Both serum (p < 0.001) and urinary BPA (p < 0.001) were found higher in T2DM with CVD and DN than T2DM without vascular complications and control. Also, T2DM with CVD and DN patients had lower serum and urinary FTA protein levels and increased serum and urinary OPG (p < 0.001) levels than T2DM without vascular complications and control. Moreover, FTA (AHSG) gene expression was negatively associated with serum BPA (p < 0.001) and urinary BPA (p < 0.01). Likewise, OPG (TNFRSF11B) gene expression was positively significant with serum BPA (p < 0.001) and urinary BPA (p < 0.01) in the study groups. These findings suggest that elevated blood and urinary BPA levels contribute to the severity of vascular complications in T2DM patients through vascular calcification.

Nogo-B Promotes Endoplasmic Reticulum Stress-Mediated Autophagy in Endothelial Cells of Diabetic Nephropathy.

Aims: Endothelial cells are the critical targets of injury in diabetic nephropathy (DN), and endothelial cell lesions contribute to the disease progression. Neurite outgrowth inhibitor B (Nogo-B), an endoplasmic reticulum (ER)-resident protein, plays a pivotal role in vascular remodeling after injury, and maintains the structure and function of the ER. Yet, the role of Nogo-B in the regulation of ER stress and endothelial cell injury remains largely unknown. Herein, we tested the hypothesis that Nogo-B activates ER stress-mediated autophagy and protects endothelial cells in DN. Results: The level of Nogo-B was decreased in glomerular endothelial cells in biopsy specimens from DN patients. In vivo and in vitro studies have shown that silencing Nogo-B activated ER stress signaling, and affected the expression of autophagy-related marker early growth response 1 and microtubule-associated protein light chain 3 (LC3) in endothelial cells in hyperglycemic condition. Conclusion and Innovation: These results denote that Nogo-B contributes to ER stress-mediated autophagy and protects endothelial cells in DN, providing new evidence for understanding the role of ER stress-mediated autophagy in endothelial cells of DN.

Human umbilical cord mesenchymal stem cell-derived exosomes ameliorate renal fibrosis in diabetic nephropathy by targeting Hedgehog/SMO signaling.

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease globally. Currently, there are no effective drugs for the treatment of DN. Although several studies have reported the therapeutic potential of mesenchymal stem cells, the underlying mechanisms remain largely unknown. Here, we report that both human umbilical cord MSCs (UC-MSCs) and UC-MSC-derived exosomes (UC-MSC-exo) attenuate kidney damage, and inhibit epithelial-mesenchymal transition (EMT) and renal fibrosis in streptozotocin-induced DN rats. Strikingly, the Hedgehog receptor, smoothened (SMO), was significantly upregulated in the kidney tissues of DN patients and rats, and positively correlated with EMT and renal fibrosis. UC-MSC and UC-MSC-exo treatment resulted in decrease of SMO expression. Invitro co-culture experiments revealed that UC-MSC-exo reduced EMT of tubular epithelial cells through inhibiting Hedgehog/SMO pathway. Collectively, UC-MSCs inhibit EMT and renal fibrosis by delivering exosomes and targeting Hedgehog/SMO signaling, suggesting that UC-MSCs and their exosomes are novel anti-fibrotic therapeutics for treating DN.

Optical coherence tomography angiography for the differentiation of diabetic nephropathy from non-diabetic renal disease

BackgroundTo provide a new non-invasive method for the differentiation of diabetic nephropathy (DN) from non-diabetic renal disease (NDRD) by assessing retinal microstructure using optical coherence tomography angiography (OCTA). MethodsOCTA parameters were recorded and their relationship with DN was analysed. A differential diagnosis regression model for DN was established, and the diagnostic efficiency was evaluated. ResultsBased on the pathological results of renal biopsy, 31 DN patients and 35 NDRD patients were included. Multivariate logistic regression analysis showed that DN was independently associated with the following parameters: 15.3 mm−1 ≤ vessel density (VD) full < 17.369 mm−1 (odds ratio [OR]=8.523; 95% confidence interval [CI]=1.387–52.352; P = 0.021), VD full < 15.3 mm−1 (OR=8.202; 95% CI=1.110–60.623; P = 0.039), DM duration > 60 months (OR=7.588; 95% CI=1.569–36.692; P = 0.012), and estimated glomerular filtration rate < 60 mL/min/1.73 m2 (OR=24.484; 95% CI=4.308–139.142; P < 0.001). The area under the receiver operating characteristic curve was 0.911, indicating a high diagnostic efficiency. ConclusionsVD full < 17.369 mm−1, DM duration > 60 months, and eGFR < 60 mL/min/1.73 m2 may indicate the presence of DN. OCTA may be an effective non-invasive method for identifying DN and NDRD.

Serum Fructosamine as a Marker for Glycemic Control in Patients with Diabetic Nephropathy

Diabetes mellitus (DM) is a metabolic disease of chronic insulin deficiency or resistance. The progression of DM is associated with long-term damage to macro- and micro-vascular body systems and causes serious health complications. Up to 40% of DM patients develop chronic kidney disease (CKD), mainly as a consequence of diabetic nephropathy (DN). Hence, strict glycemic control is recommended to slow down CKD progression. Hyperglycemia causes complications in diabetic patients through the glycation of various proteins. The interaction of glucose with the free NH2 groups of proteins results in the formation of the early glycation product fructosamine (FA). FA has a short half-life (1 to 2 weeks) and hence it has the potential of an early marker for glycemic control. Although long used in the clinical practice, the FA diagnostic and prognostic significance remains questionable. In this study, we tested the FA potential to serve as a glycemic marker in DM patients with DN. We found that DM patients have significantly higher serum FA levels than non-diabetics. Further, the serum FA level in diabetics correlates positively with the blood glucose concentration. Finally, the mean serum FA level was higher in DM patients with DN, compared to those without DN. These results establish FA as a promising marker for glycemic control in DN patients.

Correlation between Red Cell Distribution Width (RDW) and Mean Corpuscular Volume (MCV) as a Prognostic Biomarker for Diabetic Nephropathy Patients in a South Indian Hospital

Context: Diabetic nephropathy is one of the microvascular complications of diabetes mellitus, capable of leading to end-stage renal disease. Diabetic nephropathy could only be identified through renal biopsy testing, which is expensive and can impose a financial burden on patients. Therefore, there is a necessity to develop a cost-effective method for identifying diabetic nephropathy. Aim: To evaluate the correlation between RBC parameters, such as RDW and MCV values, as prognostic biomarkers for patients with diabetic nephropathy. Methods and Material: Study Design: Prospective comparative study. Study Site: Sudha Institute of Medical Science, Erode. Study Duration: Study was carried out over six-months. Sample Size: 101 diabetic nephropathy patients and 101 type 2 diabetes mellitus patients. Statistical Analysis: Pearson correlation. Results: The majority of diabetic nephropathy patients were 40 years old or older, and most of them were males. Among the study participants, a significant number of male participants had habits of smoking and alcohol consumption. The duration of diabetes and BMI exhibited a strong correlation with the occurrence of diabetic nephropathy. Furthermore, there were notable increases in urea, creatinine, FBS, RBS, PPBS, and HbA1C, alongside a decrease in MCV and eGFR as diabetic nephropathy progressed. Conclusions: Our research indicates a positive correlation between RDW and HbA1c, FBS, RBS, PPBS, urea, and creatinine. In contrast, negative correlation of RDW with MCV and eGFR. MCV is negatively correlated with HbA1c, FBS, RBS, PPBS, urea, creatinine. In contrast, positive correlation between MCV and eGFR.

The implication of miR-200a and miR-132 expression and their correlations with NF-κB/TNF-alpha signaling in adults with diabetic nephropathy

AimThe primary factor causing chronic renal failure is diabetic nephropathy (DN) worldwide. However, the current biomarkers for DN have limited diagnostic utility. Thus, this work aimed to clarify the implications of microRNA-200a (miR-200a) and microRNA-132 (miR-132) and their correlation with NF-κB (nuclear factor- kappa beta), and, TNF-α (tumor necrosis factor –alpha) signaling to identify biomarkers able to distinguish late-stage from early- stage DN. MethodsFifty healthy controls, and 271 type 2 diabetic (T2D) patients (166 male plus 105 female) were enrolled. Participants were stratified into seven groups according to along with the estimated glomerular filtration rate (eGFR), glycated hemoglobin (HbA1c%), healthy controls, diabetes without DN (G1), diabetes with mild renal impairment (G2), and four DN grades (G3a, G3b, G4, and G5). ResultsCompared to healthy controls, the DN groups exhibited linear increases in serum miR-200a, TNF-α, NF-κB, matrix metalloproteinase (MMP-9) and interleukin-6 (IL-6) levels and reductions in miR-132 serum expression. Among the patients, NF-κB and TNF-α produced a negative correlation with miR-132, while, positive correlation has been discovered with miR-200-a. The operating characteristic of the receiver curve (ROC), proved that, miR-200a also miR-132 had good diagnostic performance in distinguishing early from advanced DN. ConclusionMiR-200a as well as miR-132 expression levels, and their correlations with NF-κB/TNF-alpha signaling, were able to differentiate between DN patients with lower eGFR, suggesting their utility as diagnostic and prognostic biomarkers.

Diagnostic utility of renal shear wave elastography and renal Doppler findings in diabetic nephropathy: a case–control study

BackgroundDiabetes mellitus is a common systemic disease that affects the kidneys and could eventually develop an end-stage renal failure. Renal biopsy is considered a gold standard for histological characterization of diabetic nephropathy, of which renal fibrosis is a dominant component, affecting its stiffness. The objective of this study is to investigate a correlation between renal stiffness obtained by shear wave elastography, renal Doppler resistivity indices, laboratory findings, and the histological characterization depicted by renal biopsies (if feasible) in diabetic nephropathy patients and to compare their results with those obtained from normal population to explore the diagnostic efficacy of shear wave elastography. Shear wave elastography and color duplex US were performed in twenty-six diabetic nephropathy patients and twenty-six healthy (age and sex-matched) control subjects. The shear wave elastography-derived mean value of the renal tissue stiffness was measured (in kilopascals) as well as the resistivity indices of segmental renal arteries, and then the mean values were correlated to patients' clinical-laboratory data (serum creatinine and albumin/ creatinine ratio) and the biopsy results, if feasible.ResultsA significant positive correlation was found between the mean resistivity indices and the mean renal cortical stiffness at one hand and the patients' clinical-laboratory data with statistically significant differences found between the control, early, and late stages of diabetic nephropathy.ConclusionsShear wave elastography is a promising, non-invasive, and accurate diagnostic tool for assessment and differentiation between early and late stages of diabetic nephropathy with a significant positive correlation to the clinical-laboratory and renal Doppler findings.

Excess iron accumulation mediated senescence in diabetic kidney injury.

Cellular senescence and iron accumulation were separately observed in diabetic nephropathy (DN). Limited evidence supports that iron was significantly accumulated in senescent cells. We aimed to explore whether iron is involved in the pathogenesis role of senescence in DN.Renal cells were treated with high glucose (HG, 35 mM) for 10 or 15 days, and DN mice were induced by high-fat diet and streptozotocin. Gene ontology enrichment, gene set enrichment analysis analysis, β-galactosidase staining, 5-ethynyl-2-deoxyuridine staining, and western blot depicted the upregulated senescence pathway in vitro and in vivo of DN. Lactate dehydrogenase (LDH) release was increased by HG and reversed by p16/p21 knockdown, and the supernatant of HG-treated cells caused increased LDH release from normal cells. Iron metabolism-related protein expression was disordered after HG exposure concomitant with senescence. Ferric ammonium citrate (50 μM) upregulated gamma-H2A.X variant histone andincreased the senescence markers in HG-treated cells. The treatment of deferoxamine (0.5 μM) had the opposite effect. Compared to the non-DN individual, increased ferritin and senescence markers were verified in DN mice and patients, and the co-localization of ferritin and senescence markers was observed by immunofluorescence. These results suggested that accumulated iron was correlated with aggravated DNA damage and accelerated senescence, and revealed the role of iron in the cellular senescence of diseases.

[Correlation between weight variability and the risk of diabetic nephropathy in patients with type 2 diabetes mellitus].

Objective: To evaluate the relationship between different indexes of weight variability and the risk of diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM). Methods: A retrospective cohort study. The clinical data of 2 180 T2DM patients without DKD who underwent case management at Lee's United Clinic in Taiwan, China from 2002 to 2018 were retrospectively analyzed, including 1 103 females and 1 077 males, with an average age of (64.8±12.4) years. Regular follow-up was conducted for patients for at least 2 years, and their metabolic indexes were monitored annually. BMI variability independent of the mean (BMI-VIM), average yearly mean square successive difference (BMI-ASV), coefficient of variation (BMI-CV) and standard deviation (BMI-SD) were calculated,based on the body mass index (BMI) recorded annually by the patients. Patients were divided into four groups (Q1-Q4) based on the quartiles of the four weight variability indexes. DKD group and non-DKN group(NDKD group) were defined based on the occurrence of DKD at the end of the follow-up. Cox proportional hazards regression models were used to analyze the relationship between the four weight variability indicators and the incidence of DKD. Subgroup analysis was performed by categorizing patients into non-obesity (BMI<28 kg/m2) and obesity groups (BMI≥28 kg/m2) to investigate the impact of the four weight variability indicators on the risk of DKD. Results: After a follow-up of (4.55±2.13) years, 904 patients developed DKD. Compared with the NDKD group, patients in the DKD group had a higher proportion of females, older age, longer duration of diabetes, more insulin users, higher waist-to-hip ratio, higher levels of BMI-VIM, BMI-ASV, BMI-CV, BMI-SD, systolic blood pressure, diastolic blood pressure, and urine albumin-creatinine ratio, a lower proportion of hypoglycemic drugs, estimated glomerular filtration rate, and high-density lipoprotein cholesterol level, with statistically significant differences between the two groups(all P<0.05). Cox proportional hazards regression analysis results revealed that the risk of DKD in T2DM patients increased with the increase in BMI-SD, BMI-CV, BMI-VIM, and BMI-ASV after correcting a series of influencing factors. In the BMI-VIM subgroup, compared with the Q1 group, the risk of DKD in the Q4 group increased by 22.4% [HR=1.224 (95%CI:1.008-1.487), P=0.041]. In the BMI-ASV group, compared with the Q1 group, the risk of DKD in the Q4 group increased by 51.1% [HR=1.511 (95%CI:1.240-1.841), P<0.01]. In the BMI-CV group, compared with the Q1 group, the risk of DKD in the Q4 group increased by 22.2% [HR=1.222 (95%CI:1.006-1.485), P=0.044]. In the BMI-SD subgroup, compared with the Q1 group, the risk of DKD in the Q4 group increased by 22.2% [HR=1.222 (95%CI:1.002-1.490), P=0.048]. Sub-group analysis showed that when the non-obesity group was grouped by BMI-ASV, after correcting a series of influencing factors, compared with the Q1 group, the highest risk of DKD occurred in the Q4 group [HR=1.551 (95%CI:1.228-1.958), P<0.001];when the obesity group was grouped by BMI-ASV, after correcting a series of influencing factors, compared with the Q1 group, the highest risk of DKD occurred in the Q4 group [HR=1.703 (95%CI:1.168-2.485), P=0.006]. Conclusion: Increases in BMI-VIM, BMI-ASV, BMI-CV, and BMI-SD are associated with an increased risk of DKD in T2DM patients.

Hsa_circ_0008360 promotes high glucose-induced damage in HK-2 cells via miR-346/WNT2B axis.

Diabetic nephropathy (DN) is a leading cause of end-stage renal disease worldwide. Recent researches have shown that circular RNAs (circRNAs) could affect the progress of DN, but the mechanism isstill indistinct. In this work, we explored the roles of hsa_circ_0008360 in DN. The levels of hsa_circ_0008360, microRNA-346 (miR-346) and Winglesstype family member 2B (WNT2B) were indicated by quantitative real-time polymerase chain reaction (qRT-PCR) in DN tissues and HK2 cells. Meanwhile, the protein level of WNT2B was quantified by Western blot analysis. Besides, the function of cells was examined by Cell Counting Kit-8 (CCK8) assay, flow cytometry assay, western blot, and ELISA kit. Furthermore, the interplay between miR-346 and hsa_circ_0008360 or WNT2B was detected by dual-luciferase reporter assay. The levels of hsa_circ_0008360 and WNT2B were increased, and the miR-346 level was decreased in the serum of DN patients and HG-treated HK2 cells. For functional analysis, hsa_circ_0008360 deficiency promoted cell viability, inhibits cell apoptosis, inflammatory response, and the synthesis of related fibrotic proteins in HG-treated HK2 cells. Moreover, overexpression of miR-346 induced the proliferation and inhibit apoptosis of HG-induced HK2 cells by inhibiting WNT2B expression. In mechanism, hsa_circ_0008360 acted as a miR-346 sponge to regulate the level of WNT2B. Hsa_circ_0008360 can regulate miR-346/WNT2B axis in HG-induced HK2 cells, providing an underlying targeted therapy for DN patients.

Downregulation of lncRNA XLOC_032768 in diabetic patients predicts the occurrence of diabetic nephropathy.

LncRNA XLOC_032768 is reported to prevent renal tubular epithelial cells from cisplatin-induced apoptosis, suggesting its involvement in the development of kidney injury. The present study aimed to explore the role of XLOC_032768 in diabetic nephropathy (DN). The present study enrolled a total of 140 healthy controls (Control group) and 140 patients with type 2 diabetes (Diabetes group). Expression of XLOC_032768 in plasma from these participants was analyzed by performing RT-qPCR. The 140 diabetic patients were followed up for 5 years to monitor the occurrence of diabetic complications. The role of XLOC_032768 in predicting the occurrence of diabetic complications, including DN, diabetic cardiomyopathy (DC), diabetic retinopathy (DR), and diabetic foot (DF) were analyzed by plotting receiver operating characteristic curves and complication-free curves. On the day of admission, plasma levels of XLOC_032768 were not significantly different between Control and Diabetes groups. During follow-up, a total of 22, 15, 13, and 15 cases were diagnosed as DN, DC, DR, and DF, respectively. On the day of diagnosis, plasma levels of XLOC_032768 were only decreased in DN group, but not in other groups, compared to plasma levels of XLOC_032768 on the day of admission. Using plasma levels of XLOC_032768 on the day of admission as a biomarker, potential DN patients were effectively separated from patients with other potential complications and diabetic patients without complications. The 140 diabetic patients were grouped into high and low XLOC_032768 level groups. It was observed that low XLOC_032768 level group showed increased occurrence of DN, but not other complications, compared to high XLOC_032768 level group. Therefore, the downregulation of lncRNA XLOC_032768 in diabetic patients may predict the occurrence of DN.

Serum cell division cycle42 reflects the development and progression of diabetic nephropathy in patients with diabetes mellitus.

Cell division cycle 42 (CDC42) regulates podocyte apoptosis to take part in the development and progression of diabetic nephropathy (DN), but currently the clinical evidence is limited. The aim of the present study was to investigate the capability of serum CDC42 expression level to estimate the development and progression of DN in patients with diabetes mellitus (DM). Patients with type 2 DM (n=306) were enrolled and divided into normoalbuminuria (n=185), microalbuminuria (n=72) and macroalbuminuria (n=49) groups based on the urinary albumin-to-creatinine ratio. Serum CDC42 was measured in all subjects using enzyme-linked immunosorbent assay. The median (interquartile range) CDC42 in patients with DM was 0.461 (0.314-0.690) ng/ml (range, 0.087-1.728 ng/ml). CDC42 was positively associated with the estimated glomerular filtration rate (P<0.001), but negatively correlated with body mass index, systolic blood pressure, hemoglobin A1c, serum creatine, serum uric acid and C reactive protein (all P<0.050). CDC42 levels were lowest in the macroalbuminuria group, followed by the microalbuminuria group, and were highest in the normoalbuminuria group (P<0.001). CDC42 indicated that it was a favorable estimator for the presence of albuminuria [area under the curve (AUC), 0.792; 95% confidence interval (CI), 0.736-0.848] and macroalbuminuria (AUC, 0.845; 95% CI, 0.775-0.915). By analyses in four different multivariate logistic regression models, increased CDC42 was independently associated with the presence of microalbuminuria (all P<0.001), macroalbuminuria (most P<0.001) and microalbuminuria + macroalbuminuria (all P<0.001). Serum CDC42 level negatively correlated with microalbuminuria and macroalbuminuria in patients with DM, suggesting its ability for estimating the development and progression of DN.