Triglyceride-glucose index: A surrogate marker of homeostasis model assessment of insulin resistance to predict diabetic nephropathy.

Objectives: To determine the association of triglyceride-glucose index with homeostasis model assessment of insulin resistance in type 2 diabetes mellitus patients, and to determine the association of triglyceride-glucose index with urinary albumin-to-creatinine ratio for predicting diabetic nephropathy. METHODS: The observational, cross-sectional study was conducted from September 2021 to September 2022 at the Department of Chemical Pathology, Pakistan Railway Hospital, Rawalpindi, Pakistan and comprised recently-diagnosed type 2 diabetes mellitus patients. Recorded data included age, gender, vitals, diabetes duration, body mass index and other pertinent demographic and clinical information. Measurements included spot urine albumin-to-creatinine ratio, triglycerideglucose index, homeostasis model assesment of insulin resistance as well as fasting serum insulin, fasting plasma glucose, glycosylated haemoglobin, triglycerides, total cholesterol and serum creatinine. On the basis of triglyceride-glucose index scores, the participants were divided into 4 quartiles; Q1=4.5-5, Q2=5.1-5.5, Q3=5.6-6, and Q4=>6. Data was analysed using SPSS 26. RESULTS: Of the 218 patients, 141(64.7%) were females and 77(35.3%) were males. The overall mean age was 49.22±11.46 years. There were 102(46.8%) overweight patients, 33(15.1%) obese and 82(37.2%) had normal weight. There were 58(26.6%) patients in Q1, 86(39.4%) in Q2, 46(21.1%) in Q3 and 28(12.8%) in Q4. Those in Q4 showed elevated fasting plasma glucose, glycated haemoglobin, triglycerides, total cholesterol, low-density lipoprotein cholesterol, homeostasis model assessment of insulin resistance and urine albumin-to-creatinine ratio (p<0.05), as well as low values for high-density lipoprotein cholesterol and estimated glomerular filtration rate(p<0.05). Fasting serum insulin was negatively linked to glycated haemoglobin (r=-0.12, p=0.07). Triglyceride-glucose index (r=0.76, p<0.001), homeostasis model assessment of insulin resistance (r=0.48, p<0.001), and urine albumin-to-creatinine ratio (r=0.10,p=0.05) positively correlated with glycated haemoglobin. Fasting serum insulin (r=-0.13, p=0.05), negatively correlated with triglyceride-glucose index, while homeostasis model assessment of insulin resistance (r= 0.32, p<0.001) and urine albumin-to-creatinine ratio (r=0.28, p=0.05) had a positive correlation. The estimated glomerular filtration rate was significantly positively linked with fasting serum insulin (r=0.05, p=0.05), and correlated significantly negatively with triglyceride-glucose index (r=-0.35, p=0.01), homeostasis model assessment of insulin resistance (r=-0.01, p=0.86) and urine albumin-to-creatinine ratio (r=-0.02, p=0.8). CONCLUSIONS: The triglyceride-glucose index showed a strong association with homeostasis model assessment of insulin resistance, and surpassed it in terms of predicting diabetic nephropathy in type 2 diabetes mellitus patients.

A candidate panel of eight urinary proteins shows potential of early diagnosis and risk assessment for diabetic kidney disease in type 1 diabetes.

Diabetic kidney disease (DKD) poses a significant health challenge for individuals with diabetes. At its initial stages, DKD often presents asymptomatically, and the standard for non-invasive diagnosis, the albumin-creatinine ratio (ACR), employs discrete categorizations (normal, microalbuminuria, macroalbuminuria) with limitations in sensitivity and specificity across diverse population cohorts. Single biomarker reliance further restricts the predictive value in clinical settings. Given the escalating prevalence of diabetes, our study uses proteomic technologies to identify novel urinary proteins as supplementary DKD biomarkers. A total of 158 T1D subjects provided urine samples, with 28 (15 DKD; 13 non-DKD) used in the discovery stage and 131 (45 DKD; 40 pDKD; 46 non-DKD) used in the confirmation. We identified eight proteins (A1BG, AMBP, AZGP1, BTD, RBP4, ORM2, GM2A, and PGCP), all of which demonstrated excellent area-under-the-curve (AUC) values (0.959 to 0.995) in distinguishing DKD from non-DKD. Furthermore, this multi-marker panel successfully segregated the most ambiguous group (microalbuminuria) into three distinct clusters, with 80% of subjects aligning either as DKD or non-DKD. The remaining 20% exhibited continued uncertainty. Overall, the use of these candidate urinary proteins allowed for the better classification of DKD and offered potential for significant improvements in the early identification of DKD in T1D populations.

Resting energy expenditure based on equation estimation can predict renal outcomes in patients with type 2 diabetes mellitus and biopsy-proven diabetic kidney disease.

AIMS: The aim of this study was to investigate the relationship between resting energy expenditure (REE) based on equation estimation and renal outcomes in patients with diabetes kidney disease (DKD). METHODS: A total of 124 patients were enrolled from a retrospective cohort of Type 2 Diabetes mellitus (T2DM) patients with biopsy-proven DKD. Renal outcome defined as End-Stage Renal Disease (ESRD). To compare the predictive ability of different REE estimation equations on ESRD. Patients' REE was assessed according to the estimating equation with the best predictive power, and then the relationship between REE and ESRD risk was fitted using a restricted cubic spline curve (RCS) plot and REE cutoff values were obtained. Grouping using cutoff values, and ultimately evaluate the relationship between REE and the risk of ESRD using a Multivariate Cox regression model. RESULTS: The strongest predictive validity for renal outcomes was the NDCKD-equation. The patients were divided into the higher-REE group (n = 78) and the lower-REE group (n = 46), based on the cutoff value. During the follow-up, 30 of 124 patients (24.2%) proceeded to ESRD. Multivariate Cox regression models showed that the risk of ESRD in patients with lower REE was 6.08 times increased compared with that in those with higher REE (HR = 6.08; 95% CI, 1.28-28.80, p = 0.023). CONCLUSION: These findings suggested that the lower REE was an independent risk factor for unfavorable renal outcomes in patients with DKD.

Derivation and independent validation of kidneyintelX.dkd: A prognostic test for the assessment of diabetic kidney disease progression.

AIMS: To develop and validate an updated version of KidneyIntelX (kidneyintelX.dkd) to stratify patients for risk of progression of diabetic kidney disease (DKD) stages 1 to 3, to simplify the test for clinical adoption and support an application to the US Food and Drug Administration regulatory pathway. METHODS: We used plasma biomarkers and clinical data from the Penn Medicine Biobank (PMBB) for training, and independent cohorts (BioMe and CANVAS) for validation. The primary outcome was progressive decline in kidney function (PDKF), defined by a ≥40% sustained decline in estimated glomerular filtration rate or end-stage kidney disease within 5 years of follow-up. RESULTS: In 573 PMBB participants with DKD, 15.4% experienced PDKF over a median of 3.7 years. We trained a random forest model using biomarkers and clinical variables. Among 657 BioMe participants and 1197 CANVAS participants, 11.7% and 7.5%, respectively, experienced PDKF. Based on training cut-offs, 57%, 35% and 8% of BioMe participants, and 56%, 38% and 6% of CANVAS participants were classified as having low-, moderate- and high-risk levels, respectively. The cumulative incidence at these risk levels was 5.9%, 21.2% and 66.9% in BioMe and 6.7%, 13.1% and 59.6% in CANVAS. After clinical risk factor adjustment, the adjusted hazard ratios were 7.7 (95% confidence interval [CI] 3.0-19.6) and 3.7 (95% CI 2.0-6.8) in BioMe, and 5.4 (95% CI 2.5-11.9) and 2.3 (95% CI 1.4-3.9) in CANVAS, for high- versus low-risk and moderate- versus low-risk levels, respectively. CONCLUSIONS: Using two independent cohorts and a clinical trial population, we validated an updated KidneyIntelX test (named kidneyintelX.dkd), which significantly enhanced risk stratification in patients with DKD for PDKF, independently from known risk factors for progression.

In situ assessment of Mindin as a biomarker of podocyte lesions in diabetic nephropathy.

Diabetic nephropathy (DN) is the leading cause of chronic kidney disease and end-stage renal failure worldwide. Several mechanisms are involved in the pathogenesis of this disease, which culminate in morphological changes such as podocyte injury. Despite the complex diagnosis and pathogenesis, limited attempts have been made to establish new biomarkers for DN. The higher concentration of Mindin protein in the urine of patients with type 2 diabetes mellitus suggests that it plays a role in DN. Therefore, this study investigated whether in situ protein expression of Mindin can be considered a potential DN biomarker. Fifty renal biopsies from patients diagnosed with DN, 57 with nondiabetic glomerular diseases, including 17 with focal segmental glomerulosclerosis (FSGS), 14 with minimal lesion disease (MLD) and 27 with immunoglobulin A nephropathy (IgAN), and 23 adult kidney samples from autopsies (control group) were evaluated for Mindin expression by immunohistochemistry. Podocyte density was inferred by Wilms' tumor 1 (WT1) immunostaining, while foot process effacement was assessed by transmission electron microscopy. Receiver operative characteristic (ROC) analysis was performed to determine the biomarker sensitivity/specificity. Low podocyte density and increased Mindin expression were observed in all cases of DN, regardless of their class. In the DN group, Mindin expression was significantly higher than that in the FSGS, MCD, IgAN and control groups. Higher Mindin expression was significantly positively correlated with foot process effacement only in class III DN cases. Furthermore, Mindin protein presented high specificity in the biopsies of patients with DN (p < 0.0001). Our data suggest that Mindin may play a role in DN pathogenesis and is a promising biomarker of podocyte lesions.

Assessment of microvascular function using a novel technique Flow Mediated Skin Fluorescence (FMSF) in patients with diabetic kidney disease: A preliminary study.

BACKGROUND: Diabetic kidney disease (DKD) plays an important role in morbidity and mortality in patients with diabetes mellitus. The pathogenesis of this microangiopathy is mainly due to impaired vascular endothelial function. The Flow Mediated Skin Fluorescence (FMSF) method is an innovative, non-invasive tool for assessing the microcirculation function (especially microcirculatory response to hypoxia), also in patients with complications of diabetes mellitus (DM). MATERIAL AND METHODS: The study was conducted at the Medical University of Lodz, Poland. Total of 84 volunteers including 30 patients with DKD, 33 patients with DM without complications, and 21 healthy subjects underwent microvascular function assessments using FMSF. This technique measures changes in the intensity of nicotinamide adenine dinucleotide (NADH) fluorescence from the skin on the forearm as a function of time, in response to blocking and releasing blood flow in the forearm. In this study we asses two key parameters: Reactive Hyperemia Response (RHR) and Hypoxia Sensitivity [log(HS)] to characterize vascular circulation in patients with DKD and their response to transient ischemia. RESULTS: The patients with low reactive hyperemic response (the RHR parameter) had a significantly higher sCr than patients with moderate and high RHR value (p < 0.001, p < 0.05, respectively) and a significantly lower eGFR than the patients with moderate and high RHR parameter (p < 0.001, p < 0.01, respectively). The patients with very low and low log(HS) values had a significantly higher sCr than the patients with high log(HS) (p < 0.001, p < 0.01, respectively), and a significantly lower eGFR than the patients with high log(HS) parameter (p < 0.001, p < 0.01, respectively). The patients with very low log(HS) had a significantly higher sCr and a significantly lower eGFR than the patients with moderate (p < 0.05, p < 0.01, respectively). The mean value of the RHR parameter was significantly lower in DKD patients (18.31 ± 5.06 %) compared to both healthy subjects (34.37 ± 8.18 %, p < 0.001) and DM without complications subgroup (28.75 ± 7.12 %, p < 0.001). Similar trends were noted with the mean value of log(HS) parameter in DKD subgroup (1.03 ± 0.5) vs. healthy subjects (1.59 ± 0.53, p < 0.001), and vs. DM without complications subgroup (1.73 ± 0.52, p < 0.001). We observed a significant inverse correlation between the RHR parameter and serum creatinine (sCr) and a significant positive correlations with eGFR (R =  -0.3; p < 0.05, R = 0.61; p < 0.001, respectively). We found also a significant negative correlations of the log(HS) measure with sCr and a significant positive correlations with eGFR (R = -0.33; p < 0.01, R = 0.55; p < 0.001, respectively). We observed also a significant inverse correlation between the RHR and log(HS) parameters and advanced glycation end products (AGEs) (R = -0.6; p < 0.001, R = -0.32; p < 0.01, respectively). The AGEs parameter was also a significantly higher in patients with low RHR parameter than in patients with moderate (p < 0.01) and high (p < 0.001). CONCLUSIONS: The FMSF technique makes it possible to identify impairments of the microvascular function in patients with DKD. This study confirms that the simple two-parametric approach diagnostic tool perfectly characterizes the state of the microvascular system in diabetic patients with impaired renal function. These preliminary results require further validation in a larger patients cohort.

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

BACKGROUND: Diabetic 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. METHODS: This 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. RESULTS: The 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. CONCLUSIONS: The 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.

Resistivity index in the diagnosis and assessment of loss of renal function in diabetic nephropathy.

OBJECTIVE: The aim of this study was to determine the haemodynamics of the intrarenal arteries from the relationship between resistivity index (RI) and kidney function, and to identify the predictors of high RI among patients with diabetic nephropathy (DN) and those with diabetes mellitus (DM) without DN. METHODS: This was a cross-sectional survey of 133 participants, comprising 40 subjects with DM without DN, 53 with DM with DN and 40 healthy controls. Information obtained was demographics, lifestyle, medical and medication histories, while anthropometric and blood pressure measurements were taken. Albuminuria and estimated glomerular filtration rate were determined and RI was measured using a Doppler ultrasound scan. RESULTS: The mean intrarenal artery RIs were higher among the patients with DM without DN (0.60 ± 0.04) and the group with DM with DN (0.61 ± 0.04) than in the controls (0.56 ± 0.04) (p = 0.02). Glycated haemoglobin (HbA1c) predicted high RI in the DM without DN group (OR 2.81; CI: 1.73-9.03) while hypertension (OR 3.60; CI: 1.06-12.22) predicted high RI in the DM with DN group. CONCLUSIONS: Elevated intrarenal artery RI was prevalent among patients with DM without DN and those with DM with DN, while elevated HbA1c level and hypertension predicted elevated RI in subjects with DM without DN and those with DM with DN.

Assessment of Serum and Urine Neurophil Gelatinase- Associated Lipocalin (s-NGAL and u-NGAL) Level as a Predictive Factor of Disease Progression in Diabetic Nephropathy in Type 2 DM.

INTRODUCTION: Diabetic nephropathy (DN) is a major complication of diabetes Mellitus. Early detection and intervention of DN can slow its progression and improve patients' outcomes. Neutrophil gelatinase-associated lipocalin (NGAL) as a marker of tubular damage might become a useful biomarker for the evaluation of renal involvement in diabetic patients. We aimed to evaluate the serum and urine NGAL(s-NGAL and u-NGAL) in type 2 diabetic patients and its correlation with different stages of diabetic nephropathy. METHODS: This cross-sectional study was designed on 198 subjects consisted of 50 controls and 148 type 2 diabetes patients (50 normoalbuminuric, 58 microalbuminuric, and 40 macroalbuminuric). The study was conducted with measuring s-NGAL and u-NGAL, albumin and spot urine creatinine were also measured. RESULTS: A highly increased level of s-NGAL was detected in macroalbuminuric group compared with controls, normoalbuminurics and microalbuminurics (P < .01). Highly raised u-NGAL levels were observed in macroalbuminurics in comparison with controls (P < .01). ROC curve demonstrated the best sensitivity and specificity of s-NGAL/u-NGAL for the macroalbuminuric state (sensitivity, 26% and 60%; specificity, 98% and 72%; respectively), in which the best cut-off points for the detection of macroalbuminuric state for s-NGAL/u-NGAL were 300 ng/mL and 71.4 ng/mL, respectively. CONCLUSION: Serum and urine-NGAL are elevated in type 2 diabetic patients, with or without albuminuria, s-NGAL level clearly correlates with severity of renal damage caused by DN and u-NGAL increases in macroalbuminuric state. S-NGAL could be a useful, noninvasive, available and practical test for evaluation of diabetic renal involvement. We could suggest u-NGAL as a probable predictor of macroalbuminuria.

Comparison of the Diagnostic Relevance of Albumin Creatinine Ratio Versus Cystatin C in Assessment of Cardiovascular Complication in Type 2 Diabetics.

BACKGROUND: In a bid to reduce cardiovascular complication(s), surrogate markers such asAlbumin-creatinine ratio and Cystatin C (Cys-C) are being evaluated in order to enhance early management of cardiovascular complications of diabetes mellitus. AIM: Evaluation of the diagnostic relevance of Cystatin- C versusAlbumin-creatinine ratio in assessment of cardiovascular complications (CVC). METHODS: One hundred and two type 2 diabetic patients and 100 control subjects of same age range were recruited for this study. These were further classified according to cardiovascular complications. Cystatin-C, Microalbuminuria, serum creatinine, HBA1c and HBA1c were analysed with standard methods. RESULTS: The mean concentrations of Cys-C, Microalbuminuria and Albumin-creatinine ratio showed significant increase (p<0.05) in those with cardiovascular complication compared to those without cardiovascular complication. The ROC (receiver operator curve) showed thatAlbumin-creatinine ratio (ACR) had significant sensitivity to cardiovascular complication while Cystatin-C showed no significant sensitivity to cardiovascular complications. Logistic binary regression shows a significant association of ACR with cardiovascular complications unlike Cys-C which showed no significant association (p<0.05). CONCLUSION: Cys-C and Albumin-Creatinine ratio increased in diabetics and further deranges with cardiovascular complications. However, Albumin-creatinine ratio showed more diagnostic sensitivity to cardiovascular complications compared to cystatin-C.

CONTEXTE: Dans le but de réduire les complications cardiovasculaires, des marqueurs de substitution tels que le rapport albumine-créatinine et la cystatine C (Cys-C) sont en cours d'évaluation afin d'améliorer la prise en charge précoce des complications cardiovasculaires du diabète sucré. BUT: Évaluation de la pertinence diagnostique du rapport CystatineC versus Albumine-créatinine dans l'évaluation des complications cardiovasculaires (CVC). MÉTHODES: Cent deux patients diabétiques de type 2 et 100 sujets témoins de la même tranche d'âge ont été recrutés pour cette étude. Ceux-ci ont été classés en fonction des complications cardiovasculaires. La cystatine-C, la microalbuminurie, la créatinine sérique, HBA1c et TSH ont été analysées avec des méthodes standard. RÉSULTATS: Les concentrations moyennes de Cys-C, de microalbuminurie et de rapport albumine-créatinine ont montré une augmentation significative (p <0,05) chez les personnes souffrant de complications cardiovasculaires par rapport à celles sans complications cardiovasculaires. La ROC (courbe de l'opérateur du récepteur) a montré que le rapport albuminecréatinine (ACR) avait une sensibilité significative aux complications cardiovasculaires tandis que la cystatine-C n'a montré aucune sensibilité significative aux complications cardiovasculaires. La régression logistique binaire montre une association significative de l'ACR avec des complications cardiovasculaires contrairement à Cys-C qui n'a montré aucune association significative (p <0,05). CONCLUSION: Le rapport Cys-C et albumine-créatinine a augmenté chez les diabétiques et dérange davantage avec des complications cardiovasculaires. Cependant, le rapport albumine-créatinine a montré une plus grande sensibilité diagnostique aux complications cardiovasculaires par rapport à la cystatine-C. MOTS CLÉS: Cystatine-C; Rapport albumine-créatinine; Diabète sucré, maladies cardiovasculaires.

Combining glomerular basement membrane and tubular basement membrane assessment improves the prediction of diabetic end-stage renal disease.

BACKGROUND: To address the prognostic value of combining tubular basement membrane (TBM) and glomerular basement membrane (GBM) thickness in diabetic nephropathy (DN). METHODS: This retrospective study enrolled 110 patients with type 2 diabetes and biopsy-proven DN from 2011 to 2018. The pathological findings were confirmed according to the Renal Pathology Society classifications. GBM and TBM thicknesses were determined using the Haas' direct measurement/arithmetic mean method and orthogonal intercept method, respectively. Cox proportional hazard models were used to investigate the hazard ratios (HRs) for the influence of combined GBM and TBM thickness for predicting end-stage renal disease (ESRD). RESULTS: Patients were assigned to three groups according to the median GBM and TBM thickness: GBMlo TBMlo (GBM < 681 nm and TBM < 1200 nm), GBMhi TBMlo /GBMlo TBMhi (GBM ≥ 681 nm and TBM < 1200 nm, or GBM < 681 nm and TBM ≥ 1200 nm), and GBMhi TBMhi (GBM ≥ 681 nm and TBM ≥ 1200 nm). The GBMhi TBMlo /GBMlo TBMhi and GBMhi TBMhi groups displayed poorer renal function, a more severe glomerular classification and interstitial inflammation, and poorer renal survival rates than the GBMlo TBMlo group The GBMhi TBMlo /GBMlo TBMhi and GBMhi TBMhi groups had adjusted HRs of 1.49 (95% confidence interval [CI], 1.21-9.75) and 3.07 (95% CI, 2.87-12.78), respectively, compared with the GBMlo TBMlo group. CONCLUSIONS: TBM thickness enhanced GBM thickness for renal prognosis in patients with type 2 diabetes.

Economic Evaluation of a New Polygenic Risk Score to Predict Nephropathy in Adult Patients With Type 2 Diabetes.

OBJECTIVES: The current screening method for diabetic nephropathy (DN) is based on detection of albumin in the urine and decline of glomerular filtration rate. The latter usually occurs relatively late in the course of the disease. A polygenic risk score (PRS) was recently developed for early prediction of the risk for patients with type 2 diabetes (T2D) to develop DN. The aim of this study was to assess the economic impact of the implementation of the PRS for early prediction of DN in patients with T2D compared with usual screening methods in Canada. METHODS: A cost-utility analysis was developed using a Markov model. Health states include pre-end-stage renal disease (ESRD), ESRD and death. Model efficacy parameters were based on prediction of outcome data by polygenic risk testing of the genotyped participants in the Action in Diabetes and Vascular Disease PreterAx and DiamicronN Controlled Evaluation trial. Analyses were conducted from Canadian health-care and societal perspectives. Deterministic and probabilistic sensitivity analyses were conducted to assess results robustness. RESULTS: Over a lifetime horizon, the PRS was a dominant strategy, from both a health-care system and societal perspective. The PRS was less expensive and more efficacious in terms of quality-adjusted life-years compared with usual screening technics. Deterministic and probabilistic sensitivity analyses showed that results remained dominant in most simulations. CONCLUSIONS: This economic evaluation demonstrates that the PRS is a dominant option compared with usual screening methods for the prevention of DN in patients with T2D. Adoption of the PRS would reduce costs saving but would also help prevent ESRD and improve patients' quality of life.

Assessment of urinary NGAL for differential diagnosis and progression of diabetic kidney disease.

OBJECTIVE: Chronic kidney disease (CKD) related to diabetes has become more common than glomerulonephritis in recent years. Given the inefficient and difficult identification of diabetic kidney disease (DKD) from non-diabetic kidney disease (NDKD) as well as a result of emerging evidence supporting a role for tubular involvement in DKD, we aimed to investigate the utility of urinary neutrophil gelatinase-associated lipocalin (uNGAL) in the differential diagnosis and predictive value of DKD from NDKD. METHODS: Data for 100 type 2 diabetic patients with CKD at our center from June 2016 to August 2019 were reviewed. All the patients were categorized into 2 groups by the renal biopsy results: DKD and NDKD. Urinary NGAL levels were normalized by urinary creatinine and calculated as uNGAL/creatinine ratios (uNCR). The independent factors of the occurrence of DKD and the diagnostic implications of uNCR were explored by logistic regression and receiver-operating characteristic (ROC) curve analysis. In addition, we analyzed the relationship between uNCR and proteinuria in patients with DKD by Pearson test and linear regression. Kaplan-Meier survival analysis was performed to assess the prospective association of uNCR with the renal outcome. RESULTS: Significantly higher levels of uNCR were observed in patients with DKD when compared to those with NDKD (28.65 ng/mg vs 27.47 ng/mg, p< .001). uNCR was identified as an independent risk factor for the occurrence of DKD in diabetic patients with CKD (odds ratio [OR] = 1.020; 95%CI = [1.001-1.399], p = .042). The optimal cutoff value of uNCR for predicting DKD was 60.685 ng/mg with high specificity (90.5%) but relatively low sensitivity (55.7%). In Pearson test, uNCR was positively correlated with proteinuria, serum creatine, blood urea nitrogen, duration of diabetes, interstitial inflammation score and global sclerosis, whereas it was inversely correlated with eGFR, hemoglobin, serum albumin and 25-hydroxy vitamin D. Furthermore, in a fully adjusted model including eGFR, serum albumin and total cholesterol, the group with uNCR>60.685 ng/mg was associated with 7.595 times higher likelihood of nephrotic-range proteinuria compared to the group with uNCR≤60.685 ng/mg. In the Kaplan-Meier survival analysis, the event-free survival probability in patients with uNCR>60.685 ng/mg was significantly lower than those with uNCR≤60.685 ng/mg (p = .048). CONCLUSIONS: uNCR might serve as a potential tool for identifying cases in which there was a high clinical suspicion of DKD and that in whom confirmatory biopsy could be considered, and the best predictive cutoff value of normalized uNCR for DKD diagnosis was 60.685 ng/mg. Type 2 diabetic patients with increased level of uNCR had higher risk to nephrotic-range proteinuria and worse renal outcome.

Assessment and comparison of the antioxidant defense system in patients with type 2 diabetes, diabetic nephropathy and healthy people: A case-control study.

INTRODUCTION: Findings of previous studies in the field of antioxidant defense system in patients with type 2 diabetes (T2DM), diabetic nephropathy (DM) are limited and conflicting. Therefore, we evaluated the antioxidant defense system status in type 2 diabetes patients, diabetic nephropathy and healthy subjects in Iranian population. METHODS: This population-based case-control study was conducted in 2019 and included 30 individuals with T2DM and 30 patients with DN, as the case groups and 30 healthy subjects for the control group. Individuals entered to the study for case group were diagnosed as T2DM patients based on fast glucose blood tests (FGB) (≥126 mg/dL) and HbA1 (≥6.5%). DN was defined based on these tests and macroalbuminuria (>300 mg/day). Serum was carefully separated and antioxidant defense system status was estimated. Dietary intakes were evaluated by using a food frequency questionnaire (FFQ). RESULTS: Energy intake in control group was higher than case groups; BMI was higher in the DN group compared to the other groups. Significantly higher levels of MDA were observed in T2DM patients compared to control group in crude model (1.255 vs. 1.079 nmol/L; P = 0.006). The same results were shown after adjustment for potential confounders (1.256 vs. 1.085 nmol/L; P = 0.022). Total antioxidant capacity (TAC) was less in case groups compared with control group; level of catalase (CTL) and superoxide dismutase enzymes comparisons showed that DN patients had higher level than control group, but these associations were not significant. CONCLUSIONS: We found that MDA levels were significantly higher in T2DM patients compared to control group. Level of TAC was less in case groups in comparison to controls. SOD and CTL levels were higher in DN compared to controls; these associations were not significant.

Bioengineered Polymer/Composites as Advanced Biological Detection of Sorbitol: An Application in Healthcare Sector.

Bioengineered polymers and nanomaterials have emerged as promising and advanced materials for the fabrication and development of novel biosensors. Nanotechnology-enabled biosensor methods have high sensitivity, selectivity and more rapid detection of an analyte. Biosensor based methods are more rapid and simple with higher sensitivity and selectivity and can be developed for point-of-care diagnostic testing. Development of a simple, sensitive and rapid method for sorbitol detection is of considerable significance to efficient monitoring of diabetes-associated disorders like cataract, neuropathy, and nephropathy at initial stages. This issue encourages us to write a review that highlights recent advancements in the field of sorbitol detection as no such reports have been published till the date. The first section of this review will be dedicated to the conventional approaches or methods that had been playing a role in detection. The second part focused on the emerging field i.e. biosensors with optical, electrochemical, piezoelectric, etc. approaches for sorbitol detection and the importance of its detection in healthcare application. It is expected that this review will be very helpful for readers to know the different conventional and recent detection techniques for sorbitol at a glance.

Non-invasive assessment of vibration perception and protective sensation in people with diabetes mellitus: inter- and intra-rater reliability.

BACKGROUND: Testing of protective sensation and vibration perception are two of the most commonly used non-invasive methods of screening for diabetes-related peripheral neuropathy (DPN). However, there is limited research investigating the reliability of these tests in people with diabetes. The aim of this study was to determine the inter- and intra-rater reliability of methods used to test vibration perception and protective sensation in a community-based population of adults with type 2 diabetes. METHODS: Three podiatrists with varying clinical experience tested four- and 10-site, 10 g monofilament and vibration perception threshold (VPT). In a separate cohort, the reliability of a graduated tuning fork as well as two methods of conventional tuning fork (on/off method and dampening method) was undertaken by a new graduate podiatrist and podiatrist with one-year's clinical experience. The intra- (Cohen's К) and inter-rater (Cohen's or Fleiss' К) reliability of each test was determined. RESULTS: Fifty participants (66% male, 100% type 2, 32% with DPN) underwent monofilament and neurothesiometer testing with 44 returning for the retest. Twenty-four participants (63% male, 100% type 2, 4% with DPN) underwent tuning fork testing and returned for retest. All tests demonstrated acceptable inter-rater reliability ranging from moderate (10-site monofilament, К: 0.54, CI: 0.38-0.70, p = 0.02) to substantial (graduated tuning fork, К: 0.68, CI: 0.41-0.95, p < 0.01). The 10-site monofilament (К: 0.44-0.77) outperformed the 4-site test (К: 0.34-0.67) and the dampened tuning fork method (К: 0.41-0.49) showed lower intra-rater reliability compared to both conventional (К: 0.52-0.57) and graduated methods (К: 0.50-0.57). CONCLUSION: We support the current recommendations of using more than one test to screen and monitor progression of DPN. Four- and 10-site 10 g monofilament testing have similarly acceptable levels of reliability and the neurothesiometer is the most reliable method of assessing vibration perception function. Use of a graduated tuning fork was slightly more reliable than other methods of tuning fork application however all had substantial reliability. Years of clinical experience only marginally affected test reliability overall and due to subjective nature of the tests we suggest that testing should be performed regularly and repetitively.

Can a semi-quantitative method replace the current quantitative method for the annual screening of microalbuminuria in patients with diabetes? Diagnostic accuracy and cost-saving analysis considering the potential health burden.

OBJECTIVES: Diabetes is a global epidemic, and the high cost of annually and quantitatively measuring urine albumin excretion using the turbidimetric immunoassay is challenging. We aimed to determine whether a semi-quantitative urinary albumin-creatinine ratio test could be used as a screening tool for microalbuminuria in diabetic patients. METHODS: We assessed the diagnostic accuracy of the semi-quantitative method. The costs of false results in the semi-quantitative method were calculated based on the annual probability of disease progression analyzed through a systematic literature review and meta-analysis. The pooled long-term cost-saving effect of the semi-quantitative method compared with the quantitative test was assessed using a Markov model simulating a long-term clinical setting. Diagnostic accuracy and the cost-saving effect were also validated in an independent external cohort. RESULTS: Compared with the quantitative test, the semi-quantitative method had sensitivities of 93.5% and 81.3% and specificities of 61.4% and 63.1% in the overall sample of diabetic patients (n = 1,881) and in diabetic patients with eGFR ≥60 ml/min/1.73 m2 and a negative dipstick test (n = 1,110), respectively. After adjusting for direct and indirect medical costs, including the risk of disease progression, which was adjusted by the meta-analyzed hazard ratio for clinical outcomes, it was determined that using the semi-quantitative method could save 439.4 USD per person for 10 years. Even after adjusting the result to the external validation cohort, 339.6 USD could be saved for one diabetic patient for 10 years. CONCLUSIONS: The semi-quantitative method could be an appropriate screening tool for albuminuria in diabetic patients. Moreover, it can minimize the testing time and inconvenience and significantly reduce national health costs.

Assessment of two novel renal tubular proteins in type 2 diabetic patients with nephropathy.

Nephropathy is a common health issue associated with type 2 diabetes mellitus (T2DM). Treatment of diabetic nephropathy (DN) in an early stage can effectively inhibit its progression. Albuminuria is the currently accepted marker for detection of DN.This study aims to evaluate the urinary level of two novel renal tubular proteins (cyclophilin A and periostin) in patients with T2DM and among different nephropathy stages and also to validate the diagnostic accuracy of both cyclophilin A and periostin as potential markers for early prediction of DN relative to albuminuria.This cross-sectional study recruited 137 patients with T2DM, and they were divided based on their urinary albumin:creatinine ratio into T2DM with normoalbuminuria (group II), incipient T2DN with microalbuminuria (group III) and overt T2DN with macroalbuminuria (groupIV) beside 41 healthy subjects as group I Cyclophilin A and periostin were measured in the urine using ELISA. Diagnostic accuracy of both markers was determined for prediction of DN via receiver operating characteristic curve analyses.Urinary cyclophilin A and periostin levels were significantly higher in DN groups when compared with T2DM with normoalbuminuria group. For prediction of incipient and overt DN, areas under the curve (AUCs) of periostin were 0.954, 0.997 and cyclophilin A were 0.914, 0.937, respectively. AUCs of periostin were higher than that for cyclophilin A with a significant AUC difference (p=0.022) in overt DN stage.Periostin and cyclophilin A could be regarded as a potential urinary biomarker for early prediction of DN. Periostin exhibits a higher diagnostic accuracy than urinary cyclophilin A specifically in overt DN stage.

Impact of chronic kidney disease definition on assessment of its incidence and risk factors in patients with newly diagnosed type 1 and type 2 diabetes in the UK: A cohort study using primary care data from the United Kingdom.

AIM: To estimate the incidence and risk factors of chronic kidney disease (CKD) in patients with newly-diagnosed diabetes using different CKD definitions. METHODS: Using UK primary care data, patients with diabetes (type 1, 4691; type 2, 109,365) and no CKD were followed to identify newly-diagnosed CKD, classified by a broad and narrow CKD definition (to capture diabetes-induced CKD, termed diabetic kidney disease, DKD). Adjusted incidence rates of CKD/DKD were calculated, and risk factors identified using Cox regression. RESULTS: There were 404 CKD cases and 147 DKD cases among patients with type 1 diabetes (T1D), and 29,104 CKD cases, 9284 DKD cases among patients with type 2 diabetes (T2D). Adjusted incidence rates of CKD per 100 years were 5.4 (T1D) and 5.5 (T2D); for DKD they were 1.9 and 1.5, respectively. Risk factors for CKD/DKD were older age, high social deprivation, obesity, cardiovascular disease, hypertension and smoking. Poor glycaemic control in the year after diabetes diagnosis was a strong predictor of CKD/DKD occurrence beyond this first year, and a risk factor for CKD/DKD in T2D. CONCLUSIONS: CKD and DKD remain common in diabetics in the decade after diagnosis. Early prevention of T2D and aggressive treatment of risk factors is urgent.

Assessment of Urinary MicroRNAs by Quantitative Polymerase Chain Reaction in Diabetic Nephropathy Patients.

Urinary microRNAs show promise as noninvasive biomarkers in renal disease. Here, we describe a detailed protocol for the column-based extraction and quantification of miRNAs by reverse-transcription quantitative polymerase chain reaction (RT-qPCR) from urine samples.