Microalbuminuric Group Research Articles

Relationship between ACR and other determinants of microalbuminuria in T2DM patients

Introduction: The occurrence of microalbuminuria in type 2 diabetes mellitus (T2DM) patients is regarded as an early clinical sign of incipient kidney damage. Microalbuminuria is often evaluated as urinary albumin to urinary creatinine ratio (ACR). Aim: To assess determinants of microalbuminuria in T2DM patients without prior diagnosis of nephropathy using ACR cut-off values. Materials and Methods: ACR was measured in a total of 90 T2DM patients, during two months in three non-consecutive days, and routine biochemical analyses were performed, including glycated hemoglobin (HbA1c), serum uric acid (SUA), and atherogenic index of plasma (AIP). The cut-off values of ACR were ≤ 2.5 mg/mmol in males, and ≤ 3.5 mg/mmol in females. Duration of T2DM, history of hypertension, HbA1c, estimated glomerular filtration rate (eGFR), AIP, and SUA were investigated for association with microalbuminuria. Results: According to ACR patients were considered as non-albuminuric (n= 57) and microalbuminuric (n = 33). Compared to non-albuminuric group, microalbuminuric group had increased urinary creatinine, urinary albumin, HbA1c, triglycerides and SUA, whilst decreased HDL-cholesterol levels. Although eGFR was generally reduced, the correlation between LogACR and eGFR was not significant (p > 0.05). However, the correlation between LogACR and LogHbA1c was significant. The multiple logistic regression analysis revealed HbA1c (t = 3.42; p = 0.012) and SUA (t = 2.44; p = 0.040) as independent predictors of microalbuminuria in T2DM patients. Conclusion: At ACR cut-off values, concentrations of HbA1c and SUA were independent predictors of microalbuminuria in T2DM patients not yet diagnosed with nephropathy.

Carotid intima media thickness and associations with serum osteoprotegerin and s-RANKL in children and adolescents with type 1 diabetes mellitus with increased risk for endothelial dysfunction

Background Although carotid intima media thickness (CIMT) is an established marker of endothelial dysfunction, limited data exist on relative laboratory biomarkers in youngsters with type 1 diabetes mellitus (T1DM). Our aim was to study CIMT and the biomarkers of the osteoprotegerin (OPG)/RANKL system in young T1DM patients and controls, and also in subgroups of patients with increased risk for endothelial dysfunction, such as those with overweight/obesity, poor metabolic control or the presence of microalbuminuria. Methods CIMT and OPG/RANKL of 56 T1DM children and adolescents were compared to 28 healthy controls. Results Anthropometric, laboratory, CIMT and OPG/RANKL measurements were similar between patients and controls. Overweight/obese patients had greater CIMT than the normal weight ones (0.50 vs. 0.44 mm, p=0.001). Microalbuminuric patients had greater CIMT (0.49 vs. 0.44 mm, p=0.035) than the normoalbuminuric ones, with no difference in terms of OPG/RANKL. In the microalbuminuric group, OPG (r=-0.90, p=0.036) and RANKL (r=-0.92, p=0.024) were significantly negatively associated with CIMT. Following linear regression analysis, in the total patients group, microalbuminuria was the only factor significantly associated with CIMT (beta±SE: 0.050±0.021, p=0.035), body mass index (BMI)-z-scores were negatively associated with OPG (beta±SE: -0.25±0.12, p=0.05), while in the microalbuminuric group, CIMT was negatively associated with OPG (beta±SE: -0.070±0.019, p=0.036). During the forward stepwise procedure, microalbuminuria and age were the only variables negatively associated with RANKL (b=-0.334, p=0.034, b=-35.95, p=0.013, respectively). Conclusions In T1DM pediatric patients, overweight/obesity and microalbuminuria were associated with greater CIMT and with impaired OPG/RANKL levels, as biochemical indices of calcification of the atherosclerotic plaque.

Expression of microRNA‑377 and microRNA‑192 and their potential as blood‑based biomarkers for early detection of type 2 diabetic nephropathy.

The increased incidence of diabetic nephropathy (DN) in type 2 diabetes (T2D) requires novel markers for the early detection of DN. Previously, microRNAs (miRs) have been demonstrated to be promising disease biomarkers. The present study evaluated the biomarker potential of DN‑associated miR‑377 and miR‑192 in the early stages of DN. The study included 85participants: 55patients with T2D (30 without DN and 25 with DN) and 30healthy controls. The patients with T2D were classified according to albumin‑to‑creatinine ratio and were split into three groups: Normoalbuminuric group (n=30), microalbuminuric group (n=15) and macroalbuminuric group (n=10). Reverse transcription‑quantitative polymerase chain reaction analysis was used to evaluate blood miR expression. It was observed that there was higher miR‑377 expression and lower miR‑192 expression in T2D patients with and without DN compared with healthy controls (P<0.05). miR‑377 was higher in the normoalbuminuric group and gradually increased in the microalbuminuric and macroalbuminuric groups (P<0.05), whereas miR‑192 was lower in the macroalbuminuric group compared with the normoalbuminuric group (P<0.05). Regression analysis revealed direct associations between the two miRs and albuminuria (P<0.05). miR‑377 was independently associated with DN risk, even following multivariable adjustment, and albuminuria was the only predictor of miR‑377 (P<0.001). In discriminating overall patients from healthy subjects, ROC analysis revealed areas under the curve (AUCs) of 0.851 for miR377 and 0.774 for miR‑192 (P<0.001). In discriminating the normoalbuminuric group from the microalbuminuric/macroalbuminuric groups, the AUCs were 0.711 (P=0.008) and 0.70 (P=0.049) for miR‑377 and miR‑192, respectively. In patients with microalbuminuria and macroalbuminuria, miR‑377 correlated positively with albuminuria and negatively with renal function, whereas miR‑192 correlated negatively with albuminuria and positively with renal function (P=0.001), and the two miRs were correlated with known risk factors of DN (P<0.05). The results suggested that blood‑based miR‑377 and miR‑192 may serve as potential biomarkers for early detection of DN. Further validation studies are required with larger sample sizes.

Association of neutrophil-to-lymphocyte ratio and microalbuminuria in patients with normal eGFR.

The aim of this study was to evaluate the association between neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and microalbuminuria in patients with normal estimated glomerular filtration rate (eGFR). 174 patients who had eGFR ≥ 60 mL/min/1.73 m2 were studied. Patients were divided into two groups according to the urinary albumin excretion as microalbuminuric group (n = 105) and normoalbuminuric group (n = 69). NLR and PLR levels were calculated. NLR was significantly higher (p < 0.05) in microalbuminuric patients (1.91 ± 0.70) compared with normoalbuminuric patients (1.63 ± 0.53). A positive correlation was found between urine albumin excretion and NLR in the whole study group (r = 0.214, p < 0.005). Higher NLR levels were found in microalbuminuric patients with normal eGFR. Also a significant positive correlation was observed between albuminuria and NLR.

Renal fat fraction and diffusion tensor imaging in patients with early-stage diabetic nephropathy.

To investigate the renal fat fraction and water molecular diffusion features in patients with early-stage DN using Dixon imaging and diffusion tensor imaging (DTI). Sixty-one type 2 diabetics (normoalbuminuria: n = 40; microalbuminuria: n = 21) and 34 non-diabetic volunteers were included. All participants received three-point Dixon imaging and DTI using a 3.0-T magnetic resonance imager. The fat fraction [FF] and DTI features [fractional anisotropy (FA), apparent diffusion coefficient (ADC), tract counts and length from DTI tractography] were collected. All image features were compared between cohorts using one-way ANOVA with Bonferroni post-hoc analysis. Renal FF in the microalbuminuric group was significantly higher than in the normoalbuminuric and control groups (5.6% ± 1.3%, 4.7% ± 1.1% and 4.3% ± 0.5%, respectively; p < 0.001). Medullary FA in the microalbuminuric group was the lowest (0.31 ± 0.06) in all cohorts. The tract counts and length in the renal medulla were significantly lower in the microalbuminuric group than in the other two groups. Dixon imaging and DTI are able to detect renal lipid deposition and water molecule diffusion abnormalities in patients with early-stage DN. Both techniques have the potential to noninvasively evaluate early renal impairment in type 2 diabetes. • Dixon imaging demonstrated renal fat deposition in early-stage DN; • Renal fractional anisotropy decreased in patients with early-stage DN; • Renal tractography demonstrated reduced track counts and length in early-stage DN.

MRNA expression of platelet activating factor receptor (PAFR) in peripheral blood mononuclear cells is associated with albuminuria and vascular dysfunction in patients with type 2 diabetes

AimsRenal dysfunction in addition to diabetes is a serious risk factor for cardiovascular events. We hypothesized that some of the changes in gene expression in blood cells cause renal dysfunction and macrovascular disease through impaired endothelial function. This study aimed to define which changes in gene expression in peripheral blood mononuclear cells (PBMCs) are related to renal function parameters and endothelial function of large arteries in patients with type 2 diabetes mellitus (T2DM). MethodsWe recruited 95 patients with T2DM. After matching for gender, age, BMI and HbA1c levels, the patient cohort included 42 with normoalbuminuria, 28 with microalbuminuria, and 25 with macroalbuminuria. All patients in the three groups were assessed for urinary albumin to creatinine ratio (ACR), estimated glomerular filtration rate (eGFR), flow-mediated dilatation (FMD), and mRNA expression in PBMCs. ResultsThe mRNA expression of platelet activating factor receptor (PAFR) differed most markedly between the three groups and was significantly higher in the macroalbuminuric group (p < 0.001 vs. normoalbuminuric group; p < 0.05 vs. microalbuminuric group). PAFR mRNA expression significantly correlated with log transformed ACR (ρ = 0.424, p < 0.001) but not eGFR. PAFR mRNA expression also had a significant negative correlation with FMD (ρ = −0.379, p < 0.001). Furthermore, the prevalence of macrovascular complications, particularly stroke, was significantly higher in patients with elevated PAFR mRNA expression in PBMCs. ConclusionsPAFR overexpression in PBMCs may link diabetic nephropathy to macroangiopathy through impairment of endothelial function in patients with T2DM.

Urinary miRNA-377 and miRNA-216a as biomarkers of nephropathy and subclinical atherosclerotic risk in pediatric patients with type 1 diabetes

BackgroundUrinary microRNAs (miRNAs) play a role in the pathogenesis of chronic kidney disease (CKD). AimTo identify the expression of urinary miR-377 and miR-216a in 50 children and adolescents with type 1 diabetes (T1DM) compared with 50 healthy controls and assess their relation to the degree of albuminuria, glycemic control and carotid intimal thickness (CIMT) as an index of atherosclerosis. MethodsDiabetic subjects were divided into normoalbuminuric and microalbuminuric groups according to urinary albumin creatinine ration (UACR). Urinary miRNAs were assessed using real time polymerase chain reaction. CIMT was measured using high resolution carotid ultrasound. ResultsThe expression of urinary miR-377 was significantly higher in patients with microalbumiuria (median, 3.8) compared with 2.65 and 0.98 in normoalbuminic patients and healthy controls, respectively (p<0.05). Urinary miR-216a was significantly lower in all patients with type 1 diabetes and the lowest levels were among the microalbumiuric group. Significant positive correlations were found between urinary miR-377 and HbA1C, UACR and CIMT while urinary miR-216a was negatively correlated to these variables. ConclusionsUrinary miR-377 and miR-216a can be considered early biomarkers of nephropathy in pediatric type 1 diabetes. Their correlation with CIMT provides insights on the subclinical atherosclerotic process that occurs in diabetic nephropathy.

Cystatin-C and TGF-β levels in patients with diabetic nephropathy

ObjectiveTo evaluate renal impairment in type 2 diabetic patients with normoalbuminuria or microalbuminuria by detection of serum cystatin C and serum and urinary TGF-β levels. MethodsCross-sectional study conducted at the Department of Endocrinology in Baskent University School of Medicine. Patients with type 2 diabetes mellitus without known overt diabetic nephropathy were included in the study. Recruited patients were stratified into four groups, matched in terms of age, gender, microalbuminuria level and estimated GFR calculated with MDRD. Results78 patients were enrolled. They were categorized into four groups depending on their urinary albumin excretion and estimated glomerular filtration rate.Macrovascular complication was found to be higher in patients with microalbuminuria than in other patients (p<0.01), but there were no differences in terms of other diabetic complications. Serum cystatin C level was significantly higher in normoalbuminuric group one patients, while serum and urinary TGF-β1 levels were higher in microalbuminuric group two patients. The serum level of cystatin C was found to negatively correlate with eGFR in group two patients (r=−0.892, p<0.001). Finally, there was a negative correlation between eGFR and cystatin C in all the patient groups (r=−0.726, p=0.001). ConclusionsAlthough urinary albumin excretion is recommended for the detection of type two diabetic nephropathy, there is a group of patients with decreased eGFR but without increased urinary albumin excretion, in which serum cystatin C level was indicated to be used as an early biomarker of diabetic nephropathy.

Cystatin-C and TGF-β levels in patients with diabetic nephropathy

ObjectiveTo evaluate renal impairment in type 2 diabetic patients with normoalbuminuria or microalbuminuria by detection of serum cystatin C and serum and urinary TGF-β levels. MethodsCross-sectional study conducted at the Department of Endocrinology in Baskent University School of Medicine. Patients with type 2 diabetes mellitus without known overt diabetic nephropathy were included in the study. Recruited patients were stratified into four groups, matched in terms of age, gender, microalbuminuria level and estimated GFR calculated with MDRD. Results78 patients were enrolled. They were categorized into four groups depending on their urinary albumin excretion and estimated glomerular filtration rate.Macrovascular complication was found to be higher in patients with microalbuminuria than in other patients (p<0.01), but there were no differences in terms of other diabetic complications. Serum cystatin C level was significantly higher in normoalbuminuric group one patients, while serum and urinary TGF-β1 levels were higher in microalbuminuric group two patients. The serum level of cystatin C was found to negatively correlate with eGFR in group two patients (r=−0.892, p<0.001). Finally, there was a negative correlation between eGFR and cystatin C in all the patient groups (r=−0.726, p=0.001). ConclusionsAlthough urinary albumin excretion is recommended for the detection of type two diabetic nephropathy, there is a group of patients with decreased eGFR but without increased urinary albumin excretion, in which serum cystatin C level was indicated to be used as an early biomarker of diabetic nephropathy.

Changes of serum Mir-217 and the correlation with the severity in type 2 diabetes patients with different stages of diabetic kidney disease.

The aim of this study is to investigate the correlation between serum microRNA-217 and the severity of diabetic kidney disease determined by albuminuria. Four hundred ninety five type 2 diabetes patients were divided into three groups: normoalbuminuric group, microalbuminuric group, and macroalbuminuric group. Serum microRNA-217 levels were validated by real-time polymerase chain reaction. Serum silent information regulator 1, Hypoxia-inducible factor-1α and vascular endothelial growth factor were determined by enzyme-linked immunosorbent assay. Compared with control, serum microRNA-217 levels were significantly increased in type 2 diabetes patients and gradually increased in patients of normoalbuminuric, microalbuminuric, and macroalbuminuric groups (P < 0.01). Moreover, increased levels of serum microRNA-217, hypoxia-inducible factor-1α, vascular endothelial growth factor, diabetes mellitus duration, fasting blood glucose, fasting insulin, homeostasis model assessment for insulin resistance, glycated hemoglobin, low-density lipoprotein, total cholesterol, triglyceride, uric acid, serum creatinine, blood urea nitrogen, and decreased levels of serum silent information regulator 1 and high-density lipoprotein were significantly correlated with Ln(ACR) (P < 0.05). In addition, serum microRNA-217 was positively correlated with diabetes mellitus duration, homeostasis model assessment for insulin resistance, glycated hemoglobin, Ln(ACR), low-density lipoprotein, total cholesterol, triglyceride, uric acid, serum creatinine, blood urea nitrogen, hypoxia-inducible factor-1α, vascular endothelial growth factor (P < 0.05), and negatively correlated with serum silent information regulator 1 (P = 0.002). Our findings suggest that microRNA-217 may have an association with the development of proteinuria in type 2 diabetes patients. Serum microRNA-217 may be involved in the development of diabetic kidney disease by promoting chronic inflammation, renal fibrosis, and angiogenesis.

Changing correlations among ADMA, NO and hs-CRP in normoalbuminuric and microalbuminuric patients with type 2 diabetes

BackgroundAlbuminuria is one of the first asymptomatic clinical manifestations of microvascular damage in type 2 diabetes. High-sensitivity C-reactive protein (hs-CRP), Asymmetric dimethylarginine (ADMA), and nitric oxide (NO) are important risk factors for endothelial dysfunction. The aim of this study is to evaluate hs-CRP, ADMA, and NO levels and their correlations in patients with type 2 diabetes respect to their albuminuric states. MethodsWe quantified serum hs-CRP, ADMA, and NO levels in 40 microalbuminuric (urinary albumin excretion ≤30mg/day and <300mg/day) type 2 diabetic patients and 40 age, gender, and body mass index (BMI)-matched normoalbuminuric (urinary albumin excretion <30mg/day) diabetic patients in this case-control study. ResultsThe mean value of albuminuria was 238±58mg/day in the microalbuminuric group and 12.6±4.7mg/day in the normoalbuminuric group. Creatinine was significantly higher and GFR was significantly lower in group with microalbuminuria than normoalbuminuria (p<0.05). Albuminuric diabetic patients had significantly higher hs-CRP levels as compared to normoalbuminuric group (3.9±0.8mg/dL versus 5.7±1.4mg/dL, p<0.05). However there were no significant differences in ADMA and NO between two groups but the ADMA/NO ratio was significantly higher in albuminuric group comparing with normoalbuminuric one (0.017 vs. 0.015, p value <0.05). In control group (normoalbuminuria) age, gender and BMI-adjusted ADMA indicated a significant and positive correlation with NO (r=0.430, p value=0.022) and with hs-CRP (r=0.362, p value=0.041), and also a significant and positive correlation was found between hs-CRP and NO in case group (with microalbuminuria) (r=0.370, p value=0.026). ConclusionHs-CRP was higher in microalbuminuric patients with type 2 diabetes compare to normoalbuminuric group. Also we found changing association among ADMA, NO and hs-CRP from normoalbuminuric to albuminuric state which this finding may be linked to the role of basic inflammation in confounding some interactions and creating some new ones.

MiRNAs in Urine Extracellular Vesicles as Predictors of Early-Stage Diabetic Nephropathy.

Background. miR-192, miR-194, and miR-215 are enriched in the kidney and play roles in the pathogenesis of diabetic nephropathy (DN). Extracellular vesicles (EVs) can be detected in body fluids and may serve as disease biomarkers. Methods. Eighty type 2 diabetes patients with normoalbuminuria (n = 30), microalbuminuria (n = 30), or macroalbuminuria (n = 20), as well as 10 healthy controls, were enrolled in this study. Real-time PCR was used to evaluate urinary EV miRNAs expression. Results. The miR-192 levels were significantly higher than the miR-194 and miR-215 levels in urine EVs and all three miRNAs were significantly increased in the microalbuminuric group compared with the normoalbuminuric and control subjects but were decreased in the macroalbuminuric group. In patients with normoalbuminuria and microalbuminuria, miR-192 was positively correlated with albuminuria (r = 0.357, P = 0.005) levels and transforming growth factor- (TGF-) β1 (r = 0.356, P = 0.005) expression. Receiver operating characteristic (ROC) curve analysis revealed that miR-192 was better than miR-194 and miR-215 in discriminating the normoalbuminuric group from the microalbuminuric group. Exposure of human renal tubular epithelial cells to high glucose increased the expression of both miRNAs in cellular supernatant EVs, indicating a potential source. Conclusion. These results suggest the potential use of urinary EV miR-192 as a biomarker of the early stage of DN.

Levels of Serum 25(OH)VD3, HIF-1α, VEGF, vWf, and IGF-1 and Their Correlation in Type 2 Diabetes Patients with Different Urine Albumin Creatinine Ratio.

Objective. To investigate changes in serum 25(OH)VD3, HIF-1α, VEGF, vWf, IGF-1, and their correlation in type 2 diabetes patients at different stages of diabetic kidney disease (DKD). Methods. 502 type 2 diabetes patients were divided into three groups: Normoalbuminuric group (201 patients), Microalbuminuric group (171 patients), and Macroalbuminuric group (130 patients). Serum 25-hydroxyvitamin D3 [25(OH)VD3] was measured by chemiluminescence. Serum hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), von Willebrand factor (vWf), and insulin-like growth factor-1 (IGF-1) were determined by enzyme-linked immunosorbent assay. We detected the aforementioned serum factors in all cases and 224 control subjects. Results. Serum HIF-1α, VEGF, vWf, and IGF-1 in type 2 diabetes patients were significantly higher than those in the control group and increased with the increase of Ln(ACR), respectively (P < 0.001). Serum 25(OH)VD3 was significantly lower in type 2 diabetes patients and decreased with the increase of Ln(ACR) (P < 0.001). Ln(ACR) was positively correlated with duration, HbA1c, Scr, BUN, TC, LDL, TG, UA, HIF-1α, VEGF, IGF-1, vWf, and Fg and negatively correlated with 25(OH)VD3 and eGFR. Conclusion. Serum HIF-1α, VEGF, vWf, and IGF-1 may be involved in DKD process through inflammation, angiogenesis, and endothelial injury. Serum 25(OH)VD3 may have protective effects on DKD partly by inhibiting inflammation, abnormal angiogenesis, and vascular endothelial dysfunction.

The Value of Serum Prolidase Activity in Progression of Microalbuminuria in Patients With Type 2 Diabetes Mellitus.

Prolidase is a cytosolic exopeptidase that plays a pivotal role in collagen turnover. Diabetic nephropathy (DN) is associated with structural changes in glomerular basement membrane accompanied with increased amounts of collagen. Prolidase is known to be abundant in kidney and collagen accumulation is increased in DN, so we aimed to determine the value of serum prolidase activity (SPA) in predicting the progression of nephropathy in type 2 diabetes mellitus (DM). Thirty type 2 DM patients having microalbuminuria (microalbuminuric group), 30 type 2 DM patients without albuminuria (normoalbuminuric group), and 28 healthy controls (control group) were enrolled. Study groups had similar age, sex distribution, and body mass index (BMI). Metabolic parameters, SPA and urinary microalbumin were determined. SPA was significantly higher in microalbuminuric group when compared with normoalbuminuric and control groups (P = 0.05 and P < 0.001, respectively). Triglyceride levels were significantly higher and high density lipoprotein cholesterol (HDL-C) levels were significantly lower in microalbuminuric group compared to control group (Both P < 0.05). SPA showed a negative correlation with HDL-C level and a positive correlation with urinary albumin excretion (r = -0.219, P < 0.05 and r = 0.39, P < 0.001 respectively). In regression analysis, albumin excretion was the sole parameter influencing SPA. SPA appears to be higher in type 2 DM patients having microalbuminuria compared to patients without microalbuminuria and healthy controls. The pathophysiological role and the significance of SPA in predicting DN need to be further evaluated.

Comparison of eGFR Values Calculated by Using Serum Cystatin C and Serum Creatinine in Patients with Diabetes Mellitus

Objective: In this study, we aimed to compare estimated glomerular filtration rate (eGFR) formulas based on cystatin C and serum creatinine and investigate whether the formulas can detect the renal damage at microalbuminuric level in diabetic patients. Methods: Totally, 99 type 2 diabetic patients were included and divided into 3 groups according to 24 hour urine albumin levels as normoalbuminuric group (group 1), microalbuminuric group (group 2) and macroalbuminuric group (group 3). Creatinine clearance, Cockcroft-Gault (C-G), Modification of Diet in Renal Disease (MDRD), The Chronic Kidney Disease Epidemiology (CKD-EPI), eGFR1, eGFR2 and eGFR3 levels were calculated using formulas. Results: There were significant differences between group 1-3 and group 2-3, but there was no significant difference between group 1 and 2 in calculated GFR levels. Cystatin C-based formulas were found to have a better correlation with creatinine clearance. Conclusion: As a result, cystatin C-based formulas were found to predict creatinine clearance better than the other calculated GFR formulas in diabetic patients. However none of the formulas can discriminate the renal damage at microalbuminuric level. J Clin Exp Invest 2015; 6 (2): 91-95 Key words: eGFR, cystatin C, diabetic nephropathy, creatinine, CKD-EPI

Plasma osteoprotegerin concentrations in type 1 diabetic patients with albuminuria

BackgroundOsteoprotegerin (OPG) is a recently identified inhibitor of bone resorption. Recent studies indicate that OPG is also associated with endothelial dysfunction in diabetes. AimTo investigate the relationship between plasma OPG levels and urinary albumin excretion (UAE) in type 1 diabetes. MethodsA total of 80 type 1 diabetic subjects and 40 control subjects were enrolled. Diabetic subjects were divided into a normoalbuminuric group and a microalbuminuric group according to urinary albumin excretion rate (UAER). Plasma OPG level was measured by enzyme-linked immunoassay. ResultsThe plasma OPG levels were significantly elevated in patients with microalbuminuria (176.39±25.05pg/ml) compared with patients with normoalbuminuria (154.73±16.66pg/ml) and control subjects (44.76±8.7pg/ml). The plasma OPG level had a positive correlation with patients' age, duration of disease, HbA1C and UAER. ConclusionsPlasma OPG levels are significantly associated with UAE in patients with type 1 diabetes. These findings may support the concept that elevated plasma OPG may be associated with diabetic angiopathy.

Cardiovascular effects of copper deficiency on activity of superoxide dismutase in diabetic nephropathy.

Background:Copper (Cu) is essential both for its role in antioxidant enzymes, like Cu/zinc (Zn) superoxide dismutase (SOD) and ceruloplasmin, as well as its role in lysyl oxidase, essential for the strength and integrity of the heart and blood vessels. With such a central role in cardiovascular health, Cu has been generally overlooked in the debate over improving our cardiovascular health. Cu deficiency has produced many of the same abnormalities present in cardiovascular disease. It seems almost certain that Cu plays a large role in the development of this killer disease, not because of its excess in the diet, but rather its deficiency.Aim:This study was undertaken to investigate the cardiovascular effects of Cu deficiency on the activity of SOD in patients with type 2 diabetes mellitus (T2DM) with and without diabetic nephropathy.Materials and Methods:Fifty-five patients with T2DM were recruited in this study which were divided into two subgroups based on the presence of microalbuminuria, the first group (microal buminuric group, n = 31) had a microalbuminuria between 30 and 299 μg/mg. The second group (normoal buminuric group, n = 29) had an albumin level less than 30 μg/mg. The two diabetic groups were compared to the control group (n = 37).Results:The results of our study showed a significant reduction in the levels of SOD enzyme associated with an increased urinary Cu excretion in microalbuminuric group compared to the control group at P < 0.05.Conclusions:The current study illustrates that the regulation of the blood concentrations of Cu may be a potential therapeutic target for prevention and treatment of diabetic nephropathy.

Proteases and Protease Inhibitors of Urinary Extracellular Vesicles in Diabetic Nephropathy

Diabetic nephropathy (DN) is one of the major complications of diabetes mellitus (DM), leads to chronic kidney disease (CKD), and, ultimately, is the main cause for end-stage kidney disease (ESKD). Beyond urinary albumin, no reliable biomarkers are available for accurate early diagnostics. Urinary extracellular vesicles (UEVs) have recently emerged as an interesting source of diagnostic and prognostic disease biomarkers. Here we used a protease and respective protease inhibitor array to profile urines of type 1 diabetes patients at different stages of kidney involvement. Urine samples were divided into groups based on the level of albuminuria and UEVs isolated by hydrostatic dialysis and screened for relative changes of 34 different proteases and 32 protease inhibitors, respectively. Interestingly, myeloblastin and its natural inhibitor elafin showed an increase in the normo- and microalbuminuric groups. Similarly, a characteristic pattern was observed in the array of protease inhibitors, with a marked increase of cystatin B, natural inhibitor of cathepsins L, H, and B as well as of neutrophil gelatinase-associated Lipocalin (NGAL) in the normoalbuminuric group. This study shows for the first time the distinctive alterations in comprehensive protease profiles of UEVs in diabetic nephropathy and uncovers intriguing mechanistic, prognostic, and diagnostic features of kidney damage in diabetes.

A Gender Based Case Control Study of Anthropometric and Renal Profile in Rural Diabetic Population

OBJECTIVE: To evaluate the gender specific changes in anthropometric and renal parameters for the prediction of microvascular complications commonly diabetic nephropathy at its earlier stages through screening of diabetic patients. MATERIALS AND METHODS: We studied total 150 subjects with Type 2 diabetes mellitus, duration of diabetes within 10 years, age group 50-60 years and equal number of age and gender matched clinically proven healthy controls during March 2011 to January 2012 were enrolled in our study. Anthropometric and biochemical parameters measurements were done by standard methods. RESULTS: On comparison between non diabetics and diabetic subjects, waist circumference (WC), body mass index (BMI), waist hip ratio (WHR), obesity index, diastolic blood pressure (DBP), fasting blood sugar (FBS), serum creatinine, spot urine albumin (AER)and albumin/creatinine ratio (ACR) were significantly higher in diabetic males compared to non diabetic males and WC, BMI, DBP, FBS and SCr were significantly higher in diabetic females on comparison with non diabetic females. In Normoalbuminuric group (ACR<30mg/g) WHR and AER was higher in males compared to females and in Microalbuminuric group (ACR 30300mg/g)WHR, AER, FBS and ACR were significantly higher in males compared to females. CONCLUSION: Significant increase in WHR was observed between male and female diabetics above the cutoff values as per the recommendations made by National Institute of Health Guidelines, and this study also confirmed that AER was higher in diabetic males compared to females which are clinical hallmarks for diabetic nephropathy and cardiovascular risk factors.

Elevated brachial-ankle pulse wave velocity is independently associated with microalbuminuria in a rural population.

Microalbuminuria is a marker of generalized endothelial dysfunction resulting from arterial stiffness or insulin resistance, and brachial-ankle pulse wave velocity (baPWV) is a good measure of arterial stiffness. We aimed to investigate whether elevated baPWV is independently associated with microalbuminuria. This study included 1,648 individuals aged over 40 who participated in the baseline Multi-Rural Cohort Study conducted in Korean rural communities between 2005 and 2006. Participants were classified into less than 30 mg/g as normoalbuminuria or 30-300 mg/g as microalbuminuriausing urinary albumin creatinine ratio (UACR). The median and Q1-Q3 baPWV values were significantly higher in the microalbuminuric group both in men (1,538, 1,370-1,777 cm/s vs. 1,776, 1,552-2,027 cm/s, P < 0.001) and women (1,461, 1,271-1,687 cm/s vs. 1,645, 1,473-1,915 cm/s, P < 0.001). BaPWV was independently associated with microalbuminuria in both genders after adjusting for pulse rate; fasting blood glucose; triglyceride; homeostatic model assessment insulin resistance (HOMAIR) and, history of hypertension and diabetes. Fasting blood sugar and HOMAIR were judged as having nothing to do with multicolinearity (r = 0.532, P < 0.001). Elevated baPWV was independently associated with microalbuminuria regardless of insulin resistance among rural subjects over 40 yr.Graphical