2型糖尿病肾病患者尿ENA-78水平的变化及意义

目的:探讨上皮来源的中性粒细胞活化肽(ENA-78)在糖尿病肾病(DN)水平变化及其临床意义.方法:将56例糖尿病(DM)患者根据尿白蛋白排泄率(UAER)分为三组,对照组为健康体检者(NC)25例,应用ELISA法检测各组尿ENA-78的浓度.结果:DN患者尿ENA-78水平明显高于对照组,且临床蛋白尿组尿ENA-78水平显著高于微量蛋白尿组及正常蛋白尿组.DN组尿ENA-78水平与UAER、SCr呈正相关,与MDRD呈负相关,与LDL-C、HbAlc无统计学相关性.结论:ENA-78可能参与了DN的发生发展并起着重要作用,检测尿ENA-78对于DN早期的诊断及治疗都有重要意义.     

Urinary Guanidinoacetate and Creatine Levels in Patients with HPRT Deficiency

Neurobehavioral manifestations of complete HPRT deficiency include severe action dystonia, choreathetosis, alteration of executive functions, and self-injurious behavior. Dystonic manifestations are also present in patients with partial HPRT deficiency. Pathophysiology of these manifestations is unknown. Guanidinoacetate is a neurotoxin implicated in certain dystonic syndromes. We have examined guanidinoacetate and creatine levels in urine from 11 HPRT deficient patients (9 with Lesch-Nyhan syndrome and 2 with partial deficiency). Urinary guanidinoacetate and creatine levels in HPRT deficient patients were within the normal range. Guanidinoactetate alteration does not seem to be implicated in the pathogenesis of the neurological disease associated with HPRT deficiency.     

RPLU术对重度肾积水的上尿路结石患者尿ET-1、AQP-1、MCP-1水平的影响

摘要 目的：探讨后腹腔镜下输尿管切开取石术（RPLU）对重度肾积水的上尿路结石患者尿内皮素-1（ET-1）、水通道蛋白-1（AQP-1）、单核细胞趋化蛋白-1（MCP-1）水平的影响。方法：收集2018年4月~2019年11月我院收治的106例重度肾积水的上尿路结石患者为研究对象,按照随机数字表法分为对照组和研究组,每组53例,对照组采用输尿管镜取石术治疗,研究组采用RPLU术治疗,对比两组手术情况,手术前后血红蛋白、肾功能、尿ET-1、AQP-1、MCP-1水平,手术并发症发生情况。结果：研究组手术时间及住院时间多于对照组,结石清除率高于对照组,比较差异有统计学意义（P<0.05）;两组术中出血量、术后排气时间比较差异无统计学意义（P>0.05）。术后,两组血红蛋白较术前无显著差异（P>0.05）。术后,两组血肌酐及血尿酸氮均下降,两组比较差异无统计学意义（P>0.05）。术后,两组尿ET-1、AQP-1、MCP-1水平均下降,两组比较无统计学意义（P>0.05）。两组并发症总发生率比较无统计学意义（P>0.05）。结论：RPLU术是治疗重度肾积水的上尿路结石清除率高,创伤小,可作为重度肾积水伴上尿路结石安全、有效的术式。     

Excretion of Urinary Orosomucoid 1 Protein Is Elevated in Patients with Chronic Heart Failure

Easily screening markers for early detection of chronic heart failure (CHF) are lacking. We identified twenty differently expressed proteins including orosomucoid 1(ORM1) in urine between patients with CHF and normal controls by proteomic methods. Bioinformatics analyses suggested ORM1 could be used for further analysis. After verification by western blotting, the urinary levels of ORM1 were quantified with enzyme-linked immunosorbent assay (ELISA) by correcting for creatinine expression. The ORM1-Cr was significantly elevated in CHF patients than normal controls (6498.83±4300.21 versus 2102.26±1069.24 ng/mg). Furthermore, a Spearman analysis indicated that the urinary ORM1 levels had a high positive correlation with the classification of CHF, and the multivariate analysis suggested that the urinary ORM1 content was associated with the plasma amino-terminal pro- brain natriuretic peptide (NT-proBNP) (OR: 2.106, 95% CI: 1.213–3.524, P = 0.002) and the New York Heart Association (NYHA) classification (OR: 3.019, 95% CI: 1.329–4.721, P<0.001). In addition, receiving operating curve (ROC) analyses suggested that an optimum cut-off value of 2484.98 ng/mg with 90.91% sensitivity and 85.48% specificity, respectively, could be used for the diagnosis of CHF. To sum up, our findings indicate that ORM1 could be a potential novel urinary biomarker for the early detection of CHF.     

Study of 27 Aqueous Humor Cytokines in Type 2 Diabetic Patients with or without Macular Edema

The aim of the present study was to compare the changes in the levels of 27 aqueous humor cytokines between diabetic patients with macular edema (ME) and diabetic patients without ME. Undiluted aqueous humor samples were obtained from 68 consecutive type 2 diabetic patients without ME and 56 consecutive type 2 diabetic patients with ME. The concentrations of 27 cytokines in the aqueous humor samples were measured using a multiplex bead immunoassay. Compared with diabetic patients without ME, diabetic patients with ME had significantly higher concentrations of IL-1β, IL-6, IL-8, IP-10, MCP-1, and VEGF in the aqueous humor. However, the concentrations of IL-10 and IL-12 were significantly lower in the diabetic patients with ME. The aqueous humor levels of IL-1β, IL-6, IL-8, MCP-1, IP-10, and VEGF were closely correlated with retinal macular thickness, retinal macular volume and the severity of ME. In addition, the aqueous humor levels of IL-10 and IL-12 decreased with increasing the severity of ME. A variety of cytokines associated with inflammation and angiogenesis may contribute to the pathogenesis of diabetic macular edema, and both anti-inflammatory and antiangiogenic agents should be included in the treatment of ME simultaneously.     

A Comparative Study on the Efficacy of Solifenacin Succinate in Patients with Urinary Frequency with or without Urgency

Objectives

Patients with overactive bladder (OAB) often have trouble perceiving urgency because of difficulties in distinguishing between urgency and desire to void. Empirical antimuscarinic treatment of patients with frequency only may be reasonable if conservative management has failed. We compared the efficacy of solifenacin in patients with frequency with or without urgency.

Materials and Methods

This multicenter, 12-week, open-label, comparative, non-inferiority clinical trial assessed whether the solifenacin efficacy for frequency without urgency is non-inferior to its efficacy for frequency with urgency. All patients had micturition frequency ≥8 voids/day with or without urgency. Primary efficacy variable: daily frequency change at 12 weeks relative to baseline. Secondary efficacy variables: change at 12 weeks relative to baseline in Patients'' Perception of Bladder Condition (PPBC), OAB Symptom Score (OABSS), and Benefit, Satisfaction, Willingness to continue (BSW) questionnaire.

Results

Of the 286 enrolled patients, 240 (83.9%) completed the study (without urgency n = 115; with urgency n = 125). Full dataset analysis revealed that the groups without and with urgency exhibited significant reductions in daily micturition frequency of −2.49±0.35 (mean ± standard error) and −2.63±0.37, respectively. The lower limit of the 95% two-sided CI of the comparison of the two group means was −1.14, which is smaller than the −0.8 margin of clinical equivalence. The two groups did not differ in improvement in PPBC, OABSS, or BSW scores. Both tolerated the treatment well.

Conclusions

It was not possible to verify that the solifenacin efficacy for frequency alone was non-inferior to its efficacy for OAB. Nevertheless, solifenacin tended to be effective for frequency regardless of urgency.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00979472","term_id":"NCT00979472"}}NCT00979472     

Urinary Protein Profiles in a Rat Model for Diabetic Complications

Diabetes mellitus is estimated to affect ∼24 million people in the United States and more than 150 million people worldwide. There are numerous end organ complications of diabetes, the onset of which can be delayed by early diagnosis and treatment. Although assays for diabetes are well founded, tests for its complications lack sufficient specificity and sensitivity to adequately guide these treatment options. In our study, we employed a streptozotocin-induced rat model of diabetes to determine changes in urinary protein profiles that occur during the initial response to the attendant hyperglycemia (e.g. the first two months) with the goal of developing a reliable and reproducible method of analyzing multiple urine samples as well as providing clues to early markers of disease progression. After filtration and buffer exchange, urinary proteins were digested with a specific protease, and the relative amounts of several thousand peptides were compared across rat urine samples representing various times after administration of drug or sham control. Extensive data analysis, including imputation of missing values and normalization of all data was followed by ANOVA analysis to discover peptides that were significantly changing as a function of time, treatment and interaction of the two variables. The data demonstrated significant differences in protein abundance in urine before observable pathophysiological changes occur in this animal model and as function of the measured variables. These included decreases in relative abundance of major urinary protein precursor and increases in pro-alpha collagen, the expression of which is known to be regulated by circulating levels of insulin and/or glucose. Peptides from these proteins represent potential biomarkers, which can be used to stage urogenital complications from diabetes. The expression changes of a pro-alpha 1 collagen peptide was also confirmed via selected reaction monitoring.Diabetic nephropathy (DNP)¹ accounts for ∼44% of new cases of end stage renal disease (ESRD) (1). This high morbidity is the result of the impact of a growing population and longer life expectancy. With an increase in the prevalence of DM and a corresponding reduction in the mortality associated with both type 1 and type 2 DM, patients are living longer and are therefore at higher risk to develop complications such as nephropathy (2). Moreover, Type 1 DM patients who progress to ESRD have a substantial risk of mortality with estimated annual health care costs in the United States to be approximately $1.9 billion (3, 4). Two key therapies for the prevention and management of ESRD are aggressive glycemic control and blood pressure regulation (5, 6). Early intervention is essential in reducing the severity and course of this complication (6), and changes in urine biomarkers have historically been used to diagnose and monitor disease progression. In addition, urine represents a desirable matrix in which to detect biomarkers of nephropathy as urinary protein excretion profiles are reflective of functional changes within the kidney, such as glomerular filtration rate. Clinical determinations of urinary total protein and urinary albumin excretion are commonly used measurements to monitor and/or determine the onset of diabetic nephropathy. Unfortunately, these measurements often lead to improper diagnoses for at risk DM patients (7, 8). Therefore, new prognostic indicators are required to accurately target these patients for therapeutic intervention earlier in the course of the disease as well as identify patients who are unlikely to progress, as therapy may be of little or no benefit to them.Utilizing experimental models to study the pathophysiological changes that occur as function of disease progression has provided an approach for biomarker discovery. In diabetes, animal models have been widely used in the investigation of the progression of diabetes complications such as nephropathy. Research conducted on the association between hyperglycemia and microvascular disease in diabetes as well as the study of the effect of extracellular matrix protein expression on changes in morphology in the diabetic kidney are two such examples (9). In addition, these models have assisted in developing appropriate clinical trials for the prevention and treatment of these complications. One such example is the use of anti-hypertensive treatment regimes in genetically hypertensive rats; these have examined whether early intervention may be renoprotective and therefore delay or prevent the onset of diabetic nephropathy (10–12).STZ-induced hyperglycemia in rodents is the most extensively studied model of diabetic nephropathy and associated complications (9, 13). Hyperglycemia occurs in this model because of the toxin''s destruction of pancreatic Beta-islet cells, which are essential to the production of insulin. STZ-induced hyperglycemia is associated with reliable and consistent structural and functional deficits in specific urogenital organ function (i.e. kidney and bladder). Increased glomerular filtration and hypertrophy, as well as increased urgency and morphology changes, are structural and functional abnormalities that have been observed in the kidney and bladder, respectively, in both in humans and the STZ rat model (14–19).Currently, there are two primary methods used to monitor disease progression in diabetes. The measurement of urinary albumin excretion rates and total protein concentration are routinely used to monitor disease progression as they reflect structural and functional changes in the kidney. Measurements of albumin by immunochemical assays and size exclusion high performance liquid chromatography are routinely employed (7). However, urine consists of a multitude of proteins, many of which are also reflective of pathophysiological changes because of DM urogenital complications (20–23). Proteomics provides a powerful approach for the detection of urinary protein changes as a result of disease, and multiple proteomic techniques are available in large scale protein profiling to discover new biomarkers (24–26). To date, proteomic strategies for biomarker discovery in urine have primarily included top-down approaches, for example two-dimensional gel electrophoresis coupled with mass spectrometry and/or surface enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF-MS) analyses (27–30). In addition a number of studies using capillary electrophoresis mass spectrometry, which have a number of advantages for analysis of urine, have been successfully carried out (31–33). While these approaches can easily detect and quantify a variety of proteinaceous species including isoforms, posttranslational modifications, or degradation products, other methods could be used to expand the number of proteins that are both quantified and identified providing an expanded set of biological targets to understand the complications of disease and its progression. Recent advances in both chromatography and mass spectrometry have enabled bottom-up approaches that identify and quantify at the peptide level (34–36). One advantage of bottom-up proteomics is increased overall proteome coverage. Moreover, most bottom-up methods provide both qualitative and quantitative data in a single run, and quantifying at the peptide level leads directly into a bottom-up confirmation/validation analysis thereby avoiding the peptide selection step in this procedure. Approaches to bottom-up proteomics include specific peptide labeling or label-free analysis. Specific labeling approaches such as isobaric tag for relative and absolute quantification (iTRAQ) and ¹⁸O employ differential stable isotope labeling strategies that create specific mass tags for different samples, which are mixed and then identified and quantified using mass spectrometry (37). The utility of these techniques is that they accommodate a wide range of pre-fractionation strategies thereby improving proteome coverage.The label-free approach capitalizes on the highly reproducible chromatography and high mass accuracy available in current LC/MS systems. This method observes all detectable peptides and if interrogated by MS/MS their corresponding fragment ions. This approach quantifies a peptide by its intensity and groups each peptide across individual samples based on its accurate mass and retention time (38, 39). These intensities associated with specific mass and retention time values are organized into peptide array tables that may be further processed using statistical techniques that accommodate high-dimensional data. As with other bottom-up approaches, this method is also amenable to pre-fractionation strategies, but unlike labeled approaches, the removal of chemical or metabolic labeling steps simplifies the overall approach.Here we use a comparative label-free LC/MS/MS approach to identify and rank candidate biomarkers of urogenital complications from an STZ rat model of diabetes. We describe further technical validation of our approach by confirming the changes observed with the putative biomarker, pro-alpha (2) with an alternative method: selected reaction monitoring (SRM).     

Selenium Levels in First-Degree Relatives of Diabetic Patients

The present study was conducted to evaluate the serum selenium levels in first-degree relatives of diabetic patients (FDR) according to controls. Insulin resistance, serum lipid levels, inflammation markers, and blood pressure were also studied in these patients. Serum levels of selenium in FDR were significantly lower than control group (74.65 ± 5.9 vs 88.7 ± 8.7 μg/dl, p < 0.0001). HsCRP, HOMA-IR, insulin, homocysteine levels were significantly higher in FDR according to the control group (1.32 ± 0.9 vs 0.63 ± 0.4 mg/dL, p < 0.0001; 2.07 ± 0.84 vs 1.51 ± 0.69, p < 0.0001; 9.26 ± 3.8 vs 6.8 ± 2.98 μU/MI, p < 0.0001; 15.7 ± 7.4 vs 11.5 ± 5.1 μmol/L, p < 0.0001, respectively). There was significant correlation between selenium levels and hsCRP (r = − 0.450, p < 0.0001). There was also weak significant correlation also between HOMA-IR and selenium levels (r = −0.227, p = 0.003). There was a correlation between systolic blood pressure and BMI (r = 0.365, p < 0.0001). But there was no correlation between selenium levels and blood pressure or other parameters. HsCRP, HOMA-IR, homocysteine levels in individuals with selenium levels < 80 μg/L (n = 78) was significantly higher than hsCRP HOMA-IR, homocysteine levels in individuals with selenium levels ≥ 80 (n = 91; 1.23 ± 0.98 vs 0.81 ± 0.76 mg/dL, p < 0.003; 1.99 ± 0.88 vs 1.64 ± 0.74, p < 0.005; 15.0 ± 7.6 vs 12.9 ± 5.7 μmol/L, p < 0.049, respectively). Selenium deficiency may contribute to cardiovascular disease risk in FDR.     

Vitamin D-Binding Protein Levels in Female Patients with Primary Hyperparathyroidism

ObjectiveTo determine whether low levels of vitamin D-binding protein (DBP) are related to 25-hydroxyvitamin D (25[OH]D) deficiency in female patients with primary hyperparathyroidism (PHPT).MethodsTwenty-five female patients with PHPT (serum calcium level >10.2 mg/dL and intact parathyroid hormone (iPTH) level >66 pg/mL) and 25 healthy age- and body mass index-matched female control subjects were xaminod. Serum calcium and iPTH levels were determined by commercial laboratories. Levels of 25(OH)D and 1,25-dihydroxyvitamin D (1,25[OH]₂D) were determined by radioimmunoassay, and DBP level was determined by enzyme-linked immunosorbent assay.ResultsSerum iPTH and calcium levels were higher in PHPT patients than control subjects (P<.001). Levels of 25(OH)D, albumin, and DBP were lower in the serum of PHPT patients than control subjects (P<.01). There were no significant differences in 1,25(OH)₂D and free 25(OH) D levels between PHPT patients and control subjects. DBP level was inversely correlated with calcium (r = -0.47; P<.01) and iPTH (r = −0.31; P<.05) levels. The 25(OH)D level correlated positively with both DBP (r = 0.28; P <.05) and albumin (r = 0.44; P<.05) levels.ConclusionsBoth serum 25(OH)D and DBP levels were lower in female patients with PHPT compared with control subjects. We suggest that a low DBP level contributes to the low 25(OH)D level observed in female PHPT patients. The etiology of the decrease in DBP and its relationship to calcium, 25(OH)D, and PTH levels require further investigation. (Endocr Pract. 2013;19:609-613)     

The Expression of Tristetraprolin and Its Relationship with Urinary Proteins in Patients with Diabetic Nephropathy

Objective

Tristetraprolin (TTP), also known as zinc finger protein 36, is an RNA binding protein that has a significant role in regulating the expression of mRNAs containing AU-rich elements. We postulated that TTP might regulate interleukin (IL)-6 and IL-18 expression in diabetes. This study aimed to test the hypothesis that the levels of TTP are correlated with nephropathy in patients with type 2 diabetes.

Methods

Eighty-seven patients (61.3±9.6 years old) who had been diagnosed with type 2 diabetes mellitus and 41 age and sex matched healthy control subjects were enrolled. The diabetes patients were classified into those without proteinuria, with microalbuminuria, and with clinical proteinuria groups according to the ratio of urinary excretion of albumin/creatinine (ACR).

Results

Serum and urinary levels of IL-6 and IL-18 were significantly elevated, but those of TTP were significantly decreased in patients with diabetes as compared with control subjects. In addition, serum and urinary levels of IL-6 and IL-18 were significantly higher, but those of TTP were significantly lower in patients with proteinuria than in patients without proteinuria or with microalbuminuria. There was a significant correlation between serum TTP and IL-6/IL-18 (correlation coefficients of -0.572 and -0.685, P < 0.05).

Conclusion

These results show that diabetes with clinical proteinuria is accompanied by decreased urinary and serum level of TTP and increased levels of IL-6 and IL-18. Decreased TTP expression might occur prior to the increase in IL-6 and IL-18, and decrease of TTP might provide an earlier marker for glomerular dysfunction than IL-6 and IL-18.     

Urinary Exosomes: A Novel Means to Non-Invasively Assess Changes in Renal Gene and Protein Expression

Background

In clinical practice, there is a lack of markers for the non-invasive diagnosis and follow-up of kidney disease. Exosomes are membrane vesicles, which are secreted from their cells of origin into surrounding body fluids and contain proteins and mRNA which are protected from digestive enzymes by a cell membrane.

Methods

Toxic podocyte damage was induced by puromycin aminonucleoside in rats (PAN). Urinary exosomes were isolated by ultracentrifugation at different time points during the disease. Exosomal mRNA was isolated, amplified, and the mRNA species were globally assessed by gene array analysis. Tissue-specific gene and protein expression was assessed by RT-qPCR analysis and immunohistochemistry.

Results

Gene array analysis of mRNA isolated from urinary exosomes revealed cystatin C mRNA as one of the most highly regulated genes. Its gene expression increased 7.5-fold by day 5 and remained high with a 1.9-fold increase until day 10. This was paralleled by a 2-fold increase in cystatin C mRNA expression in the renal cortex. Protein expression in the kidneys also dramatically increased with de novo expression of cystatin C in glomerular podocytes in parts of the proximal tubule and the renal medulla. Urinary excretion of cystatin C increased approximately 2-fold.

Conclusion

In this proof-of-concept study, we could demonstrate that changes in urinary exosomal cystatin C mRNA expression are representative of changes in renal mRNA and protein expression. Because cells lining the urinary tract produce urinary exosomal cystatin C mRNA, it might be a more specific marker of renal damage than glomerular-filtered free cystatin C.     

缺血性脑卒中患者血清C-反应蛋白和内皮素-1水平变化及临床意义

目的:探讨缺血性脑卒中患者不同病变时期血清C-反应蛋白(CRP)和内皮素-1(ET-1)水平变化与缺血性脑卒中关系.方法:临床确诊缺血性脑卒中患者68例,分别检测不同病变时期(入院时、入院第7天和出院前)的血清CRP和ET-1的含量,并记录病例的神经功能缺损评分.选择30例除外心脑血管疾病的体检者作为对照组.结果:①血清CRP含量在入院时、入院第7天和出院前分别为6.83±1.51 mg/L、4.89±1.33 mg/L、4.12±1.24 mg/L.较对照组(2.82±0.66 mg/L)均有显著升高(p＜0.05);血清ET-1含量在入院时、入院第7天和出院前分别为133.69±38.93 ng/L、125.234±32.45 ng/L、108.32±31.51 ng/L,较对照组(45.67±10.02mg/L)均有显著升高(p＜0.01).②随着病程的发展,CRP含量逐渐下降,与病程呈负相关,与神经功能缺损评分呈正相关;ET-1含量也逐渐下降,但仍维持在较高水平,与病程进展和神经功能缺损程度无明显的相关性.结论:缺血性脑卒中患者血清CRP和ET-1水平存在着动态变化.随着病情恢复,CRP含量明显下降,但ET-1含量仍维持在较高水平.     

Distinct Roles of Urinary Liver-Type Fatty Acid-Binding Protein in Non-Diabetic Patients with Anemia

BackgroundVarious stresses including ischemia are known to up-regulate renal L-FABP gene expression and increase the urinary excretion of L-FABP. In diabetic patients with anemia, the urinary excretion of L-FABP is significantly increased. We studied the clinical significance of urinary L-FABP and its relationship with anemia in non-diabetic patients.ResultsUrinary L-FABP levels were significantly higher in patients with anemia compared to those in patients without anemia. Similarly, the urinary L-FABP levels were significantly higher in patients with albuminuria compared to those in patients without albuminuria. Urinary L-FABP levels correlated with urinary albumin-to-creatinine ratios, estimated glomerular filtration rates, body mass index, and hemoglobin levels. Multivariate linear regression analysis determined that hemoglobin levels (β = -0.249, P = 0.001) and urinary albumin-to-creatinine ratios (β = 0.349, P < 0.001) were significant predictors of urinary L-FABP levels.ConclusionsUrinary L-FABP is strongly associated with anemia in non-diabetic patients.     

Long-Term Follow-Up of Proteinuria and Estimated Glomerular Filtration Rate in HIV-Infected Patients with Tubular Proteinuria

Objective

The objective of this prospective observational study was to describe the evolution of tubular proteinuria detected in HIV-infected patients, and to evaluate the impact of tenofovir disoproxil fumarate (TDF) discontinuation.

Methods

Proteinuria and estimated glomerular filtration rate (eGFR) were followed during a median duration of 32 months, in 81 HIV-infected patients with tubular proteinuria and eGFR ≥ 60 ml/min/1.73 m² (determined using the Chronic Kidney Disease Epidemiology (CKD-EPI) Collaboration equation). Tubular proteinuria was defined by urine protein to creatinine ratio (uPCR) ≥200 mg/g and albumin to protein ratio (uAPR) <0.4.

Results

Twenty per cent of patients had persistence of tubular proteinuria: TDF continuation was the main factor associated with this persistence [OR 9.0; 95%CI: 1.9–41.4; p = 0.01]. Among the 23 patients who discontinued TDF, uPCR returned below the threshold of 200 mg/g in 11 patients. Overall, eGFR decreased with a mean rate of decline of 3.8 ml/min/1.73m²/year. The decline in eGFR was lesser after discontinuation of TDF (5.8 ml/min/1.73m²/year during TDF exposure versus 3 ml/min/1.73m²/year after TDF discontinuation; p = 0.01).

Conclusions

The continuation of TDF was the main factor associated with the persistence of proteinuria. Moreover, proteinuria was normalized in only half of the patients who discontinued TDF. The clinical significance of TDF-related low level of proteinuria as a factor associated with renal disease progression and bone loss remains poorly understood.     

Corneal Confocal Microscopy Detects Neuropathy in Patients with Type 1 Diabetes without Retinopathy or Microalbuminuria

Objective

Corneal innervation is increasingly used as a surrogate marker of human diabetic peripheral neuropathy (DPN) however its temporal relationship with the other microvascular complications of diabetes is not fully established. In this cross-sectional, observational study we aimed to assess whether neuropathy occurred in patients with type 1 diabetes, without retinopathy or microalbuminuria.

Materials and Methods

All participants underwent detailed assessment of peripheral neuropathy [neuropathy disability score (NDS), vibration perception threshold (VPT), peroneal motor nerve conduction velocity (PMNCV), sural sensory nerve conduction velocity (SSNCV) and in vivo corneal confocal microscopy (IVCCM)], retinopathy (digital fundus photography) and albuminuria status [albumin: creatinine ratio (ACR)].

Results

53 patients with Type 1 diabetes with (n=37) and without retinopathy (n=16) were compared to control subjects (n=27). SSNCV, corneal nerve fibre (CNFD) and branch (CNBD) density and length (CNFL) were reduced significantly (p<0.001) in diabetic patients without retinopathy compared to control subjects. Furthermore, CNFD, CNBD and CNFL were also significantly (p<0.001) reduced in diabetic patients without microalbuminuria (n=39), compared to control subjects. Greater neuropathic severity was associated with established retinopathy and microalbuminuria.

Conclusions

IVCCM detects early small fibre damage in the absence of retinopathy or microalbuminuria in patients with Type 1 diabetes.     

康柏西普对糖尿病视网膜病变患者视网膜厚度及血清VEGF、IGF-1水平的影响

目的:探讨康柏西普对糖尿病视网膜病变患者视网膜厚度及血管内皮生长因子(VEGF)、胰岛素样生长因子-1(IGF-1)水平的影响。方法:以2015年1月～2017年1月在我院进行治疗的120例糖尿病视网膜病变患者进行研究,随机分为观察组和对照组,每组60例。对照组给予曲安奈德注射液治疗,观察组给予康柏西普眼用注射液治疗,两组均治疗1个月。观察并比较两组患者临床疗效、视网膜厚度、最佳矫正视力(BCVA)、VEGF、IGF-1、生活质量、不良反应等情况。结果:观察组患者总有效率为91.67%(55/60),高于对照组的76.67%(46/60)(P0.05)。治疗后两组患者视网膜厚度、VEGF、IGF-1水平均低于治疗前,且观察组低于对照组,治疗后两组患者BCVA高于治疗前,且观察组高于对照组(P0.05)。治疗后两组患者的生活质量评分均高于治疗前,且观察组高于对照组(P0.05)。观察组不良反应发生率为6.67%(4/60),低于对照组的20.00%(12/60)(P0.05)。结论:康柏西普治疗糖尿病视网膜病变患者的临床疗效显著,促进患者视力快速恢复,用药安全性好,能够提高患者生活质量。     

Ferritin Levels and Hepcidin mRNA Expression in Peripheral Mononuclear Cells from Anemic Type 2 Diabetic Patients

This study aims to measure iron nutrition parameters and to determine the presence of anemia in obese type 2 diabetic patients and to analyze the mRNA relative abundance of genes related to inflammation, immune system, iron metabolism, and mitochondrial activity. Obese type 2 diabetic (OBDM, n?=?30) and healthy subjects (Cn, n?=?30) were studied. Biochemical, anthropometric, and iron nutrition parameters were determined. Peripheral mononuclear cells from type 2 diabetic and control group were challenged with high concentrations of iron (Fe) and glucose and total mRNA was isolated. The frequency of anemia among diabetic patients was 4/30. OBDM patients with or without anemia had higher levels of ferritin and high-sensitivity C-reactive protein than the Cn group. mRNA relative abundance of nuclear factor kappa-light-chain-enhancer of activated B cells was elevated in OBDM with anemia, and mRNA expression of interleukin-6 and toll-like receptor (TLR) 2 was increased in OBDM group in basal high Fe and high glucose concentrations. The expression of tumor necrosis factor alpha and TLR-4 was increased in OBDM with anemia in all experimental conditions. Hepcidin mRNA expression was increased in OBDM with anemia even in basal Fe concentration, and mitofusin 2 was decreased in all experimental conditions. This study shows that obese type 2 diabetic patients have iron distribution disorders associated to their proinflammatory state, and anemic subjects have a marked elevation of hepcidin mRNA expression.     

Uncommon Fungi Isolated from Diabetic Patients Toenails With or Without Visible Onychomycoses

Kodamaea ohmeri and Prototheca wickerhamii are rare pathogens for humans, and even more rare as cause of onychomycosis. This work reports the second case of onychomycosis by K. ohmeri and the fourth of onycoprotothecosis; it was made in public health institutions in the Hidalgo State, Mexico, studying 261 diabetic patients during 2005 and 2006. Kodamaea ohmeri was isolated from toenails of a 51-year-old female patient, and P. wickerhamii from three female patients of 48, 49, and 61 years old, respectively, all of them with type 2 diabetes mellitus (DM 2). Identifications were done by standard microbiological methods and a commercial system. Only one patient infected with P. wickerhamii showed mixed infection with dermatophytes. Out of the total studied DM 2 patients, 1.15% presented onycoprotothecosis and 0.38% onychomycosis by K. ohmeri, high percentages if it is considered that few cases have been reported of K. ohmeri and P. wickerhamii as onychomycosis causal agents.