Type 2 Diabetic Nephropathy Patients Research Articles

Dry Eye and Some Related Factors in Patients with Type 2 Diabetic Nephropathy: A Cross-Sectional Study in Vietnam.

To determine the prevalence of dry eye (DE) and some related factors in patients with type 2 diabetic nephropathy (T2DN). We performed a cross-sectional study on 338 people, who were divided into 2 groups: 169 T2DN patients and 169 patients diagnosed with type 2 diabetic mellitus (T2DM) without renal complications as a control group. The Ocular Surface Disease Index (OSDI) and test fluorescein tear-film break-up time (TBUT) were done in all 338 subjects. Patients with OSDI scores < 13 and TBUT values equal to or under 10 seconds were diagnosed with dry eye. The prevalence of DE in T2DN patients was significantly higher than T2DM group (55.6% versus 37.3%). The T2DN groups with dry eye had a median duration of DM, the proportion of hypertension, peripheral nerve complications, anemia, proportion of using insulin, and concentration of plasma glucose, HbA1C, urea, creatinine, CRP-hs significantly higher than those of T2DN without dry eye. Advanced age, high HbA1C level, and decreased eGFR were independent factors associated with dry eye in T2DN patients. Dry eye was a common condition associated with advanced age, high HbA1C levels, and decreased GFR in T2DN patients.

Clinical value of miR-23a-3p expression in early diagnosis of diabetic kidney disease.

The objective was to observe the expression of miR-23a-3p in the serum of patients with type 2 diabetic nephropathy (T2DN) and to explore its clinical significance. 112 patients with type 2 diabetes were divided into a simple diabetes mellitus (NON) group, T2DN microalbuminuria (MIC) group, and T2DN macroalbuminuria (MAC) group, according to the urinary protein-creatinine ratio (uACR). Clinical data were collected, miR-23a-3p levels in serum were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR), and clinical parameters were measured by an automatic biochemical analyser; the influencing factors of diabetic kidney disease (DKD) and the correlation between miR-23a-3p expression and clinical parameters were analysed. The expression of miR-23a-3p in the serum of the DKD group was lower than that of the normal control (CON) and NON groups. Correlation analysis showed that miR-23a-3p was positively correlated with urinary albumin (Albu), glycosylated haemoglobin (HbA1c), total cholesterol (CHOL), glycated albumin (GA-L), serum creatinine (Scr), fasting blood glucose (GLU), and uric acid (UA), negatively correlated with uACR and high-density lipoprotein cholesterol (HDL-C), but not correlated with urinary creatinine (CREA). The area under the receiver operating characteristic (ROC) curve (AUC) of miR-23a-3p for the diagnosis of DKD was 0.686 [95% confidence interval (CI): 0.599-0.773], with a sensitivity of 64.5% and a specificity of 71.2%; the AUC for differentiating NON from DKD was 0.700 (95% CI: 0.598-0.802), with a sensitivity of 61.8% and a specificity of 77.8%. Multivariate logistic regression analysis showed that serum miR-23a-3p levels were not associated with the development of DKD after adjusting for other levels of influence and were not significant for the differentiation of NON and DKD. Serum miR-23a-3p levels are decreased in T2DN patients, and this change becomes more significant with the severity of the disease, which may be a marker for the early diagnosis and progression of T2DN.

Association of albumin, globulin and albumin/globulin ratio with renal injury in type 2 diabetic nephropathy patients

BackgroundStudies have shown that albumin/globulin ratio (AGR) can assess the extent of kidney damage in type 2 diabetic nephropathy (T2DN). However, there is a lack of similar clinical data to support this.ObjectivesThis study sought to inquire into the correlation of albumin (ALB), globulin (GLB) and albumin/globulin ratio (AGR) with renal injury in patients with type 2 diabetes mellitus (T2DM).MethodsA retrospective analysis was performed on the clinical data of 82 patients with T2DM (Control group) and 110 patients with type 2 diabetic nephropathy (T2DN) who were admitted to the First Affiliated Hospital of Wannan Medical College from October 2019 to April 2022. T2DN patients were classified into mild renal impairment group (n = 75) and moderate renal impairment group (n = 35) according to urinary albumin excretion rate (UAER). Then, the general data of all groups were compared. Furthermore, Pearson correlation was used to analyze the correlation of serum ALB, GLB and AGR with UAER in the three groups. A receiver operating characteristic curve (ROC) was utilized to evaluate the diagnostic value of ALB, GLB and AGR for moderate renal injury in T2DN patients.ResultsThere were significant differences in course of disease, history of hypertension, levels of fasting plasma glucose and glycosylated hemoglobin among the three groups. Besides, compared with the Control group, the levels of ALB and AGR were lower while GLB levels were higher in the mild and moderate renal impairment group. In particular, ALB and AGR levels were lower in the moderate renal impairment group relative to the mild renal impairment group, but the GLB levels exhibited no significant difference between the two groups. According to the results of Pearson correlation analysis, a negative correlation of ALB and AGR levels with UAER was revealed in T2DN patients. ROC curves displayed the area under the curve (AUC) of ALB (0.88) and AGR (0.71) predicting moderate renal injury in T2DM patients (p < 0.05). However, GLB has no significant diagnostic value for moderate renal injury in patients with T2DN.ConclusionThe course of disease, hypertension and glycemic control may affect the occurrence and development of T2DN. ALB and AGR are of high value in predicting renal injury in patients with T2DN and can serve as the foundation for the clinical diagnosis of the condition.

Relationship between periodontal status and dyslipidemia in patients with type 2 diabetic nephropathy and chronic periodontitis: A cross-sectional study.

The aim of this study was to investigate the association between periodontitis and total serum cholesterol level in patients with type 2 diabetic nephropathy (T2DN). Periodontitis is now recognized as the sixth complication of diabetes and can also affect other complications of diabetes, including nephropathy and coronary artery diseases. Studies have considered dyslipidemia as a risk factor for exacerbation of periodontitis. A total of 119 T2DN patients with chronic periodontitis were included in this observational study. Participants were stratified into the Normal (serum total cholesterol <5.17 mmol/L, n=89) and the Dyslipidemia groups (serum total cholesterol ≥5.17 mmol/L, n=30). Participants completed a validated questionnaire that collected information on oral hygiene behaviors and knowledge of oral health and underwent a clinical oral examination. The number of remaining teeth, probing depth (PD), clinical attachment level (CAL), and bleeding index (BI) was recorded. Physical examination and laboratory tests (fasting plasma glucose, serum glycosylated hemoglobin (HbA1c), total cholesterol, high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), triglyceride, and high-sensitivity C-reactive protein levels) were performed. Means of CAL and BI were significantly higher in the Dyslipidemia group compared with the Normal group. In the Dyslipidemia group, PD and percent of sites with PD ≥4 mm were positively correlated with urinary albumin/creatinine ratios; PD and percent of sites with PD ≥4 and PD ≥5 mm were positively correlated with HbA1c level; a number of remaining teeth were negatively correlated with serum LDL-C level. After adjusting for age, gender, body mass index, smoking, FPG, and serum HbA1c and triglyceride levels, BI was found to be positively associated with dyslipidemia in T2DN patients with periodontitis. T2DN patients with chronic periodontitis had a 2.355-fold higher risk of developing dyslipidemia, implying an important relationship between periodontitis and blood lipid control among T2DN patients.

The role of vitamin D deficiency and elevated inflammatory biomarkers as risk factors for the progression of diabetic nephropathy in patients with type 2 diabetes mellitus

Abstract Diabetic nephropathy (DN) is the leading cause of end-stage renal disease worldwide. Albuminuria is the most sensitive marker for the early recognition of DN. Therefore, we aimed to study the risk factors of albuminuria as a marker of DN among diabetic patients. The study included 41 patients with type 2 diabetes mellitus (T2DM), 50 type 2 diabetic nephropathy (T2DN) patients with macroalbuminuria, 43 T2DN patients with microalbuminuria and 38 healthy controls. Logistic regression was used to detect the most significant risk factors for albuminuria. A high statistically significant difference was found between the groups regarding age, sex, body mass index (BMI), diabetes mellitus (DM) duration, glucose, glycated haemoglobin (HbA1c), creatinine, glomerular filtration rate (GFR), lipid profile, tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP), the albumin–creatinine ratio (ACR), vitamin D, total parathyroid hormone (PTH), urea, total calcium and chemerin (p &lt; 0.001). It was found that the duration of DM, BMI, glucose, GFR, total cholesterol (TC), low-density lipoprotein (LDL), TNF-α, IL-6, CRP, ACR, vitamin D, PTH and chemerin are significant albuminuria risk factors in DN. Vitamin D deficiency and associated inflammatory mediators such as chemerin, TNF-α, IL-6 and CRP are the most essential risk factors for albuminuria in T2DM patients.

1264-PUB: Association between Serum Fatty Acid Metabolism Profile and Diabetic Nephropathy: A Study in Northeastern China

Background: Type 2 diabetic nephropathy (T2DN) is one of the most common chronic microvascular complications of type 2 diabetes (T2DM). Researchers found that free fatty acids(FFA) is an independent risk factor for vascular complications of T2DM. It is particularly important to analyze whether the changes in the metabolic spectrum of FFA is associate with the development of T2DN in diabetic patients.Method: 612 subjects were enrolled in the present study in Dalian, a city in Northeast China. The study population consisted of 51 T2DN, 108 T2DM, and 453 healthy individuals. 23 kind of serum FFAs including docosahexaenoic acid(DHA, C22:6), nervonic acid (C24:1) were measured by LC-MS technology.Result: The levels of nervonic acid and DHA are significantly lower in T2DN group when compared to the healthy control group. Multi-factor Logistic regression analysis shows that nervonic acid (OR 95% CI:0.943 (0.890 ~0.999), p<0.05), DHA (OR 95% CI:0.983 (0.968~0.998), p<0.05) may act as protective factors in patients with T2DN.Conclusion: The present study found that the content of neuronic acid and DHA in T2DN patients is relatively low, which indicates that neuronic acid and DHA may have protective effects on T2DN. Hence, this study provides a new idea for potential clinical intervention and supplementation of exogenous FFAs for the prevention and treatment of T2DN.View largeDownload slideView largeDownload slide DisclosureY. Liu: None. Y. Li: None. M. Zhou: None. X. Xia: None. H. Shen: None. Y. Li: None. Y. Xu: None. C. Han: None.

MO639THE ASSOCICATION BETWEEN SERUM INTERLEUKIN 1 BETA AND HEPARAN SULFATE IN DIABETIC NEPHROPATHY PATIENTS

Abstract Background and Aims The global diabetes mellitus (DM) prevalence in 2019 is estimated to be 9.3%. Approximately 20% to 40% of patients with DM develop diabetic nephropathy (DN). DN is the leading cause of end stage renal disease (ESRD). Inflammation is considered to be an important mechanism in the development of DM and persists for a long time before the occurrence of DN. Many studies demonstrated that decrease of endothelium glycocalyx (EG) was negatively correlated with proteinuria. Whether EG damage induced by inflammasome in DM patients leads to the occurrence of micro albuminuria (MA) and accelerating the progress of DKD is rarely studied. Method: This prospective, observational cohort study screened 300 diagnosed diabetic patients from departments of nephrology and endocrinology of our hospital. The exclusion criteria were: type 1 diabetes; acute infections; usage antibiotics within 3 months; kidney disease before; heart failure; malignancy. Finally 70 patients were invited to this study and were divided into type 2 DM (T2DM) group and type 2 diabetic nephropathy (T2DN) group. T2DM group were defined as patients with normal MA and without diabetic retinopathy (n=35). T2DN group were defined as patients with increased MA and diabetic retinopathy (n=35). Laboratory data were measured via routine laboratory methods. Heparan sulfate (HS) and interleukin 1 beta (IL-1β) were noted as EG biomarker and inflammasome biomarker respectively. Serum samples of patients were collected, and serum IL-1β and HS were measured by ELISA. SPSS 18.0 was used for all statistical analyses. Results: T2DN patients had higher serum IL-1β (27.85 vs. 21.35 pg/ml), higher HS (2.17 vs. 1.47 ng/ml), higher urea nitrogen (6.30 vs. 5.33 umol/L), higher CRP (2.03 vs. 0.81 mg/L), higher hemoglobin (128 vs. 141 g/L), higher neutrophil (4.1 vs. 3.4 × 109/L) and higher neutrophilic granulocyte percentage (63% vs. 56%) compared with T2DM patients (all P&amp;lt;0.05). Logistic regression analyses demonstrated serum HS was independently associated with T2DN. Furthermore in T2DN patients, serum IL-1β was positively correlated with HS (r = 0.6, P&amp;lt;0.01) and was and independent associated factor. The relationship of HS and IL-1β was not significant in T2DM patients. Conclusion T2DN patients had higher serum IL-1β and HS than T2DM patients in our study. In T2DN patients IL-1β was an independent associated factor of HS. The results suggested that the inflammasome may damage the EG in diabetic patients, which induced the occurrence of MA and accelerating the progress of DN.

Expansion of Myeloid-Derived Suppressor Cells Correlates with Renal Progression in Type 2 Diabetic Nephropathy.

Type 2 diabetic nephropathy (T2DN) progresses with an increasingly inflammatory milieu, wherein various immune cells are relevant. Herein, we investigated the levels of myeloid-derived suppressor cells (MDSCs) and their clinical implication in patients with T2DN. A total of 91 subjects (T2DN, n=80; healthy, n=11) were recruited and their PBMCs were used for flow cytometric analysis of polymorphonuclear (PMN-) and monocytic (M-) MDSCs, in addition to other immune cell subsets. The risk of renal progression was evaluated according to the quartiles of MDSC levels using the Cox model. The proportion of MDSCs in T2DN patients was higher than in healthy individuals (median, 6.7% vs. 2.5%). PMN-MDSCs accounted for 96% of MDSCs, and 78% of PMN-MDSCs expressed Lox-1. The expansion of PMN-MDSCs was not related to the stage of T2DN or other kidney disease parameters such as glomerular filtration rate and proteinuria. The production of ROS in PMN-MDSCs of patients was higher than in neutrophils of patients or in immune cells of healthy individuals, and this production was augmented under hyperglycemic conditions. The 4th quartile group of PMN-MDSCs had a higher risk of renal progression than the 1st quartile group, irrespective of adjusting for multiple clinical and laboratory variables. In conclusion, PMN-MDSCs are expanded in patients with T2DN, and may represent as an immunological biomarker of renal progression.

Association of Angiotensin Converting Enzyme Gene Insertion/Deletion Polymorphism with Type 2 Diabetic Nephropathy in Gaza Strip-Palestine

Introduction: The insertion/deletion (I/D) polymorphism of 287 bp Alu repeat sequence in intron 16 of Angiotensin Converting Enzyme (ACE) gene resulting in three genotypes I/D, D/D and I/I. ACE gene expression is associated with ACE levels in cells and in the plasma. It indicated that the polymorphism may modulate the expression of the ACE gene. The D/D genotype is believed to confer deleterious effect to many pathogenesis, also, it might be a cause-effect for type 2 diabetic nephropathy (T2DN). In this study, we evaluated the frequency of the different genotypes of ACE gene and investigated if there is an association between ACE gene polymorphism and T2DN by comparing the genotypes results of T2DN patients to healthy control, Type 2 diabetes mellitus (T2DM) and nephropathy patients in Gaza Strip.&#x0D; Methodology: The study included 170 subjects, consisting of 43 T2DM patients undergoing dialysis "T2DN" compared to 41 T2DM patients who were not undergoing dialysis, 43 patients undergoing dialysis without T2DM and 43 healthy individuals. Blood samples were collected in EDTA tubes for DNA extraction. Polymerase Chain Reaction (PCR) was used to detect ACE gene polymorphism. All subjects were asked to fill the questionnaire interview.&#x0D; Results and Conclusion: The initial results showed that there is no statistically significant association between ACE genotypes and T2DN, also between the T2DM and nephropathy when compared to the healthy control (p&gt; 0.05). The (D/D) genotype was the most frequent in all study groups. Moreover, no association was observed between ACE genotypes and gender, diabetic nephropathy, nephropathy, diabetes, hypertension, obesity and various other diabetes complications.&#x0D;

Relationship between transforming growth factor-\u03b21 and type 2 diabetic nephropathy risk in Chinese population

BackgroundDiabetes mellitus (DM) is divided into four different etiological categories: type 1 DM (T1DM), type 2 DM (T2DM), other specific types, and gestational DM. One severe complication of T2DM is type 2 diabetic nephropathy (T2DN). The possible association of serum transforming growth factor-β1 (TGF-β1) levels and the TGF-β1 T869C gene polymorphism with patient susceptibility to T2DN in Chinese population is unclear at present. This study was conducted to assess these relationships in Chinese population by a meta-analysis.MethodsAssociation reports were searched and pulled from the Cochrane Library, the China Biological Medicine Database (CBM), and PubMed on March 1, 2018, and eligible studies were selected and used for calculations. The results were expressed as weighted mean differences (MD) for continuous data. Odds ratios (OR) were used to express the results for dichotomous data. Additionally, 95% confidence intervals (CI) were calculated.ResultsForty-eight reports for the relationship between serum TGF-β1 levels and the risk of T2DN and 13 studies on the association of the TGF-β1 T869C gene polymorphism with susceptibility to T2DN in Chinese population were retrieved from this study. Serum TGF-β1 levels in the T2DM group were higher than those in the normal control group (MD = 17.30, 95% CI: 12.69–21.92, P < 0.00001). The serum TGF-β1 level in the T2DN group was significantly higher than that in the normal control group (MD = 70.03, 95% CI: 60.81–79.26, P < 0.00001;). The serum TGF-β1 level in the T2DN group was significantly higher than that in the T2DM group (MD = 56.18, 95% CI: 46.96–65.39, P < 0.00001). Serum TGF-β1 levels in T2DM patients with microalbuminuria were increased when compared with those in T2DM patients with normoalbuminuria. Furthermore, serum TGF-β1 levels in T2DM patients with macroalbuminuria were increased when compared with those in T2DM patients with microalbuminuria. The TGF-β1 T allele, TT allele and CC genotype were associated with T2DN susceptibility in Chinese population (T: OR = 0.74, 95% CI: 0.59–0.92, P = 0.007; TT: OR = 0.55, 95% CI: 0.31–0.96, P = 0.04; CC: OR = 1.38, 95% CI: 1.14–1.67, P = 0.001).ConclusionsHigh levels of TGF-β1 are associated with susceptibility to T2DM, T2DN and the progression of proteinuria in T2DN patients in Chinese population. Further, the TGF-β1 T allele, and TT genotype were protective factors against the onset of T2DN and CC genotype was a risk factor for the susceptibility of T2DN in Chinese populations.

The Kidney Specific Protein myo-Inositol Oxygenase, a Potential Biomarker for Diabetic Nephropathy

Background/Aims: Renal tubular injury plays an important role in the progression of diabetic nephropathy (DN). However, there is a lack of specific biomarkers for tubular damage in incipient DN. We have evaluated the role of myo-inositol oxygenase (MIOX) in the tubular injury of DN, but whether it could serve as a new biomarker for the early diagnosis of DN is unclear. Methods: Ninety patients with type 2 diabetes mellitus (T2DM) were divided into normoalbuminuria, microalbuminuria and macroalbuminuria groups. Fifteen patients from the last group were pathologically diagnosed as type 2 DN (T2DN), and fifteen patients with minimal change disease served as a control group. The expression of MIOX and silent information regulator 1 (Sirt1) in renal biopsies was determined by immunohistochemistry (IHC), and serum/urine MIOX, Sirt1, KIM-1 and NGAL were measured using enzyme-linked immunosorbent assays (ELISAs). Spearman’s correlation and multiple regression analyses were carried out for statistical analyses. Results: Compared with the controls, MIOX expression was significantly increased in the renal tissues of T2DN patients, and was positively correlated with tubulointerstitial lesions and renal ROS production but inversely correlated with Sirt1 expression. In addition, the serum and urine MIOX were significantly increased and gradually elevated with the increasing of UACR. Interestingly, elevated MIOX levels in serum and urine were found in diabetic patients without early signs of glomerular damage (normoalbuminuric group). Further multivariate regression analysis showed that sMIOX and uMIOX correlated significantly with HbA1c, serum creatinine and logUACR, respectively. Conclusion: These data indicate that increased MIOX expression in the kidney contributes to tubular damage in DN. The concentration of MIOX in the serum and urine may serve as a new biomarker for the early diagnosis of DN.

Serum TNF-α concentrations in type 2 diabetes mellitus patients and diabetic nephropathy patients: A systematic review and meta-analysis

ObjectivesThe aim of this study was to investigate whether the concentrations of serum tumor necrosis factor-α (TNF-α), a pro-inflammatory cytokine, increased in type 2 diabetes mellitus (T2DM) and type 2 diabetic nephropathy (T2DN) patients. MethodsThe four databases (PubMed, CNKI, WanFang and Chinese-Cqvip) were searched from Jan 1, 1999 to October 1, 2016 for all clinical case-control studies about the serum TNF-α concentrations in T2DM and T2DN patients. All relevant data were extracted from published reports. The meta-analysis was performed to compare the changes of serum TNF-α concentrations of T2DN and T2DM patients in Eastern and Western with healthy controls. We further evaluated concentrations of serum TNF-α in T2DN patients with mincroalbuminuria or macroalbuminuria. Random-effects models were adopted to assess the pooling data among various variations. ResultsIn total of 6 studies (744 patients and 277 healthy controls) were included in this study. Compared with healthy controls (both p<0.01), the groups of different albuminuria levels and ethnicities both showed that the serum TNF-α levels were significantly elevated in T2DN patients as well as in eastern T2DN patients (p=0.001), but not significant changed in western T2DN patients (p=0.081). The results were stable through sensitivity analysis and no significant publications bias existed in this meta-analysis. ConclusionsSerum TNF-α concentrations are obviously increased in T2DN and T2DM patients, but higher in T2DN patients, suggesting an elevated inflammatory burden in T2DN patients.

Changes of transforming growth factor beta 1 in patients with type 2 diabetes and diabetic nephropathy: A PRISMA-compliant systematic review and meta-analysis.

Background:The existing evidence indicates increased levels of transforming growth factor beta 1 (TGF-β1) in patients with type 2 diabetes mellitus (T2DM) and those with type 2 diabetic nephropathy (T2DN); yet no meta-analysis displays a reliable result. Here we conducted a meta-analysis to evaluate characteristic changes of TGF-β1 in T2DM and diabetic nephropathy.Methods:A systematic search was conducted for eligible studies, which reported the association of TGF-β1 withT2DM and T2DN patients, in PubMed, Wangfang, Chinese-Cqvip, and China National Knowledge Infrastructure database, from February 1, 1991 to December 15, 2015. The association of serum and urine TGF-β1 in T2DM and T2DN patients should be evaluated in case-control studies. The Newcastle-Ottawa Scale was used to access the quality of the included studies, and pooling data were synthesized as standard mean difference (SMD) and 95% confidence interval (CI). The collected data were synthesized according to Cochrane Handbook for Systematic Reviews criteria. Subgroup analysis was conducted by albuminuria and ethnicity. Regression analysis and sensitivity analysis were used to explore the sources of heterogeneity. Publication bias was judged by the Egger test.Results:Sixty-three case-control studies of 364 T2DM patients (1604 T2DN patients) and 2100 healthy controls were included for meta-analysis. Compared with the controls, the cases had increased TGF-β1 levels in both serum (T2DM: SMD 1.78 μg/L; 95% CI 0.98–2.59, P < .001; T2DN: SMD 4.70 μg/L, 95% CI 3.55–5.85, P < .001) and urine samples (T2DM: SMD 1.27 pg/mg.creatinine, 95% CI 0.16–2.38, P < .001; SMD 1.19 ng/L, 95% CI 0.77–1.62, P < .001; T2DN: SMD 3.14 pg/mg.creatinine, 95% CI 2.15–4.13, P < .001; SMD 4.50 ng/L, 95% CI 3.16–5.83, P < .001). The increase of serum TGF-β1 persisted in patients with either microalbuminuria or macroalbuminuria (all P < .001) in Chinese and non-Chinese population. High heterogeneity exists in some comparisons and small-sample studies.Conclusions:Patients with T2DM and those with albuminuria, Chinese or non-Chinese, had increased serum and urine TGF-β1 levels.

Effects of vitamin D combined with pioglitazone hydrochloride on bone mineral density and bone metabolism in Type 2 diabetic nephropathy.

The study aims to investigate the effect of vitamin D (VD) combined with pioglitazone hydrochloride (PIO) on bone mineral density (BMD) and bone metabolism in patients with Type 2 diabetic nephropathy (T2DN). T2DN patients were selected and assigned into mild, moderate, and severe groups. In each group, three therapy regimens (VD, PIO, and VD plus PIO) were administered. X-ray absorptiometry was used to measure BMD. Intact parathyroid hormone (iPTH) and 25-hydroxyvitamin D3 (25-OH-VD3) were measured by chemiluminescence meter. ELISA was applied to detect levels of osteoprotegerin (OPG), bone gla protein (BGP), C-terminal telopeptides of type I collagen (β-CTX), procollagen type I N-propeptide (PINP), pyridinoline (Pyr), and deoxypyridinoline (D-Pyr). Compared with the mild group, T2DN patients in the moderate and severe groups had longer course of disease and higher levels of total cholesterol (TC), triglyceride (TG), serum phosphorus, fasting plasma glucose (FPG), glycosylated hemoglobin (HbAlc) and creatine (Cr), and lower blood calcium. The BMD in different parts increased among the mild, moderate, and severe groups, and the highest BMD was found after VD plus PIO treatment. OPG, iPTH, BGP, β-CTX, Pyr/Cr, and D-Pyr/Cr levels were reduced, while 25-OH-VD3 and PINP levels were elevated among three groups after different treatments, and the most obvious change was observed after VD plus PIO treatment. Our findings indicate that VD combined with PIO may be more effective in improving BMD and bone metabolism than VD or PIO alone in the treatment of T2DN patients, especially for T2DN patients with mild disease.

Urinary RBP and NGAL Levels are Associated with Nephropathy in Patients with Type 2 Diabetes

Background/Aims: The diagnosis of type 2 diabetic nephropathy (T2DN) patients is important to prevent the long-term damaging effects of kidney loss in patients with diabetes and is decisive for patient outcomes. The aim of this study was to explore urine retinol binding protein (RBP) and neutrophil gelatinase-associated lipocalin (NGAL) in T2DN patients with and without albuminuria. Methods: A total of 293 T2DN patients were divided into three groups according to their urine albumin/urine creatinine ratio (UACR): normoalbuminuria group (UACR<30 mg/g, n=100), microalbuminuria group (UACR 30–300 mg/g, n=100) and macroalbuminuria group (UACR>300 mg/g, n=93); 50 non-diabetic subjects were recruited as the control group. The levels of urine RBP, NGAL, TNF-α and IL-18 in T2DN patients and non-diabetic subjects were measured using ELISA assays. Results: We first analyzed the clinical characteristics of the control and T2DN groups and found that urine NGAL, RBP, TNF-α and IL-18 levels were significantly increased and significantly correlated with the degree of albuminuria. In addition, univariate linear regression analysis showed that urine RBP was associated with UACR, BMI, Scr, BUN, TG, disease duration, SBP, NGAL, TNF-α and IL-18 levels, and urine NGAL was positively correlated with UACR, Scr, BUN, RBP, TNF-α and IL-18 levels. Conclusion: The results indicate that urine levels of NGAL and RBP may be independently associated with albuminuria in T2DN and may serve as novel biomarkers for the identification of T2DN.

Clinical verification of a novel urinary microRNA panal: 133b, -342 and -30 as biomarkers for diabetic nephropathy identified by bioinformatics analysis.

Because microvascular disease is one of the major drivers of diabetic complications, early detection of diabetic nephropathy (DN) by assessing the expression of exosomal microRNAs (miRNAs) in DN patients and healthy controls, may be of clinical value. The aim of this study wasto identify a novel miRNA panel of DN by combining bioinformatics analysis of miRNA databases and clinical verification to evaluate the significance of this panel as urine biomarkers for type 2 diabetic nephropathy (T2DN). Public miRNA databases e.g miro-Ontology and miRWalk were analyzed and a novel panel of 3 microRNAs was retrieved. Meanwhile, combinatorial target prediction algorithms were applied. Multiple case-matched normal were examined by quantative RT-PCR for differential expression in urine exosomes from 210 participants, and the three identified miRNAs were validated as DN biomarkers. We found urinary exosomalmiR-133b, miR-342, and miR-30a were expressed at significantly elevated levels in T2DN patients (P<0.001) compared to normal. Furthermore, high-level expression of the 3 miRNAs was associated withHbA1c,systolic-diastolic blood pressure, LDL, serum creatinine, urinary albumin creatinine ratio and estimated glomerular filtration rate(eGFR). Moreover, 39.3%, 19.6% and 17.9% of patients with normo-albuminuria had positive (miR-133b, miR-342 and miR-30a, respectively); indicating the possibility of molecular changes in these patients before onset of albuminuria. We have identified novel urinary exosomal miRNA biomarkers of DN which were altered not only in micro and macroalbuminuric groups but also in some normoalbuminuria cases prior to albuminuria.

Association between homocysteine status and the risk of nephropathy in type 2 diabetes mellitus

BackgroundIt is well documented that hyperhomocysteinemia induces renal injury. However, the association between homocysteine level and type 2 diabetic nephropathy (T2DN) remains elusive. MethodsWe evaluated the alteration of plasma level of homocysteine in T2DN patients with macroalbuminuria or microalbuminuria compared with type 2 diabetes mellitus (T2DM) controls without albuminuria by performing a meta-analysis. We searched the PubMed, Embase and Cochrane databases from January 1990 to October 2013 to identify studies that met predefined criteria. ResultsSeven studies were included in this investigation. T2DN patients with macroalbuminuria demonstrated a significantly higher level of plasma homocysteine than T2DM without albuminuria (4 studies, random effects SMD: 1.66, 95% CI: 0.46 to 2.87, P=0.007) and T2DN with microalbuminuria (3 studies, random effects SMD: 0.99, 95% CI: 0.62 to 1.36, P<0.001). T2DN patients with microalbuminuria demonstrated significantly higher level of plasma homocysteine than T2DM without albuminuria (6 studies, random effects SMD: 1.29, 95%.CI: 0.59 to 2, P<0.001). Exclusion of any single study had little impact on the pooled SMDs. No evidence of publication bias was observed. ConclusionsOur findings indicate that the status of plasma homocysteine is associated with both the risk and severity of nephropathy in T2DM. Frequent monitoring and early intervention should be recommended.

The role of renal damage on cardiac remodeling in patients with diabetic nephropathy

Cardiovascular damage and diabetic nephropathy are major complications in patients with Type 2 diabetic nephropathy (T2DN); however, the role of renal damage on cardiac remodeling is not yet fully known. A retrospective research was conducted in 254 T2DN patients. All were divided into three groups according to urinary albumin excretion (UAE): the normoalbuminuria group (UAE < 30 mg/g, n = 18), the microalbuminuria group (UAE 30 - 300 mg/g, n = 99) and the macroalbuminuria group (UAE > 300 mg/g, n = 137). The parameters of cardiac remodeling, left atrial diameter (LAD), left ventricular diameter at the end of diastole (LVDd), interventricular septum (IVS), posterior wall of left ventricle (PWLV) and ejection fraction (EF), were determined by Doppler echocardiography. The effects of renal damage on cardiac remodeling were analyzed. Among the 254 patients, LAD and LVDd enlargement was found in 180 (70.86%) and 53 (20.86%) patients, respectively; 46 cases (18.11%) suffered from both LAD and LVDd enlargement. Compared with normal LAD/LVDd groups, creatinine clearance (Ccr) and hemoglobin (Hb) were significantly lower in the left atrial (LA) and left ventricular (LV) dilated groups. LAD was positively correlated with mesangial sclerosis, tubular-interstitial lesions, interstitial fibrosis, as well as tubular basement membrane thickness (r = 0.273, 0.208, 0.176, 0.155, p < 0.05, respectively). Moreover, in comparison to patients with LA enlargement, more severe renal damage was detected in patients with LV enlargement. There is a strong correlation between echocardiographic parameters and kidney lesions in patients with T2DN in China; the more severe the renal damage, the more severe the cardiac structural alteration. Renal damage contributes to cardiac remodeling, which may provide new insights into the pathogenesis of cardiovascular complications ,in diabetes mellitus.

Effect of high-dose zinc supplementation with oral hypoglycemic agents on glycemic control and inflammation in type-2 diabetic nephropathy patients

Objective:The study aims to evaluate the effect of zinc sulfate on markers of glycemic control, lipid profile and inflammation in type-2 diabetes with microalbuminuria patients.Materials and Methods:Type-2 diabetes with microalbuminuria patients on oral hypoglycemic agents (OHA) and angiotensin converting enzyme (ACE) inhibitors were selected and divided into 2 groups: One group (n = 27) continued with OHA alone, second group (n = 27) was on OHA and in addition 50 mg elemental zinc as zinc sulphate supplementation for 12 weeks. Fasting, post-prandial blood glucose, glycosylated hemoglobin, lipid profiles, inflammatory marker hs-CRP and urine microalbumin were measured.Results:There were no significant differences in biochemical status among groups at baseline. After receiving zinc, the mean fasting blood glucose (FBS), post-prandial blood glucose (PPBS) and glycosylated hemoglobin (HbA1c) were decreased significantly (P = 0.0001). Significant decrease was observed in TG (P = 0.002) and VLDL-cholesterol (P = 0.002), whereas there was no significant decrease in TC and LDL-cholesterol. The high-density lipoprotein (HDL) cholesterol was significantly (P = 0.0001) increased from baseline. Zinc supplementation had significant effects in decreasing serum hs-CRP from 10.51 ± 1.68 mg/L to 7.75 ± 1.56 mg/L (P = 0.0001) and microalbumin level from 146.87 ± 30.83 mg/day to 80.70 ± 33.99 mg/day (P = 0.0001). There were no significant changes in the levels of all these parameters in OHA group.Conclusion:Our results conclude that supplementation of zinc improved the effectiveness of OHA and may be beneficial in decreasing blood glucose, TG, urinary albumin excretion and inflammation in diabetic nephropathy patients and thus reducing the risk of complications.