Nephropathy Complications Research Articles

Integrating cardioprotective glucose-lowering medications into clinical practice.

Patients with type 2 diabetes suffer from both microvascular and macrovascular complications. Optimal glycemic control is well known to reduce the microvascular complications of retinopathy, nephropathy, and neuropathy. However, despite having multiple classes of antidiabetes medications, we have not been able to favorably affect the cardiovascular (CV) complications of diabetes, which cause considerable morbidity and premature CV mortality in patients with diabetes. The recent publication of the EMPA-REG Outcome and the LEADER studies demonstrating favorable CV outcomes with empagliflozin and liraglutide have led to a decision by the Food and Drug Administration to approve an additional indication (besides glucose lowering) - to reduce the risk of myocardial infarction, stroke, and CV death with liraglutide, and to reduce the risk of CV death with empagliflozin in adult patients with type 2 diabetes mellitus and established CV disease. This represents a paradigm shift in diabetes management and will have a major impact on diabetes treatment algorithms.

Association between Transcription Factors 7-like 2 (rs7903146) Polymorphism and Some Renal Biomarkers with Type 2 Diabetic Nephropathy Complications

Diabetes mellitus as the most prevalent metabolic disease is a multifactorial disease which is infuenced by environmental and genetic factors. In this systematic review, we assessed the association between genetic variants and diabetes/its complications in studies with Iraqi populations Conducted in this study was to investigate the possible role TCF7L2 rs7903146 (C/G) variant on susceptibility of T2DM among Iraqi type 2 diabetic patients with nephropathy complications and its relations with some type of kidney biomarkers. This case-control study included 100 T2DM patients and 100 patient with kidney failure 100 healthy person (control group). The results confrm the association between the TCF7L2 rs7903146 polymorphism and increase risk for type 2 diabetes in Iraqi an populations.

Pengaruh Ekstrak Etanol Daun Jambu Air (Syzygium aqueum (Burm f.)Alston) terhadap Glukosa Darah, Ureum dan Kreatinin Tikus Putih (Rattus norvegicus)

Diabetes mellitus with complications of Diabetic Nephropathy become one of the most common cause of end-stage renal failure in the world. Impaired kidney function is measured by Glomerular Filtration Rate (GFR). Where the decline in GFR was followed by increased levels of blood glucose, urea and creatinine. This study aimed to determine whether there is the content of secondary metabolites in leaves of Sizygium aqueum leaf extract, at a dose of extract what impact the blood glucose, urea and creatinine levels of male rats and whether the water extract of guava leaves have an influence on the blood glucose, urea and creatinine white male rats. This study uses a randomized block design with six treatment groups consisting of five test animals. Group I was normal control (CMC Na suspension 0.5%). Group II negative control (streptozotocin 40 mg/kg). positive control group III (suspension glibenclamide). Group IV given guava leaf extract 100 mg/kg BW. V group awarded guava leaf extract 200 mg/kg BW. Group VI given guava leaf extract 300 mg/kg BW. Treatment was given for 28 days and measured levels of blood glucose urea and creatinine on days 0, 7, 14, 21 and 28. The results showed nefroprotektif effect on all groups and most effective extract are a group of guava leaf extract 100 mg/kg BW).
 Keywords: Diabetic nephropathy, urea, creatinine, Syzygium aqueum

Comparative analysis of diabetic nephropathy and non-diabetic nephropathy disease.

ObjectiveClinical symptoms of diabetic nephropathy patients and non-diabetic nephropathy are compared and analyzed, hemodialysis effect and quality of life of two kinds of nephrotic patients are analyzed.MethodsRespectively extract 1300 cases of diabetic nephropathy and non-diabetic nephropathy patients admitted to different hospitals during December 2011-December 2014. Based on whether the patient suffers from diabetes, they were divided into diabetic group and control group. Hemodialysis of two groups of patients were followed up to observe effectiveness of blood treatment, and complications were observed after one year of follow-up.ResultsHematodialysis effectiveness of diabetic nephropathy patients is significantly lower than that of non-diabetic nephropathy group. After 1 year’s follow-up, it can be found that survival rate of diabetic nephropathy patients is much lower than that of control group. In statistical comparison of data involved in the two groups of patients, P < 0.05, the difference is statistically significant.ConclusionTreatment effect of diabetic nephropathy patients is relatively poor compared to that of non-diabetic patients. In clinics, management and prevention of diabetic patients should be strengthened to avoid complication of nephropathy which brings serious injury to patients.

Emerging Evidence of Epigenetic Modifications in Vascular Complication of Diabetes.

Genes, dietary, and lifestyle factors have been shown to be important in the pathophysiology of diabetes and associated microvascular complications. Epigenetic modifications, such as DNA methylation, histone acetylation, and post-transcriptional RNA regulation, are being increasingly recognized as important mediators of the complex interplay between genes and the environment. Recent studies suggest that diabetes-induced dysregulation of epigenetic mechanisms resulting in altered gene expression in target cells can lead to diabetes-associated complications, such as diabetic cardiomyopathy, diabetic nephropathy, retinopathy, and so on, which are the major contributors to diabetes-associated morbidity and mortality. Thus, knowledge of dysregulated epigenetic pathways involved in diabetes can provide much needed new drug targets for these diseases. In this review, we constructed our search strategy to highlight the role of DNA methylation, modifications of histones and role of non-coding RNAs (microRNAs and long non-coding RNAs) in vascular complications of diabetes, including cardiomyopathy, nephropathy, and retinopathy.

Tyrosines-740/751 of PDGFRβ contribute to the activation of Akt/Hif1α/TGFβ nexus to drive high glucose-induced glomerular mesangial cell hypertrophy

Glomerular mesangial cell hypertrophy contributes to the complications of diabetic nephropathy. The mechanism by which high glucose induces mesangial cell hypertrophy is poorly understood. Here we explored the role of the platelet-derived growth factor receptor-β (PDGFRβ) tyrosine kinase in driving the high glucose-induced mesangial cell hypertrophy. We show that high glucose stimulates the association of the PDGFRβ with PI 3 kinase leading to tyrosine phosphorylation of the latter. High glucose-induced Akt kinase activation was also dependent upon PDGFRβ and its tyrosine phosphorylation at 740/751 residues. Inhibition of PDGFRβ activity, its downregulation and expression of its phospho-deficient (Y740/751F) mutant inhibited mesangial cell hypertrophy by high glucose. Interestingly, expression of constitutively active Akt reversed this inhibition, indicating a role of Akt kinase downstream of PDGFRβ phosphorylation in this process. The transcription factor Hif1α is a target of Akt kinase. siRNAs against Hif1α inhibited the high glucose-induced mesangial cell hypertrophy. In contrast, increased expression of Hif1α induced hypertrophy similar to high glucose. We found that inhibition of PDGFRβ and expression of PDGFRβ Y740/751F mutant significantly inhibited the high glucose-induced expression of Hif1α. Importantly, expression of Hif1α countered the inhibition of mesangial cell hypertrophy induced by siPDGFRβ or PDGFRβ Y740/751F mutant. Finally, we show that high glucose-stimulated PDGFRβ tyrosine phosphorylation at 740/751 residues and the tyrosine kinase activity of the receptor regulate the transforming growth factor-β (TGFβ) expression by Hif1α. Thus we define the cell surface PDGFRβ as a major link between high glucose and its effectors Hif1α and TGFβ for induction of diabetic mesangial cell hypertrophy.

A study of Microalbuminuria and its association with various cardiovascular risk factors and complications in patients with Type II Diabetes Mellitus

Background: Microalbuminuria is a key risk factor for several cardiovascular diseases and renal impairment. This is particularly true for diabetics, in whom it is common and can be used to predict the development of complications. Materials and Methods: A prospective observational study. Participants were divided into 3 different groups: Group I – Control (n = 20), Group II – Patients with type II diabetes mellitus (n = 300), Group III – Diabetic patients with retinal changes (n = 50). Medical history, physical examination, complete blood count, ECG, chest X-ray and urine examination, tests for microalbuminuria, echocardiogram and fluorescein angiography were performed. Results: Mean age of patients in group I and II were 57.60 ± 11.07 and 57.04 ± 11.57 years respectively. 46% participants were taking oral anti diabetic agents. Out of 300 patients of type 2 DM–64% were micral test negative and 36% were micral test positive. In group III, 32% were normoalbuminuric and 68% were microalbuminuric. Positive correlation was found between duration of DM and presence of microalbuminuria. Serum cholesterol and serum triglycerides level were more in microalbuminurics than normoalbuminurics and the difference was statistically significant while the difference in the levels of serum LDL and serum HDL was statistically insignificant between two groups. 55.6% of the diabetics with microalbuminuria were hypertensive. Conclusion: Microalbuminuria can be considered as one of the predictive factors for overt nephropathy and various complications of DM. Thus, detection of microalbuminuria at an early stage may help in preventing the diabetic complications.

MicroRNA-184 is a downstream effector of albuminuria driving renal fibrosis in rats with diabetic nephropathy

Aims/hypothesisRenal fibrosis is a common complication of diabetic nephropathy and is a major cause of end-stage renal disease. Despite the suggested link between renal fibrosis and microRNA (miRNA) dysregulation in diabetic nephropathy, the identification of the specific miRNAs involved is still incomplete. The aim of this study was to investigate miRNA profiles in the diabetic kidney and to identify potential downstream targets implicated in renal fibrosis.MethodsmiRNA expression profiling was investigated in the kidneys of 8-month-old Zucker diabetic fatty (ZDF) rats during overt nephropathy. Localisation of the most upregulated miRNA was established by in situ hybridisation. The candidate miRNA target was identified by in silico analysis and its expression documented in the diabetic kidney associated with fibrotic markers. Cultured tubule cells served to assess which of the profibrogenic stimuli acted as a trigger for the overexpressed miRNA, and to investigate underlying epigenetic mechanisms.ResultsIn ZDF rats, miR-184 showed the strongest differential upregulation compared with lean rats (18-fold). Tubular localisation of miR-184 was associated with reduced expression of lipid phosphate phosphatase 3 (LPP3) and collagen accumulation. Transfection of NRK-52E cells with miR-184 mimic reduced LPP3, promoting a profibrotic phenotype. Albumin was a major trigger of miR-184 expression. Anti-miR-184 counteracted albumin-induced LPP3 downregulation and overexpression of plasminogen activator inhibitor-1. In ZDF rats, ACE-inhibitor treatment limited albuminuria and reduced miR-184, with tubular LPP3 preservation and tubulointerstitial fibrosis amelioration. Albumin-induced miR-184 expression in tubule cells was epigenetically regulated through DNA demethylation and histone lysine acetylation and was accompanied by binding of NF-κB p65 subunit to miR-184 promoter.Conclusions/interpretationThese results suggest that miR-184 may act as a downstream effector of albuminuria through LPP3 to promote tubulointerstitial fibrosis, and offer the rationale to investigate whether targeting miR-184 in association with albuminuria-lowering drugs may be a new strategy to achieve fully anti-fibrotic effects in diabetic nephropathy.

HbA1c in relation to incident diabetes and diabetes-related complications in non-diabetic adults at baseline

AimsWe compared the utility of glycated hemoglobin (HbA1c) and oral glucose tolerance (oGTT) in non-diabetic patients for identifying incident diabetes; all-cause mortality; cardiovascular disease (CVD) mortality; CVD, coronary heart disease (CHD), and ischemic stroke events; and diabetes microvascular complications. MethodsData from a New Zealand community setting were prospectively linked to hospitalization, mortality, pharmaceutical and laboratory test results data. After applying exclusion criteria (prior laboratory diagnosis or history of drug treatment for diabetes or hospitalization for diabetes or CVD event), there were 31,148 adults who had an HbA1c and 2-h 75g oGTT. HbA1c was measured by ion-exchange high-performance liquid chromatography, and glucose using a commercial enzymatic method. We compared glycemic measures and outcomes using multivariable Cox proportional hazards regression. ResultsThe median follow-up time was 4years (range 0 to 13). The mean age was 57·6years and 53·0% were male. After adjusting for other glycemic measures (fasting glucose, 2-h glucose and/or HbA1c where relevant) in addition to age, sex, ethnicity and smoking habit, the hazard ratios for incident diabetes and diabetes complications of retinopathy and nephropathy were highest for 2-h glucose levels, followed by HbA1c and lastly by fasting glucose. However, all-cause mortality and CHD were significantly associated with HbA1c concentrations only, and ischemic stroke and CVD events with 2-h glucose only. Circulatory complications showed a stronger association with HbA1c. ConclusionApart from neuropathy, HbA1c showed stronger associations with outcomes compared to fasting glucose and provides a convenient alternative to an oGTT.

The impact of glycemic variability on diabetic peripheral neuropathy.

Mean glucose values alone cannot explain the patterns of morbidity and mortality due to dysglycemia in diabetes. Development of continuous glucose monitoring systems has improved the analysis and interpretation of glycemic variability. The roles of glycemic components other than constant hyperglycemia in diabetic complications must be investigated because large clinical studies have indicated that risk factors besides the average glucose value of HbA1c are involved in chronic macrocomplications/microcomplications of diabetes. Among these complications, the pathogenesis of diabetic peripheral neuropathy is particularly complex, and several factors related to glucose and nonglucose pathways have been suggested as risk factors. There is little information regarding the effect of glycemic variability on diabetic peripheral neuropathy, unlike other microvascular complications of retinopathy and nephropathy, and whether glycemic variability causes harmful effects is still a matter of debate. In this review, we discuss the relationships between glycemic variability and diabetic peripheral neuropathy, focusing on somatosensory peripheral neuropathies rather than autonomic neuropathies.

Association of elevated frequency of micronuclei in peripheral blood lymphocytes of type 2 diabetes patients with nephropathy complications.

The increasing incidence of type 2 diabetes mellitus globally has increased the incidence of diabetes-associated complications such as nephropathy. DNA damage induced by oxidative stress might be one of the important mechanisms in the pathogenesis of diabetic complications. Two hundred Iranian individuals with the conditions of type 2 diabetes, diabetic nephropathy and nephropathy patients with no sign of diabetes and normal unaffected sex- and age-matched controls (50 in each group) were enrolled in the study. The background and the net levels of micronucleus (MN) formation as well as other cellular damages induced after in vitro treatment with 25 µg/ml of bleomycin (BLM) were evaluated using cytokinesis block MNs cytome assay (CBMN cyt) in peripheral blood lymphocytes. The background and net BLM-induced levels of MNs were significantly higher in all patient groups compared with the control (P < 0.01, P < 0.001, respectively). The frequency of MNs was significantly higher in those patients with prior incidence of nephropathy than those without. A positive association was observed between basal and net MN frequency among study groups and also between net genetic damages and serum creatinine value and duration of diabetes. The rate of basal and net apoptosis was significantly higher in patients with hyperglycemia. Our results indicate that increased genomic instability expressed as MNs is associated with nephropathy in all pathological stages. Therefore, implementation of MN assay in clinical level may potentially enhance the quality of management of patients with diabetes and its complications such as nephropathy.

Clinical investigation on diabetes mellitus in very elderly patients

Objective To study the clinical characteristics of very elderly patients aged 80 years and over with diabetes mellitus (DM). Methods Clinical data of 95 very elderly patients with diabetes mellitus were retrospectively analyzed. Results Among 95 patients, patients with type 2 diabetes mellitus accounted for 98.9% (94/95), patients with asymptomatic onset accounted for 35.8% (34/95). The incidence of acute complications of diabetes mellitus was 11.6% (11/95). Chronic complications of peripheral neuropathy and diabetic nephropathy were more common, and their incidences were 83.2% (79/95) and 45.3% (43/95), respectively.The percentage of patients with multiple chronic complications was up to 45.3% (43/95). The percentage of DM patients combined with hypertension, coronary heart disease, cerebral infarction, hyperlipidemia or cardiac valve calcification was 80.0% (76/95), 48.4% (46/95), 77.9% (74/95), 42.1% (40/95) and 33.7% (32/95), respectively.There were 29 patients (30.5%) with the simultaneous presence of DM, hypertension, cerebral infarction, coronary heart disease, and hyperlipidemia in a same patient.The proportion of DM patients with low serum albumin was 47.4% (45/95), and the rate achieving the target low density lipoprotein level was only 35.8% (34/95). In the treatment, 67.4% (64/95) of patients were treated with oral hypoglycemic agents combined with insulin injection.The incidence of hypoglycemia was 24.2% (23/95), and 69.6% (16/23) of them had no self-conscious hypoglycemic symptoms. Conclusions Chronic complications are common in elderly diabetes mellitus patients.The elderly DM patients are prone to have many complications at the same time, with a higher incidence of hypoglycemic value under 3.9 mmol/L and lower rate of hypoglycemic symptoms. Key words: Diabetes mellitus; Diabetes complications

Abstract P053: Glycated Hemoglobin in Relation to Incident Diabetes and Cardiovascular Disease in Non-diabetic Adults

Introduction: We compared the utility of glycated hemoglobin (HbA1c) and oral glucose tolerance (oGTT) in non-diabetic patients for identifying incident diabetes, all-cause mortality, cardiovascular disease (CVD) mortality, all-CVD events, coronary heart disease (CHD) events, ischaemic stroke events and diabetes microvascular complications. Hypothesis: HbA1c will provide the similar information to an oGTT. Methods: Data from a New Zealand community setting were prospectively linked to hospitalization, mortality, pharmaceutical and laboratory test results data. After applying exclusion criteria (prior laboratory diagnosis or history of drug treatment for diabetes or hospitalisation for diabetes or CVD event), there were 31,148 adults who had an HbA1c and 2-hr 75g oGTT. HbA1c was measured by ion-exchange high-performance liquid chromatography, and glucose using a commercial enzymatic method. We compared glycaemic measures and outcomes using multivariable Cox proportional hazards regression. Results: The median follow-up time was 4 years (range 0 to 13). The mean age was 57.6 years and 53.0% were male. After adjusting for other glycaemic measures (fasting glucose, 2-hr glucose and/or HbA1c where relevant) in addition to age, sex and ethnicity, the hazard ratios for incident diabetes, and diabetes complications of retinopathy, nephropathy and neuropathy were highest for 2-hr postchallenge glucose levels, followed by HbA1c and lastly by fasting plasma glucose. However, all-cause mortality was significantly associated with HbA1c concentrations only. CHD events were most strongly associated with HbA1c, followed by 2-hr glucose and circulatory complications showed stronger associations with HbA1c. Conclusion: HbA1c showed stronger associations with adverse outcomes compared to fasting glucose and provides a convenient alternative to an oGTT.

English

Free radical-induced damage plays a significant role in the development of type 2 diabetes and its complications. Extracellular superoxide dismutase (EC-SOD) or SOD3 is one of the important scavenger enzymes that protects against oxidative damage and the formation of free radicals. EC-SOD is a copper- and zinc-containing secretory enzyme located in tissues and primarily in the extracellular matrix. EC-SOD has been proposed to protect against pancreatic beta-cell damage, insulin resistance and vascular function in diabetic patients. The association between EC-SOD gene polymorphism and Type 2 diabetes mellitus is not completely understood. The aim of the study is to investigate the EC-SOD gene polymorphism in the exon 3 region and the susceptibility to type 2 diabetes mellitus and its complications among Lebanese patients. For this purpose, a genotype analysis involving 60 Type 2 Diabetes patients and 46 control subjects was carried out using PCR-based direct DNA sequencing. Results showed that the frequency of the Ala40Thr polymorphism of EC-SOD gene was significantly higher in type 2 diabetic patients compared to control group. Evaluation of clinical parameters of diabetic patients with their relative genotypes showed that patients with the Thr allele have higher HbA1c levels and fasting blood glucose compared to their Ala genotypes indicating a poor diabetes control in these patients. When diabetic complications including retinopathy, nephropathy and cardiovascular complications were correlated with Ala40Val polymorphism, a significant association was detected for complications and particularly for cardiovascular diseases in diabetic patients. Key words: Type 2 diabetes mellitus, oxidative stress, extracellular superoxide dismutase, genetic biomarker.

Effect of ipragliflozin, an SGLT2 inhibitor, on progression of diabetic microvascular complications in spontaneously diabetic Torii fatty rats

AimsWe investigated the effect of the selective sodium-dependent glucose cotransporter 2 inhibitor ipragliflozin on the simultaneous progression of diabetic microvascular complications of retinopathy, nephropathy and neuropathy in individual Spontaneously Diabetic Torii (SDT) fatty rats. Main methodsIpragliflozin was administered to male SDT fatty rats for 12weeks. Male Sprague–Dawley rats of the same age were used as non-diabetic controls. Non-fasting plasma glucose and glycated hemoglobin levels were measured every 4weeks. Cataract formation was monitored once a week, and the electroretinogram was measured after 6weeks of treatment. After the treatment period, motor nerve conduction velocity was measured and urinalysis was conducted. Tissue samples were then dissected for histopathological examination. Key findingsTreatment with ipragliflozin reduced glycated hemoglobin levels, inhibited the progression of cataract formation, prevented the prolongation of oscillatory potential peaks in the electroretinogram, ameliorated the slowing of motor nerve conduction velocity, and reduced the severity of glomerulosclerosis in SDT fatty rats. SignificanceThese results suggest that the control of hyperglycemia with ipragliflozin slows the progression of the diabetic complications of retinopathy, nephropathy, and neuropathy.

Effect of mitochondrial DNA 5178 C/A polymorphism on risks for type 2 diabetes mellitus and its complications

To explore the role of mitochondrial DNA 5178 C/A (Mt5178) polymorphism of NADH-dehydrogenase subunit 2 (ND2) gene in type-2 diabetes mellitus (T2DM) among ethnic Han Chinese through a case-control study. The Mt5178C/A polymorphism was determined by sequencing 1103 T2DM patients and 791 healthy controls. Logistic regression analysis was conducted to estimate odds ratios (OR) and 95% confidence intervals (CI). To confirm the results, a meta-analysis was conducted based on published literature on the association of Mt5178 variant with T2DM. No significant association was found between the Mt5178C/A variant and T2DM either by our study or the meta-analysis which included eight published studies. Nevertheless, it was found that the T2DM patients with 5178C genotype were at a higher risk for nephropathy complication (OR=1.49, 95%CI: 1.005-2.197, P<0.05) and at significantly lower risk for hypertension complication (OR=0.744, 95%CI: 0.556-0.996, P<0.05) compared with those carrying a 5178A genotype. No association was found between the Mt5178C/A polymorphism of mitochondrial ND2 gene with the increased risk of T2DM. However, the polymorphism may affect the development of nephropathy and hypertension complications among T2DM patients.

Efficiency of Egyptian mulberry water extracts in controlling nephropathy complications in diabetic rats

The aim of the present study was to determine the amount and antifree radical activity of Deoxynojirimycin (DNJ) in Egyptian white and black mulberry fruits and leaves water extracts. Moreover, the study aimed to evaluate the water extracts effect of Egyptian white and black mulberry fruits and leaves, on improving hyperglycemic condition and renal complications in diabetic rats. Seventy-two adult male albino rats Sprague-Dawley strain were equally divided into six groups: group (1) healthy control and group (2) diabetic control were given tap water by gavage tube, groups (3-6) diabetic treated with different water extracts of mulberry white fruits (WMFWE), white leaves (WMLWE), black fruits (BMFWE) and black leaves (BMLWE) (containing 50mg DNJ/kg body weight) by gavages' tube daily for 28 days. At the end of the experiment, rats were sacrificed under ether anesthesia. Blood samples were collected to separate serum; also kidneys were removed for biochemical parameters estimation. The High Performance Liquid Chromatography (HPLC) analysis of the mulberry extracts showed that water extracts contained higher amount of DNJ than methanol or ethanol extracts. Also mulberry leaves had higher amount of DNJ than fruits and the amount of DNJ in black mulberry was more than the white one. The treatment with mulberry water extracts effectively decreased the blood glucose level, glycated hemoglobin percentage, renal aldose reductase activity and renal protein level as compared to untreated diabetic control rats; on the other hand there was an elevation of insulin level. Also mulberry extracts ameliorate the oxidative stress status with significant elevation in nonenzymatic antioxidant with significant improvement in kidney function parameters. Based on the presented data in this study, it can be concluded that mulberry extracts possess antidiabetic effect and improving properties of nephropathy complications.

Serum 25-hydroxyvitamin D level and diabetic nephropathy in patients with type 2 diabetes mellitus.

Patients with chronic kidney disease have a very high prevalence of deficiency of 25-hydroxyvitamin D [25(OH)D]. We evaluate the association between 25(OH)D and diabetic nephropathy (DN) in a Chinese sample with type 2 diabetes mellitus. The subjects were patients with diabetes mellitus who were hospitalized at our hospital during the period from June 2012 to July 2014. Serum levels of 25(OH)D were tested at admission. DN was defined as a urinary albumin-to-creatinine ratio ≥30 mg/g in a random spot urine sample. Multivariate analyses were performed using logistic regression models. We found that serum 25(OH)D levels were significantly lower in diabetes with DN as compared to without DN [8.5 (IQR 6.8-11.3) vs. 13.9 (IQR 11.2-18.2) ng/ml, P < 0.0001]. Based on the ROC curve, the optimal cutoff value of serum 25(OH)D levels as an indicator for diagnosis of DN was projected to be 10.5 ng/ml, which yielded a sensitivity of 82.6 % and a specificity of 72.7 %, with the area under the curve at 0.807 [95 % confidence interval (CI) 0.764-0.849]. Multivariate logistic regression analysis adjusted for common risk factors showed that with serum 25(OH)D level ≤10.5 ng/ml was an independent indicator of DN [odds ratio (OR) = 6.559; 95 % CI 2.864-11.368]. Our findings suggested that diabetes with DN had lower serum 25(OH)D levels and that determination of 25(OH)D statuses might be used to identify patients at increased risk of developing nephropathy complications.

Elevated serum levels of mannose-binding lectin and diabetic nephropathy in type 2 diabetes.

ObjectiveInflammation and complement activation initiated by mannose-binding lectin (MBL) may be implicated in the pathogenesis of diabetic vascular complications. We investigated serum MBL levels in type 2 diabetes with diabetic nephropathy (DN) and with persistent normoalbuminuria.MethodSerum MBL levels were determined in 242 type 2 diabetes with overt nephropathy and 242 type 2 diabetes with persistent normoalbuminuria matched for age, sex, and duration of diabetes, as well as in 100 healthy control subjects. The prediction value of MBL was compared with HbA1c, Hs-CRP and with other known predictors. Multivariate analyses were performed using logistic regression models.ResultsThe serum MBL levels were significantly higher in diabetes with DN as compared to with persistent normoalbuminuria (P<0.0001). Multivariate logistic regression analysis adjusted for common factors showed that serum MBL levels≥2950ug/L was an independent indictor of DN (OR=7.55; 95%CI: 3.44–19.04). Based on the ROC curve, the optimal cutoff value of serum MBL levels as an indicator for diagnosis of DN was projected to be 2950ug/L, which yielded a sensitivity of 77.2 % and a specificity of 80.8%, with the area under the curve at 0.809 (95%CI, 0.769—0.848).ConclusionOur findings suggested that MBL may be involved in the pathogenesis of DN in type 2 diabetes, and that determination of MBL status might be used to identify patients at increased risk of developing nephropathy complications.

Association between red blood cell distribution and renal function in patients with untreated type 2 diabetes mellitus

We assessed whether red cell distribution width (RDW) is associated with microalbuminuria (MAU) in a group of 320 patients with newly diagnosed type 2 diabetes mellitus (T2DM), recruited in Zhengzhou. Patients were divided into normal group and MAU group. Compared with the normal group, the patients with MAU had higher red blood cell count (p = 0.005) and RDW (p < 0.001). The multiple logistic regression indicated that RDW (OR = 3.89, 95% CI: 1.98–7.66, p < 0.001) was an independent risk factor of MAU in newly diagnosed T2DM. Other factors include smoking (OR = 4.44, 95% CI: 2.90–8.72, p < 0.001), higher waist index (OR = 2.17, 95% CI: 1.89–5.26, p = 0.002), FBG level (OR = 2.05, 95% CI: 1.21–3.84, p = 0.008) and uric acid level (OR = 2.18, 95% CI: 1.05–4.52, p = 0.037). The receiver operating characteristic (ROC) curves explored the relationship between MAU and RDW. The area under the curve was 0.79 (95% CI: 0.74–0.84; p < 0.001). Using a cut-off point of 12.8, the RDW predicted MAU in the T2DM patients with a sensitivity of 71.3% and specificity of 66.9%. RDW may be independently associated with MAU in patients with newly diagnosed T2DM. RDW may be treated as effective predictive index in the evaluation of diabetes nephropathy or diabetes-associated complications.