Expression of Angiopoetin-Like Protein-4 and Kidney Injury Molecule-1 as Preliminary Diagnostic Markers for Diabetes-Related Kidney Disease: A Single Center-Based Cross-Sectional Study.

The purpose of the study was to examine the urinary levels of kidney injury molecule-1 (KIM-1) and angiopoietin-like protein-4 (ANGPTL-4) in individuals with diabetic kidney disease (DKD) and their association with established DKD diagnostic markers such as albuminuria and estimated glomerular filtration rate (eGFR). Levels of ANGPTL-4 and KIM-1 were estimated in urine samples. A total of 135 participants were recruited into three groups: 45 diabetes type 2 patients in the control group and 90 DKD patients in two disease groups. Concentrations of ANGPTL-4 and KIM-1 were conclusively related to the urinary albumin-creatinine ratio (UACR). Also, the levels of both ANGPTL-4 and KIM-1 were negatively associated with the eGFR. Multivariable Poisson regression analysis showed that urinary ANGPTL-4 (PR: 3.40; 95% CI: 2.32 to 4.98; p < 0.001) and KIM-1 (PR: 1.25; 95% CI: 1.14 to 1.38; p < 0.001) were prevalent in DKD patients. Receiver operating characteristic (ROC) analysis of urinary ANGPTL-4 and KIM-1 in the combined form resulted in an area under curve (AUC) of 0.967 (95%CI: 0.932-1.000; p < 0.0001) in the microalbuminuria group and 1 (95%CI: 1.000-1.000; p < 0.0001) in the macroalbuminuria group. The association of urinary levels of ANGPTL-4 and KIM-1 with UACR and eGFR and significant prevalence in the diabetic kidney disease population illustrates the diagnostic potential of these biomarkers.

Insight into the Exemplary Physical Properties of Zn-Based Fluoroperovskite Compounds XZnF3 (X = Al, Cs, Ga, In) Employing Accurate GGA Approach: A First-Principles Study.

Using the full-potential linearized augmented plane wave (FP-LAPW) method, dependent on density functional theory, the simple cubic ternary fluoroperovskites XZnF3 (X = Al, Cs, Ga, In) compound properties, including structural, elastic, electronic, and optical, are calculated. To include the effect of exchange and correlation potentials, the generalized gradient approximation is applied for the optimization operation. This is identified, when we are changing the metallic cation specified as "X" when shifting to Al from Cs, the value of the bulk modulus is found to increase, showing the rigidity of a material. Depending upon the value of the bulk modulus, we can say that the compound AlZnF3 is harder and cannot be compressed as easily as compared to the other three compounds, which are having a lower value of the bulk modulus from AlZnF3. It is also found that the understudy compounds are mechanically well balanced and anisotropic. The determined value of the Poisson ratio, Cauchy pressure, and Pugh ratio shows our compounds have a ductile nature. From the computation of the band structure, it is found that the compound CsZnF3 is having an indirect band of 3.434 eV from (M-Γ), while the compounds AlZnF3, GaZnF3, and InZnF3 are found to have indirect band gaps of 2.425 eV, 3.665 eV, and 2.875 eV from (M-X), respectively. The optical properties are investigated for radiation up to 40 eV. The main optical spectra peaks are described as per the measured electronic structure. The above findings provide comprehensive insight into understanding the physical properties of Zn-based fluoroperovskites.

Nicotinamide Therapy in Dialysis Patients: A Systematic Review of Randomized Controlled Trials.

Randomized controlled trials (RCTs) have presented variable findings concerning the reduction of phosphorous level by nicotinamide. This systematic review is aimed to explore the safety and efficacy of nicotinamide in hemodialysis patients and was conducted by adhering to the PRISMA guidelines. Studies for inclusion were identified by running the suitable keywords in PubMed, Embase, and Cochrane Central till June 13, 2018. Cochrane risk of bias tool was used to judge the quality of the included RCTs. The primary outcome was change in serum phosphorus, calcium, and calcium-phosphorus product levels. Change in other biochemical parameters including serum calcium, parathormone, platelets, lipid profile parameters, and the safety profile was considered under secondary outcomes. Review Manager (RevMan v5.3) was used for the risk of bias estimate. A total of 12 articles were qualified for inclusion in this study. All the included RCTs showed a statistically significant reduction in mean serum phosphorous and calcium-phosphorus product levels in the treatment arm as compared to the placebo group. Among several biochemical parameters analyzed, only high-density lipoprotein (HDL) was found to be significantly increased from baseline to the endpoint of the study in the nicotinamide group, while the placebo group showed no significant difference. Flushing and diarrhea, followed by thrombocytopenia, were the most commonly reported adverse events in the treatment group. Nicotinamide was found to be effective in reducing the phosphorous level and calcium-phosphorus product level and increasing the HDL cholesterol level in dialysis patients. The safety profile was found to be satisfactory.

Pharmacological screening of fenofibrate-loaded solid dispersion in fructose-induced diabetic rat.

OBJECTIVES: Hyperlipidaemia is a common phenomenon in diabetes mellitus. Fenofibrate (FF) is a good candidate for the treatment of lipid abnormalities in patients with type 2 diabetes. But the bioavailability as well as therapeutic efficacy of this drug is limited to its dissolution behaviour. Here, the authors assess the therapeutic efficacy of a newly formulated solid dispersion of fenofibrate (SDF) having enhanced dissolution profiles in contrast to pure FF using fructose-induced diabetic rat model. METHODS: Fructose-induced diabetic rat model was developed to assess the pharmacological efficacy of the formulated SDF, and the results were compared with the effects of conventional FF therapy. KEY FINDINGS: The 14 days treatment showed better improvement in lipid-lowering potency of SDF than pure FF. SDF containing one-third dose of pure FF showed similar effect in terms of triglyceride, total cholesterol and low-density lipoprotein lowering efficacy, whereas increased high-density lipoprotein at same extent. The similar dose of SDF produced more prominent effect than FF. Histological studies also demonstrated the enhanced lipid clearance from liver by SDF than FF that was concordant with the biochemical results. CONCLUSIONS: This newly formulated SDF would be a promising alternative for conventional fenofibrate in treating hyperlipidaemia.

Potential biomarkers for early detection of diabetic kidney disease.

INTRODUCTION: To assess the potential of galectin-3 and growth differentiation factor-15 (GDF-15) biomarkers for the early detection of diabetic kidney disease (DKD). METHODOLOGY: This was a cross-sectional study conducted over a period of 1.2 years. Patients were stratified based on estimated glomerular filtration rate (eGFR) and albuminuria level. The receiver operating characteristic (ROC) curve was plotted to assess the diagnostic potential of biomarkers. RESULTS: A total of 90 patients included in this study. Patients were grouped as normoalbuminuria (30 patients), microalbuminuria (30 patients), and macroalbuminuria (30 patients). Galectin-3 and GDF-15 levels were significantly elevated in T2DM patients with macroalbuminuria (p = <0.05). Higher levels of galectin-3 and GDF-15 were found in patients with poor kidney function (Stage IV-V CKD). Negative correlation was observed between galectin- 3 (r = -0.472) and eGFR (p = 0.000), GDF-15 (r = -0.917) and eGFR (p <0.000). The ROC analysis yielded an area under curve (AUC) of 0.776 (95% CI: 0.677 to 0.875; p = <0.0001) for galectin-3 and an AUC of 0.963 (95% CI: 0.929 to 0.997; p = <0.0001) for GDF-15. CONCLUSION: In DKD patients the galectin-3 and GDF-15 levels were inversely related to the eGFR which was further confirmed by the ROC curve demonstrating the potential of galectin-3 and GDF-15 as a biomarker.

Prevalence of peripheral neuropathy and associated pain in patients with diabetes mellitus: Evidence from a cross-sectional study.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is the most common and troublesome complication of diabetes mellitus. It affects almost half the population with diabetes and worsens quality of life of the patient. This study was aimed to determine the prevalence of peripheral neuropathy and associated pain in patients with diabetes mellitus. METHODS: This was a cross-sectional study conducted over a period of six months. Patient's ≥ 18 years with confirmed diagnosis of diabetes mellitus were included in the study. Patients with hypothyroidism, medical illness such as cancer, liver or renal disease, cervical or lumbar spondylosis, pregnant patients with diabetes and patients receiving any treatment that might influence nerve function (e.g., cytotoxic or antiepileptic agents) were excluded from the study. DPN was diagnosed using 10 g monofilament test. The S-LANSS questionnaire was used to assess the associated painful symptoms. Association was calculated using chi-square test. A p- value of ≤0.05 was considered statistically significant. All the statistical analysis was performed using SPSS v22. RESULT: The overall prevalence of DPN was found to be 28.85% from which 88% patients were found to have painful symptoms. A significant association of DPN was observed with the duration of diabetes (p = 0.004), poor glycaemic control (p = 0.03) and other diabetic complications such as nephropathy (p = 0.002). No association of neuropathy was found with retinopathy and hypertension. Duration of diabetes (>15 years), and HbA1c (>9%) was found to be positively associated the painful DPN. CONCLUSION: The current study found a high prevalence of DPN and it was found to be significantly associated with duration of diabetes, poor glycaemic control and nephropathy.

Anemia prevalence and its impact on health-related quality of life in Indian diabetic kidney disease patients: Evidence from a cross-sectional study.

AIM: The aim of the study was to determine the prevalence, predictors of anemia, and its impact on health-related quality of life among diabetic kidney disease (DKD) patients. METHODS: Patients with a confirmed diagnosis of type 2 diabetes mellitus (T2DM), and had any stages of CKD (stages I to IV), based on their estimated glomerular filtration rate (eGFR) were enrolled in the study. Anemia was defined using the World Health Organization (WHO) criteria and quality of life was assessed using the EQ-5D scale. All the statistical analysis was performed using SAS v9.4. RESULTS: A total of 323 patients completed the study. The mean ± SD age of patients was 56 ± 11.25 years, and 51.7% were female. Mean duration of diabetes was 9.6 ± 4.57 years. A total of 227 (70.27%) had anemia as per the WHO criteria. Linear association was observed between the eGFR and hemoglobin. After controlling for the possible confounders in multivariate logistic regression analysis, older age (odds ratio [OR]: 2.46 [95% CI: 1.16 to 5.28], P = .021), diabetes duration (OR: 1.53 [95% CI: 1.04 to 2.25], P = .022), and CKD stage III (OR: 3.63 [95% CI: 0.99 to 13.32], P = .004) were found to be significantly associated with the anemia. Consistently lower EQ-5D index values were observed for the anemic group. CONCLUSION: This study reported a high prevalence of anemia and impaired quality of life among DKD patients. Routine screening of anemia can be the most preventive measure to deal with this burdening co-morbid condition.

Limited Knowledge of Chronic Kidney Disease among Type 2 Diabetes Mellitus Patients in India.

Diabetes and hypertension are the two major causes of chronic kidney disease (CKD). Epidemiological studies have found poor knowledge about the CKD among the general population. Hence, this study aimed to assess the awareness of CKD among type 2 diabetes mellitus (T2DM) patients in India. Patients with confirmed T2DM were included in the study. Patients receiving dialysis or with a history of a kidney transplant were excluded. A validated questionnaire was used to assess knowledge about CKD. Demographic characteristics were presented using descriptive statistics and trends in groups were calculated using the chi-square test. Statistical analysis was performed using SAS v9.4. A total of 323 patients completed the study. The mean age of the patients was 56 ± 11.25 years, and 51.7% were female. Only 33.43% of the patients correctly identified diabetes and hypertension as risk factors for CKD, while 44.27% were aware of the kidney's function. Statistically significant associations were observed between kidney disease knowledge and education status (p = 0.004), socioeconomic status (p = 0.000), and income status (p = 0.003). No association was observed between the knowledge about CKD and age, gender, hypertension stages, CKD stages, duration of diabetes as well as hypertension and co-morbidities. Based on the results of this study, we found poor knowledge of CKD among Indian T2DM patients. The government should start a CKD awareness programme to deal with this rising co-morbid condition.

Warfarin use increases bleeding risk in hemodialysis patients with atrial fibrillation: A meta-analysis of cohort studies.

BACKGROUND AND AIM: Atrial fibrillation is one of the most common comorbid conditions in hemodialysis patients, and warfarin is widely prescribed anticoagulant to prevent thromboembolic complications in such patients. In the last decade, several epidemiological studies pointed out the risk of bleeding with the use of warfarin. So, this meta-analysis is aimed to assess the bleeding risk associated with the use of warfarin. METHODS: This meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. PubMed, Embase, Scopus, and Cochrane central databases were searched from inception to June 10, 2018. The primary outcome was to quantify the bleeding risk associated with warfarin use. The secondary outcome was to assess the bleeding risk based on different subgroups. Review Manager (RevMan) version 5.3 was used for performing statistical analysis. RESULTS: A total of 15 studies, constituting a pooled sample of 53 581 patients (37.14% female), were included. Of these, 17 469 were warfarin users. We found that warfarin use had a significant association with the bleeding risk. The pooled relative risk (RR) of bleeding was estimated to be 1.35 (95% CI: 1.18-1.53, P = < 0.00001), and the pooled RR of major bleeding (five studies) was estimated to be 1.32 (95% CI: 1.07-1.63, P = 0.009). Subgroup analysis revealed a significant association of warfarin use with the intracranial hemorrhage/hemorrhagic stroke (nine studies) (pooled RR: 1.43 [95% CI: 1.20-1.71, P = < 0.0001]). CONCLUSIONS: The results indicate that warfarin use increases the risk of bleeding in hemodialysis patients with atrial fibrillation.

Design, synthesis, and molecular docking study of benzothiazolotriazine derivatives for anticonvulsant potential.

A series of newer benzothiazolotriazine derivatives (4a-k) was designed, synthesized, and characterized as anticonvulsant agents against the two classically used MES and scPTZ animal models. The synthesized derivatives were tested in vivo in both the animal models, followed by a neurotoxicity study by the rotarod method. Compound 4e, 8-chloro-4-(2-chlorocyclohexa-1,5-dien-1-yl)-2-((4-methoxybenzyl)thio)-10aH-benzo[4,5]thiazolo[3,2a][1,3,5]triazine was found most promising among the series in both the animal models, with no neurotoxicity. From this it may be confirmed that the presence of a methoxy (OCH3 ) group at the lipophilic aryl ring was showing high anticonvulsant potency. In the molecular modeling study, compound 4e (docking score = -8.70) showed important hydrogen bond interaction with the amino acids LYS 329, SER 137, GLY 136 and π-π interactions with PHE 189 at the active site of GABA-AT. These derivatives can be further explored for the development of newer/novel anticonvulsant agents.

Prevalence of depression among type 2 diabetes mellitus patients in India: A meta-analysis.

Depression as a co-morbid condition in type 2 diabetes mellitus (T2DM) patients is associated with significant morbidity, mortality, and rising health economic burden. Indian healthcare system is heavily burdened with T2DM, and it is important to understand the prevalence of depression associated with T2DM. This meta-analysis conducted as per the registered protocol (PROSPERO registration: CRD42016051552), searched for published studies in the databases including MEDLINE and Embase till 31st August 2018. The modified Newcastle-Ottawa Scale was used to assess the methodological quality. The pooled prevalence of depression among T2DM patients was estimated as primary outcomes, while prevalence based on demographic sub-group was estimated as the secondary outcome. In total, 43 studies including 10,270 patients fulfilled the eligibility criteria and were included in the analysis. The pooled prevalence of depression in T2DM patients was found to be 38% (95% CI: 31%-45%). Presence of depression in people with type 2 diabetes was more often associated with the presence of complications with an odds ratio of 2.33, 95% CI: 1.62-3.36, p < 0.00001. Overall, the study found a high prevalence of depression among T2DM patients in India. Diabetes management programs in India may consider early screening of depression in T2DM patients.

Proton pump inhibitors' use and risk of hip fracture: a systematic review and meta-analysis.

In the last decade, epidemiological studies presented inconsistent findings concerning the proton pump inhibitors (PPI) use and the risk of hip fracture. So, this systematic review and meta-analysis were performed with the aim to quantify the risk of hip fracture associated with PPI use. PubMed® and Cochrane Central databases were searched from inception to January 2018. The quality of included studies in meta-analysis was assessed using Newcastle-Ottawa scale. Primary outcome of this study was to assess the risk of hip fracture among PPI user. Secondary outcomes include subgroup analysis based on study design, study quality, duration of PPI use, calcium intake, and geographical region. Sensitivity analysis was also performed. Review Manager (RevMan) was used to perform statistical analysis. This meta-analysis was based on seventeen studies. Pooled risk ratio showed a statistically significant association between PPI use and hip fracture risk (RR 1.26 [95% CI 1.17-1.35], p < 0.00001). Subgroup analysis, based on the study design, showed a highly significant association between PPI use and risk of hip fracture (p < 0.0001). The risk of hip fracture persisted even when stratified by calcium adjustment and the duration of PPI use (p < 0.0001). This meta-analysis suggests that PPI user have a 26% increased risk of hip fracture as compared to non-PPI user. Physicians should take caution in prescribing PPI to patients who are at increased risk of hip fracture.

Calcium channel blocker use reduces incident dementia risk in elderly hypertensive patients: A meta-analysis of prospective studies.

Calcium channel blockers (CCBs) are an established class of drug for the management of hypertension. Observational studies have found that CCB use is associated with a reduction in the risk of developing dementia; however, studies have variably linked the CCBs use with the risk of dementia. This meta-analysis aims to assess whether, in elderly hypertensive patients, the use of CCBs alters the risk of developing dementia. We searched PubMed, Embase and Cochrane from August 2013 to 21st August 2017. Studies were screened on the basis of title and abstract. Quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS). The primary outcome was an estimate of the risk of dementia in elderly hypertensive CCBs users. The pooled relative risk (RR) was calculated using a generic inverse variance method. A subgroup analysis was also performed based on CCB class. Statistical analyses were performed using Review Manager Version 5.3. The meta-analysis included ten studies comprising 75,239 patients (53.16% female) with a median age and follow-up duration of 72.24 years and 8.21 years respectively. All of the studies were of high quality. The use of CCBs was associated with a significant reduction in the risk of developing dementia in elderly hypertensive patients (RR 0.70 [95% CI: 0.58-0.85] p = 0.0003) compared to those not using CCBs. In subgroup analysis we found that the dihydropyridine class was associated with a 44% [RR 0.56 (95% CI: 0.40-0.78) p = 0.0005] reduction in the dementia risk. The use of CCBs was associated with a significant reduction in the risk of developing dementia in elderly hypertensive patients.

Potential Association of Triglyceride Glucose Index with Cardiac Autonomic Neuropathy in Type 2 Diabetes Mellitus Patients.

Cardiac autonomic neuropathy (CAN) is a common and most neglected complication of diabetes, estimated to be roughly 8% in recently diagnosed patients and greater than 50% in patients with chronic disease history. The insulin resistance (IR) itself is bidirectionally associated with increased risk of type 2 diabetes mellitus (T2DM) and CAN is a predisposing factor. The primary objective of the present study was aimed to find a correlation of triglyceride glucose index (TyG index) in CAN patients along with the prevalence of CAN in T2DM patients as a secondary objective. This prevalence study was conducted on 202 patients visiting the diabetic clinic of Hamdard Institute of Medical Sciences and Research, Jamia Hamdard (HIMSR) teaching hospital in New Delhi, India who fulfilled the inclusion criteria. The Ewings autonomic function test was used for diagnosis of CAN. TyG index was calculated for patients based on fasting levels of glucose and triglyceride. The CAN was diagnosed in 62 participants out of 202 T2DM patients (overall prevalence 30.7%). The mean ± standard deviation (SD) for TyG index was 10.3 ± 0.2 and 9.5 ± 0.2 in CAN positive, T2DM patients, respectively. The difference of TyG index, in CAN positive and T2DM patients, was highly significant (P < 0.001). Further correlation analysis was performed to find an association of TyG index, duration, and age with patient groups. TyG index showed a positive correlation with heart rate during deep breathing (HRD), heart rate variation during standing (HRS), blood pressure (BP) response to handgrip and BP response to standing. Our finding highlights the TyG index, low-cost IR index, might be useful as an alternative tool for the early screening of patients at a high risk of diabetic neuropathy.

In vivo analysis of toxic effect of hydrose used in food preparations in Bangladesh

Objective: To evaluate the toxic effect of hydrose used in the molasses preparation in Bangladesh.Methods:Molasses were collected from open markets in different parts of Bangladesh. The presence of hydrose in selected molasses was detected using commercial kit. To evaluate the toxic effect of hydrose, Swiss albino male mice were divided into four groups. Group I was used as control, while Groups II, III and IV received hydrose mixing food (5, 10 and 25 g/kg food), respectively, and these supplementations were continued to the end of the study (16 weeks). Blood was collected from thoracic arteries of the mice under ether anesthesia and then organs were taken. To determine the effect of hydrose on host, blood indices related to liver, heart and kidney dysfunctions were measured.Results:Creatinine and urea levels were significantly (P<0.05) increased in a dose dependent manner in hydrose treated mice, whereas calcium level was significantly decreased in hydrose exposed mice compared to control mice. Histological study of kidney showed the glomeruler inflammation, increased diameter of renal glomeruli and enlargement of proximal tubular lumen of kidneys of mice exposed to hydrose compared to that of control animals. Conclusions: The results of this study indicated that use of hydrose in molasses and other food preparations in Bangladesh may cause kidney impairment.