Incidence Of Diabetic Nephropathy Research Articles

Association between protein arginine N-methyltransferase 1 polymorphism and overt diabetic nephropathy: Role of asymmetric dimethylarginine in vascular tone

Backgroundω-NG,NG-asymmetric dimethylarginine (ADMA) regulates vascular tone and may participate in the pathogenesis of diabetic nephropathy (DN). ObjectiveTo investigate whether single-nucleotide polymorphisms (SNPs) around the protein arginine N-methyltransferase 1 gene (PRMT1) influence ADMA dynamics and DN incidence and severity. MethodsThis study utilized a hospital-based database containing 310 Japanese patients with type 2 diabetes mellitus (T2DM). The association of PRMT1-related tagged SNPs with DN stage distribution was examined using a dominant model of minor alleles. PRMT1 mRNA, serum ADMA, reactive hyperemia-peripheral arterial tonometry index (RHI), and brachial-ankle pulse wave velocity (baPWV) were compared between the genotype-based subgroups of causal SNP, and correlations between these variables were evaluated. ResultsThe composition of DN stages significantly differed between the GG and GA + AA subgroups of rs892151 (p = 0.026). In a propensity-matching cohort of rs892151, the GA + AA subgroup had an increased incidence of overt DN (odds ratio 2.92, 95 % confidence interval 1.12–7.62, p = 0.028), along with higher PRMT1 mRNA, serum ADMA levels, and baPWV than the GG subgroup (p < 0.001, p = 0.023 and 0.047, respectively). There were correlations between PRMT1 mRNA and serum ADMA levels, between serum ADMA levels and RHI, and between baPWV and urinary albumin excretion (r = 0.335, p < 0.001, r = -0.221, p = 0.029, and r = 0.254, p = 0.004, respectively). ConclusionsT2DM patients carrying the PRMT1-related variant rs892151 were susceptible to overt DN. ADMA-mediated endothelial dysfunction and arterial stiffness may be involved in the variant-related pathogenesis of overt DN.

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.

The association between statin use and diabetic nephropathy in US adults: data from NHANES 2005 - 2018.

A serious consequence of diabetes is diabetic nephropathy (DN), which is commonly treated by statins. Studies evaluating the effects of statin medication have yielded inconsistent results regarding the potential association with diabetic nephropathy. To manage diabetic nephropathy's onset and improve the quality of life of patients, it is imperative to gain a comprehensive understanding of its contributing factors. Our study was conducted using the National Health and Nutrition Examination Survey (NHANES) as well as weighted multivariate logistic regression models to determine the odds ratio (OR) and 95% confidence intervals (95%CI) for diabetic nephropathy. We conducted stratified analyses to examine the impact of statins and the duration of their usage on diabetic nephropathy in different subgroups. A nomogram model and the receiver operating characteristic (ROC) curve were also developed to predict DN risk. Statin use significantly increased the incidence of DN (OR=1.405, 95%CI (1.199,1.647), p<0.001). Individuals who used statins for 5 to 7 years were more likely to develop diabetic nephropathy (OR=1.472, 95%CI (1.057,2.048), p=0.022) compared to those who used statins for 1-3 years (OR=1.334, 95%CI (1.058,1.682), p=0.015) or <1 year (OR=1.266, 95%CI (1.054,1.522), p = 0.012). Simvastatin has a greater incidence of diabetic nephropathy (OR=1.448, 95%CI(1.177, 1.78), P < 0.001). Taking statins long-term increases the risk of DN. Statin use is associated with an increased risk of DN. Caution should be exercised when prescribing atorvastatin and simvastatin for long-term statin therapy.

Gender Differences in the Incidence of Nephropathy and Changes in Renal Function in Patients with Type 2 Diabetes Mellitus: A Retrospective Cohort Study.

This research aims to examine and scrutinize gender variations in the incidence of diabetic nephropathy (DN) and the trajectory of renal function in type 2 diabetes mellitus (T2DM) patients. We conducted a retrospective cohort study that enrolled 1549 patients diagnosed with T2DM from May 2015 to July 2023. We separately compared the clinical characteristics of male and female participants with and without DN. We utilized the Kaplan-Meier method to examine the cumulative incidence of DN among T2DM patients of varying genders. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using univariable and multivariable Cox proportional hazards regression analysis to evaluate the correlation between various factors and the risk of DN incidence. Multiple linear regression was utilized to investigate the relationship between ΔeGFR% and each factor. Logistic regression with cubic spline function and smooth curve fitting was employed to analyze the nonlinear link between ΔeGFR% and the risk of DN among participants of different genders. The prevalence of DN was higher in female participants (17.31%) than in male participants (12.62%), with a significant cumulative risk ratio (1.33 [1.02-1.73], P = 0.034). Multiple linear regression analysis revealed that creatinine, female gender, blood urea nitrogen, alkaline phosphatase, and total cholesterol had a significant impact on ΔeGFR% in T2DM patients, with standardized β coefficients of -0.325, -0.219, -0.164, -0.084, and 0.071, respectively. The restricted cubic spline analysis demonstrated a strong negative association between ΔeGFR% and the risk of developing DN (P < 0.001). Both male and female patients with T2DM had a higher prevalence of DN over the 5-year follow-up period. However, women had a greater risk of developing DN and a faster decline in renal function compared to men.

Influence of Fibrinogen/Albumin Ratio and Fibrinogen/Pre-Albumin Ratio on Cardiac Autonomic Neuropathy in Type 2 Diabetes.

Subclinical inflammation may be involved in the pathogenesis of diabetic cardiac autonomic neuropathy (DCAN). The purpose of the study is to explore the relationship between novel inflammation biomarkers fibrinogen-albumin ratio (FAR), fibrinogen-prealbumin ratio (FPR), and DCAN in type 2 diabetes mellitus (T2DM). A total of 715 T2DM patients were enrolled in this retrospective study, divided into non-DCAN (n=565) and DCAN (n=150) groups by Ewing's test. Serum fibrinogen, albumin, prealbumin, routine inflammatory and other biochemical markers were measured. Patients with versus without DCAN had higher FAR (10.29 ± 4.83 vs 7.22 ± 2.56 g/g, P < 0.001) and FPR (2.19 ± 1.85 vs 1.43 ± 0.93 g/mg, P < 0.001). As FAR and FPR quartiles increased, the incidence of DCAN increased (Quartile 1 vs Quartile 4: 8.4 vs 42.7%, 9.6 vs 39.2%, respectively, P < 0.001), heart rate variability parameters decreased (P < 0.001); the incidence of diabetic nephropathy, retinopathy and peripheral neuropathy tended to be higher and inflammation factors were more active (P < 0.01). FAR (OR, 95% CI: 1.16, 1.08-1.25, P < 0.001) and FPR (OR, 95% CI: 1.22, 1.03-1.44, P = 0.021) were independent determinants of DCAN; the risk of DCAN increased by approximately 65% and 27% with each increase in the standard deviation (SD) of FAR (OR per SD, 95% CI: 1.65, 1.29-2.11, P < 0.001) and FPR (OR per SD, 95% CI: 1.27, 1.04-1.56, P = 0.021). FAR and FPR are independent risk factors and may influence DCAN development through inflammation.

Efficacy of "Dihuang pill prescriptions" combined with conventional treatment for diabetic kidney disease: A network meta-analysis and systematic review.

With the increasing incidence of diabetic nephropathy, there is currently no means to completely cure the disease. However, a large number of clinical data proved that traditional Chinese medicine combined with modern medical conventional treatment of diabetic kidney disease has achieved better efficacy than simple Western medicine conventional treatment. Based on the mesh meta-analysis method, the objective evaluation of clinical efficacy of conventional treatment of diabetic kidney disease and comparison provided more evidence-based basis for the treatment of diabetic kidney disease and further select effective intervention measures to delay the process of diabetic kidney disease. 41 randomized controlled trials were included, involving 4 kinds of "Dihuang pill prescriptions," with a total sample size of 3562 cases, including 1793 patients in the experimental group and 1769 patients in the control group. Network meta-analysis suggested that the best SUCRA-ranked 2 interventions were Jingui Shenqi pills/decoction + Western medicine routine" and Jisheng Shenqi pills/decoction + Western medicine routine in terms of reducing 24-hour urinary protein. In terms of reducing urinary albumin excretion rate, the top 2 SUCRA-ranked interventions were Zhibai Dihuang pills/decoction + Western medicine routine and Liuwei Dihuang Pills/decoction + Western medicine routine. In terms of reducing serum creatinine, the top 2 SUCRA ranked interventions were Jisheng Shenqi pills/decoction + Western medicine routine, Zhibai Dihuang Pills/decoction + Western medicine routine. In terms of lowering fasting blood glucose, the top 2 SUCRA-ranked interventions were Zhibai Dihuang pills/ decoction + Western medicine routine and Jisheng Shenqi pills/decoction + Western medicine routine. The results showed that the treatment plan of conventional Western medicine combined with Chinese patent medicine could reduce serum creatinine, 24-hour urinary protein, fasting blood glucose urine protein excretion rate and improve the total clinical effective rate. The combination of medicine was obviously better than conventional Western medicine alone.

Association of Thiazide Diuretics With Diabetes Progression, Kidney Disease Progression, Cardiovascular Outcomes, and Death Among Patients With Diabetes Who Initiate Statins

Statins have been associated with diabetes mellitus (DM) progression but their cardiovascular benefit in patients with DM outweigh the harm. However, the effects of concurrent use of other medications that similarly increase blood glucose level, such as thiazide diuretics, are not well studied. This study aimed to evaluate the association of concurrent use of thiazide diuretics and statins on DM progression, cardiovascular and renal outcomes, and death in patients with DM. This is a retrospective cohort study of Veterans with DM who initiated statins between 2003 and 2015. The cohort comprised thiazide users (concomitantly used thiazides and statins for ≥6months) and active comparators (concomitantly used calciun channel blockers [CCB] but not thiazides and statins for ≥6months). We excluded patients who were <18 years old, with chronic kidney disease stage 4 or worse, or used loop diuretics. We propensity-score-matched comparison groups on 99 baseline characteristics including demographics, healthcare utilization, co-morbidities, cardiovascular and co-morbidity scores, vital signs, laboratory data, and medication class usage. Outcomes were: (1) DM progression (new insulin initiation, increase in the number of glucose-lowering medication classes, and hyperglycemic episodes); (2) kidney disease progression (doubling of serum creatinine, incidence of chronic kidney disease stage 5, initiation of renal replacement therapy, and incidence of diabetic nephropathy); (3) cardiovascular outcomes (acute myocardial infarction, stroke, cardiac arrest); and (4) total mortality. From 297,967 statin users (228,509 Thiazide-statin users and 69,458 active comparators), we successfully matched 67,614 pairs. In comparison to active comparators, thiazide-statin users had increased risk of DM progression (65.6% in CCB group vs 68.1% in thiazide group; odds ratio [OR]: 1.12, 95% confidence interval [CI]: 1.09 to 1.15), decreased risk of kidney progression (16.9% in CCB group vs 16.5 in thiazide group; OR: 0.97, 95% CI: 0.94 to 0.99), decreased risk of cardiovascular outcomes (15.7% in CCB group vs 14.6% in thiazide group; OR: 0.92, 95% CI: 0.89 to 0.95), and similar risk of total mortality (19.7% in each group; OR: 1.00, 95% CI: 0.98 to 1.03). This study attempted to answer an important clinical question whether thiazide diuretics should be discontinued or substituted upon statin initiation. Our results showed that concurrent use of statin and thiazides in patients with DM was associated with DM progression but with less kidney progression and cardiovascular outcomes and no difference in mortality. Clinicians should closely monitor DM control when thiazides and statins are used concurrently.

Ang-(1-7) attenuates podocyte injury induced by high glucose in vitro.

The incidence of diabetic nephropathy (DN) is gradually increasing worldwide. Podocyte injury, such as podocyte apoptosis and loss of the slit diaphragm (SD)-specific markers are early pathogenic features of DN. The cultured mouse podocytes were separated into a high glucose-treated (HG, 30mM) group to mimic DN in vitro, a low glucose-treated (LG, 5mM) group as a control and HG+ angiotensin-(1-7)(Ang-(1-7)) and HG+Ang-(1-7) + D-Ala7-Ang-(1-7) (A779, Ang-(1-7)/Mas receptor antagonist) experimental groups. The Cell Counting Kit-8 (CCK-8) method and flow cytometry was used to detect podocyte activity and podocyte apoptosis respectively. The expression of angiotensin type 1 receptor (AT1R), Mas receptor (MasR) and podocyte-specific markers were examined by q-PCR and Western blot, respectively. The results showed that the decrease in podocyte activity; the increase in podocyte apoptosis; the decreased mRNA and protein expression of nephrin, podocin, WT-1 and MasR; and the upregulated expression of AT1R induced by HG could be reversed by Ang-(1-7). However, these effects were blocked by A779. The possible mechanisms of the Ang-(1-7)-mediated effect depended on MasR. In addition, the protective effect of Ang-(1-7) on podocyte activity was dose-dependent and most obvious at 10 µM. A779 had the greatest antagonistic action against Ang-(1-7) at a concentration of 10 μM. This study reveals that binding of Ang-(1-7) to its specific receptor MasR may counteract the effects of Ang II mediated by AT1R to significantly attenuate podocyte injury induced by high glucose. Ang-(1-7)/MasR targeting in podocytes may be a therapeutic approach to attenuate renal injury in DN.

#5344 EPIDEMIOLOGY OF GLOMERULAR DISEASES IN THE PRE- AND POST-COVID-19 ERA IN CENTRAL QUEENSLAND, AUSTRALIA

Abstract Background and Aims Development of new onset and recurrent glomerular diseases (GD) following Covid-19 infection or vaccination are increasingly reported in the literature with various proposed pathogenic mechanisms. Australia reported its first case of Covid-19 in January 2020. Currently in Australia, there has been 11.3 million cases of Covid-19 infection and 98% of individuals aged ≥ 16 years received at least 1 dose of Covid-19 vaccination. However, there are no studies in Australia that evaluate the risk of GD after Covid-19 infection or vaccination. We compared kidney biopsy results pre- (01/01/2017-31/12/2019) and post- (01/01/2020-31/12/2022) Covid-19 era to assess for potential changes in the epidemiology of kidney biopsy-proven GD. Method In this single-centred retrospective study, all renal biopsies performed in Central Queensland (CQ) between 01/01/2017 and 31/12/2022 were reviewed. This pilot study is a subset of Queensland Kidney Biopsy Registry which has captured all renal biopsies of adults residing in CQ with a regional population of 220,912 with a land area of 497,714 km2. Results Eighty-seven percent of the CQ population received at least one dose of Covid-19 vaccination and 53,234 cases of Covid-19 infection were confirmed by rapid antigen test (RAT) as of the end of January 2023. The total number of kidney biopsies performed pre- and post-Covid-19 era were 47 vs 58, respectively, and the majority were native kidney biopsies (94% vs 95%) in CQ whereby the number of nephrologists in the respective catchment areas and access availability to kidney biopsies remained similar. The mean age of patients was 55.3 years (standard deviation, SD 16.4) vs 55.6 years (SD 15.6) and the majority were males (70% vs 62%) and Caucasians (77% vs 76%). No case of recurrent GD was diagnosed in pre-Covid-19 era whereas 5 cases of recurrent GD {2 membranous nephropathy, 1 minimal change disease, 1 lupus nephritis class III-IV, and 1 ANCA associated vasculitis (AAV)} in post-Covid-19 era, p = 0.025. The commonest cause of GD in the pre-Covid-19 era was IgA nephropathy (IgAN) whereas diabetic nephropathy and AAV was the most common GD during the post-Covid-19 era. The incidence of IgAN decreased from 12 cases (18.1 cases/million person years) in pre-Covid-19 era to 3 cases (4.5 cases/million person years) in the post-Covid-19 era (incidence rate ratio, IRR of 0.25, 95% CI 0.05-0.93, p = 0.020). The incidence of diabetic nephropathy increased from 1 case (1.5 cases million person years) during the three years pre-Covid-19 era to 13 cases (19.6 cases/million person years) for three years post-Covid-19 era (IRR of 13.1, 95% CI 1.95-552.47, p = 0.001). In the post-Covid-19 era, the mean age of patients with diabetic nephropathy was 51.2 years (SD 11.9) and the majority were indigenous Australian (n = 8, 62%) with poor diabetic control. They had kidney biopsies for nephrotic range proteinuria with or without acute kidney injury and haematuria. The incidence of AAV increased from 3 cases (4.5 cases/million person years) during the three years pre-Covid-19 era to 10 cases (15.1 cases/million person years) for three years post-Covid-19 era (IRR of 3.4, 95% CI 0.86-18.85, p = 0.052). In the post-Covid-19 era, the mean age of patients with AAV was 68.4 years (SD 16.1) with Caucasian (n = 10, 100%). PR3-AAV (n = 5) and MPO-AAV (n = 5) are equally prevalent, and 3 patients (30%) had concomitant pulmonary complications. Three cases of AAV each occurred in the first and second years and 4 cases in the third year during the post-Covid-19 era. There was no increase in the incidence rate for other types of glomerular diseases. Conclusion Our findings suggest the frequency of incident and recurrent GD may vary with the emergence of Covid-19 and steps taken to minimise viral complications that include primary preventative measures via vaccination. Larger epidemiological studies are required to better elucidate the risk of Covid-19 infection and vaccination in relation to GD.

Long-term effect of intensive lifestyle intervention on cardiometabolic risk factors and microvascular complications in patients with diabetes in real-world clinical practice: a 10-year longitudinal study

IntroductionIntensive lifestyle intervention (ILI) has significantly reduced incidence of diabetes and improved many cardiovascular disease risk factors. We evaluated long-term effects of ILI on cardiometabolic risk factors, and microvascular and...

Antidiabetic Therapy in Patients Related to CKD (Chronic Kidney Disease)

Patients with type 2 diabetes mellitus (T2DM) are more likely to have chronic kidney disease (CKD) in stages 3-5 (glomerular filtration rate [GFR] 60 mL/min) by roughly 25–30%. Despite the limits of most oral anti-diabetic medications in people with CKD, incretin-based treatments are being utilized more frequently to treat type 2 diabetes. This study examines the impact of CKD on the pharmacokinetics of glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors, as well as the efficacy/safety profile of these medications when used in patients with T2DM and CKD. Sitagliptin, Vildagliptin, Saxagliptin, and Alogliptin are the most common DPP-4 inhibitors that are primarily excreted by the kidneys. This led to recommendations for appropriate dose reductions based on the severity of CKD after pharmacokinetic studies revealed that total exposure to the medication is increased in proportion to the fall in GFR. Clinical investigations found that patients with CKD had a high effectiveness and safety profile under these circumstances. Lintagliptin, on the other hand, is primarily excreted through the hepatobiliary system. No dose adjustment of lintagliptin is necessary in the setting of CKD because a pharmacokinetic investigation revealed that lower GFR had a negligible impact on total exposure. Patients with CKD have less experience using GLP-1 receptor agonists. Exenatide should not be administered to patients with severe CKD because it is excreted through renal processes. Due to the limited experience with CKD patients, ligarglutide should be administered with caution even if the kidneys do not remove it from the body. For lixisenatide, exenatide long-acting release (LAR), and other once-weekly GLP-1 receptor agonists now under development, only scant pharmacokinetic data are also available. GLP-1 receptor agonists have been implicated in several case reports of acute renal failure, which was most likely brought on by dehydration brought on by gastrointestinal side effects. Nevertheless, improving GLP-1 may also have advantageous renal effects that could help lower the incidence of diabetic nephropathy. In conclusion, the physician has new chances due to the DPP-4 inhibitors' broad and encouraging experience in CKD patients, whereas the limited experience with GLP-1 receptor agonists in this population calls for greater caution.

RELATIONSHIP BETWEEN HBA1C AND COMPLETE BLOOD COUNT PARAMETERS IN ADULT PATIENTS WITH TYPE 2 DIABETES IN SAUDI ARABIA

Background: Hemoglobin A1c (HbA1c) measures blood glucose over a period of 2–3 months, and its level is closely related to the risk of complications. Several factors affecting HbA1c levels have not been studied. This study mainly focused on the relationship between HbA1c levels and complete blood count (CBC) parameters. Objectives: This study aimed to analyze the relationship between HbA1c levels and CBC parameters in patients with type 2 diabetes mellitus (T2DM) and to evaluate the association of CBC parameters with abnormal HbA1c levels and diabetic complications. Methods: This was a retrospective study of 385 Saudi patients with T2DM aged ≥18 years attending King Khalid University Hospital (KKUH) primary care clinics. Patients with type 1 diabetes mellitus, hematological diseases, infections, or allergies were excluded. AnElectronic System for Integrated Health Information (e-SiHi)was used to collect data, which were analyzed using SPSS 22 using t-test and analysis of variance, with P &lt;0.05 considered significant. Results: This study showed that the mean patient age was 59±13 years, with no significant difference between the sexes. In addition, the mean duration of disease was 10 years, and the mean HbA1c level was 8.5±1.9 %. CBC values were averaged according to their mean values, except for the erythrocyte sedimentation rate (ESR) (36±27 mm/hr) which was higher than the normal value (1.0–25 mm/hr). Conclusion: This study showed an association between HbA1c levels and duration of T2DM and hemoglobin. The progression of diabetic complications was related to CBC changes a high ESR was associated with the incidence of diabetic nephropathy and increased white blood cell count with neuropathy, vasculopathy, and nephropathy. Among all complications, vasculopathy occurred more frequently with each increase in HbA1c values.

Myokines: Novel therapeutic targets for diabetic nephropathy.

With the increasing incidence of diabetic nephropathy (DN), there is an urgent need to find effective DN preventive and therapeutic modalities. It is widely believed that effective exercise is good for health. However, the beneficial role of exercise in kidney disease, especially in DN, and the underlying molecular mechanisms have rarely been reported. Muscle is not only an important motor organ but also an important endocrine organ, secreting a group of proteins called "myokines" into the blood circulation. Circulating myokines then move to various target organs to play different biological roles. In this review, we summarize the currently known myokines and the progress in research relating them to DN and discuss its potential as a therapeutic target for DN.

Association of baseline and cumulative remnant cholesterol with incidence of diabetic nephropathy: A longitudinal cohort study

AimsTo evaluate the longitudinal association of remnant cholesterol with the incidence of diabetic nephropathy using a Chinese diabetes cohort. MethodsWe included 4237 individuals with type 2 diabetes during 2013–2014 from Beijing Health Management Cohort. Remnant cholesterol was defined by Martin–Hopkins equation. Diabetic nephropathy was confirmed by urine albumin/creatinine ratio and estimated glomerular filtration rate. We calculated the hazard ratio (HR) and 95% confidence interval (CI) for incident diabetic nephropathy using adjusted Cox proportional hazards regression. ResultsThe median [IQR] age was 55 [48, 64] years, and 3 256 (76.8 %) were men. During follow-up, 248 (5.9 %) participants developed diabetic nephropathy. One-SD increase of baseline and average cumulative remnant cholesterol were significantly associated with an increased risk of diabetic nephropathy, and the adjusted HRs were 1.208 (95 % CI: 1.098–1.329) and 1.216 (95 % CI: 1.102–1.341), respectively. Individuals in the highest tertile of baseline and average cumulative remnant cholesterol had a 82.3 % and 87.6 % excess risk of diabetic nephropathy, compared with those in the lowest. ConclusionRemnant cholesterol is independently associated with incident diabetic nephropathy in type 2 diabetes.

Peripheral Blood circRNA Microarray Profiling Identities hsa_circ_0001831 and hsa_circ_0000867 as Two Novel circRNA Biomarkers for Early Type 2 Diabetic Nephropathy.

PurposeType 2 diabetes mellitus (T2DM) increases the incidence of diabetic nephropathy (DN) and eventually progresses to end-stage renal disease. Circular RNAs (circRNAs) are a class of non-coding RNAs that are promising as diagnostic biomarkers and therapeutic targets for human diseases. The aim of this study was to analyze the differential expression of circRNAs (DECs) in peripheral blood from patients with early type 2 diabetic nephropathy (ET2DN), T2DM and controls, which will facilitate to discover some new biomarkers for ET2DN.Patients and MethodsTwenty ET2DN patients, 20 T2DM patients, and 20 normal controls were included in this study. Blood samples from 3 random subjects of age- and sex-matched patients in each group, respectively, were used to detect circRNA expression profiles by circRNA microarray, and the circRNA expression of remaining subjects was validated by real-time quantitative polymerase chain reaction (qRT-PCR). Further functional assessment was performed by bioinformatic tools.ResultsThere were 586 DECs in ET2DN vs T2DM group (249 circRNAs were upregulated and 337 circRNAs were downregulated); 176 circRNAs were upregulated and 101 circRNAs were downregulated in T2DM vs control group; 57 circRNAs were upregulated and 5 circRNAs were downregulated in ET2DN vs control group. The functional and pathway enrichment of DECs were analyzed by GO and KEGG. qRT-PCR results revealed that hsa_circ_0001831 and hsa_circ_0000867 were significantly upregulated in ET2DN group compared to both of T2DM and control group. The ROC curve demonstrated that hsa_circ_0001831 and hsa_circ_0000867 have high sensitivity and specificity associated with ET2DN.ConclusionOur study showed the expression profiles of circRNAs in ET2DN patients and demonstrated that hsa_circ_0001831 and hsa_circ_0000867 can be used as novel diagnostic biomarkers for ET2DN.

The Role of Angiotensinogen rs699 in Diabetic Nephropathy Among Type 2 Diabetes Mellitus Patients with Uncontrolled Postprandial Glucose Levels

Diabetic Nephropathy (DN) is the most common complication of Type 2 Diabetes Mellitus (T2DM), leading to the highest mortality rate of DM complications. However, its etiology is still questionable. Hyperglycemia, hypertension, and particular genetic susceptibility are associated with DN. Not all patients with uncontrolled hyperglycemia suffer DN. Thus, genetic susceptibility may be a risk factor for DN. The genetic variant of angiotensinogen rs699 is known to be associated with the risk of DN with inconsistent results between ethnicities. This study aims to reveal the correlation between the AGT rs699 with the incidence of diabetic nephropathy among type-2 diabetes mellitus patients with uncontrolled postprandial glucose levels in the Jambi Malay ethnicity. This study was observational analytic research with a cross-sectional design. It used 48 DNA samples from type-2 diabetes mellitus patients with uncontrolled postprandial glucose levels. The authors took 24 DNA samples from patients with DN and 24 without DN (as a control group). The genotyping method used ARMS-PCR specific for AGT rs699. Subjects with the CT genotype had a lower risk for diabetic nephropathy than the CC genotype, but it was not statistically significant (p=0.247; OR=0.508; 95%CI=0.160-1.607). In addition, subjects with the T allele (p=0.331; OR=0.621; 95%CI-0.237-1.630) had a lower risk for diabetic nephropathy than the C allele, but it was not statistically significant. In conclusion, Angiotensinogen rs699 is not a risk factor for diabetic nephropathy among type-2 diabetes mellitus patients with uncontrolled postprandial glucose levels in the Jambi Malay ethnicity.

Immune responses in diabetic nephropathy: Pathogenic mechanisms and therapeutic target

Diabetic nephropathy (DN) is a chronic, inflammatory disease affecting millions of diabetic patients worldwide. DN is associated with proteinuria and progressive slowing of glomerular filtration, which often leads to end-stage kidney diseases. Due to the complexity of this metabolic disorder and lack of clarity about its pathogenesis, it is often more difficult to diagnose and treat than other kidney diseases. Recent studies have highlighted that the immune system can inadvertently contribute to DN pathogenesis. Cells involved in innate and adaptive immune responses can target the kidney due to increased expression of immune-related localization factors. Immune cells then activate a pro-inflammatory response involving the release of autocrine and paracrine factors, which further amplify inflammation and damage the kidney. Consequently, strategies to treat DN by targeting the immune responses are currently under study. In light of the steady rise in DN incidence, this timely review summarizes the latest findings about the role of the immune system in the pathogenesis of DN and discusses promising preclinical and clinical therapies.

Assessment of Renal Function in Type 2 Diabetic Patients in University of Ilorin Teaching Hospital, Ilorin, Nigeria

Background: Nephropathy is one of the leading causes of mortality and morbidities among type 2 diabetic patients globally. Early detection through regular screening for micro-albuminuria has proven immense value. This study aims to assess renal function status of type 2 diabetic patients in a tertiary health institution in Nigeria. Method: This study involves 132 type 2 diabetic patients and 50 apparently healthy controls. Blood specimens were used to assay plasma creatinine, fasting plasma glucose (FPG), urea levels and glycated haemoglobin (HbA1c), while early morning midstream urine was collected for albumin and creatinine. Albumin-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) were calculated. Data were analysed using SPSS 15.0. Variables were expressed as mean ±SD. Student T-test was used to compare means, and p-value &lt; 0.05 was considered significant. Results: When compared to controls, diabetic patients had significantly higher (p&lt;0.05) BMI, waist circumference, blood pressure, ACR, mean urine albumin excretion, FPG, and HbA1c. However, the estimated glomerular filtration rate in the cases was significantly lower (p&lt;0.05) than in the control. Furthermore, serum creatinine, HbA1c, FPG, and eGFR increased significantly (p&lt;0.05) in normal, micro, and macro-albuminuric type 2 diabetic patients compared to controls. Conclusion: When compared to prior studies, our study found an alarming increase in the incidence of diabetic nephropathy in our sample population. This necessitates immediate intervention in the management of type 2 diabetic patients through early screening for micro- and macro-albuminuria via tight and good glycaemic control techniques. Keywords: type 2 diabetes, renal function, albuminuria

Long-term effectiveness of a disease management program to prevent diabetic nephropathy: a propensity score matching analysis using administrative data in Japan

BackgroundExisting reviews indicated that disease management for patients with diabetes may be effective in achieving better health outcomes with less resource utilization in the short term. However, the long-term results were inconsistent because of the heterogeneous nature of the study designs. In the present study, we evaluated the 5-year follow-up results of a local disease management program focused on diabetic nephropathy prevention under the universal public health insurance scheme in Japan.MethodsPatients diagnosed with type 2 diabetes who had stage 3 or 4 diabetic kidney disease and were aged between 20 and 75 years were invited to join a disease management program to support self-management and receive a recommended treatment protocol between 2011 and 2013. Follow-up data were collected from an electronic claims database for the public insurance scheme. Considering the non-random selection process, we prepared two control groups matched by estimated propensity scores to compare the incidence of diabetes-related complications, death, and resource utilization.ResultsThe treatment group was more likely to receive clinical management in accordance with the guideline-recommended medication. After propensity score matching, the treatment group had lower incidence of diabetic nephropathy and emergency care use than the control group selected from a beneficiary pool mainly under primary care. Comparisons between the treatment group and the control group with more selected clinical conditions did not show differences in the incidence rate and resource utilization.ConclusionsThe present results demonstrated limited effectiveness of the program for reducing complication incidence and resource utilization during the 5-year follow-up. Further research on the long-term effectiveness of co-management by primary care physicians, subspecialists in endocrinology and nephrology, and nurse educators is required for effective management of diabetes-related nephropathy.

Development and Validation of a Model That Predicts the Risk of Diabetic Nephropathy in Type 2 Diabetes Mellitus Patients: A Cross-Sectional Study.

PurposeTo develop a nomogram model that predicts the risk of diabetic nephropathy (DN) incidence in type 2 diabetes mellitus (T2DM) patients.MethodsWe collect information from electronic medical record systems. The data were split into a training set (n=521) containing 73.8% of patients and a validation set (n=185) holding the remaining 26.2% of patients based on the date of data collection. Stepwise and multivariable logistic regression analyses were used to screen out DN risk factors. A predictive model including selected risk factors was developed by logistic regression analysis. The results of binary logistic regression are presented through forest plots and nomogram. Lastly, the c-index, calibration plots, and receiver operating characteristic (ROC) curves were used to assess the accuracy of the nomogram in internal and external validation. The clinical benefit of the model was evaluated by decision curve analysis.ResultsPredictors included serum creatinine (Scr), hypertension, glycosylated hemoglobin A1c (HbA1c), blood urea nitrogen (BUN), body mass index (BMI), triglycerides (TG), and Diabetic peripheral neuropathy (DPN). Harrell’s C-indexes were 0.773 (95% CI:0.726–0.821) and 0.758 (95% CI:0.679–0.837) in the training and validation sets, respectively. Decision curve analysis (DCA) demonstrated that the novel nomogram was clinically valuable.ConclusionOur simple nomogram with seven factors may help clinicians predict the risk of DN incidence in patients with T2DM.