Indicator Of Diabetic Nephropathy Research Articles

Bidirectional association between depression and diabetic nephropathy by meta-analysis.

Studies suggested that the association between depression and diabetic nephropathy may be bi-directional, but this hypothesis remains investigating. In this meta-analysis, the bi-directional relationship between depression and diabetic nephropathy was investigated. A search for the publications on depression and diabetic nephropathy in the databases of PubMed, Web of science, and Embase from the earliest available to August 2022 was conducted. Two sets of pooled risk estimates were calculated using random effects models: diabetic nephropathy predicting depression and depression predicting diabetic nephropathy. Cross-sectional studies were assessed using Agency for Healthcare Research and Quality (AHRQ), cohort and case-control studies were assessed using Newcastle-Ottawa Scale (NOS). Of the 974,121 patients in 30 clinical studies, 24 studies met eligibility for diabetic nephropathy predicting onset of depression, representing 28,438 incident cases. The other 6 studies met criteria for depression predicting onset of diabetic nephropathy, representing 945,683 incident cases. The pooled odds ratio (OR) of diabetic nephropathy predicting depression was 1.46 (95% CI 1.27-1.67). The OR of depression predicting diabetic nephropathy was 1.22 (95% CI 1.13-1.31). This meta-analysis shows that the relationship between depression and diabetic nephropathy may be bidirectional. Diabetic nephropathy may be a predictor of depression, and depression may also be an indicator of diabetic nephropathy. The mechanisms underlying the bidirectional relationship need to be further investigated and interventions of the comorbidity of depression and diabetic nephropathy need be studied in clinical practice.

Platelet Indices as Indicator of Diabetic Nephropathy among Patients Attending a Tertiary Care Centre in South-India

Introduction: Diabetes mellitus, a chronic metabolic disease affects various organs of the body on a long-term basis. Studies have been conducted on different aspects of the disease, to understand its complications and to detect them earlier to avoid irreversible damage like nephropathy.
 Aim: The study aims at comparing platelet indices like Plateletcrit (PCT), Platelet Distribution Width (PDW) and Mean Platelet Volume (MPV), with serum creatinine among diabetes, prediabetes patients and non-diabetes controls, to understand the association of the platelet indices and creatinine, an indicator of renal damage.
 Materials and Methods: The cross-sectional study conducted over a period of three months involved 30 non-diabetic controls with normal HbA1c, 30 diabetics and 30 prediabetic subjects, of age group 18-35 years. The groups were classified based on their HbA1c concentration. The blood samples were analyzed for parameters PCT, PDW, MPV, creatinine and HbA1c by their respective methods. The study will guide in understanding the role of platelets in pathogenesis of diabetic nephropathy.
 Results: Platelet indices like Plateletcrit (PCT), Platelet Distribution Width (PDW) and Mean Platelet Volume (MPV) were found to be increased in diabetics and 30 prediabetic subjects than the non-diabetics. The Platelet indices were also correlating with the serum creatinine levels of the three study groups.
 Conclusion: There is a positive association between the Platelet indices and creatinine, in patients with pre-diabetes and diabetes who have the risk of progression to diabetic nephropathy. Hence, the Platelet indices shall be included as early and cost-effective biomarkers of diabetic nephropathy.

Platelet indicies as an indicators of diabetic nephropathy

Background: Diabetic nephropathy is considered one of the most common microvascular complications. Insulin resistance and impaired insulin secretion are very important in the pathogenesis, It can be suggested that increased platelet volume may be an important factor in the enhanced risk of vascular complications.Patients and Method: This study included 50 diabetic patients, 50 diabetic patients with nephropathy & 50 healthy age and sex-matched subjects as controls. Blood samples were obtained for CBC, Anticoagulated blood (ethylene diamine tetracetic acid) was collected and analyzed in an automated blood cell counter for platelet count and indices (MPV, PDW, P-LCC & P-LCR), Glucose, HbA1c, Kidney function (creatinine & urea), Albumin/creatinine ratio & lipid profile (cholesterol, triglyceride, HDL, LDL & VLDL) were also done.Results: MPV, PDW and P-LCR were all significantly higher in diabetic patients compared to the control subjectswith (P= 0.001, 0.05, 0.02 respectively). Among the diabetics, MPV was higher in diabetic patient with nephropathy as compared to those without nephropathy (P= 0.001).Conclusions:Platelet indices, especially MPV were different between diabetics and controls as well as diabetic nephropathy. Discriminant analysis using MPV and PDW could classify majority of patients with nephropathy.

Preparation and Characterization of Chitosan-Stabilized Selenium Nanoparticles for Ameliorating Experimentally Induced Diabetic Nephropathy in Rats

Chitosan-stabilized selenium nanoparticles (CTS-SeNPs) were prepared by reduction technique. Single phase structure of the SeNPs was confirmed using X-ray diffraction (XRD). Transmission Electron Microscope (TEM) showed that the particle size of the samples in the range of 15 nm. This experiment aimed to study the potential effect of (CTS-SeNPs) as a therapeutic factor in diabetic nephropathy in rats. Streptozotocin (STZ) was used to induce diabetes in rats; thirty-six numbers were divided into three groups; control, STZ-induced diabetic, and STZ-induced diabetic rats taken CTS-SeNPs groups at a dose (2 mg Se/kg/d). All groups were given respective treatment orally via gastric tube for 2 month. The obtained data showed that, the diabetic group revealed presence of Microalbuminurea, the indicator of diabetic nephropathy and showed a significant increase in fasting blood glucose, urea, creatinine, TAC and MDA, it is significant that high expression level of TGF-β1 and aldose reductase while the group treated with CTS-SeNPs revealed significant decline in all values compared to the diabetic group. Diabetic group showed a significant decrease in insulin level, GPx and SOD activity while, the treated group showed significant increase in these values compared to the diabetic group. Kidney tissue showed normal histological picture except for mild vascular and glomerular congestion in treated group when compared with diabetic one. Our experiment suggests that CTS-SeNPs can moderate diabetic nephropathy in streptozotocin-induced diabetic rats.

Association of serum sestrin 2 and betatrophin with serum neutrophil gelatinase associated lipocalin levels in type 2 diabetic patients with diabetic nephropathy

PurposeUnderstanding the pathogenesis and the molecular mechanisms of diabetic nephropathy (DN) helps its timely detection and prevention. The current work aims tomeasure serum sestrin 2 and betatrophin levels in healthy and type diabetic (T2DM)subjects with/or without diabetic nephropathy (DN) and also to test their correlation with serum neutrophil gelatinase associated lipocalin (sNGAL); indicator of DN.MethodsThis study included 96 subjects; 20 healthy (G1) and 76 T2DM [22 normoalbuminuric (G2), 35 microalbuminuric (G3) and 19 macroalbuminuric (G4)]. Serum sestrin 2, betatrophin and NGAL were measured by their corresponding kits.ResultsSignificant low levels of serum sestrin 2 andhigh levels of serum betatrophin were found in T2DM group when compared to G1 (p = 0.002,p > 0.001, respectively) and this difference is manifested in G4 followed, in order, by G3, G2 then G1 (p= > 0.001 for both). Also, serum sestrin2 levels showed significant negative correlations with sNGAL in G1 (r = −0.497, p = 0.026), G2 (r = −0.784, p > 0.001), G3 (r = −0.894, p > 0.001) and G4 (r = −0.896, pp. > 0.001) while serum betatrophin levels showed significant positive correlations with sNGAL in G2 (r = 0.681, p > 0.001), G3 (r = 0.518, p > 0.001) and G4 (r = 0.727, p > 0.001).ConclusionSerum sestrin 2 levels decrease significantly while betatrophin levels increase significantly in T2DM patients with DN especially those with macroalbuminuria. These levels have significant effect strengths on the indicator of diabetic nephropathy; sNGAL which might indicate theirvaluablerole in the timely detection and prevention of the development of DN.

Aortic Stiffness Index And Carotid Intima-Media Thickness Are Independently Associated With The Presence Of Microalbuminuria In Patients With Type 2 Diabetes Mellitus.

PurposeMicroalbuminuria is a premature and widely used indicator of diabetic nephropathy and is reported to be related with a higher cardiovascular risk in diabetic patients. We aimed to examine whether the echocardiographic parameters, such as epicardial fat thickness (EFT), carotid intima-media thickness (CIMT) and aortic stiffness index (ASI) are associated with microalbuminuria in patients with diabetes mellitus type 2 (T2DM).Patients and methodsA total of 272 consecutive patients were enrolled and after the exclusion criteria, the data of 180 patients with T2DM were used in this cross-sectional study. Patients were divided into two groups: 82 patients with microalbuminuria and 98 patients without microalbuminuria (normoalbuminuria). The laboratory results and echocardiographic EFT, CIMT and ASI parameters were noted.ResultsCompared with the normoalbuminuria group, EFT, CIMT and ASI were significantly higher in the microalbuminuria group (p<0.05 for all). In logistic regression analysis; CIMT (OR: 3.15, p=0.024) and ASI (OR: 4.19, p=0.016) were independently associated with microalbuminuria in patients with T2DM.ConclusionIn addition to CIMT, as a novel finding, ASI which is an indicator for the elastic properties of the aortic root was independently associated with microalbuminuria. CIMT and ASI measurement by echocardiography may be helpful in identifying the accompanying factors in the development of nephropathy.

27-LB: Alteration of the Gut Microbiome by Resveratrol Is Associated with Improvement in Function of Kidney in db/db Mice

Oral administration of resveratrol is able to amelioration the progression of diabetic nephropathy, but the underlying cause is unknown. In this report, we demonstrated that resveratrol relieved a series of indicators of diabetic nephropathy. Oral administration of resveratrol was able to sequester negatively charged bacterial endotoxin in the gut, leading to 1) reduced plasma endotoxin levels, 2) resolved systemic inflammation and the Intestinal environment, and 3) lowered renal inflammation and improved renal function. Gut dysbiosis, characterized as an increment of Bacteroides, Alistipes, Turicibacter and Parabacteroides, and reduction of Enterococcus , was fully modulated by resveratrol, indicating that inflammatory-associated microbiome in the gut are critical for the metabolic endotoxemia. Furthermore, fecal bacteria transplant, derived from heathy resveratrol-treated mices, was sufficient to antagonize the renal dsyfunction and rebalance of gut microbiome in the recipient mice. These results indicate that resveratrol mediated changes in the gut microbiome may play an important role in the mechanism of action of resveratrol, which provide supporting evidence for the gut-kidney axis in DN. Disclosure D. Dafa: None. L. Yibing: None. C. Tingting: None. Y. Xiaolong: None. M. Jianhua: None. Funding Major Research and Development Project of Jiangsu (BE2016800); Nanjing Science and Technology Plan Project (BE201715015)

Urinary transferrin as an early biomarker of diabetic nephropathy

Background/Aim. Diabetic nephropathy is one of the leading cause of chronic kidney disease and end-stage renal disease. It occurs in 20%?40% of patients with diabetes mellitus and microalbuminuria is still considered as the first sign of diabetic nephropathy. Low sensitivity and specificity of microalbuminuria lead to more sensitive biomarkers that may be used to detect diabetic nephropathy at an earlier stage with a higher accuracy. This study was carried out to determine whether urinary transferrin can serve as an indicator of diabetic nephropathy. Methods. Our study included 80 type 2 diabetic patients who were classified into two groups: group 1 ? normoalbuminuric patients (albumin excretion up to 30 mg/d); group 2 ? microalbuminuric patients (albumin excretion from 30?300 mg/d), and 10 healthy controls. All patients were older than 18, having the diabetic disease more than one year, glomerular filtration rate more than 60 mL/min/1.73 m2. Serum creatinine, glycosylated hemoglobin (HbA1c), and concentration of transferrin in the 24 h urine samples as well as in spot urine were measured using a highly sensitive one-step sandwich enzyme immunoassay kit. Results. Urinary transferrin was significantly higher in the microalbuminuric patients than in the normoalbuminuric ones and healthy control subjects. When comparing these goups according to the urinary transferrin concentration, we found a statistically significant positive correlation r = 0.584 (p &lt; 0.001). There was no correlation between level of urinary transferrin and glycoregulation, and no correlation was found between transferrin and duration of diabetes. Conclusions. The results from this study provide the evidence that the urinary transferrin levels could be used as an early marker of diabetic nephropathy.

Maximum home blood pressure is a useful indicator of diabetic nephropathy in patients with type 2 diabetes mellitus: KAMOGAWA-HBP study.

Maximum home systolic blood pressure has been shown to predict target organ damage. We aimed to clarify the association between maximum home systolic blood pressure and urine albumin to creatinine ratio, an indicator of early-phase diabetic nephropathy in patients with type 2 diabetes. In 1040 patients, we assessed the relationship of mean or maximum home systolic blood pressure and urine albumin to creatinine ratio, and compared the area under the receiver operating characteristic curve of mean or maximum home systolic blood pressure for diabetic nephropathy (urine albumin to creatinine ratio ⩾30 mg/g Cr). Multivariate linear regression analyses indicated that mean morning systolic blood pressure ( β = 0.010, p < 0.001) and maximum morning systolic blood pressure ( β = 0.008, p < 0.001) were significantly associated with urine albumin to creatinine ratio. Area under the receiver operating characteristic curve (95% confidence interval) for diabetic nephropathy in mean and maximum morning systolic blood pressure was 0.667 (0.634-0.700; p < 0.001) and 0.671 (0.638-0.703; p < 0.001), respectively. Maximum home systolic blood pressure, as well as mean home systolic blood pressure, was significantly associated with diabetic nephropathy in patients with type 2 diabetes.

ApoM/HDL-C and apoM/apoA-I ratios are indicators of diabetic nephropathy in healthy controls and type 2 diabetes mellitus

BackgroundApolipoprotein M (apoM) concentrations were decreased in type 2 diabetes mellitus (T2DM). ApoM was selectively expressed in renal tubular epithelial cells. We investigated the changes in plasma apoM concentrations in diabetic nephropathy (DN) patients and the potential of apoM as a biomarker of DN. MethodsA total of 96 DN patients and 100 age- and sex-matched diabetic non-nephropathy (non-DN) patients and 110 healthy controls were included. All T2DM patients were divided into 3 groups according to urinary albumin excretion: normoalbuminuria (n=100), microalbuminuria (n=50) and macroalbuminuria (n=46). Plasma apoM concentrations were measured by enzyme-linked immunosorbent assay. ResultsDN Patients had higher plasma apoM concentrations than those in non-DN patients (22.23±11.69 vs. 18.96±7.85ng/μl, P<0.05). In addition, microalbuminuria group showed higher plasma apoM concentrations than those in normoalbuminuria group (22.67±11.40 vs. 18.96±7.85ng/μl, P<0.05). The areas under curve (AUC) of apoM using a receiver-operating characteristic (ROC) curve analysis showed that plasma apoM concentrations were not indicators for identification of DN from healthy people (AUC=0.478, P=0.585) and from T2DM (AUC=0.563, P=0.125). DN patients had higher ratios of apoM/HDL-C and apoM/apoA1 than those in healthy controls and in non-DN patients. ApoM/HDL-C and apoM/apoA1 ratios could be used as indicators for identification of DN from healthy people (AUC=0.597, P=0.016; AUC=0.665, P=0.000, respectively) and from T2DM (AUC=0.580, P=0.050; AUC=0.601, P=0.015, respectively). ConclusionsApoM/HDL-C and apoM/apoA1 ratios could be used as indicators for identification of DN from healthy people and from T2DM patients.

Рівень гідроґену сульфіду у пацієнтів з цукровим діабетом 2 типу залежно від наявності діабетичної нефропатії

Aim.&nbsp;To investigate the level of hydrogen sulfide in patients with type 2 diabetes depending on the presence of diabetic nephropathy. Material and Methods.&nbsp;The investigation included 70 patients with T2D (40 men and 30 women). Besides standard laboratory examination, additional sample of blood for hydrogen sulfide was taken and a 24-hour urine sample for microalbuminuria was collected. All patients were divided in two groups: patients without DN and with DN. Patients underwent antidiabetic treatment with metformin. Independent Student t-test was used to compare the differences between the groups, and Pearson correlation coefficient (r) was calculated. Results and Discussion.&nbsp;It was revealed that hydrogen sulfide level in patients with diabetic nephropathy is significantly decreased and shows negative correlates with indicators of diabetic nephropathy - microalbumin and glomerular filtration rate. Conclusions.&nbsp;Level of hydrogen sulfide is decreased in patients with diabetic nephropathy and can serve as its early indicator.

Cathepsin S Cleavage of Protease-Activated Receptor-2 on Endothelial Cells Promotes Microvascular Diabetes Complications.

Endothelial dysfunction is a central pathomechanism in diabetes-associated complications. We hypothesized a pathogenic role in this dysfunction of cathepsin S (Cat-S), a cysteine protease that degrades elastic fibers and activates the protease-activated receptor-2 (PAR2) on endothelial cells. We found that injection of mice with recombinant Cat-S induced albuminuria and glomerular endothelial cell injury in a PAR2-dependent manner. In vivo microscopy confirmed a role for intrinsic Cat-S/PAR2 in ischemia-induced microvascular permeability. In vitro transcriptome analysis and experiments using siRNA or specific Cat-S and PAR2 antagonists revealed that Cat-S specifically impaired the integrity and barrier function of glomerular endothelial cells selectively through PAR2. In human and mouse type 2 diabetic nephropathy, only CD68(+) intrarenal monocytes expressed Cat-S mRNA, whereas Cat-S protein was present along endothelial cells and inside proximal tubular epithelial cells also. In contrast, the cysteine protease inhibitor cystatin C was expressed only in tubules. Delayed treatment of type 2 diabetic db/db mice with Cat-S or PAR2 inhibitors attenuated albuminuria and glomerulosclerosis (indicators of diabetic nephropathy) and attenuated albumin leakage into the retina and other structural markers of diabetic retinopathy. These data identify Cat-S as a monocyte/macrophage-derived circulating PAR2 agonist and mediator of endothelial dysfunction-related microvascular diabetes complications. Thus, Cat-S or PAR2 inhibition might be a novel strategy to prevent microvascular disease in diabetes and other diseases.

Diyabetik Retinopati Saptanmadan Nefropati Gelişen Nadir Bir Diabetes Mellitus Olgusu

Diabetes mellitus frequency is increasing gradually. Microvascular and macrovascular complications cause severe morbidity and mortality. Diabetic nephropathy is the leading cause of kidney disease. Diabetic retinopathy is a major cause of blindness. Microvascular complications mostly seen together. Diabetic retinopathy may be an indicator for diabetic nephropathy. Diabetic nephropathy is mostly diagnosed in patient with diabetic retinopathy. In our case the patient was 68 -year-old man, followed by 10 years for diabetes mellitus, 1 year hypertension, 1 year coronary heart disease, admitted with severe proteinuria. Fundoscopic examination performed and retinopathy was not detected. Renal biopsy was performed for evaluation of proteinuria and biopsy results were compatible with diabetic nephropahty. Our case is remarkable for development of diabetic nephropathy without development of retinopathy.

Effects of Garlic (Allium sativum) on indicators of diabetic nephropathy

The anti‐diabetic, antioxidant and anti‐nephropathic effects of an aqueous extract of raw garlic (RGE) were studied in diabetic rats. Diabetes was induced by IP injection of streptozotocin (STZ) and a fasting blood sugar &gt;;300 mg/dl indicated diabetes. Diabetic rats were divided into 2 groups; control and garlic‐treated. RGE was administered daily for 8 weeks. Blood glucose and serum creatinine and urea were elevated in diabetic rats, and lowered by RGE treatment. In contrast, serum and kidney protein and antioxidants, and serum albumin levels were decreased in diabetic rats, and increased in RGE‐treated diabetic rats. Serum insulin levels were decreased over 10 fold in diabetic rats and increased by RGE treatment. In addition, total urine creatinine, protein and albumin were elevated in diabetic animals and decreased by RGE treatment. In contrast, urine urea was decreased in diabetic rats and elevated by RGE treatment. Plasma and kidney antioxidant enzymes (GR, GPx, catalase) were lower in diabetic rats with RGE‐treated diabetic rats having increased activities. Lipid peroxidation (MDA levels) were increased in kidneys of diabetic rats and lowered in RGE‐treated diabetic rats. Urine enzymes (LDH, ALP and NAG) were increased in diabetic controls and decreased in RGE‐treated diabetic rats. Immunochemical analysis of angiotensin receptor expression and localization in kidney tissues indicated that AT1 receptors were up‐regulated and AT2 receptors were down‐regulated in kidneys of diabetic rats, while these changes were reversed in RGE‐treated diabetic rats. Thus, RGE relieved oxidative stress and nephropathy in diabetic rats.The study was supported by KU grant #SL 09/10.

Plasma pentraxin 3 levels are associated with carotid IMT in type 1 diabetic patients

AimsPentraxin3 (PTX3), a recently discovered inflammatory mediator, is produced abundantly in various cells in atherosclerotic lesions, and therefore, its plasma level could reflect local inflammation at the site of atherosclerotic lesion. The present study evaluated whether plasma PTX3 levels are associated with subclinical atherosclerosis in young subjects with type 1 diabetes. MethodsPlasma PTX3 levels, urinary albumin excretion, diabetic retinopathy, and carotid intima-media thickness (IMT) were examined in 78 Japanese type 1 diabetic patients (30 men and 48 women, aged 28.5±5.3 years (±SD), duration of diabetes 19.7±6.5 years). ResultsThere was statistically significant association between plasma PTX3 levels and Max-IMT (r=0.363, p=0.001). A stepwise multivariate regression analysis including conventional coronary risk factors as independent variables revealed that plasma PTX3 levels (β=0.389, p<0.001), duration of diabetes (β=0.256, p=0.035), and serum triglyceride levels (β=0.371, p<0.001) were independent determinants of Max-IMT. In addition, plasma PTX3 levels was an independent determinant of urinary albumin excretion, an indicator of diabetic nephropathy (β=0.258, p=0.018). However, there was no significant association between plasma PTX3 levels and diabetic retinopathy. ConclusionsIncreased levels of plasma PTX3 are associated with accelerated atherosclerotic change and increased albuminuria in young patients with type 1 diabetes.

Study of autoantibodies against advanced glycation endproducts of the Maillard reaction

Long-term incubation of proteins with reducing sugar proceeds to advanced glycation end products (AGEs). We previously demonstrated the presence of AGE structures in human and animal tissues, and suggested the implication of AGEs in aging and diabetic complications. In this study, we tested whether AGEs present in vivo, such as N ε-(carboxymethyl) lysine (CML) adduct, could serve as immunogens for generating autoantibodies. Plasma samples from STZ-induced diabetic rats reacted positively with AGE-proteins as well as CML-BSA, suggesting the presence of autoantibodies against AGE-structures, particularly CML in diabetic rats; the activity of the autoantibody increased with the duration of diabetic states, reflecting the accumulation of AGE proteins in these diabetic rats. An autoantibody fraction purified from the plasma of diabetic patients showed a positive reaction to AGE-proteins as well as to CML proteins, and also to human lens proteins which are known to undergo CML modification in vivo. Patients with renal failure caused by diabetes or nondiabetic pathologies had a higher autoantibody activity against AGE structures than that in normal subjects or diabetic patients without renal failure. These results suggest that AGEs accumulated in vivo serve as immunological epitopes for developing autoantibodies against AGEs, particularly against a CML structure, which might be used as an indicator of diabetic nephropathy or chronic renal failure.

Transplantation of normal islets into the portal vein of Otsuka Long Evans Tokushima Fatty rats prevents diabetic progression.

To investigate the long-term effects of normal pancreatic islet transplantation on progression of obese type 2 diabetes mellitus (DM), 1500 normal islets (per rat) from Wistar King A rats at 8 weeks of age were transplanted into the liver through the portal vein of Otsuka Long Evans Tokushima Fatty (OLETF) rats, an animal model of obese type 2 DM, at 12 weeks of age. Body weight in the transplanted OLETF (IT) rats 8 and 28 weeks after islet transplantation did not differ from that in the corresponding sham-operated (SO) rats, but was greater than that in lean littermates (LETO rats; P < 0.05 for each group). In the early phase, 8 weeks after transplantation, rats in both IT and SO groups were normoglycemic, but hyperinsulinemic (P < 0.05 for each compared with LETO rats), probably resulting from increased body weight. In the late phase, 28 weeks after transplantation, hyperglycemia in the IT group was greatly attenuated compared with the SO group (P < 0.05), but hyperinsulinemia remained in both the IT and the SO groups compared with that in the LETO group (P < 0.05 for each). Immunohistochemical studies demonstrated that hypertrophic and fibrotic changes in pancreatic islets, together with mesangial proliferation of the glomerular matrix, an indicator for diabetic nephropathy, were attenuated predominantly in the IT group at the late phase after transplantation compared with those in the corresponding phase of the SO group. Islet transplantation into the liver of OLETF rats thus prevented further progression of obese type 2 DM. A possible mechanism is that islet transplantation may prevent development of hyperglycemia by improving abnormal hepatic glucose metabolism and consequently insulin resistance, which may lead to blockade of a vicious cycle between advancing damage to pancreatic islet cells and increased demand for insulin secretion, thus sparing original pancreatic cells from exhaustion induced by increased demand for insulin secretion.

Urinary excretion of the vitronectin receptor (integrin αυβ 3 ) in patients with non-insulin dependent diabetes mellitus

Background. Diabetic nephropathy is one of the major complications in patients with diabetes mellitus. We investigated the urinary excretion of the vitronectin receptor (VNR; integrin αυβ3) to determine whether it would be a useful indicator of diabetic nephropathy. Methods. We measured the urinary excretion of β3 originating from VNR in 217 patients with non-insulin dependent diabetes mellitus (NIDDM; normoalbuminuria; n = 75, microalbuminuria; n = 75, macroalbuminuria; n = 67) and 44 healthy controls by immunoblotting analysis. Immunofluorescence microscopy analysis for VNR was also performed, using urinary sediments from patients with macroalbuminuria as samples. Results. The amount of urinary β3 originating from VNR significantly increased with the development of diabetic nephropathy. Immunofluorescence microscopy revealed the expression of β3 in the urinary sediments of the NIDDM patients. Conclusion. We conclude that urinary VNR level may be a useful index of diabetic nephropathy in NIDDM.

A rapid and sensitive method for estimating low concentrations of albumin in human urine

A chemiluminescence immunoassay has been developed for the measurement of albumin concentrations in human urine, as an indicator of diabetic nephropathy. The assay involved competition between analyte albumin and an acridinium ester labelled albumin tracer for binding to a rabbit (anti-human albumin) antibody. Immune complexes were separated using sheep (anti-rabbit immunoglobulin G) antibodies coupled to paramagnetic particles. The total incubation time was ninety minutes at room temperature followed by sedimentation and washing of the solid-phase using a magnetic rack. Chemiluminescence emission was quantified rapidly (2 s) using a commercially available luminometer. The assay was sufficiently sensitive (10 ng/ml) for the detection of microalbuminuria with the advantages of rapidity and use of stable reagents. The assay correlated well with both RIA and rate nephelometry.

Urinary enzymes and low-molecular-mass proteins as indicators of diabetic nephropathy.

We measured the excretion rates of six urinary enzymes that either originate from the proximal renal tubule, like alanine aminopeptidase (EC 3.4.11.2), alkaline phosphatase (EC 3.1.3.1), gamma-glutamyltransferase (EC 2.3.2.2), and N-acetyl-beta-D-glucosaminidase (EC 3.2.1.30), or that are typical low-molecular-mass proteins, like lysozyme (EC 3.2.1.17) and pancreatic ribonuclease (EC 3.1.27.5). These rates were compared with those of total protein and albumin in urine of 36 insulin-dependent diabetic men and 30 healthy men. Seventeen of the diabetics had "clinical proteinuria," defined as excretion of more than 7.5 g of protein per mole of urinary creatinine (group B). Group A comprised the 19 diabetics without proteinuria. Except for gamma-glutamyltransferase, the excretions of enzymes and proteins were significantly higher in diabetics than in controls and were greater in group B than in group A. N-Acetyl-beta-D-glucosaminidase was the analyte most often increased in group A (89%), followed by albumin and alkaline phosphatase (each 32%). All patients in group B showed increased excretion of N-acetyl-beta-D-glucosaminidase. We conclude from the comparative data that this enzyme may be useful as an early predictor of diabetic nephropathy.