The manganese superoxide dismutase Val16Ala polymorphism is associated with decreased risk of diabetic nephropathy in Chinese patients with type 2 diabetes

The aim of the present study was to evaluate the relationship of the manganese superoxide dismutase (MnSOD) Val16Ala (V16A) polymorphism with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN) in Chinese patients, a case-control study was performed. This case-control study included 172 non-diabetic (non-DM) subjects and 257 T2DM patients with or without DN. Among T2DM patients, 154 had DN [albumin excretion rate (AER) >or= 30 mg/24 h] and 103 did not (AER < 30 mg/24 h), but the latter with known diabetes duration >or=10 years. The DN patients were further divided into groups with microalbuminuria (DN-1; n = 92; 300 > AER >or= 30 mg/24 h) and overt albuminuria nephropathy (DN-2; n = 62; AER >or= 300 mg/24 h). PCR-restriction fragment length polymorphism (RFLP) was used to detect genotypes of the V16A polymorphism for all subjects. The genotypic distributions of the V16A polymorphism in non-DM and T2DM subjects were in Hardy-Weinberg equilibrium and Ala allelic frequencies did not differ (11.9% vs. 9.1%; P > 0.05). The AA+VA genotypic frequencies of DN patients were significantly lower than those of non-DN patients (11.6% vs. 24.3%; P = 0.008). Multiple logistic regression analysis revealed that except for HbA1C, triglyceride, and BMI, which were high risk factors for the development of DN, the AA+VA genotype of the MnSOD-V16A polymorphism was an independent protective factor from the development of DN (odds ratio = 0.42; 95% CI = 0.18-0.95; P = 0.037) in T2DM patients. Our results suggested that the MnSOD-V16A polymorphism is associated with decreased risk of diabetic nephropathy in Chinese patients with type 2 diabetes.     

High levels of circulating interleukin-10 in diabetic nephropathy patients

AIMS: The aim of our study was to analyse the level of circulating interleukin-10 (IL-10) and relate it to the grade of albuminuria in patients with diabetic nephropathy (DN) due to type 1 diabetes mellitus (DM). Since IL-10 has met the criteria for an anti-inflammatory and an immunosuppressive cytokine, its activity may be important for clinical outcome of DN. METHODS: The IL-10 level was measured by ELISA in serum samples from thirty patients with DN due to type 1 DM, and compared with thirty patients with type 1 DM without DN and a control group of thirty, healthy, age- and sex-matched people. RESULTS: We observed a greatly elevated concentration of circulating IL-10 in 30/30 DM patients with DN (mean 140 pg/mL +/- 102), compared to DM patients without DN in whom IL-10 was detectable in only 11/30 patients (0.79 pg/mL +/- 1.24), and the group of healthy people in whom IL-10 was detectable in only 3/30 donors (0.92 pg/mL +/- 0.17). IL-10 appeared to be the strongest independent predictor of albuminuria, followed by HbA1c, diastolic blood pressure and DN duration. There was a positive correlation between the values of IL-10 and albuminuria in DM patients with DN. The patients in the fourth quartile of albuminuria had a distinctly higher concentration of IL-10 than those in the lower quartiles. CONCLUSIONS: The increased concentration of IL-10 in the serum samples from DM patients with DN seems to depend on the severity of the nephropathy. The excessive IL-10 production may indirectly contribute towards DN progression. On the other hand, it may explain the relatively long course of diabetic nephropathy.     

血小板/淋巴细胞比值在老年2型糖尿病患者肾功能损害及病情评估中的应用价值

目的:研究血小板/淋巴细胞比值(PLR)在老年2型糖尿病(T2DM)患者肾功能损害及病情评估中的应用价值。方法:测定506例T2DM患者及250例健康体检者(对照组)的血常规、血糖、血脂、肝肾功等生化指标,并收集尿液测定尿白蛋白/肌酐比值(ACR)。根据《糖尿病肾病防治专家共识(2014年版)》,将T2DM患者分为DN组(n=279)和非DN组(n=227),并根据ACR将DN组分为微量白蛋白尿组(n=165,30～300 mg/24 h)、大量白蛋白尿组(n=114,≥300 mg/24 h)。比较各组患者临床指标,分析PLR与老年T2DM患者并发DN的相关性。结果:与对照组比较,非DN组、DN组HbAlc、FPG、2h PG、Scr、BUN、PLT、PLR明显升高,LYM明显下降(P0.05);与非DN组比较,微量白蛋白尿组HbAlc、2h PG、Scr、UAER、eGFR明显升高,大量白蛋白尿组HbAlc、FPG、2h PG、Scr、BUN、UAER、eGFR、PLT、PLR明显升高,LYM明显下降(P0.05);与微量白蛋白尿组,大量白蛋白尿组FPG、Scr、BUN、UAER、eGFR、PLT、PLR明显升高,LYM明显下降(P0.05)。多因素logistics回归分析显示HbAlc、PLR是T2DM患者进展为DN的独立危险因素,而eGFR则是保护性因素(P0.05)。HbAlc、eGFR、PLR联合预测T2DM患者并发DN的敏感性、特异性分别为83.1%,特异度为81.9%,均显著高于三个指标单独评估的敏感性、特异性(P0.05)。结论:PLR是老年T2DM患者肾功能损害的独立危险因素,综合HbAlc、eGFR、PLR有助于老年T2DM患者并发DN及病情评估。     

Comparison of 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels using mass spectrometer and urine albumin creatinine ratio as a predictor of development of diabetic nephropathy

Abstract

Background. Measurement of urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) has recently become more popular as a means of assessing oxidative stress in the human body. The aim of this study is to compare the levels of urine 8-OHdG in patients with type 2 diabetes with and without nephropathy and to evaluate its role as a biochemical marker for distinguishing these patients from healthy and patients without complications. Methods. For this purpose, 52 patients with type 2 diabetes mellitus (32 with nephropathy (DMN), 20 without nephropathy (DM)) and 20 healthy control subjects (C) were included in this study. The urine concentrations of 8-OHdG were measured by modified LC-MS/MS method and compared with the first morning voiding urine albumin/creatinine ratio (UACR) and HbA1c values of the same patients. Results. The concentrations of urine 8-OHdG in DMN and DM patients were higher than those of the control subjects (3.47?±?0.94, 2.92?±?1.73, 2.1?±?0.93 nmol/mol creatinine, respectively). But there was no statistical difference between DMN and DM (p =?0.115). There is significant correlation between urinary 8-OHdG and UACR (r =?0.501, p <?0.001). According to ROC analysis, the AUC value of HbA1c was higher than the value of the AUC of 8-OHdG (0.882 and 0.771, respectively). Conclusions. This study shows that the urine 8-OHdG levels increase in diabetic patients. However, urinary 8-OHdG is not a useful clinical marker, compared with UACR, to predict the development of diabetic nephropathy in diabetic patients.     

Diabetic Retinopathy,Classified Using the Lesion-Aware Deep Learning System,Predicts Diabetic End-Stage Renal Disease in Chinese Patients

Objective: To characterize the relationship between diabetic retinopathy (DR) and diabetic nephropathy (DN) in Chinese patients and to determine whether the severity of DR predicts end-stage renal disease (ESRD).Methods: Bilateral fundic photographs of 91 Chinese type 2 diabetic patients with biopsy-confirmed DN, not in ESRD stage, were obtained at the time of renal biopsy in this longitudinal study. The baseline severity of DR was determined using the Lesion-aware Deep Learning System (RetinalNET) in an open framework for deep learning and was graded using the Early Treatment Diabetic Retinopathy Study severity scale. Cox proportional hazard models were used to estimate the hazard ratio (HR) for the effect of the severity of diabetic retinopathy on ESRD.Results: During a median follow-up of 15 months, 25 patients progressed to ESRD. The severity of retinopathy at the time of biopsy was a prognostic factor for progression to ESRD (HR 2.18, 95% confidence interval 1.05 to 4.53, P = .04). At baseline, more severe retinopathy was associated with poor renal function, and more severe glomerular lesions. However, 30% of patients with mild retinopathy and severe glomerular lesions had higher low-density lipo-protein-cholesterol and more severe proteinuria than those with mild glomerular lesions. Additionally, 3% of patients with severe retinopathy and mild glomerular changes were more likely to have had diabetes a long time than those with severe glomerular lesions.Conclusion: Although the severity of DR predicted diabetic ESRD in patients with type 2 diabetes mellitus and DN, the severities of DR and DN were not always consistent, especially in patients with mild retinopathy or microalbuminuria.Abbreviations: CI = confidence interval; DM = diabetic mellitus; DN = diabetic nephropathy; DR = diabetic retinopathy; eGFR = estimated glomerular filtration rate; ESRD = end-stage renal disease; HbA1c = hemoglobin A1c; HR = hazard ratio; NPDR = nonproliferative diabetic retinopathy; PDR = proliferative diabetic retinopathy; SBP = systolic blood pressure; T2DM = type 2 diabetes mellitus; VEGF = vascular endothelial growth factor     

Proteome analysis of serum from type 2 diabetics with nephropathy

Diabetic nephropathy (DN) is a renal disease which develops as a consequence of diabetes mellitus. Microalbuminuria is the earliest clinical sign of DN. There are no specific diagnostic biomarkers for type 2 diabetics with nephropathy other than microalbuminuria and macroalbuminuria. However, microalbuminuria does not constitute a sole independent indicator for type 2 diabetics with nephropathy, and thus, another screening method, such as a biomarker assay, is required in order to diagnose it more correctly. Therefore, we have utilized two-dimensional electrophoresis (2-DE) to identify human serum protein markers for the more specific and accurate prediction of progressive nephropathy in type 2 diabetes patients, via comparisons of the serum proteome in three experimental groups: type 2 diabetes patients without microalbuminuria (DM, n = 30), with microalbuminuria (MA, n = 29), and with chronic renal failure (CRF, n = 31). As a result, proteins which were differentially expressed with statistical significance (p < 0.05) in MA and CRF groups as compared to those in DM group were selected and identified by ESI-Q-TOF MS/MS. Among these identified proteins, two proteins which might be useful as diagnostic biomarkers of type 2 diabetics with nephropathy were verified by Western blotting: extracellular glutathione peroxidase (eGPx) and apolipoprotein (ApoE) were found to exhibit a progressive reduction in MA and CRF groups. Notably, eGPx was further verified by ELISA using DM (n = 100) and MA (n = 96) patient samples. Collectively, our results show that the two proteins identified in this study may constitute potential biomarkers for the diagnosis of type 2 diabetics with nephropathy.     

Blood Glucose,HbA1c Level,and its Correlation with VEGF-A (+405G/C) Polymorphism as Biomarker Predicts the Risk of Retinopathy and Nephropathy in Type 2 Diabetic Patients

Background:Diabetes-related vascular complications linked to increase in the expression of VEGF and its receptors. It helps to accelerate tissue damage inflicted by hyperglycemia, which is potential risk for diabetic complications. The study aimed to assess VEGF genetic polymorphism and its correlation with glucose and HbA1C level among Sudanese patients with diabetic retinopathy and nephropathy.Methods:A case-control study was conducted among a total of 252 subjects and divided into four groups of 63 subjects each. Glucose and HBA1c were measured then the VEGF gene was amplified using polymerase chain reaction. The data were analyzed using SPSS.Results:The HBA1c, and blood glucose levels had significantly (P value≤0.00001) highest mean in the DR group, DN group followed by DM. There is a non-significant correlation between VEGF Genotypes and HbA1c, and blood glucose levels (P value≤0.102, 0.173) Patients with GC genotypes will be 74.6%, and 54% higher at risk to develop DR, and DN respectively and 40 % lower at risk to develop DM than those without GC genotype. While patients with CC genotypes will be 22.2% higher at risk of developing DM and 9.5%, 12.2% higher at risk of developing DR and DN respectively.DiscussionThe VEGF +405G/C gene polymorphism is linked to diabetic retinopathy, and diabetic nephropathy in type 2 Sudanese diabetics, and the presence of the GC genotypes and G allele is a significant predictor for retinopathy. There is no significant relation between HbA1C serum levels, blood glucose, and the VEGF +405G/C gene polymorphism.Key Words: Diabetic Nephropathy, Diabetic Retinopathy, Blood Glucose, HbA1c, Gene polymorphism, VEGF-A     

BsmI polymorphisms in vitamin D receptor gene are associated with diabetic nephropathy in type 2 diabetes in the Han Chinese population

We investigated the relationship between BsmI/ApaI polymorphisms in vitamin D receptor gene and diabetic nephropathy in a Han Chinese population. PCR-restriction fragment length polymorphism was used to test the genotype and allele frequency of BsmI and ApaI polymorphisms in 304 patients with type 2 diabetes mellitus (DM group) and 100 control individuals (ND group). The DM group was further divided into DN0 (no diabetic nephropathy), DN1 (diabetes with small amount of albuminuria), DN2 (diabetes with large amount of albuminuria), L/NDN (late-onset DN after 5 years/no DN over the whole follow-up period of 5 years) and EDN (early-onset diabetic nephropathy occurring within first year) subgroup. We found that (1) genotype and allele frequency of BsmI polymorphism had significant difference between DM and ND group; BB+Bb genotype and B allele frequency were significantly higher in DN2 group than in ND and DN0 group; the ApaI polymorphism and allele frequency did not show any difference between DM and ND group; (2) BsmI BB+Bb genotype and B allele frequency were significantly higher in EDN group than in L/NDN group; (3) among patients with nephropathy, albumin excretion rate (AER) in 24-hour urine was significantly higher in those with BB+Bb phenotype than in those with bb phenotype (P<0.01), (4) unconditional logistic regression analysis showed that BsmI BB+Bb genotype was not only correlated with type 2 diabetic nephropathy, but also correlated with early-onset type 2 diabetic nephropathy. We conclude that the allele B (BB or Bb genotype) in vitamin D receptor gene is correlated with large amount albuminuria in the Han Chinese population with type 2 diabetes, and is probably a risk factor for early-onset diabetic nephropathy.     

Angiotensin converting enzyme (ACE) activity levels in insulin-independent diabetes mellitus and effect of ACE levels on diabetic patients with nephropathy

Involvement of complications is considered to be one of the major factors in the prognosis of diabetes mellitus (DM). Recent studies indicate that most diabetic complications such as nephropathy and hypertension are vascular-originated. Renin-angiotensin involvement, especially changes in ACE activity level, is considered to be a key factor since ACE converts angiotensin I to angiotensin II which is a potent vasoconstrictor and plays a vital role in the regulation of blood pressure. Our present study focused on ACE activity levels along with blood glucose and HbA(1c) levels in diabetic patients with (n=18) or without (n=25) nephropathy as compared to control subjects (n=25). Blood glucose levels were significantly higher in both diabetic groups compared to controls (p<0.001). On the other hand, compared to controls, blood HbA(1c) levels were slightly higher in DM patients without complications whereas they were significantly increased in nephropatic DM patients (p<0.001). There was a very strong increase (p<0.001) at the level of ACE activity in both of the diabetic groups (with nephropathy: 47.11+/-3.70 U l(-1); without complications: 43.72+/-2.93 U l(-1); controls: 25.15+/-2.30 U l(-1)). ACE activity levels were also significantly higher in diabetic patients with nephropathy than in type II DM patients without complication (p<0.01). Our results demonstrate that ACE activity levels are increased in diabetic patients. Additional significant increase in ACE activity levels in diabetic patients with complications such as nephropathy supports the hypothesis that ACE activity has an essential role in the development of complications in diabetes.     

Increased serum levels of interleukin-18 in patients with diabetic nephropathy

In the present study we measured interleukin-18 (IL-18) and tumour necrosis factor-alpha (TNF-alpha) levels by enzyme linked immunosorbent assay (ELISA) in sera from 65 diabetic [30 with type 1 insulin dependent diabetes mellitus (IDDM) and 35 with type 2 non-insulin dependent diabetes mellitus (NIDDM)] patients and 15 healthy volunteers, to investigate their associations with metabolic parameters and to elucidate their roles in the pathogenesis of diabetic complications especially diabetic nephropathy. Levels of IL-18 and TNF-alpha were significantly higher in both IDDM and NIDDM individuals as compared to the control group. Similarly, their levels in patients with diabetic nephropathy increased gradually according to the clinical stage of the disease, being highest in macroalbuminuric stage. Correlation analyses showed that the serum IL-18 and TNF-alpha concentration were positively correlated with each other and positively with fasting plasma glucose (FPG), 2h postprandial glucose, glycosylated hemoglobin (HbA1c), triglyceride, and urinary albumin levels and negative correlation between TNF-alpha and high density lipoprotein cholesterol (HDL-C) were also found in diabetic subjects. High serum levels of IL-18 and TNF-alpha suggested that they might play a role in the pathogenesis of DM and in the development of nephropathy in diabetic patients whether of type 1 or 2.     

维吾尔族2 型糖尿病患者糖尿病肾病相关因素分析

目的:探讨维吾尔族2型糖尿病肾病(DN)发病的相关临来因素。方法:分析292例维吾尔族2型糖尿病患者的临床资科。结果:维吾尔族2型糖尿病患者糖尿病肾病(DN)发病率为43.49%(127/292)。DN患者的病程、SBP、TC、TG、FBG、HbAIC、LDL-C、BUN和Cr均显著高于NDN患者(P<0.05);但DBP、HDL-C、BMI之间无统计学差异(P>0.05)。Logistic归分析结果显示,DM病程、患病年龄、SBP、FBP、TC、TG、LDL-C、HbA1c、BUN、Cr是DN的危险因素(OR值>1)。结论:维吾尔族2型糖尿病患者的DM病程、患病年龄、SBP、FBP、TC、TG、LDL-C、HbA1c、BUN、Cr等参数与糖尿病肾病并发率之间有相关性。     

Gene polymorphisms in patients with type 2 diabetes and diabetic nephropathy

A considerable variability in the incidence and prevalence of diabetic nephropathy (DN) coheres with an important contribution of multigenetic predisposition in the development of DN. Some genes, which probably participate in the pathogenesis of diabetic nephropathy, also play a role in the regulation of blood pressure, familial hyperlipidemia, familial hypertension and other diseases of the cardiovascular system. We have examined the association of diabetic nephropathy, nephropathy of non-diabetic origin, hypertension and of type 2 diabetes itself with several genetic polymorphisms (the insertion/deletion polymorphism in the gene for angiotensin-converting enzyme, the G/T polymorphism in the glucose transporter 1 gene, the G/T (894) polymorphism and the T/C (−786) polymorphism in the eNOS gene in three groups of patients with diabetes mellitus: 1) patients without diabetic nephropathy (DM); 2) patients with DN; 3) patients with nephropathy of non-diabetic origin (NDRD). Angiotensin-converting enzyme is an important factor in a development of arterial hypertension, but in our groups of Central European diabetic patients the I/D polymorphism was not associated with diabetic nephropathy. Furthermore, we have confirmed that the T/C (T786C) polymorphism in the eNOS gene is associated with metabolic syndrome including type 2 diabetes.     

糖尿病肾病患者血清亲环素水平及其临床意义

目的:探讨糖尿病肾病(DN)患者血清亲环素A(Cy PA)水平及其临床意义。方法:将我院2014年10月-2015年10月收治的86例2型糖尿病肾病(T2DN)患者依据24 h尿白蛋白排泄率(UAER)水平分为3组,即糖尿病无肾病组(SDM组) 30例、早期糖尿病肾病组(EDN组)28例、糖尿病肾病组(CDN组)28例。另选取同期本院健康体检者26例为对照组(NC组)。比较4组的血清Cy PA水平、收缩压(SBP)、舒张压(DBP)、糖化血红蛋白(HbA1c)、血肌酐(Cr)、尿素氮(BUN)水平。以EDN组为实验组,在常规控制血压、血糖、血脂等基础上,给予小剂量雷公藤多甙片治疗4周,分析Cy PA水平与24 h UAER的相关性。结果:SDM组、EDN组、CDN组的HbAlc水平显著高于CN组(P0.05)。EDN组、CDN组的24 h UAER水平显著高于SDM组和CN组(P0.05),CDN组的24 h UAER水平显著高于EDN组(P0.05),而EDN组和CN组的24 h UAER水平比较差异无统计学意义(P0.05)。SDM组、EDN组、CDN组、CN组血清Cy PA水平依次升高,两两比较差异均有统计学意义(P0.05)。糖尿病肾病患者血清Cy PA水平与24 h UAER呈正相关(r=0.697,P0.05)。结论:血清Cy PA水平在一定程度上能反映糖尿病肾病患者的肾损伤严重程度。     

The Association of Serum Bilirubin on Kidney Clinicopathologic Features and Renal Outcome in Patients with Diabetic Nephropathy: A Biopsy-Based Study

Objective: To explore the relationship between serum bilirubin concentration and clinicopathologic features and renal outcome in biopsy-diagnosed diabetic nephropathy (DN) in patients with type 2 diabetes mellitus.Methods: In this retrospective study, 118 patients with DN were enrolled. Participants were divided into two groups according to their median baseline serum bilirubin concentration: Group 1 (serum bilirubin ≤7.5 μmol /L); Group 2 (serum bilirubin >7.5 μmol /L). Basic clinical parameters were measured at the time of renal biopsy, and the relationships between serum bilirubin and the clinicopathologic features and renal outcome were analyzed.Results: Patients in Group 1 often had inferior renal function. Compared with Group 2, the glomerular classification and interstitial inflammation were more severe in subjects of Group 1, while arteriolar hyalinosis and interstitial fibrosis and tubular atrophy (IFTA) were comparable between the groups. Serum bilirubin was negatively correlated with the severity of the glomerular classification, interstitial inflammation, and IFTA. In the prognostic analysis, higher serum bilirubin level was associated with a lower risk of progression to end-stage renal disease, which was independent of the effects of age, gender, duration of diabetes, anemia, serum glucose, and hypertension but not of estimated glomerular filtration rate (hazard ratio, 0.406; 95% confidence interval, 0.074 to 2.225; P = .299).Conclusion: Our study showed a negative correlation between serum bilirubin level and renal pathologic lesions in patients with DN; serum bilirubin showed an inverse association with DN progression, but this was not independent.Abbreviations: CI = confidence interval; CKD = chronic kidney disease; DM = diabetes mellitus; DN = diabetic nephropathy; DR = diabetic retinopathy; eGFR = estimated glomerular filtration rate; ESRD = end-stage renal disease; HbA1c = glycated hemoglobin; HO-1 = heme oxygenase 1; HR = hazard ratio; IFTA = interstitial fibrosis and tubular atrophy; log-BIL = log-transformed baseline serum bilirubin; T2DM = type 2 diabetes mellitus     

Clinicopathologic Features and Prognosis of Type 2 Diabetes Mellitus and Diabetic Nephropathy in Different Age Groups: More Attention to Younger Patients

Objective: Our study sought to investigate the clinicopathologic features and renal prognosis of patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN) in different age groups.Methods: A total of 315 patients with T2DM and biopsy-proven DN were enrolled and divided into three groups by age: the Youth group (≤44 years old), the Middle-aged group (45 to 59 years old), and the Elderly group (≥60 years old).Results: The Youth group, Middle-aged group, and Elderly group accounted for 19.05% (60/315), 59.37% (187/315), and 21.59% (68/315) of the patients in our study, respectively. The patients in the Youth group had a higher estimated glomerular filtration rate (calculated using the Chronic Kidney Disease–Epidemiology collaboration formula) (P<.001), a higher incidence of diabetic retinopathy (P = .044), and a higher incidence of being in the lower-risk chronic kidney disease heat map category (P = .046) but lower duration of diabetes (P = .016). Histologically, patients in the Youth group had the highest incidence of glomerular classification in class I (P = .006) and arteriolar hyalinosis score of 0 (P = .005). The renal survival among the three groups was comparable (P>.05).Conclusion: This study indicated that there were different clinicopathologic features among Chinese DN patients in different age groups. Although the Youth group had a relatively lower rapid kidney disease progression rate, there were no significant differences in renal survival rate among the three groups, which calls more attention to early supervision and prevention for younger DN patients.Abbreviations: CKD = chronic kidney disease; DN = diabetic nephropathy; DR = diabetic retinopathy; eGFR = estimated glomerular filtration rate; ESRD = end-stage renal disease; G&Y&O = green and yellow and orange; IFTA = interstitial fibrosis and tubular atrophy; T2DM = type 2 diabetes mellitus     

Co-inheritance of specific genotypes of HSPG and ApoE gene increases risk of type 2 diabetic nephropathy

The objective of this paper is to investigate co-inheritance of specific HSPG and ApoE genotypes in the development of Chinese type 2 diabetic nephropathy. PCR-RFLP was used to detect HSPG and ApoE genotypes in 385 Chinese subjects including 298 patients with type 2 diabetes mellitus (T2DM) and 87 non-diabetic controls (Non-DM). The T2DM group was subdivided into patients with (TDN; n = 218) and without diabetic nephropathy (Non-DN; n = 80). The latter group was further subdivided into groups of patients with microalbuminuria nephropathy (DN-1; n = 129) and severe diabetic nephropathy (DN-2; n = 89). We then compared the relative frequencies of various HSPG and ApoE genotypes and alleles among the groups, searching for predictive trends. The T allele of the HSPG gene occurred more frequently in the DN-2 group than in the Non-DN or DN-1 or groups, their (Fisher's exact p was 1.05 × 10^–3 and 6.58 × 10^–6; odds ratios were 2.09 (95% CI 1.32–3.30) and 2.48 (95% CI 1.64–3.74), respectively. The E2 allele of the ApoE gene occurred more frequently in the T2DM than in the Non-DM group, the Fisher's exact p was 0.0087; odds ratio was 3.45 (95% CI 1.30–9.81). Genotype analysis showed that the TT or TG of HSPG gene were paired with the E2/2 or E2/3 of ApoE gene significantly more frequently in the TDN group than in the Non-DN group, with an odds ratio of 3.03 (95% CI 1.03–8.90). There was no significant differences in other combinations of genotypes in HSPG and ApoE genes between TDN and Non-DN group. These results suggest that the HSPG T allele is a risk factor for the development of severe diabetic nephropathy in type 2 diabetic patients, and that the ApoE E2 allele is a risk factor for the occurrence of type 2 diabetes mellitus in Chinese general population. In addition, we find that co-inheritance of T/E2 confers a higher risk of type 2 diabetes mellitus progression to diabetic nephropathy in Chinese.     

Identification of the Locus Associated with Diabetic Nephropathy in Type 1 Diabetes Mellitus

Polymorphic tetranucleotide microsatellites D3S1512, D3S1744, D3S1550, and D3S2326 were used to study the association of chromosome region 3q21–q25 neighboring the angiotensin II receptor type 1 gene (AT ₂ R1) with diabetic nephropathy (DN) in diabetes mellitus type 1 (DM1). Allele and genotype frequencies were compared for DM1 patients with (N = 39) or without (N = 62) DN. Fisher's exact test with Bonferroni's correction revealed significant differences in frequencies of two D3S2326 alleles, one D3S1512 allele, and one allele and one genotype of D3S1550. No significant difference was observed with D3S1744. Thus, region 3q21–q25 proved tightly associated with DN in ethnic Russians with DM1 from Moscow.     

Comparison of 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels using mass spectrometer and urine albumin creatinine ratio as a predictor of development of diabetic nephropathy

Abstract Background. Measurement of urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) has recently become more popular as a means of assessing oxidative stress in the human body. The aim of this study is to compare the levels of urine 8-OHdG in patients with type 2 diabetes with and without nephropathy and to evaluate its role as a biochemical marker for distinguishing these patients from healthy and patients without complications. Methods. For this purpose, 52 patients with type 2 diabetes mellitus (32 with nephropathy (DMN), 20 without nephropathy (DM)) and 20 healthy control subjects (C) were included in this study. The urine concentrations of 8-OHdG were measured by modified LC-MS/MS method and compared with the first morning voiding urine albumin/creatinine ratio (UACR) and HbA1c values of the same patients. Results. The concentrations of urine 8-OHdG in DMN and DM patients were higher than those of the control subjects (3.47?±?0.94, 2.92?±?1.73, 2.1?±?0.93 nmol/mol creatinine, respectively). But there was no statistical difference between DMN and DM (p =?0.115). There is significant correlation between urinary 8-OHdG and UACR (r =?0.501, p 相似文献   

2型糖尿病患者心脏代谢指数与白蛋白尿的关系研究

摘要 目的：探讨2型糖尿病（T2DM）患者心脏代谢指数（CMI）与白蛋白尿的关系。方法：选取2012年2月~2020年7月期间在江苏大学附属医院内分泌代谢科就诊且被诊断为T2DM的患者555例,收集患者的临床资料。根据CMI不同数值将患者分为低CMI（L-CMI）组（n=185）、中CMI（M-CMI）组（n=185）和高CMI（H-CMI）组（n=185）,按照尿白蛋白/肌酐比值（UACR）将研究对象分为正常白蛋白尿组（n=294）、微量白蛋白尿组（n=209）和大量白蛋白尿组（n=52）,然后对CMI与T2DM患者发生异常白蛋白尿的关系进行分析,通过受试者工作特征（ROC）曲线评估CMI对T2DM患者发生异常白蛋白尿的预测价值。结果：不同UACR组的收缩压（SBP）、舒张压（DBP）、体质量指数（BMI）、CMI、甘油三酯（TG）、总胆固醇（TC）、高密度脂蛋白胆固醇（HDL-C）、糖化血红蛋白（HbA1c）、空腹血糖（FPG）、空腹胰岛素（FINS）、空腹C肽（FC-P）、稳态模型评估胰岛素抵抗指数（HOMA-IR）、尿素氮（BUN）、血尿酸（SUA）、血肌酐（Scr）及肾小球滤过率（eGFR）比较均有统计学差异（P＜0.05）。L-CMI组、M-CMI组、H-CMI组异常白蛋白尿发生比例分别为21.08%、42.70%、77.30%,异常白蛋白尿发生比例呈显著递增趋势（P＜0.05）。Spearman秩相关分析结果显示,T2DM患者UACR与FINS、BUN、 CMI、Scr、SUA、SBP、DBP、BMI、TG、TC、HbA1c、FPG、FC-P、HOMA-IR呈正相关（P<0.05）,与eGFR、HDL-C呈负相关（P<0.05）。多元线性回归分析显示,CMI对UACR的影响强度最大（P＜0.05）。Logistic回归分析结果显示,年龄、SBP、CMI、TC、LDL-C及HbA1c是T2DM患者发生异常白蛋白尿的独立危险因素（P＜0.05）。CMI预测异常白蛋白尿发生的曲线下面积为0.801,预测异常白蛋白尿的敏感性、特异性分别为68.60%、76.90%。结论：T2DM患者异常白蛋白尿发生风险与CMI密切相关,提示CMI有望成为临床上糖尿病肾病（DKD）的预测指标。