Serum matrix metalloproteinases MMP-2 and MMP-9 and metalloproteinase tissue inhibitors TIMP-1 and TIMP-2 in diabetic nephropathy

BACKGROUND: The regulation of mesangial extracellular matrix (ECM) turnover engages a number of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). High glucose concentration affects ECM degradation and the activities of MMPs and TIMPs. ECM accumulation is involved in the pathogenesis of diabetic nephropathy. METHODS: Serum MMP-9, MMP-2, TIMP-2 and TIMP-1 were measured with ELISA in patients with either chronic renal failure (CRF, n=20), type 2 diabetes mellitus (DM2, n=16) or diabetic nephropathy (DM2+CRF, n=14), and healthy controls (n=20). RESULTS: Diabetic nephropathy was related with profound decrease of serum TIMP-2 (122.2 +/- 47.2 vs. 263.0 +/- 89.2 ng/mL), TIMP-1 (242.5 +/- 96.9 vs. 347.4 +/- 87.2 ng/mL) and MMP-2 (385.4 +/- 42.6 vs. 517.2 +/- 75.4 ng/mL) (p<0.001). Both TIMP-1 and TIMP-2 were reduced in diabetic nephropathy in comparison with either diabetes alone (p<0.01 and p<0.001; respectively) or CRF alone (p<0.001 for both). An approximately 2-fold increase of MMP-9/TIMP-1 and MMP-2/TIMP-2 ratio was found in diabetic nephropathy when compared with diabetes with normal renal function (p<0.01). Further, in DM2 patients, TIMP-2 was decreased when compared with CRF alone (219.2 +/- 71.8 vs. 296.8 +/- 58.4 ng/mL). MMP-2 was lowered in both groups of DM2 and CRF patients (413.8 +/- 59.0 ng/mL and 409.7 +/- 93.1 ng/mL, vs. normal control value of 517.2 +/- 75.4 ng/mL; p<0.001). CONCLUSIONS: These data indicate that circulating TIMP-1, TIMP-2 and MMP-2 are decreased in patients with diabetic nephropathy when compared with either CRF or diabetes.     

2型糖尿病兼或有肾脏病者颈总动脉内中膜厚度与血清淀粉样蛋白A水平的关系

目的探讨2型糖尿病肾脏病患者颈总动脉内中膜厚度（CCA-IMT）与血清淀粉样蛋白A（SAA）水平的相关关系。方法2型糖尿病患者107例,依据尿蛋白排泄率（UAER）结果分为单纯糖尿病组（SDM组）38例：UAER〈30mg／24h;糖尿病肾脏病组（DKD组）69例：UAER≥30mg／24h。DKD组依据肾小球滤过率（GFR）水平分为2组,DKD早中期组34例：GFR〉30ml／min;DKD中晚期组35例：GFR≤30ml／min。测定血清SAA及CCA-IMT水平,进行多因素分析。结果DKD组SAA水平、CCA-IMT较SDM组高;DKD中晚期组SAA水平、CCA-IMT较SDM组、DKD早中期组升高。SAA水平与腰臀比、CAEA-IMT、三酰甘油呈正相关;年龄、SAA及UAER是影响CCA-IMT的相关因素。结论2型糖尿病肾脏病患者血清SAA明显升高,并与CCA-IMT密切相关。     

Low-molecular-weight AGEs are associated with GFR and anemia in patients with type 2 diabetes

BACKGROUND: Advanced glycation end products (AGEs) are implicated in the development and progression of diabetic nephropathy. We examined the predictors of low-molecular-weight (LMW) AGEs in a cross-sectional survey of 604 patients with type 2 diabetes in a single clinic. METHODS: A clinical history and results of routine blood and urine testing were obtained for all patients over a 2-year period. Fluorescent LMW AGEs were estimated in serum samples taken concurrently, using an established flow injection method. Predictors of LMW AGEs were identified using multiple regression analysis. RESULTS: LMW AGEs were 34% higher in patients with diabetes than nondiabetic volunteers from the same community (P < 0.001). Independent predictors for LMW AGEs in patients with diabetes were glomerular filtration rate (GFR) and hemoglobin (both P < 0.001). While patients with renal impairment and anemia had the highest levels of LMW AGEs, both GFR and hemoglobin remained predictive when patients with a serum creatinine or hemoglobin within the "normal range" were analyzed separately. Patients with hyperfiltration had significantly lower LMW AGEs than those with normal renal function. Gender was also a significant independent predictor of LMW AGEs in patients without anemia. However, LMW AGEs were not associated with metabolic control or the presence of macrovascular disease. CONCLUSION: Circulating levels of LMW AGEs are elevated in patients with diabetes, especially those with impaired renal function or anemia. These findings extend the evidence for an association between AGEs and progressive renal injury in patients with type 2 diabetes. Whether LMW AGEs contribute to, or are a marker of, renal damage needs to be established by prospective studies.     

Advanced glycation end products decrease mesangial cell MMP-7: a role in matrix accumulation in diabetic nephropathy?

Increased extracellular matrix material is a pathological hallmark of diabetic nephropathy. In addition to collagens, a variety of non-collagenous glycoproteins such as fibronectin also accumulate in the kidney of diabetics. The effect of diabetes on degradative pathways, in particular those involving non-collagenous proteins, are relatively unexplored. In this study, we determined the expression of the major matrix metalloproteinase (MMP) responsible for degrading the non-collagenous matrix glycoprotein fibronectin. Furthermore, the modulation of these MMPs by advanced glycation end products (AGE), a key factor in the diabetic milieu, was explored. Exposure of mesangial cells to AGEs led to a significant reduction in MMP-7, but not MMP-3 or -10. MMP-7 expression was normalized by both aminoguanidine, an inhibitor of glycation product formation, or by a neutralizing anti-transforming growth factor-beta (TGF-beta) antibody. In streptozotocin-induced diabetic rats, the diminution in MMP-7 expression and excessive fibronectin accumulation were attenuated by aminoguanidine. Humans with type 2 diabetes and nephropathy displayed similar alterations in MMP-7 to their rodent counterparts. Our findings suggest that diminished expression of the glycoprotein-degrading enzyme, MMP-7, may play a role in fibronectin accumulation in the diabetic kidney in response to AGEs and/or TGF-beta.     

Development and validation of a predictive model for the differential diagnosis of diabetic nephropathy and non-diabetic renal disease in patients with type 2 diabetes mellitus

Objective To develop and validate a predictive model for the differential diagnosis of diabetic nephropathy (DN) and non-diabetic renal disease (NDRD) in patients with type 2 diabetes mellitus. Methods A retrospective study with patients with type 2 diabetes who underwent renal biopsy in the First Affiliated Hospital of Zhengzhou University from February 2012 to January 2015 was conducted. The dataset was randomly split into development (70.0%) and validation (30.0%) cohorts. Baseline predictors for model development was selected by using univariable and multivariable logistic regression. The model's performance in the two cohorts, including discrimination and calibration, was evaluated by the C-statistic, calibration curve and the P value of the Hosmer-Lemeshow test. Results Among the 931 patients with type 2 diabetes, 478 cases (51.3%) diagnosed as DN alone, 214 cases (23.0%) as NDRD alone and 239 cases (25.7%) as DN plus superimposed NDRD (MIX). Among NDRD and MIX patients, membranous nephropathy was the most common pathological type, followed by IgA nephropathy. The variables selected in the final predictive model were age, duration of diabetes, diabetic retinopathy, systolic blood pressure, hemoglobin, fasting blood glucose, glycosylated hemoglobin, cystatin C. The model performed well with good discrimination and calibration. The C-statistics were 0.913(95%CI 0.892-0.935) in the derivation cohort and 0.897(95%CI 0.876-0.919) in the validation cohort. The model had the best P value of 0.934 of the Hosmer-Lemeshow test. Conclusions A simple predictive model with high accuracy is constructed for predicting the presence of NDRD and MIX for type 2 diabetic patients. The nomogram can be used as a decision support tool to provide a non-invasive method for differential diagnosis of DN and NDRD, which may help clinicians assess the risk-benefit ratio of kidney biopsy for type 2 diabetic patients with renal impairment.     

Non-diabetic renal disease with or without diabetic nephropathy in type 2 diabetes: clinical predictors and outcome

Abstract

Background: Renal involvement in type 2 diabetes is mostly due to diabetic nephropathy (DN), but a subset of diabetic patients could present with pure non-diabetic renal disease (NDRD) or NDRD superimposed on DN. We conducted a prospective cohort study to identify the underline renal pathology in type 2 diabetic patients with defined clinical criteria for renal biopsy. Methods: A total of 46 patients (27 female, mean age of 48.9?±?11.9 years) with type 2 diabetes mellitus (DM) and atypical features of DN with unexpected proteinuria, hematuria, and/or renal impairment were enrolled in this study. Results: Of 46 patients with type 2 diabetes, 16 (34.8%) had DN, 20 (43.5%) had NDRD, and 10 (21.7%) had NDRD superimposed on DN. Membranous nephropathy (34%) was the most common NDRD. Patients with NDRD had a lower frequency of diabetic retinopathy (5%), shorter duration of diabetes, higher range of proteinuria, and better kidney survival. In multiple logistic regression analysis, only lack of diabetic retinopathy was independent predictor of NDRD. Positive and negative predictive value of diabetic retinopathy (DR) for diabetic nephropathy was 94 and 68%, respectively. Conclusion: Kidney biopsy is strongly recommended for patients with type 2 diabetes and atypical renal presentation for DN, particularly in the absence of DR. This approach could lead to diagnosis of NDRD with better renal survival.     

25-(OH)VD与2型糖尿病患者的糖尿病肾病相关性研究

目的 探讨25-(OH)VD与2型糖尿病患者的糖尿病肾病相关性。方法 收集937例未接受维生素D补充治疗的2型糖尿病患者,测定各临床指标以分析糖尿病肾病的相关因素。结果 与正常尿微量白蛋白组患者相比,微量或大量尿白蛋白组患者的25-(OH)VD 水平较低且具有显著统计学差异。相关性分析显示,用性别和BMI作为校正指数,年龄、糖尿病病程、高血压病程、收缩压、糖化血红蛋白、肌酐、尿素氮与尿微量白蛋白呈正相关,而25-(OH)VD 水平与尿微量白蛋白呈负相关。结论 25-(OH)VD 水平与2型糖尿病患者的尿微量白蛋白呈显著负相关。     

Change and clinical significance of microRNA-148b-3p level in the serum of patients with type 2 diabetes mellitus and diabetic nephropathy

Objective To detect the serum microRNA-148b-3p level in patients with diabetes mellitus and diabetic nephropathy, and to analyze its correlation with clinical and pathological indexes. Methods The research crowd was divided into three groups (1) diabetic nephropathy group: biopsy with diabetic nephropathy (n=25, 14 males, 11 females); (2) type 2 diabetes mellitus group: type 2 diabetes mellitus patients with normal urinary microalbumin /urinary creatinine value (n=10, 4 males, 6 females); (3) normal control group: healthy subjects (n=9, 3 males and 6 females). Clinical indicators included gender, age, 24-hour urine protein, systolic blood pressure (SBP), diastolic blood pressure (DBP), serum creatinine (Scr), urea (Urea), cystatin-C (Cys-C), blood albumin (ALB), urine microalbumin (UMA), triacylglycerol (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), serum uric acid (UA), fasting blood glucose (FBG), glycated hemoglobin (HbA1c), urine microalbuminuria / urinary creatinine (UACR), and estimated glomerular filtration rate (eGFR) calculated by CKD-EPI formula. Real-time quantitative PCR was applied to verify the expression of microRNA-148b-3p in serum samples of the research crowds. The relationships between microRNA-148b-3p level and clinical features was also analyzed. Results The levels of serum microRNA-148b-3p in diabetic nephropathy group and in type 2 diabetes mellitus group were 1.82 times and 1.73 times of that in normal control group (P＜0.05, respectively). The level of serum microRNA-148b-3p was significantly correlated with HDL-C (r=-0.374, P=0.013), UMA (r=0.426, P=0.004), FBG (r=0.330, P=0.046) and TG (r=0.423, P=0.005). Multiple linear regression analysis showed that UMA level was independently associated with serum microRNA-148b-3p level (β=0.338, P=0.044). The area under the receiver operating characteristic curve (ROC) of serum microRNA-148b-3p in diagnosing type 2 diabetes mellitus and diabetic nephropathy was 0.835 and 0.665, respectively. Conclusions The level of serum microRNA-148b-3p of patients with type 2 diabetes mellitus or diabetic nephropathy significantly increases. The level of UMA is independently associated with serum microRNA-148b-3p level. Serum microRNA-148b-3p is expected to be a potential biomarker for the diagnosis of diabetic nephropathy.     

Increased frequency of angiotensin-converting enzyme DD genotype in patients with type 2 diabetes in Taiwan.

BACKGROUND: Diabetes is one of the major causes of end-stage renal failure in the Taiwanese population. Previous studies have shown that angiotensin-converting enzyme (ACE) inhibitor can improve glucose utilization and suppress hepatic glucose production and the renin-angiotensin system may play an important role in the initiation and progression of diabetic nephropathy. Thus, ACE gene polymorphism may be associated with type 2 diabetes and diabetic nephropathy. METHODS: To investigate the distribution of ACE-I/D genotype in type 2 diabetes and diabetic nephropathy, we examined 336 patients with type 2 diabetes (157 without nephropathy and 179 with nephropathy) and 263 age-matched normal controls. The diagnosis of nephropathy was made when daily protein loss exceeded 500 mg. ACE gene polymorphism was analysed by use of polymerase chain reaction. RESULTS: Our study revealed that the frequency of the D allele of the ACE gene was 29.3% in normal controls. The frequency of ACE DD genotype was significantly higher in type 2 diabetics compared with normal controls (18.2 vs 9.1%, P<0.01). The frequency of ACE DD genotype in patients with diabetic nephropathy was significantly higher than in patients without nephropathy (22.3 vs 13.4%, P<0.05). To determine whether ACE gene polymorphism was associated with the severity of diabetic nephropathy, we divided patients with diabetic nephropathy into dialysis and non-dialysis groups. The frequency of ACE DD genotype in the dialysis group was significantly higher than in non-dialysis group (28.7 vs 15.3%, P<0.05). CONCLUSION: Our results indicate that the frequency of ACE DD genotype is markedly higher in patients with type 2 diabetes, and the ACE DD genotype is significantly associated with diabetic nephropathy.     

The predictive value of diabetic retinopathy on subsequent diabetic nephropathy in patients with type 2 diabetes: a systematic review and meta-analysis of prospective studies

This systematic review and meta-analysis aimed to assess the predictive value of diabetic retinopathy (DR) on further diabetic nephropathy (DN) risk in patients with type 2 diabetes (T2D) based on the prospective cohort studies. PubMed, Embase, and the Cochrane Library were systematically searched for eligible prospective cohort studies through March 2020. The predictive value of DR was assessed using sensitivity, specificity, positive likelihood ratio (PLR) and negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the receiver operating characteristic curve (AUC) through the bivariate generalized linear mixed model and the random-effects model. Ten prospective cohort studies recruited 635 patients with T2D. The pooled sensitivity and specificity of DR for predicted DN were noted to be 0.64 (95% CI, 0.54–0.73) and 0.77 (95% CI, 0.60–0.88), respectively. The pooled PLR and NLR of DR for predicted DN were 2.72 (95% CI, 1.42–5.19) and 0.47 (95% CI, 0.33–0.67), respectively. The summary DOR for the relationship between DR and subsequent DN for T2D patients was 5.53 (95% CI, 2.00–15.30), and the AUC of DR for predicted DN was 0.73 (95% CI, 0.69–0.77). This study found significant associations between DR and subsequent DN risk for patients with T2D. Moreover, the predictive value of DR on subsequent DN risk was relatively lower.     

Pyridoxal phosphate prevents progression of diabetic nephropathy.

BACKGROUND: We have demonstrated that pyridoxal 5'-phosphate (PLP), an active form of vitamin B6, inhibits formation of advanced glycation end-products (AGEs) by trapping 3-deoxyglucosone. The present study aimed to clarify if PLP could exert beneficial effects on nephropathy in diabetic rats. METHODS: Streptozotocin (STZ)-induced diabetic rats were treated by oral administration of PLP or pyridoxamine (PM), another active form of vitamin B6, at a dose of 600 mg/kg/day for 16 weeks. AGEs [imidazolone, N(epsilon)-(carboxymethyl)lysine (CML) and N(2)-carboxyethyl-2'-deoxyguanosine (CEdG)], transforming growth factor-beta1 (TGF-beta1), type 1 collagen and fibronectin were detected in the kidneys using immunohistochemistry. Gene expression of TGF-beta1 and receptor for AGEs (RAGEs) in the kidneys was determined using real-time quantitative polymerase chain reaction. RESULTS: Administration of PLP significantly inhibited albuminuria, glomerular hypertrophy, mesangial expansion, and interstitial fibrosis as compared with diabetic rats. PLP markedly inhibited accumulation of AGEs such as imidazolone, CML and CEdG, a DNA-linked AGE, in glomeruli. PLP significantly inhibited expression of TGF-beta1, type 1 collagen, fibronectin and RAGE in the kidneys. PLP was superior to PM in inhibiting accumulation of AGEs, expression of TGF-beta1, type 1 collagen, and fibronectin, and the development of diabetic nephropathy. CONCLUSIONS: PLP prevented progression of nephropathy in STZ-induced diabetic rats by inhibiting formation of AGEs. PLP is considered a promising active form of vitamin B6 for the treatment of AGE-linked disorders such as diabetic nephropathy.     

2型糖尿病患者血清Metrnl水平与骨密度的相关性研究

目的 探讨2型糖尿病(diabetes mellitus type 2,T2DM)患者血清Metrnl浓度与骨密度的相关性及其影响因素。方法 选取江苏大学附属医院就诊的T2DM患者146例,对所有受试者进行糖耐量、胰岛素兴奋实验、血生化检测等。ELISA检测血清Metrnl水平。所有受试者均接受双能X线骨密度仪检测,根据骨密度结果分为T2DM合并骨密度(bone mineral density, BMD)正常组和BMD异常组。结果 与T2DM合并BMD正常组相比,T2DM合并BMD异常组血清Metrnl水平显著升高(P<0.05)。进一步在调整性别、年龄等因素后,T2DM患者血清Metrnl水平与第1腰椎(L1)、L2、L3、L2～L4、L1～L4等BMD值,以及L1～L4 T值呈显著负相关(P<0.05)。Logistic回归结果显示,T2DM患者血清Metrnl水平与骨量异常独立相关。ROC曲线模型分析结果显示,血清Metrnl预测T2DM患者骨量异常的曲线下面积为0.720(95%CI=0.638～0.802,P<0.001)。结论T2DM合并BMD异常患者血清...     

Dinucleotide repeat polymorphism of matrix metalloproteinase-9 gene is associated with diabetic nephropathy

BACKGROUND: Although genetic susceptibility has been proposed as an important factor for the development and progression of diabetic nephropathy, the definitive gene has not been identified. To identify the genetic marker for diabetic nephropathy, we examined the association between the (A-C)n dinucleotide repeat polymorphism upstream of the matrix metalloproteinase-9 (MMP-9) gene and diabetic nephropathy in a group of Japanese patients with type 2 diabetes. METHODS: Patients were divided into three groups based on their urinary albumin excretion rate (AER) and the stage of diabetic retinopathy as follows: uncomplicated group (U), normal albuminuria (AER <20 microg/min) without proliferative retinopathy and with the duration of diabetes more than 20 years (N = 32); microalbuminuria group (M), 20 < or = AER < 200 microg/min (N = 155); overt nephropathy group (O), AER > or = 200 microg/min (N = 63). The region containing the dinucleotide repeat upstream of MMP-9 gene was amplified by polymerase chain reaction (PCR). The amplified products were analyzed with 7% formamide/urea acrylamide gel electrophoresis. The promoter constructs of the MMP-9 gene were transfected with the CMV-beta-galactosidase construct into 293 cells using the liposome method. Twenty-four hours after transfection, cells were harvested, and luciferase and beta-galactosidase activities were measured. RESULTS: Nine alleles of the dinucleotide repeat polymorphism (17 to 25 repeats) were identified, and the frequency of each allele in diabetic subjects was not different from that in nondiabetic controls. The frequency of the allele containing 21 repeats (A21) was most abundant (42.4% in control and 45.6% in diabetic subjects), followed by the allele with 23 repeats (A23; 35.4% in control and 27.6% in diabetic subjects). The A21 allele was less frequent in M and O than U (O, 38.9%; M, 45.5%; U, 59.3%, chi2 = 7.18; P < 0.05, O vs. U), while the frequency of the alleles other than A21 was not different among each group. The calculated odds ratio for nephropathy in the noncarrier, heterozygote, or homozygote of A21 allele was 3.38, 1.97, and 0.2, respectively. Furthermore, the promoter assay for the MMP-9 gene revealed that the A21 allele had a higher promoter activity compared with other alleles. No significant correlation was observed between serum MMP-9 concentrations and the MMP-9 gene polymorphism. CONCLUSION: These results indicate that the patients with A21 allele of the MMP-9 gene may be protected from the development and progression of diabetic nephropathy. Thus, the microsatellite polymorphism upstream of the MMP-9 gene could be a useful genetic marker for diabetic nephropathy.     

结直肠癌合并糖尿病患者术后感染对机体Th17相关因子、sICAM－1、MMP－12表达的影响

目的探讨分析结直肠癌合并糖尿病患者术后感染对机体辅助性T细胞17(Th17)相关因子、可溶性细胞间黏附分子－1(sICAM－1)、基质金属蛋白酶－12(MMP－12)表达的影响。 方法回顾性分析2015年8月至2018年8月行结直肠癌根治术且合并2型糖尿病患者117例资料，采用ROC曲线分析IL－17、sICAM－1及MMP－12对患者术后感染的预测价值。采用SPSS 22.0统计软件进行数据分析，Th17、Treg细胞等水平比较采用t检验，计数资料比较采用χ²检验，采用ROC曲线分析IL－17、sICAM－1及MMP－12对患者术后感染的预测价值，以P<0.05为差异统计学意义。 结果117例患者31例发生术后感染(26.5%)，共分离病原菌38株，革兰阴性菌24株(63.2%)、革兰阳性菌13株(34.2%)、真菌1株(2.6%)。感染组外周血Th17、Th17/Treg显著高于未感染组(P<0.05)，外周血Treg细胞显著低于未感染组(P<0.05)，血清IL－17、sICAM－1、MMP－12水平显著高于未感染组(P<0.05)。IL－17、sICAM－1及MMP－12术后感染预测价值ROC曲线下面积分别为0.814、0.867、0.742(P<0.05)。 结论结直肠癌合并糖尿病术后感染可致机体Th17/Treg失衡，引发自身免疫应答及炎症反应，引起血清IL－17、sICAM－1、MMP－12水平升高，血清IL－17、sICAM－1、MMP－12检测可作为术后感染早期诊断指标。     

Predictors of cardiovascular events in patients with type 2 diabetic nephropathy and hypertension: a case for albuminuria

Individuals with type 2 diabetes and nephropathy represent a particularly high-risk group for both adverse cardiac as well as renal events. Using the Irbesartan in Diabetic Nephropathy Trial (IDNT) cohort, our objective was to determine baseline characteristics of individuals with type 2 diabetic nephropathy and hypertension predictive for cardiac events. IDNT identified 1715 individuals with type 2 diabetic nephropathy and hypertension having serum creatinine of 1.0 to 3.0 mg/dL and urinary albumin excretion rates > or = 900 mg/day. A cardiovascular (CV) composite was used consisting of CV death, nonfatal MI, hospitalization for heart failure, stroke, amputation, and coronary and peripheral revascularization. Using multivariable Cox regression analysis, 41 baseline characteristics determined a priori were analyzed for their potential relationship to risk of experiencing a CV event. Of the 1715 individuals, 518 (30.2%) had at least one of the CV composite end points. Older age, male gender, longer duration of diabetes, history of cardiovascular disease, history of CHF, high urinary albumin:creatinine ratio, and low serum albumin were strong predictors for CV events; of these, prior history of CVD (RR 2.00, 95% CI 1.63-2.45; P < 0.0001) and high urinary albumin:creatinine ratio (RR 1.29 per natural log unit, 95% CI 1.13-1.48; P = 0.0002) at baseline were highly predictive for cardiovascular events. In conclusion, among individuals with hypertension and diabetic nephropathy, both the degree of albuminuria and lower serum albumin levels provide additional prognostic information concerning cardiovascular risk, in addition to traditional coronary risk factors.     

2型糖尿病患者低血糖风险预测模型的构建与验证

目的 构建2型糖尿病患者低血糖风险预测模型,并验证其临床预测效果.方法 采用便利抽样法选取1 149例2型糖尿病患者相关资料,随机分为建模组(766例)、验证组(383例),采用Logistic回归分析构建预测模型、Hosmer-Lemeshow(H-L)检验模型的拟合优度及受试者工作特征曲线下面积判断模型的预测效果....     

人参皂苷对糖尿病大鼠肾组织基质金属蛋白酶2表达的影响

目的：研究人参皂苷对糖尿病大鼠肾组织基质金属蛋白酶2（MMP-2）及Ⅳ型胶原（ColⅣ）表达的影响,从而探讨人参皂苷防治糖尿病肾脏病变的可能机制。方法：糖尿病大鼠用人参皂苷治疗,肾标本用MMP-2、ColⅣ单克隆抗体行免疫组化染色后经图像分析仪分析。结果：糖尿病大鼠肾小球MMP-2表达较正常对照组明显下降（P〈0.05）,而肾间质MMP-2与正常对照组比较,有增高趋势,但无统计学差异（P〉0.05）。用人参皂苷治疗后,可逆转上述改变。ColⅣ的表达在肾小球和肾间质均较正常对照组上升,经人参皂苷治疗后下降。结论：人参皂苷对糖尿病大鼠肾脏病变有部分保护作用,其机制可能部分通过改善肾组织MMP-2的表达有关。     

Endocan and albuminuria in type 2 diabetes mellitus

Background: Endocan is a newly identified proteoglycan released from endothelium, stimulating angiogenesis and when increased, indicates endothelial activation (inflammation). Our aim was to examine the association between serum endocan levels and urine albumin–creatinine ratio (UACR).

Method: One hundred and thirty-seven patients with type 2 diabetes mellitus and normal serum creatinine who had no co-morbidities other than hypertension, diabetic nephropathy, retinopathy, or neuropathy were divided into normoalbuminuria (G1), microalbuminuria (G2), and macroalbuminuria (G3) groups and compared cross-sectionally regarding serum endocan levels.

Result: There were 55, 47, and 35 patients in G1, G2, and G3, respectively. The groups were comparable in terms of gender, age, duration of diabetes, diabetic neuropathy/retinopathy, fasting glucose, HbA1c, serum creatinine level, and eGFR. Patients in G3 had significantly higher blood pressure but lower serum albumin and endocan levels. UACR showed a negative bivariate correlation with serum endocan levels (r?=??.282, p?=?.001). There was bivariate positive correlation between endocan and systolic blood pressure (r=.185, p?=?.030). In linear regression analysis, UACR was negatively correlated with endocan while positively correlated with systolic blood pressure, duration of diabetes, and platelet distribution width.

Conclusion: Patients with macroalbuminuria had lower endocan levels, and increasing UACR was associated with decreasing serum endocan levels. Despite the occurrence of angiogenesis and glomerular hypertrophy in the early phase of diabetic nephropathy, ensuing significant renal injury over time may reduce the expression of endocan. Serum endocan levels may represent a novel marker for nephropathy progression.     

Analysis of clinical manifestations and outcomes of idiopathic membranous nephropathy compared with diabetic nephropathy in patients with type 2 diabetes

Objective To evaluate the predictive factors and renal outcomes of idiopathic membranous nephropathy (IMN) in patients with type 2 diabetes (T2DM). Methods In this retrospective study, clinical data of 101 IMN patients with T2DM and 96 patients with diabetic nephropathy (DN) were consecutively collected. Logistic regression was used to assess potential clinical factors indicating IMN and COX regression was employed to analyze risks of IMN in developing to end-stage renal disease (ESRD), as compared with that of DN, in patients with T2DM. Results In a multivariate model, age≥55 years old, presence of nephrotic syndrome, estimated glomerular filtration rate (eGFR)＞60 ml?min-1?(1.73 m2)-1, duration of diabetes≤5 years and absence of diabetic retinopathy, were associated with IMN, as compared with DN, in patients with T2DM. In T2DM patients presented with nephrotic syndrome, age≥55 years old, eGFR＞60 ml?min-1?(1.73 m2)-1, duration of diabetes≤5 years and absence of diabetic retinopathy, were also associated with IMN, as compared with DN. Receiver operating characteristic curve (ROC) showed eGFR 65.5 ml?min-1?(1.73 m2)-1 was an optimal cutoff in differentiating DN and IMN. DN was associated with 16.8 times as high risk of incident ESRD as compared with IMN in T2DM patients. Conclusions In patients with T2DM, age≥55 years, presence of nephrotic syndrome, early stage of CKD, duration of diabetes≤5 years and absence of retinopathy, may indicate IMN rather than DN. T2DM patients with IMN have much better renal prognosis as compared with DN.     

Advanced glycation end products in adolescents and young adults with diabetic angiopathy

The aim of this study was to evaluate serum advanced glycation end products (S-AGEs) in a group of adolescents and young adults with type 1 (insulin-dependent) diabetes mellitus and with diabetic microvascular complications (nephropathy or retinopathy). Fifty-two patients were included in the study (age range 14.2–28.8 years, onset of diabetes before the age of 12 years, duration of diabetes longer than 7 years); 45 patients without diabetic angiopathy and 63 healthy controls were also selected. S-AGEs were significantly increased in patients with diabetic angiopathy compared with controls (19.9±3.8 vs. 11.8±2.8 U/ml, P<0.001). Higher S-AGE levels were found in patients with severe diabetic nephropathy and retinopathy. When the albumin excretion rate (AER) was >100 μg/min per 1.73 m², S-AGE levels were 23.1±2.4 U/ml; when the AER was 50–100 μg/min per 1.73 m² levels were 19.8±1.9 U/ml, and for an AER of 20–50 μg/min per 1.73 m² the corresponding value was 16.1±2.1 U/ml (P<0.005). Patients with proliferative retinopathy had S-AGE levels of 22.2±2.6 U/ml, those with preproliferative retinopathy 20.7±2.2 U/ml, and background retinopathy 17.6±1.9 U/ml (P<0.01). A significant correlation was found between levels of glycosylated hemoglobin (HbA_1c) and S-AGE (r=0.43, P<0.01). S-AGE concentrations are markedly increased in type 1 diabetic adolescents and young adults with diabetic nephropathy and retinopathy. The severity of diabetic angiopathy is related to the serum levels of AGEs. Received: 22 April 1999 / Revised: 22 November 1999 / Accepted: 5 January 2000