Normoalbuminuric Group Research Articles

Modification Effects of Albuminuria on the Association Between Kidney Function and Development of Anemia in Diabetes.

Previous studies failed to adjust for estimated glomerular filtration rate (eGFR) in evaluating the association between albuminuria and anemia development, and we aimed to investigate whether albuminuria independently affects anemia development. We conducted a retrospective cohort study and retrospectively identified adults with diabetes from a Japanese nationwide clinical database (JMDC, Tokyo, Japan). To assess the modification effects of albuminuria on the association between eGFR and anemia development, we estimated prevalence of anemia, defined as hemoglobin < 13 g/dL in men and < 12 g/dL in women, using a modified Poisson regression and marginal standardization form of predictive margins, stratified by albuminuria severity after adjusting for eGFR. Hence, we revealed at which eGFR level this modification effect appeared and the extent to which this modification effect increased the prevalence of anemia. We identified 327 999 data points from 48 056 individuals [normoalbuminuria: 186 472 (56.9%), microalbuminuria: 107 170 (32.7%), and macroalbuminuria: 34 357 (10.5%)]. As eGFR declined, anemia prevalence increased. Albuminuria severity modified this association induced by decreased eGFR among individuals with eGFR <30 mL/min/1.73 m2 after adjusting for multivariable factors, including age, sex, comorbidities, and medication use. Compared with the normoalbuminuric group, the macroalbuminuric group had a 5% to 20% higher anemia prevalence among individuals with eGFR of <30 mL/min/1.73 m2. We revealed that the severity of albuminuria modified the association between eGFR and anemia development among individuals with eGFR <30 mL/min/1.73 m2, highlighting the modification effect of albuminuria on the association between kidney function and anemia development in diabetes.

Urine Zinc-alpha-2-glycoprotein as a Potential Biomarker for Incipient Diabetic Nephropathy: A Pilot Study at a Tertiary Care Hospital

Introduction: Urine albumin-creatinine ratio (UACR) continues to be used as an indicator for detecting diabetic nephropathy (DN); however, damage starts much before that. Currently, no biomarkers are there to indicate incipient damage. As a result, researchers are looking for new biomarkers that could be used to detect DN threats sooner and perhaps hinder the development of end-stage renal disease. The present study intended to know if urine Zinc-alpha-2-glycoprotein (ZAG) levels correlate with glomerular filtration rate (GFR) in the study participants of type 2 diabetes mellitus (T2DM). Materials and Methods: The study included 68 participants with a known history of T2DM. Serum urea and creatinine levels, fasting plasma glucose, serum cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, total protein, glycated hemoglobin (HbA1c) and urine ZAG were estimated and UACR along with estimated GFR (eGFR) were calculated for all individuals. The characteristics of the study participants in the microalbuminuric and normoalbuminuric groups were compared. Results: The levels of urine ZAG in the microalbuminuric and normoalbuminuric groups were not observed to be substantially different. The relationship between urine ZAG and diabetes mellitus duration was found to be highly significant in normoalbuminuric patients. Urinary ZAG and correlation with categories of HbA1c % (good &lt;7, 7–9 moderate, &gt;9 poor) among normoalbuminuric individuals were not found to be significant. Conclusion: Despite previous research, we were unable to find a positive relationship between urinary ZAG concentrations and eGFR in this study. Prospective studies with greater sample sizes and follow-up are required to fully comprehend the possible use of ZAG as a biomarker in diabetic nephropathy.

#4941 A METABOLOMIC FINGERPRINT PERSPECTIVE OF GUT-DERIVED METABOLITES ON EARLY DIABETIC KIDNEY DISEASE IN TYPE 2 DIABETES MELLITUS PATIENTS

Abstract Background and Aims Type 2 diabetes mellitus (T2DM) is the first cause of end stage renal disease worldwide. Metabolite profiling is an emerging field of great significance, as T2DM prevalence is continuously rising. The subtle dynamics of gut microbiota derived metabolites may have important implications in diabetic kidney disease (DKD) development. Nitrogen metabolic pathway and retinoic acid signaling pathway seem to be involved in early pathogenic mechanisms of DKD. The aim of study was to discover new putative gut-derived biomarkers that interfere with early physio-pathological mechanisms in DKD, regarding the podocyte, tubule, and the renal endothelium. Method The serum and urine of 90 T2DM patients (P group) and 20 healthy subjects (C group), were assessed in a cross-sectional study, by ultra-high-performance liquid chromatography coupled with electrospray ionization-quadrupole-time of flight-mass spectrometry (UHPLC-QTOF-ESI+-MS) techniques. P group was divided in 3 subgroups (normoalbuminuria-P1, microalbuminuria-P2, macroalbuminuria-P3). Statistical analysis was performed by untargeted multivariate (PLSDA, VIP scores, Random Forest, Biomarker analysis) and univariate (One Way ANOVA, Biomarker Analysis) methods. Results Multivariate analysis, by which the P group vs. C group were compared, displayed: (1) in serum samples: increased levels (P&amp;gt;C) of all-trans retinoic acid, cysteine-S sulfate, oleoylglicine, threonylglycine and decreased levels (P&amp;lt;C) of phenylalanine, tyrosine, kynurenic acid; (2) in urine samples, there were increased levels of: all-trans retinoic acid, indoxyl suflate, serotonin sulfate and glycylprolylarginine. Subsequently, by applying univariate analysis, the biomarkers derived from gut microbiota were selected: (1) in serum: all-trans retinoic acid (C&amp;lt;P1&amp;lt;P2&amp;lt;3), phenylalanine, tyrosine, and kynurenic acid with levels decreasing progressively from C to P1-P2-P3 (2) in urine: all trans retinoic acid, indoxyl sulfate, and serotonin sulfate, showing good differentiation between C and P1, and slight differences between P1∼P2∼P3 subgroups. The study suggests that ATRAs dynamic is disturbed in the normoalbuminuric stage of DKD. While its urinary levels correlated significantly with albuminuria, the changes observed in P1 subgroup, in serum and urine, may be correlated to the loss of renal tubular tight junction as a result of claudin downregulation. Phenylalanine and tyrosine, a part of nitrogen metabolic pathway, are indicators of the new-onset DKD. Their levels were upregulated in serum vs. urine, indicating their possible involvement in early DKD when comparing C vs. P1-P2-P3. Kynurenic acid and indoxyl-sulfate result from tryptophan metabolism. Low levels in serum of kynurenic acid may suggest its possible implication in incipient endothelial dysfunction in DKD. Indoxyl-sulfate (IS) urinary excretion is dependent on albuminuria. The study shows an elevated excretion of IS, in the normoalbuminuric group compared to controls and may suggest a tubular damage that precedes the glomerular modifications in DKD. Conclusion UHPLC-QTOF-ESI+-MS untargeted analysis reveals a particular metabolite fingerprint in early DKD. The study describes all-trans retinoic acid, phenylalanine, tyrosine, kynurenic acid, and indoxyl sulfate, as potential key biomarkers involved in early DKD pathogenesis, their levels being expressed in P1 subgroup compared with C group, and P2, P3 subgroups.

Plasma copeptin level in type 2 diabetic patients and its role in diabetic nephropathy

BackgroundCopeptin, the stable COOH-terminal portion of pre-provasopressin and a surrogate marker of vasopressin, was shown to be positively associated with the decline in kidney function in the general population. However, the impact of copeptin on renal function in diabetic patients remains unclear. This study aims to assess the clinical significance of plasma copeptin level in type 2 diabetic patients with and without nephropathy and to evaluate its relation to various clinical and laboratory parameters.MethodsThis study was carried out on 45 type 2 diabetic patients, divided according to urinary albumin/creatinine ratio into 15 with normoalbminuria, 15 with microalbminuria and 15 with macroalbminuria. Also, 15 healthy subjects were included as a control group. Plasma copeptin level, glycosylated hemoglobin percentage, urinary albumin/ creatinine ratio and serum creatinine were measured. Estimated glomerular filtration rate (eGFR) was calculated.ResultsThe mean plasma copeptin level was statistically significantly higher in patients with microalbuminuria as compared to the control and normoalbuminuric groups. It was also, higher in patients with macroalbuminuria as compared to the control, normoalbuminuric and microalbuminuric groups. Plasma copeptin level was positively correlated with glycosylated hemoglobin, urinary albumin /creatinine ratio and serum creatinine but negativey correlated with eGFR.ConclusionAn increased plasma copeptin level is considered as a good predictor for deterioration of renal function in diabetic patients, suggesting that copeptin can be used to identify diabetics at risk for diabetic kidney disease development. Clearly, further well-designed prospective studies are required to prove this hypothesis.

Kidney injury molecule-1 and cystatin C as early biomarkers for renal dysfunction in Iraqi type 2 diabetes mellitus patients

Diabetic kidney disease (DKD) is caused by a variety of processes. As a result, one biomarker is insufficient to represent the complete process. This study Evaluate the diagnostic value of serum kidney injury molecule-1(KIM-1) and cystatin C (CysC) as early biochemical markers of DKD and predictive their sensitivities and specificities as biomarkers of nephropathy in Iraqi type 2 diabetic (T2DM) patients. This cross-sectional study include 161 T2DM patients from Diabetes and Endocrinology Center at Merjan medical city in Babylon. Patients divided according to urinary albumin creatinine ratio(ACR) (Group1:ACR≤30mg/g,Group2:ACR&gt;30mg/g). Random spot urine and fasting blood samples were taken from each patient and urinary ACR, blood glycated hemoglobin(HbA1c), and serum glucose, creatinine(SCr), lipid profile, CysC, KIM-1 were assayed, and the estimated glomerular filtration rat (eGFR) was calculated. When compared to the normoalbuminuric group, the DKD group had significantly greater prevalence of retinopathy, and significantly elevated HbA1c and total cholesterol values. Also had significantly greater serum levels of KIM-1 and CysC, and there is a significant (P-value&lt; 0.01) positive correlation between them. In contrast, GFR was significantly higher in normoalbuminuric group and was significantly negatively correlated with both CysC and KIM-1. Multiple linear regression analysis, found that there were a significant positive association between CysC, KIM-1 and ACR. ROC analysis reveal that eGFR had the highest area under the curve(AUC=0.717), while SCr had the lowest AUC(0.556). In conclusion, Serum KIM-1 and CysC levels consider as early biomarker for DKD along with eGFR that consider the best diagnostic indicator of DKD, Additionally, there is a strong correlation between serum CysC and KIM-1 as well as other renal measures that indicate deteriorating kidney function.

Assessment of the relationship between 25-hydroxyvitamin D and albuminuria in type 2 diabetes mellitus

BackgroundDiabetic nephropathy occurs in about one-third of diabetic patients. This health problem is characterized by increased urinary albumin excretion, leading to decreased glomerular filtration rate and renal failure. In this regard, previous investigations have revealed the possibility of a relationship between vitamin D deficiency and diabetic nephropathy. The present study assessed the relationship between vitamin D deficiency and albuminuria in patients with type 2 diabetes.MethodsThis study was conducted with 200 participants with type 2 diabetes mellitus from December 2019 to January 2021. The patients’ 25-hydroxyvitamin D (25OHD) serum level and urinary albumin-to-creatinine ratio (UACR) were measured concurrently. Afterward, the subjects were divided into three groups based on their albuminuria level. Finally, 25OHD serum level and other clinical characteristics were compared among these albuminuria groups, and the relation between albuminuria level and 25OHD was analyzed.ResultsThe prevalence of vitamin D deficiency in macroalbuminuric patients (UACR≥300 mg/g) was 61.8%, and in microalbuminuric (30 ≤ UACR< 300 mg/g) and normoalbuminuric groups (UACR< 30 mg/g) was 33.3% and 24%, respectively. Further analysis revealed a significant negative relationship between 25OHD and albuminuria(r = − 0.257, p-value< 0.001). According to ROC curve analysis, a 25OHD level ≤ 21 ng/ml was considered an optimal cut-off point value for having macroalbuminuria in diabetic patients.ConclusionsThe current study evaluates the relation between vitamin D deficiency and the prevalence of albuminuria in the setting of diabetes. Overall, the prevalence of macroalbuminuria increased when the 25OHD serum level was less than 20 ng/ml.

Podocalyxin as an early marker predicting diabetic nephropathy and its correlation with stages of diabetic nephropathy in type two diabetic patients

Abstract Background Nephropathy, a major complication of diabetes, is the leading cause of end-stage renal disease. Early identification of nephropathy in diabetes patients is crucial because it creates opportunity for preventing the incidence of DN and/or even slows down the process of end-stage renal disease attributed to diabetes. Human podocytes (Pods) have been demonstrated to be functionally and structurally injured in the natural history of diabetic nephropathy. Aim of the Work To evaluate the possible association between the urinary podocalyxin levels and severity and grade of diabetic nephropathy and to use urinary podocalyxin as a non-invasive marker for early stage of diabetic nephropathy in type 2 DM. Patients and Methods We collected 60 known clinically and biochemically type 2 diabetic patients.20 diabetic patients with no evidence of diabetic nephropathy, 20 patients diagnosed as diabetic nephropathy in microalbuminuria stages and 20 patients diagnosed as diabetic nephropathy in macroalbuminuria stages from Ain Shams University hospitals between April and December 2018 and 20 apparently healthy volunteers will included as a control group. Results Urinary PCX was significantly higher in patients group compared to control group. Urinary PCX was significantly higher in microalbuminuric group than in normoalbuminuric group and higher in macroalbuminuric group than in microalbuminuric group. There was a positive significant correlation between FBS, 2HrPP, HBA1C and urinary PCX. There was a positive significant correlation between s.create and urinary PCX. There was a positive significant correlation between ACR and urinary PCX. Conclusion Urinary podocalyxin seems to be beneficial as an early marker for early stages of diabetic nephropathy in type 2 DM patients.

Association of microalbuminuria with left ventricular dysfunction in type 2 diabetes mellitus

BackgroundThe prevalence of diabetes mellitus is on rising trend in developing countries like India. In type 2 diabetes patients, albuminuria has been shown to predict development of dysfunction in other organ systems such as kidneys, nervous system, and retina and increase risk of cardiovascular (CV) morbidity and mortality. In this study, we plan to assess association of microalbuminuria with left ventricular dysfunction in type 2 diabetes mellitus.ResultsThis cross-sectional study was conducted among 100 type 2 diabetes mellitus patients attending a tertiary care hospital in Gujarat, Western India. Based on urine albumin excretion status, they were divided in two groups of 50 each—normoalbuminuric and microalbuminuric patients. The mean FBS, PPBS, and HbA1c level was significantly lower in normoalbuminuric group compared to microalbuminuric group. There was an increase in cholesterol, triglyceride, VLDL, and LDL levels and decrease in HDL levels in microalbuminuric group as compared to normoalbuminuric group. Multivariate logistic regression analysis revealed that increase in age and a decrease in E/A ratio in patients with microalbuminuria was significantly associated with left ventricular diastolic dysfunction (LVDD).ConclusionThe presence of microalbuminuria is associated with increased likelihood of LVDD in type 2 diabetes patients. Increase in age and decrease in E/A ratio show direct and independent association with LVDD in normotensive diabetic patients with microalbuminuria. Therefore, diabetes patients who have microalbuminuria should be regularly (or more frequently) evaluated for development of LVDD using Echocardiography. This can allow early identification of myocardial diastolic dysfunction.

STUDY OF MICROALBUMINURIA IN PATIENTS WITH NORMOGLYCEMIC HYPERTENSION

INTRODUCTION:Hypertension is one of the most important risk factors for cardiovascular disease. The incidence of microalbuminuria is more common among hypertensive patients, even in nondiabetic patients. Microalbuminuria is an independent predictor of cardiovascular morbidity and mortality in patients with essential hypertension. Therefore, current guidelines recommend routine screening of microalbuminuria in hypertensive patients to ensure appropriate interventions are initiated early in the disease process before progression to chronic kidney disease and/or renal failure. AIMS &amp; OBJECTIVES:This study is done to estimate the prevalence of microalbuminuria in patients with normoglycemic hypertension and to identify other variables associated with it. MATERIAL &amp; METHODS:In this study, we randomly selected 100 patients with essential hypertension based on inclusion and exclusion criteria. CBC, renal function test, 24-hour urine albumin excretion (UAE), Body mass index (BMI), and arterial blood pressure measurement were done among all selected patients. Data entry was done in Microsoft Ofce Excel and analysis was done using the software package Epi Info (Version 7.1.5) from CDC, Atlanta, U.S.A. OBSERVATIONS &amp; RESULTS: The study was conducted among 100 hypertensive patients out of which 74 were male and 24 were female. Out of 100 patients, microalbuminuria was present in 44 patients. Mean arterial pressure was found high among patients with microalbuminuria than patients without microalbuminuria. The presence of microalbumin in urine was found to increase with the increasing severity of hypertension. Mean body mass index and serum creatinine were found higher in the microalbuminuric group than the normoalbuminuric group. CONCLUSION:The incidence of microalbuminuria is more common among hypertensive patients, even in nondiabetic patients. The presence of microalbuminuria is an independent predictor of cardiovascular morbidity and mortality in patients with essential hypertension. Screening for microalbuminuria is a relatively simple process, should facilitate early vascular disease detection.

Serum irisin level and its relation to diabetic nephropathy in patients with type 2 diabetes mellitus

Background Irisin is an adipo-myokine, which has broad implications for metabolism and energy homeostasis. However, evidence about its association with diabetic nephropathy (DN) is limited. Aim To evaluate serum irisin level and its relation to DN in patients with type 2 diabetes. Patients and methods This case–control study was conducted on 60 patients with type 2 diabetes and 30 healthy age-matched and sex-matched individuals. Patients were divided into three groups according to urinary albumin–creatinine ratio (ACR), namely, normoalbuminuric group, which included 15 patients; microalbuminuric group, which included 30 patients; and macroalbuminuric group, which included 15 patients. Detailed history, clinical examination, and anthropometric measurements were assessed for all participants. Fasting blood glucose and 2-h postprandial blood glucose, total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, urea, creatinine, uric acid, estimated glomerular filtration rate, and irisin were measured for all participants. Glycosylated hemoglobin and urinary ACR were measured for patients only. Results Irisin was significantly lower in diabetic groups compared with controls. Irisin was positively correlated with estimated glomerular filtration rate but negatively correlated with fasting blood glucose, creatinine, and ACR. Multivariable regression analysis revealed that lower irisin level was considered as an independent predictor for DN. Conclusion Serum irisin is significantly related to diabetic kidney disease, and it might be progressively decreasing with development of the different stages of DN.

Blood pressure variability in diabetic patients with or without albuminuria

Introduction: Various studies considered albuminuria as one of the first asymptomatic paraclinical manifestation of the micro-vascular damages in type 2 diabetes mellitus (DM). Hypertension (HTN) is common in type 2 DM, which has a correlation with the greater risks of cardiovascular morbidity and death. Objectives: The present research evaluated the relationship between blood pressure (BP) variability in diabetic patients who have or not albuminuria. Patients and Methods: In this analytical-descriptive research, we divided 90 type 2 diabetic patients into two groups of micro-albuminuric (urinary albumin excretion ≥30 mg/d and &lt;300 mg/d) and the normo-albuminuric (urinary albumin excretion &lt;30 mg/d) diabetic patients. We evaluated systolic and diastolic BP and 24-hour Holter monitor BP and heart rate, with respect to their albuminuric states and glomerular filtration rate (GFR) stages. Results: According to the findings, a considerably greater BMI (body mass index) and retinopathy was observed in microalbuminuric group in comparison with the normoalbuminuric group (P&lt;0.05). Additionally, non-dipping pattern was greater in the microalbuminuric patients (P&lt;0.05). In addition, patients were divided into dippers and non-dippers, the mean daytime and nighttime BP and heart rate were compared. Mean arterial BP (MAP) and nighttime BP and substantially in the subgroup of patients with GFR below 60 mL/min, systolic blood pressure (SBP) were considerably greater in the micro-albuminuric patients (P&lt;0.05). Conclusion: In patients with diabetes, the existence of albuminuria is related to the increase in the incidence of non-dipping pattern compared with patients without albuminuria. According to high levels of SBP in albuminuric patients with low GFR, the pattern of HTN and then albuminuria and the subsequent reduction of renal function can be similar to that of type 1 DM patients. Moreover, 24-hour Holter monitoring and BP should be monitored closely in diabetic patients.

Study of The Podocalyxin as An Early Marker for Diabetic Nephropathy and Its Correlation with Stages of Diabetic Nephropathy in A Sample of Egyptian Patients with T2DM

Background: Nephropathy is a major complication of diabetes, and is the main cause of end-stage kidney disease. Early recognition of nephropathy in diabetic patients is critical because it creates an opportunity to prevent the occurrence of diabetic nephropathy and/or even slow down the process of end-stage kidney disease attributable to diabetes. Human cells; podocytes (pods) have been shown to be functionally and structurally affected in the natural history of diabetic nephropathy. Objective: Study of the podocalyxin as an early marker for diabetic nephropathy and its correlation with stages of diabetic nephropathy in a sample of Egyptian patients with type 2 diabetes mellitus (T2DM). Patients and Methods:This study was a cross sectional study conducted on 80 subjects divided into four groups: Group 1: 20 diabetic patients with normalbuminuria. Group 2: 20 diabetic patients with nephropathy and microalbuminuria stages. Group 3: 20 diabetic patients with nephropathy and macroalbuminuria stages, Group 4:20 apparently healthy volunteers were included as a control group. Results: Urinary podocalyxin (PCX) was significantly higher in patients group compared to control group. Urinary PCX was significantly higher in macroalbuminuric group followed by microalbuminuric group then normoalbuminuric group. There was a positive significant correlation between urinary PCX and glycemic profile [Fasting blood sugar (FBS), 2hrPP, Glycosylated Hemoglobin (HbA1C)], serum creatinine and albumin creatinine ratio (ACR). Conclusion: Urinary podocalyxin is a beneficial as an early marker for early stages of diabetic nephropathy in type 2 DM patients.

Study of The Podocalyxin as An Early Marker for Diabetic Nephropathy and Its Correlation with Stages of Diabetic Nephropathy in A Sample of Egyptian Patients with T2DM

Background: Nephropathy is a major complication of diabetes, and is the main cause of end-stage kidney disease. Early recognition of nephropathy in diabetic patients is critical because it creates an opportunity to prevent the occurrence of diabetic nephropathy and/or even slow down the process of end-stage kidney disease attributable to diabetes. Human cells; podocytes (pods) have been shown to be functionally and structurally affected in the natural history of diabetic nephropathy. Objective: Study of the podocalyxin as an early marker for diabetic nephropathy and its correlation with stages of diabetic nephropathy in a sample of Egyptian patients with type 2 diabetes mellitus (T2DM). Patients and Methods:This study was a cross sectional study conducted on 80 subjects divided into four groups: Group 1: 20 diabetic patients with normalbuminuria. Group 2: 20 diabetic patients with nephropathy and microalbuminuria stages. Group 3: 20 diabetic patients with nephropathy and macroalbuminuria stages, Group 4:20 apparently healthy volunteers were included as a control group. Results: Urinary podocalyxin (PCX) was significantly higher in patients group compared to control group. Urinary PCX was significantly higher in macroalbuminuric group followed by microalbuminuric group then normoalbuminuric group. There was a positive significant correlation between urinary PCX and glycemic profile [Fasting blood sugar (FBS), 2hrPP, Glycosylated Hemoglobin (HbA1C)], serum creatinine and albumin creatinine ratio (ACR). Conclusion: Urinary podocalyxin is a beneficial as an early marker for early stages of diabetic nephropathy in type 2 DM patients.

Assessment of Serum (YKL-40) As an Early Diagnostic Marker of Diabetic Nephropathy in Patients with Type 2 Diabetes Mellitus

Background: YKL-40 is an inflammatory marker, a positive association between elevated circulating YKL-40 levels and increasing levels of albuminuria, which have been described in patients with type 1 and type 2 diabetes indicating a role of YKL-40 in the progressing vascular damage resulting in microvascular disease. Objectives: To assess serum YKL-40 as an early diagnostic marker of diabetic nephropathy in type 2 diabetes mellitus. Patients and Methods: 70 patients with type 2 diabetes mellitus (46 males and 24 females) were included in this study, another 19 healthy volunteers (12 males and 7 females) were chosen as a control group (group I). Patients were further classified according to their Albumin/creatinine ratio into three groups: group II; Diabetic normoalbuminuric, group III; Diabetic microalbuminuric and group IV; Diabetic macroalbuminuric. All subjects (patients and controls) participating in the study were subjected to full history and clinical examination and routine laboratory investigations and also specific laboratory investigations include glycated hemoglobin (HbA1c), urine creatinine, microalbumin, albumin creatinine ratio, and serum YKL 40. Results: The present study showed that serum YKL-40 significantly increased in diabetic patients than in the control group. In addition, there was a significant increase of YKL-40 in the macroalbuminuric group compared to the normoalbuminuric group and microalbuminuric group and a significant increase of YKL-40 in a microalbuminuric group compared to the normoalbuminuric group. Conclusion: The serum levels of YKL-40 in type 2 DM were significantly higher than in normal patients, and its level increased with increasing urinary albumin excretion rate.

Diabetic microvascular complications associated with myocardial repolarization heterogeneity evaluated by Tp-e interval and Tp-e/QTc ratio

IntroductionThe heterogeneity in myocardial repolarization increases the risk of ventricular arrhythmias and sudden death in patients with diabetes mellitus (DM). The Tp-e interval and Tp-e/QTc ratio are found to be useful in the prediction of ventricular arrhythmias. In this study, we aimed to investigate the Tp-e interval and Tp-e/QTc ratio in diabetic patients with and without microvascular complications. Materials and methodsThis cross-sectional observational study included patients with type 2 DM who presented to the endocrinology outpatient clinic. Diabetic microvascular complications were evaluated. The Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio were also calculated. ResultsA total of 240 patients with type 2 DM (148 patients had microvascular complications) were included in the study. Diabetic neuropathy rate was 30.4%, diabetic nephropathy rate was 38.4%, and diabetic retinopathy rate was 21.7%. Upon comparing patients according to Tp-e/QTc ratio, the median Tp-e/QTc interval of the group of patients with complications was 0.21 (0.19–0.23) and the median Tp-e/QTc ratio of the group of patients without complications was 0.19 (0.18–0.20) (p < 0.001). When patients were grouped according to the presence and severity of retinopathy, the Tp-e/QTc ratio was more prolonged in the proliferative retinopathy group [0.27 (0.23–0.30)] than the non-proliferative retinopathy group [0.20 (0.19–0.22), p < 0.001]. When patients were grouped according to the presence and severity of nephropathy, the Tp-e/QTc ratio was more prolonged in the macroalbuminuria and microalbuminuria group than the normoalbuminuric group [0.25 (0.21–0.30), 0.23 (0.19–0.24), and 0.19 (0.20–0.22), respectively, p = 0.002]. ConclusionsOur study is the first to demonstrate the association of the Tp-e interval and Tp-e/QTc ratio with the presence and severity of microvascular complications in patients with type 2 DM.

Pentraxin-3 and adropin as inflammatory markers of early renal damage in type 2 diabetes patients.

Renal inflammatory response is involved in the development and progression of diabetic kidney disease (DKD). We sought to evaluate pentraxin-3 (PTX3) and adropin variability as inflammatory markers among type 2 diabetes mellitus (T2DM) patients with different urinary albumin, and to examine if these factors assist in the early diagnosis of diabetic kidney disease. We enrolled 447 T2DM patients and 100 healthy non-diabetic control subjects in this study. The patients with T2DM were divided into three groups based on their urinary albumin/creatinine ratio (UACR): the normoalbuminuric group (DM group, UACR < 30mg/g); the microalbuminuric group (DKD1 group, 30 ≤ UACR ≤ 300mg/g); the macroalbuminuric group (DKD2 group, UACR > 300mg/g). The levels of PTX3 and adropin were determined by enzyme-linked immunosorbent assay (ELISA). Spearman correlation and multiple linear regression analysis were performed to determine the correlations among these inflammatory markers and other clinical parameters. Receiver operating characteristic (ROC) curves analysis was used to assess the diagnostic potential of PTX3 and adropin for DKD. Compared to non-diabetes, serum levels of PTX3 were distinctly elevated, whereas the adropin were significantly declined in diabetic patients (p < 0.05). Significantly higher levels of PTX3 and lower levels of adropin were seen in the macroalbuminuric patients compared with the microalbuminuric patients (p < 0.05). Multiple stepwise linear regression analysis showed that the control of hemoglobin A1c (HbA1c) and UACR were independent factors associated with PTX3 and adropin. In addition, ROC curves analysis showed PTX3 and adropin could be used to evaluate the early detect of DKD, further adropin might be a better marker than PTX3 in compliance with their veracity. As inflammatory markers, the diverse changes of pentraxin-3 and adropin showed that they may forecast the renal damage in diabetic patients in varying degrees and link with the pathogenesis of diabetic kidney disease.

Evaluation of early biomarkers of renal dysfunction in diabetic patients.

Objectives:To evaluate 2 renal tubular enzymes; urinary neutrophil gelatinase-associated lipocalin (uNGAL), and urinary N-acetyl-beta-D-glucosaminidase (uNAG), and serum Cystatin C as candidate biomarkers for early diagnosis of early stage of diabetic nephropathy (DB) in patients with type 2 diabetes mellitus (T2DM).Methods:This cross-sectional study was carried out at King Abdulaziz University Hospital (KAUH), Jeddah, Saudi Arabia during the period between May 2017 and May 2018 and was conducted on 86 patients with T2DM. Patients were classified according to their albumin/creatinine ratio (ACR) into 3 groups; a normal albuminuria group with ACR <30 mg/g creatinine, a moderately increased albuminuria group with ACR: 30-299 mg/g creatinine, and a severely increased albuminuria group with ACR ≥300 mg/g. Healthy adults were recruited as a control group. Urine uNGAL, uNAG, and serum Cystatin C were measured in all patients.Results:Compared with healthy control, diabetic patients with normal albuminuria excreted significantly higher levels of uNGAL (p<0.001). In addition, significantly elevated uNGAL, uNAG and cystatin C levels were observed in moderately increased albuminuria and severely increased albuminuria groups when compared to the control and normoalbuminuric groups (p<0.001). urinary neutrophil gelatinase-associated lipocalin, urinary N-acetyl-beta-D-glucosaminidase and Cystatin C showed a positive correlation with fasting blood glucose (FBG), HbA1c, duration of diabetes, urea, creatinine, and ACR.Conclusion:Our results indicated that uNGAL could be a sensitive biomarker for early renal dysfunction in diabetic patients while uNAG and serum Cystatin C might have prognostic value.

Urinary Cyclophilin A and serum Cystatin C as biomarkers for diabetic nephropathy in children with type 1 diabetes

Currently, microalbuminuria is the gold standard for detection and prediction of diabetic nephropathy (DN). However, microalbuminuria appears once significant kidney damage has actually occurred. We investigated the diagnostic role of urinary Cyclophilin-A (uCypA), uCypA/creatinine ratio (uCypA/Cr) and serum Cystatin-C (sCysC) as biomarkers for early detection of DN in children with type 1 diabetes mellitus (T1DM) of short duration (2-5 years) before microalbuminuria emerges. uCypA, uCypA/Cr, and sCysC levels were assessed in three age- and sex-matched groups; microalbuminuric diabetic group (n = 31), normoalbuminuric diabetic group (n = 29), and control group (n = 30). Glomerular filtration rate was estimated (eGFR) based on both serum creatinine (eGFR-Cr) and sCysC (eGFR-CysC). Significantly higher sCysC and lower eGFR-CysC were detected in both diabetic groups compared to controls and in microalbuminuric compared to normoalbuminuric group. No detected significant difference in eGFR-Cr values across the studied groups. Both uCypA and uCypA/Cr were significantly elevated in microalbuminuric compared to both normoalbuminuric and control groups with no difference between normoalbuminuric and control groups. Prediction of microalbuminuria was conducted using sCysC with area under curve up to 0.980. Combined use of sCysC and uCypA had better diagnostic value than uCypA alone. sCysC is a promising early biomarker for DN in childhood T1DM before albuminuria detection. eGFR-CysC is superior to eGFR-Cr in evaluating renal status in childhood T1DM. uCypA and uCypA/Cr were useful tools in predicting microalbuminuria, although not regarded as diagnostic biomarkers for early-stage DN in T1DM children by the current study.

Related factors for microalbuminuria in adult type 1 diabetes patients of short disease duration

Objective: To investigate related factors for microalbuminuria in adult type 1 diabetes (T1D) patients of short disease duration (less than 5 years), and provide evidence for prevention of early diabetic kidney disease in this population. Methods: All adult patients enrolled in the Guangdong T1D translational medicine study between 2011 and 2017 with a disease duration of less than 5 years were included in this analysis. At enrollment, patients' demographic and clinical data were documented, and blood and urine samples were collected for the measurements of blood lipids, glycated hemoglobin A1c and urine albuminuria. Insulin resistance was evaluated by estimated glucose disposal rate (eGDR). Patients were categorized into groups based on urine albumin creatitine ratio (UACR): normoalbuminuric group (UACR<30 mg/g) and microalbuminuric group (UACR≥30 mg/g). Stepwise multivariate linear regression analysis was used to analyze risk factors for microalbuminuria in adult T1D patients of short disease duration. Results: A total of 384 patients were included in this analysis, and 51.3% (197/384) of which was female. The onset age of patients was (24.6±12.5) years, with a disease duration of 2.1(0.6, 3.5) years, body mass index of (19.8±3.2) kg/m(2), waist hip ratio of 0.85±0.21, and glycated hemoglobin A1c of (9.8±3.3)% at enrollment. Microalbuminuria occurred in 62 patients (16.1%). Multivariate linear analysis showed that higher glycated hemoglobin A1c, higher systolic blood pressure and more severe insulin resistance were related factors for microalbuminuria (t=2.322, 2.868 and -2.373, respectively, all P<0.05). Conclusions: Microalbuminuria was not rare in adult T1D patients of short disease duration. Inadequate glycemic control and insulin resistance were independent related factors for microalbuminuria in this population.

Changes of Plasma and Urine hsa-miR-223-3p Was Correlated with the Severity in Different Stages of Diabetes Kidney Disease of Type 2 Diabetes Patients in China

We have previously shown that hsa-miR-223-3p can be as a candidate novel biomarker performing important roles in Diabetes Kidney Disease (DKD) disease process,resulted from co-expression analysis from miRNA (Agilent chips) and lncRNAs (Affymetrix HTA2.0 chips) in plasma.This study involved into 90 patients with type 2 diabetes mellitus (T2DM) and normal control (n=28). Then we divided these diabetes patients into Normoalbuminuric groups(DM) (n=30), Microoalbuminuric group (Micro-DKD) (n=30) and Macroalbuminuric group (Macro-DKD) (n=30), according to urinary albumin to creatinine ratio (ACR) levels (&amp;lt;30mg/g; 30-300mg/g; &amp;gt;300mg/g). The clinical data and biochemical indexes of all the subjects were collected. Real-time qPCR to detect miR-223-3p expression of plasma and urine were reported and compared by using the one-way ANOVA. Statistical analysis was performed using SPSS version 23 software. Receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC) were used to estimate the diagnostic value of the candidate miRs. Compared with controls, the expression of miR-223-3p in plasma were decreased significantly from DM,Micro-DKD to Macro-DKD groups (P &amp;lt;0.001), and the decline was gradually accompanied with the progression of DKD (P &amp;lt;0.001). Same decline pattern was observed in urine expression among four groups, however discrimination was not significant due to the limited patients enrollment in the study. The ROC curve showed that the level of miR-223-3p in plasma can be distinguished among Micro-DKD, Macro-DKD with controls [AUC = 0.750, 95% CI = 0.569-0.923, p = 0.009; AUC = 0.998, 95% CI =0.992-1.000, p = 0.000]. Therefore, plasma hsa-miR-223-3p is a novel biomarker for the severity in Different Stages of DKD in China. Disclosure J. He: None. R. Li: None. L. Li: None. Y. Wu: None. Q. Yang: None. L. Zhang: None.