Clinical study of different prediction models in predicting diabetic nephropathy in patients with type 2 diabetes mellitus

BACKGROUND Among older adults,type 2 diabetes mellitus(T2DM)is widely recognized as one of the most prevalent diseases.Diabetic nephropathy(DN)is a frequent com-plication of DM,mainly characterized by renal microvascular damage.Early detection,aggressive prevention,and cure of DN are key to improving prognosis.Establishing a diagnostic and predictive model for DN is crucial in auxiliary diagnosis.AIM To investigate the factors that impact T2DM complicated with DN and utilize this information to develop a predictive model.METHODS The clinical data of 210 patients diagnosed with T2DM and admitted to the First People’s Hospital of Wenling between August 2019 and August 2022 were retrospectively analyzed.According to whether the patients had DN,they were divided into the DN group(complicated with DN)and the non-DN group(without DN).Multivariate logistic regression analysis was used to explore factors affecting DN in patients with T2DM.The data were randomly split into a training set(n=147)and a test set(n=63)in a 7:3 ratio using a random function.The training set was used to construct the nomogram,decision tree,and random forest models,and the test set was used to evaluate the prediction performance of the model by comparing the sensitivity,specificity,accuracy,recall,precision,and area under the receiver operating characteristic curve.RESULTS Among the 210 patients with T2DM,74(35.34%)had DN.The validation dataset showed that the accuracies of the nomogram,decision tree,and random forest models in predicting DN in patients with T2DM were 0.746,0.714,and 0.730,respectively.The sensitivities were 0.710,0.710,and 0.806,respectively;the specificities were 0.844,0.875,and 0.844,respectively;the area under the receiver operating characteristic curve(AUC)of the patients were 0.811,0.735,and 0.850,respectively.The Delong test results revealed that the AUC values of the decision tree model were lower than those of the random forest and nomogram models(P<0.05),whereas the difference in AUC values of the random forest and column-line graph models was not statistically significant(P>0.05).CONCLUSION Among the three prediction models,random forest performs best and can help identify patients with T2DM at high risk of DN.

Tiliroside protects against diabetic nephropathy in streptozotocininduced diabetes rats by attenuating oxidative stress and inflammation

BACKGROUND Diabetic nephropathy(DN),affecting half of diabetic patients and contributing significantly to end-stage kidney disease,poses a substantial medical challenge requiring dialysis or transplantation.The nuanced onset and clinical progression of kidney disease in diabetes involve consistent renal function decline and persistent albuminuria.AIM To investigate Tiliroside's(Til)protective effect against diabetic nephropathy(DN)in rats under diabetic conditions.METHODS Five groups of six rats each were included in this study:Rats treated with DMSO by intraperitoneal injection as controls,those treated with STZ by intraperitoneal injection,those treated with STZ+Til(25 mg/kg body weight[bwt])or Til(50 mg/kg bwt),and those treated with anti-diabetic medication glibenclamide(600μg/kg bwt).Biochemical markers,fasting blood glucose,food intake,kidney weight,antioxidant enzymes,inflammatory and fibrotic markers,and renal injury were monitored in different groups.Molecular docking analysis was performed to identify the interactions between Til and its targeted biomarkers.RESULTS Til significantly reduced biochemical markers,fasting blood glucose,food intake,and kidney weight and elevated antioxidant enzymes in diabetic rats.It also mitigated inflammatory and fibrotic markers,lessened renal injury,and displayed inhibitory potential against crucial markers associated with DN as demonstrated by molecular docking analysis.CONCLUSION These findings suggest Til's potential as a therapeutic agent for DN treatment,highlighting its promise for future drug development.

Glucokinase regulatory protein rs780094 polymorphism is associated with type 2 diabetes mellitus, dyslipidemia, non-alcoholic fatty liver disease, and nephropathy

In this editorial,we comment on the article by Liu et al published in the recent issue of the World Journal of Diabetes(Relationship between GCKR gene rs780094 polymorphism and type 2 diabetes with albuminuria).Type 2 diabetes mellitus(T2DM)is a chronic disorder characterized by dysregulated glucose homeostasis.The persistent elevated blood glucose level in T2DM significantly increases the risk of developing severe complications,including cardiovascular disease,re-tinopathy,neuropathy,and nephropathy.T2DM arises from a complex interplay between genetic,epigenetic,and environmental factors.Global genomic studies have identified numerous genetic variations associated with an increased risk of T2DM.Specifically,variations within the glucokinase regulatory protein(GCKR)gene have been linked to heightened susceptibility to T2DM and its associated complications.The clinical trial by Liu et al further elucidates the role of the GCKR rs780094 polymorphism in T2DM and nephropathy development.Their findings demonstrate that individuals carrying the CT or TT genotype at the GCKR rs780094 locus are at a higher risk of developing T2DM with albuminuria compared to those with the CC genotype.These findings highlight the importance of genetic testing and risk assessment in T2DM to develop effective preventive strategies and personalized treatment plans.

Association of XbaI GLUT1 Polymorphism with Susceptibility to Type 2 Diabetes Mellitus and Diabetic Nephropathy

Objectives: Diabetic nephropathy (DN) is one of the chronic microangiopathic complications of type 2 diabetes (T2DM) and has become the most frequent cause of end-stage renal disease. The XbaI polymorphism in the glucose transporter (GLUT1) has been suggested in the development of DN. We examined the association between XbaI polymorphism of GLUT1 and susceptibility to T2DM and development of DN. Methods: The study included 227 T2DM patients divided into 107 without DN (DM ? DN) and 120 with DN (DM + DN), in addition to 100 apparently healthy controls. Genotyping was done by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Results: The GLUT1 XbaI T allele was associated with increased susceptibility to T2DM, when comparing the healthy controls to the whole diabetic group, odds ratio (OR) = 1.899, 95% confidence interval (CI) (1.149 - 3.136), p = 0.011. This association was also significant between healthy controls and DM ? DN OR = 1.997 (1.079 - 3.699), p = 0.026 as well as between healthy controls and DM + DN OR = 1.818 (1.016 - 3.253), p = 0.042. However there was no significant association of XbaI polymorphism with DN when comparing DM ? DN to DM + DN OR = 0.910 (0.474 - 1.747), p = 0.777. Conclusion: XbaI T allele is associated with increased susceptibility to T2DM, but not to development of DN. Further studies are needed to replicate such findings.

RELATION OF HYPERTENSION TO DIABETIC NEPHROPATHY IN PATIENTS WITH NON-INSULIN-DEPENDENT DIABETES MELLITUS—A PAIR-MATCHED CASE-CONTROL STUDY

To assess the role of hypertension and family history of hypertensio n in the development of nephropathy in patients with non insulin dependent dia betes mellitus (NIDDM).Methods. A retrospective analysis was done on 2 groups of NIDDM patients, one g roup without proteinuria (urine protein< 300mg/24h, n=106) and the other group w ith proteinuria (urine protein≥500mg/24h, n=106). The 2 groups were matched by age(≤±3yrs), sex, ethnic and resident place. Some information of these subject s including demographic; history of disease, family history of diseases, lifesty le and behavior style variables was obtained by questionnaire; some variables w ere measured, including systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), quantity of protein in 24h urine. Then condi tional logistic regression analysis was performed.Results. Some factors, including history of hypertension, longer duration of hy pertension, higher levels of the past highest SBP and DBP, were independently as sociated with the occurrence risk of diabetic nephropathy (DN). Their correspond ing odd ratios (OR) with 95% confidence intervals (CI) were 2.00(1.17～3.43), 1 .25(1.08～1.46), 1.38(1.15～1.66), and 1.33(1.09～1.62) respectively, but family history of hypertension was not significantly associated with the development o f DN. When the above mentioned relations were respectively adjusted by some pos sible confounding factors, they still existed.Conclusions. History of hypertension, longer duration of hypertension, higher l evels of the past highest SBP and DBP are independent risk factors for DN in Chi nese NIDDM patients.

Relationship Between Postprandial Blood Glucose,Fasting Insulin,and Glycated Hemoglobin Levels and Early Diabetic Nephropathy in Patients with Type 2 Diabetes Mellitus

Objective:To investigate the relationship between postprandial blood glucose(PBG),fasting insulin(FINS),and glycated hemoglobin(HbA1c)levels and early diabetic nephropathy in patients with type 2 diabetes.Methods:96 cases of type 2 diabetes mellitus treated in our hospital from May 2021 to May 2022 were selected as the research subjects.The patients were divided into two groups according to the urinary albumin excretion rate(UAER),with 53 cases in the type 2 diabetes group(UAER<30μg/min)and 43 cases in the early diabetic nephropathy group(30μg/min≤UAER<300μg/min).PBG,FINS,and HbA1c levels were detected in 87 healthy patients.Results:The levels of PBG,FINS,and HbA1c in the early diabetic nephropathy group were higher than those in the control group(P<0.01)and the type 2 diabetes group(P<0.01).Conclusion:PBG,FINS,and HbA1c are factors affecting the occurrence of diabetic nephropathy in patients with type 2 diabetes;thus,controlling the levels of PBG,FINS,and HbA1c can effectively prevent the occurrence of diabetic nephropathy in type 2 diabetes mellitus.

Acute worsening of microvascular complications of diabetes mellitus during rapid glycemic control:The pathobiology and therapeutic implications

While chronic hyperglycaemia resulting from poorly controlled diabetes mellitus(DM)is a well-known precursor to complications such as diabetic retinopathy,neuropathy(including autonomic neuropathy),and nephropathy,a paradoxical intensification of these complications can rarely occur with aggressive glycemic management resulting in a rapid reduction of glycated haemoglobin.Although,acute onset or worsening of retinopathy and treatment induced neuropathy of diabetes are more common among these complications,rarely other problems such as albuminuria,diabetic kidney disease,Charcot’s neuroarthropathy,gastroparesis,and urinary bladder dysfunction are also encountered.The World Journal of Diabetes recently published a rare case of all these complications,occurring in a young type 1 diabetic female intensely managed during pregnancy,as a case report by Huret et al.It is essential to have a comprehensive understanding of the pathobiology,prevalence,predisposing factors,and management strategies for acute onset,or worsening of microvascular complications when rapid glycemic control is achieved,which serves to alleviate patient morbidity,enhance disease management compliance,and possibly to avoid medico-legal issues around this rare clinical problem.This editorial delves into the dynamics surrounding the acute exacerbation of microvascular complications in poorly controlled DM during rapid glycaemic control.

Association of Interleukin-6-174G/C Polymorphism with the Risk of Diabetic Nephropathy in Type 2 Diabetes:A Meta-analysis

Previous studies reported the association between interleukin-6(IL-6)-174G/C gene polymorphism and the risk of diabetic nephropathy in type 2 diabetes mellitus(T2DN).However,the results remain controversial.In the present study,we conducted a meta-analysis to further examine this relationship between IL-6-174G/C gene polymorphism and T2DN.Three databases(PubMed,SinoMed and ISI Web of Science)were used to search clinical case-control studies about IL-6-174G/C polymorphism and T2DN published until Apr.14,2018.Fixed-or random-effects n lodels were used to calculate the effect sizes of odds ratio(OR)and 95%confide nee intervals(95%CI).Moreover,subgroup analysis was performed in tenns of the excretion rate of albuminuria.All the statistical analyses were con ducted using Stata 12.0.A total of 11 case-control studies were included in this study,involving 1203 cases of T2DN and 1571 cases of T2DM without DN.Metaanalysis showed that there was an association between IL-6-174G/C polymorphism and increased risk of T2DN under the allelic and recessive genetic models(G vs.C:OR=1.10,95%CI 1.03-1」&P=0.006;GG vs.CC+GC:OR=1.11,95%CI 1.02-1.21,P=0.016).In the subgroup analysis by albuminuria,a significant association of IL-6-174G/C polymorphism with risk of T2DN was noted in the microalbuminuria group under the recessive model(OR=1.54,95%CI 1.02-2.32,P=0.038).In conclusion,this meta-analysis suggests that IL-6-174G/C gene polymorphism is associated with the risk of T2DN.

New perspectives in the management of diabetic nephropathy

Diabetic nephropathy(DN)is the leading cause of end-stage renal disease and is also associated with increased risk for cardiovascular events.Until recently,strict glycemic control and blockade of the renin-angiotensin system(RAS)constituted the mainstay of treatment of DN.However,randomized controlled trials showed that sodium-glucose cotransporter 2 inhibitors further reduce the progression of DN.Therefore,these agents are recommended in all patients with DN regardless of DN stage and HbA1c levels.Moreover,additional blockade of the RAS with finerenone,a selective non-steroidal mineralocorticoid receptor antagonist,was also shown to prevent both the decline of renal function and cardiovascular events in this population.Finally,promising preliminary findings suggest that glucagon-like peptide 1 receptor agonists might also exert reno-and cardioprotective effects in patients with DN.Hopefully,this knowledge will improve the outcomes of this high-risk group of patients.

Dual therapy of rosiglitazone/pioglitazone with glimepiride on diabetic nephropathy in experimentally induced type 2 diabetes rats

Diabetic nephropathy is a major cause of end-stage renal disease （ESRD） in the general population. It is estimated that diabetic nephropathy will eventually develop in about 40% of all patients with diabetes; therefore, prevention is critical for delaying the development and progression of diabetic kidney disease. Despite extensive efforts, medical advances are still not successful enough to prevent the progression of the disease. In the present study, we focused on the comparison of combination therapies and whether they offered additional renoprotection. Type 2 diabetes mellitus was induced by intraperitoneally administering streptozotocin （90 mg/kg） in neonatal rats and then these rats were treated with rosiglitazone （1.0 mg/kg） in combination with glimepiride （0.5 mg/kg） or with pioglitazone （2.5 mg/kg） in combination with glimepiride （0.5 mg/kg）. Diabetic nephropathy markers were evaluated by biochemical and ELISA kits and renal structural changes were examined by light microscopy and transmission electron microscopy. Results show that the combination of pioglitazone with glimepiride is more effective in amelioration of diabetic nephropathy than rosiglitazone with glimepiride drug therapy due to glycemic control, suppressing albumin excretion rate, total protein excretion rate and augmented TNF-α signaling during the development of streptozotocin induced type 2 diabetic nephropathy.

Prevalence of Microvascular Complications and Associated Risk Factors among Diabetes Mellitus Patients Attending Nyeri County Referral Hospital, Kenya: A Cross-Sectional Study

Microvascular complications are one of the major causes of morbidity and mortality worldwide among patients with diabetes mellitus (DM). More than 50% of Nyeri County Referral Hospital (NCRH) admissions result from non-communicable diseases (NCDs) and over 55% of hospital deaths are attributable to NCDs. In Kenya, Nyeri County has the highest prevalence of diabetes mellitus compared to other counties. This study therefore sought to assess the prevalence of microvascular complications and the associated risk factors among patients attending Nyeri County Referral Hospital in Kenya. A hospital-based cross-sectional study was conducted on 314 DM patients on follow-up at NCRH from August 2022 to October 2022. Data were analyzed using STATA version 17. Univariate and multivariate logistic regression analyses are used to determine the risk factors associated with Microvascular complications of DM. Among the 314 participants with DM, 58% were females. The overall prevalence of Microvascular complications (MVCs) is 36.62%. Diabetic peripheral neuropathy was the most frequent complication (27.4%). Inadequate physical exercise was a risk factor for all MVCs. Age, marital status, and level of education were risk factors for neuropathy while smoking and alcohol intake were risk factors for nephropathy. Non-smokers were 98% less likely to have nephropathy (OR = 0.024;95% CI 0.003 - 0.145). The odds of those who exercise once weekly getting retinopathic complications reduced by 83% (OR = 0.18, 95% CI 0.049 - 0.398) compared to those who exercise daily. The findings highlight the implication of lifestyle factors in the development of MVCs among DM patients. Therefore, benefits of microvascular complications prevention should thus be factored into the management of patients with diabetes mellitus.

Non-Diabetic Renal Disease in Patients with Type 2 Diabetes Mellitus with Proteinuria

Background: Diabetes mellitus (DM) is the leading cause of end stage renal disease (ESRD) worldwide. Although DM with proteinuria is the ultimate result of diabetic nephropathy (DN), a wide spectrum of non-diabetic renal diseases (NDRD) can occur in such patients. Objective: To observe the frequency and histological pattern of NDRD in diabetic patients with proteinuria and to explore their association with clinical and laboratory parameters. Methods: This cross-sectional study was conducted in the Department of Nephrology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from April 2016 to September 2017. In this study a total of 38 cases of DM with proteinuria (>1 gm/24-hour) were selected purposively. Renal biopsy was done in all patients. Based on histological findings they were categorized into two groups;Group 1 with NDRD and Group II with DN. Their clinical and laboratory parameters were analyzed and compared. Results: Among the total study subjects, 21 (55.3%) were male and 17 (44.7%) were female, mean (±SD) age 43.45 ± 9.99 years in the NDRD group and 41.57 ± 9.50 years in the DN group. Thirty one cases (81.6%) out of thirty eight had NDRD and seven (18.4%) cases had isolated DN;therefore more than two third cases had NDRD. Duration of DM was found to be significantly shorter (p = 0.004) in the NDRD group. Diabetic retinopathy was present in 12.9% cases in NDRD group vs. 57.1% cases in DN group (p = 0.025). Frequency of microscopic hematuria was significantly higher (90.3%) in NDRD patients (p = 0.002). Conclusion: The frequency of NDRD in type 2 diabetic patients other than diabetic nephropathy is relatively high. Membrano proliferative glomeru-lonephritis and membranous nephropathy are more common in NDRD. Absence of diabetic retinopathy, presence of hematuria and shorter duration of DM are markers associated with NDRD in type 2 DM, which are important indicators for renal biopsy in diabetic patients with proteinuria.

Unleashing the pathological role of epithelial-to-mesenchymal transition in diabetic nephropathy: The intricate connection with multifaceted mechanism

Renal epithelial-to-mesenchymal transition(EMT)is a process in which epithelial cells undergo biochemical changes and transform into mesenchymal-like cells,resulting in renal abnormalities,including fibrosis.EMT can cause diabetic neph-ropathy through triggering kidney fibrosis,inflammation,and functional impair-ment.The diverse molecular pathways that drive EMT-mediated renal fibrosis are not utterly known.Targeting key signaling pathways involved in EMT may help ameliorate diabetic nephropathy and improve renal function.In such settings,un-derstanding precisely the complicated signaling networks is critical for develo-ping customized therapies to intervene in EMT-mediated diabetic nephropathy.

Establishment of a metabolite diagnostic model for the risk of diabetic nephropathy in type 2 diabetic population:Based on a cross-sectional study in China

Introduction:This study aimed to investigate the correlation between various plasma metabolites and the likelihood of developing diabetic nephropathy(DN)and construct a diagnostic model for DN in Chinese patients with type 2 diabetes mellitus(T2DM).Methods:A cross-sectional investigation was conducted in a hospital setting.Based on medical data,a total of 743 patients from a tertiary hospital were selected and categorized into two groups:the diabetic nephropathy group(DN group)and the non-diabetic nephropathy group(non-DN group).Plasma levels of metabolites,including amino acids and acylcarnitines,were determined using a laser counter measurement system(LC-MS).Subsequently,partial least-squares regression was used to assess the significance of these metabolites.Receiver operating characteristic(ROC)curves were generated for factors that ranked highest in terms of relevance.Model performance was assessed using the curve(AUC).Results:Of the 743 patients with T2DM admitted to the hospital,145 had DN.Compared with the non-DN group,the DN group exhibited elevated systolic blood pressure(P=0.001),high-density lipoprotein cholesterol(P=0.01),and low-density lipoprotein cholesterol(P=0.042).Additionally,the DN group had a higher prevalence of stroke patients(P<0.001)and diabetic retinopathy patients(P<0.001).Finally,a risk model that included citrulline,leucine,tyrosine,valine,propionylcarnitine(C3),and palmitoylcarnitine(C16)was developed.This model achieved an AUC of 0.709,with a 95%confidence interval(CI)ranging from 0.626 to 0.793.Conclusions:A diagnostic model consisting of six plasma metabolites to assess the risk of DN in Chinese patients with T2DM may provide clues for future research.

Diversity of Intestinal Flora in Elderly Patients with Type 2 Diabetes Mellitus with Early Nephropathy

Objective:To investigate the intestinal flora in elderly patients with type 2 diabetes mellitus with early nephropathy.Methods:43 elderly patients with type 2 diabetes mellitus with early nephropathy(diabetic nephropathy group)and 51 elderly patients with type 2 diabetes mellitus(type 2 diabetes mellitus group)admitted to our hospital from January 2021 to October 2022 were retrospectively analyzed,with 39 healthy people who underwent a physical examination in our hospital during the same period as the control group.The fecal specimens of the three groups were collected,and the 16S rDNAs of bacteria in the fecal samples were extracted,amplified,and sequenced for intestinal flora operational taxonomic unit(OTU)classification and Alpha diversity analysis.Results:(1)Intestinal flora OTUs:there were 545 intestinal flora OTUs unique to the control group,424 intestinal flora OTUs unique to diabetic nephropathy,and 321 intestinal flora OTUs unique to the type 2 diabetes group.There were 403 intestinal flora OTUs common to the control group and diabetic nephropathy group,256 intestinal flora OTUs common to the control group and type 2 diabetes group,and 298 intestinal flora OTUs common to the type 2 diabetes group and diabetic nephropathy group.235 intestinal flora OTUs were common to all 3 groups of subjects.(2)Alpha diversity:The statistical analysis indicated that there was a statistically significant difference(P<0.05)in the Alpha diversity of intestinal flora,as assessed by the Ace index and Simpson’s index,among the three subject groups.However,no statistical significance(P>0.05)was observed when comparing the Chao 1 index and Shannon index.Further observation of the Ace index and Simpson index in the three groups revealed that both the diabetic nephropathy group and the type 2 diabetes mellitus group had lower values than the control group.Conclusion:The diversity of intestinal flora decreases in elderly patients with type 2 diabetes mellitus with early nephropathy.

Study of Angiotensin Converting Enzyme Gene Polymorphism in Egyptian Type 2 Diabetes Mellitus with Diabetic Kidney Disease

Objective: Diabetic kidney disease DKD (Diabetic nephropathy DN) is considered one of the chronic micro vascular complications of diabetes mellitus and considered the commonest cause leading to chronic renal failure and chronic renal dialysis. Genetic susceptibility has been implicated in DKD. The angiotensin converting enzyme (ACE) is one of the key roles in the renin angiotensin system cascade by converting angiotensin I to angiotensin II which plays a key role in regulation of blood pressure as well as electrolytes and fluid balance. This study addressed the association of (ACE) gene polymorphisms with DN in Egyptian (T2DM) patients. Methods: Our research comprised of 75 cases of T2DM with diabetic kidney disease, 100 cases of T2DM without DKD and 94 healthy volunteers. Different genotypes of ACE gene were determined by SSP-PCR analysis. Results: Gene polymorphism of ACE (DD, ID, II) in diabetic patient with DKD is 44%, 52%, 4% respectively and for T2DM individuals without DKD is 23%, 72%, 5% respectively. (DD) had significant higher frequencies in T2DM patients with DKD compared to those without DKD (p < 0.005) and (ID) had significant higher frequencies in T2DM without DKD (p < 0.0001). These results indicated that there is an association between ACE gene polymorphisms and susceptibility of diabetic patients to be affected by diabetic kidney disease. Conclusion: From our results, we can conclude that genotype of ACE in Egypt DD is the genotype of cases diabetic kidney disease. So the presence of D allele has a significant relation with diabetic kidney disease. Our data confirm the role of ACE in its relationship with diabetic kidney disease in Egyptian type 2 diabetic patients.

Clinical Features and Microvascular Complications Risk Factors of Early-onset Type 2 Diabetes Mellitus

The aim of this research was to study the clinical features and microvascular complications risk factors of early-onset type 2 diabetes mellitus(T2DM).We analyzed the clinical data from 1421 T2DM inpatients at Wuhan Union Hospital.Subjects were divided into early-onset T2DM group(diagnostic age<40 years)and late-onset T2DM group(diagnostic age>40 years).All subjects underwent a standardized assessment of microvascular complications.Data were compared with independent-samples t test or Chi-square test.Multiple logistic regression was used to determine the risk factors of microvascular complications.Patients with early-onset T2DM were more inclined to have a lower systolic blood pressure(SBP),a longer duration of diabetes and higher levels of body mass index(BM1),uric acid(UA),fasting plasma glucose(FPG),total cholesterol(TC),triglyceride(TG)and glycosylated hemoglobin(HbAlc)than those with lateonset T2DM(P<0.05).The prevalence of diabetic retinopathy(DR)was significantly higher and that of diabetic peripheral neuropathy(DPN)was significantly lower in early-onset group than in late-onset group(P<0.05).For DN,UA was an independent risk factor in early-onset T2DM.SBP and TG were independent risk factors in late-onset T2DM.For DR,duration of diabetes and SBP were independent risk factors in early-onset T2DM.Duration of diabetes,SBP and HbAlc were independent risk factors in late-onset T2DM.This study demonstrated that the clinical characteristics of early-onset T2DM were metabolic disorders,including glucose metabolism,lipid metabolism and amino acid metabolism.Early-onset T2DM was more likely to be associated with DR.The potential pathogenesis of early and late-onset T2DM might be different.The management of metabolic risk factors especially HbA1c,SBP,TG and UA is advised to be performed in the early stage of diabetes.

Association of genetic variants with diabetic nephropathy

Diabetic nephropathy accounts for the most serious microvascular complication of diabetes mellitus. It is suggested that the prevalence of diabetic nephropathy will continue to increase in future posing a major challenge to the healthcare system resulting in increased morbidity and mortality. It occurs as a result of interaction between both genetic and environmental factors in individuals with both type 1 and type 2 diabetes. Genetic susceptibility has been proposed as an important factor for the development and progression of diabetic nephropathy, and various research efforts are being executed worldwide to identify the susceptibility gene for diabetic nephropathy. Numerous single nucleotide polymorphisms have been found in various genes giving rise to various gene variants which have been found to play a major role in genetic susceptibility to diabetic nephropathy. The risk of developing diabetic nephropathy is increased several times by inheriting risk alleles at susceptibility loci of various genes like ACE, IL, TNF-α, COL4A1, e NOS, SOD2, APOE, GLUT, etc. The identification of these genetic variants at a biomarker level could thus, allow the detection of those individuals at high risk for diabetic nephropathy which could thus help in the treatment, diagnosis and early prevention of the disease. The present review discusses about the various gene variants found till date to be associated with diabetic nephropathy.

Development and Validation of a Model for Predicting Diabetic Nephropathy in Chinese People

Objective To develop a risk model for predicting later development of diabetic nephropathy （DN） in Chinese people with type 2 diabetes mellitus （T2DM） and evaluate its performance with independent validation. Methods We used data collected from the project ＇Comprehensive Research on the Prevention and Control of Diabetes＇, which was a community-based study conducted by the Jiangsu Center for Disease Control and Prevention in 2013. A total of 11,771 eligible participants were included in our study. The endpoint was a clear diagnosis of DN. Data was divided into two components： a training set for model development and a test set for validation. The Cox proportional hazard regression was used for survival analysis in men and women. The model＇s performance was evaluated by discrimination and calibration. Results The incidence （cases per 10,000 person-years） of DN was 9.95 （95% CI; 8.66-11.43） in women and 11.28 （95% CI; 9.77-13.03） in men. Factors including diagnosis age, location, body mass index, high-density-lipoprotein cholesterol, creatinine, hypertension, dyslipidemia, retinopathy, diet control, and physical activity were significant in the final model. The model showed high discrimination and good calibration. Conclusion The risk model for predicting DN in people with T2DM can be used in clinical practice for improving the quality of risk management and intervention.

Is there a role for glucagon-like peptide-1 receptor agonists in the management of diabetic nephropathy?

Chronic kidney disease constitutes a major microvascular complication of diabetes mellitus.Accumulating data suggest that glucagon-like peptide-1 receptor agonists(GLP-1 RAs)might have a role in the management of diabetic kidney disease(DKD).GLP-1 RAs appear to reduce the incidence of persistent macro-albuminuria in patients with type 2 diabetes mellitus.This beneficial effect appears to be mediated not only by the glucose-lowering action of these agents but also on their blood pressure lowering,anti-inflammatory and antioxidant effects.On the other hand,GLP-1 RAs do not appear to affect the rate of decline of glomerular filtration rate.However,this might be due to the relatively short duration of the trials that evaluated their effects on DKD.Moreover,these trials were not designed nor powered to assess renal outcomes.Given than macrolbuminuria is a strong risk factor for the progression of DKD,it might be expected that GLP-1 RAs will prevent the deterioration in renal function in the long term.Nevertheless,this remains to be shown in appropriately designed randomized controlled trials in patients with DKD.